9781118145296...he prevention of infectious disease transmission from human exposure to contaminated...
TRANSCRIPT
QUANTITATIVEMICROBIAL RISKASSESSMENT
SECOND EDITION
QUANTITATIVEMICROBIAL RISKASSESSMENT
CHARLES N HAAS
JOAN B ROSE
CHARLES P GERBA
Copyright copy 2014 by John Wiley amp Sons Inc All rights reserved
Published by John Wiley amp Sons Inc Hoboken New JerseyPublished simultaneously in Canada
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Limit of LiabilityDisclaimer of Warranty While the publisher and author have used their best effortsin preparing this book they make no representations or warranties with respect to the accuracy orcompleteness of the contents of this book and specifically disclaim any implied warranties ofmerchantability or fitness for a particular purpose No warranty may be created or extended bysales representatives or written sales materials The advice and strategies contained herein may not besuitable for your situation You should consult with a professional where appropriate Neither thepublisher nor author shall be liable for any loss of profit or any other commercial damages including butnot limited to special incidental consequential or other damages
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Library of Congress Cataloging-in-Publication Data
Haas Charles NQuantitative microbial risk assessment Charles N Haas Joan B Rose Charles P Gerba ndash Second edition
p cmIncludes bibliographical references and indexISBN 978-1-118-14529-6 (cloth alk paper)
1 Communicable diseasesndashEpidemiologyndashMethodology 2 Health risk assessment 3 InfectionndashMathematical models 4 Environmental healthndashMathematical models I Rose Joan B II GerbaCharles P 1945- III Title
RA643H22 2014615902ndashdc23
2014002690
Printed in the United States of America
10 9 8 7 6 5 4 3 2 1
CONTENTS
PREFACE xi
CHAPTER 1 MOTIVATION 1
Prevalence of Infectious Disease 1
Prior Approaches 4
Scope of Coverage 4
Potential Objectives of a QMRA 5
Site-Specific Assessment 5
Ensemble of Sites 6
Secondary Transmission 7
Outbreaks versus Endemic Cases 7
References 10
CHAPTER 2 MICROBIAL AGENTS AND TRANSMISSION 15
Microbial Taxonomy 15
Eukaryotes 15
Prokaryotes 18
Viruses 20
Prions 22
Clinical Characterization 24
Microorganisms of Interest 27
Viruses 27
Bacteria 37
Protozoa 42
Transmission Routes 45
Inhalation 48
Dermal Exposure 50
Oral Ingestion 50
References 55
CHAPTER 3 RISK ASSESSMENT PARADIGMS 63
Chemical Risk Assessment National Academy of Sciences Paradigm 63
Ecological Risk Assessment 67
Approaches for Assessing Microbial Risks 71
Background 71
v
The QMRA Framework 74
Hazard Identification 74
DosendashResponse Assessment 74
Exposure Assessment 76
Risk Characterization 77
Risk Management 79
Development of the QMRA Framework and Processes 79
QMRA and the Safety of Water 82
QMRA Food Safety and the HACCP System 84
References 86
CHAPTER 4 CONDUCTING THE HAZARD IDENTIFICATION (HAZ ID) 91
Identifying and Diagnosing Infectious Disease 92
Health Outcomes Associated with Microbial Infections 95
Sensitive Populations 100
Women during Pregnancy Neonates and Young Babies 101
Diabetes 102
The Elderly 102
The Immunocompromised 104
Databases for Statistical Assessment of Disease 106
ICD Codes 107
Waterborne and Foodborne Outbreaks 111
Epidemiological Methods for Undertaking HAZ ID 117
Controlled Epidemiological Investigations 118
HAZ ID Data Used in the Risk Assessment Process 119
Recommendations for Updating Quantitative Data for HAZ ID Information 121
References 122
CHAPTER 5 ANALYTICAL METHODS AND THE QMRA FRAMEWORKDEVELOPING OCCURRENCE AND EXPOSURE DATABASES 129
Introduction 129
Approaches for Developing Occurrence and Exposure Databases 132
Overview of Methodological Issues 134
Sampling Water 136
Sampling Surfaces and Food 138
Sampling Aerosols 138
Specific Techniques for Bacteria Protozoa and Viruses 140
Bacteria 140
Protozoa 142
Viruses 143
Molecular Techniques 145
Probes (FISH) 146
Typing 146
vi CONTENTS
Metagenomics 147
PCR and Quantitative PCR 147
References 151
CHAPTER 6 EXPOSURE ASSESSMENT 159
Conducting the Exposure Assessment 159
Characterizing ConcentrationDuration Distributions 160
Random (Poisson) Distributions of Organisms 160
Estimation of Poisson Mean in Count Assay (Constant and Variable Volumes) 162
Count Assay with Upper Limits 163
Estimation with Quantal Assay 164
Goodness of Fit to Poisson Plate Assay 168
Goodness of Fit MPN 178
Confidence Limits Likelihood 182
Implications for Risk Assessment 187
Consumption Distributions 214
Systematic Subpopulation Differences 221
Afterword 223
Appendix 224
Microsoft Excel 224
MATLAB 225
R 227
References 230
CHAPTER 7 PREDICTIVE MICROBIOLOGY 235
Objective 235
Basic First-Order Processes and Deviations 236
Biological and Physical Bases for Deviations 236
Physical Removal 238
Types of Decay Processes 238
General Forms of Decay and Reasons for Nonlinearity 238
SpontaneousEndogenous 240
Chemical Agents 241
Thermally Induced 243
Ionizing and Nonionizing Radiation 243
Predation and Antagonism 245
Types of Growth Processes 245
Mathematical Modeling of Growth Curves 246
Substrate Dependency 252
Structured Growth Models 255
Incorporation of Decay into Growth Models 256
Systems Biology Approaches 258
CONTENTS vii
Dependence of Growth Parameters on Other Environmental Variables 258
Interacting Populations 258
Data Sources 260
References 263
CHAPTER 8 CONDUCTING THE DOSEndashRESPONSE ASSESSMENT 267
Plausible DosendashResponse Models 268
Framework for Mechanistic DosendashResponse Relationships 269
Exponential DosendashResponse Model 271
Beta-Poisson DosendashResponse Model 272
Simple Threshold Models 274
Negative Binomial Dose Distributions 277
Variable Threshold Models 278
Other Mixture Models 279
Biological Arguments for One-Hit Models 281
Empirical Models 282
Fitting Available Data 283
Types of Data Sets 284
Potential Impacts of Immune Status 298
Relationship between Dose and Severity (Morbidity and Mortality) 299
Morbidity Ratio (PDI) 299
Mortality Ratio 303
Reality Checking Validation 304
Validation 1993 Milwaukee Outbreak 304
Use of Indicators and Other Proxy Measures in DosendashResponse 305
Indicator Methods 305
Molecular Methods 307
Advanced Topics in DosendashResponse Modeling 308
DosendashResponsendashTime Models 308
Physiological Models 313
Appendix 315
References 317
CHAPTER 9 UNCERTAINTY 323
Point Estimates of Risk 324
Terminology Types of Uncertainty 326
Sources of Uncertainty 327
Sources of Variability 328
Variability that is Uncertain 329
Approaches to Quantify Parametric Uncertainty 329
Likelihood 329
Bootstrap 330
Other Methods 330
viii CONTENTS
Applications 332
Exposure Assessment 332
DosendashResponse Assessment 338
Combining Parametric Uncertainty from Multiple Sources 344
Propagation Methods 344
Monte Carlo Analyses 347
Overall Risk Characterization Example 365
Second-Order Methods 368
Model Uncertainty and Averaging 370
References 373
CHAPTER 10 POPULATION DISEASE TRANSMISSION 377
Introduction Models for Population and Community Illnesses 377
Basic SIR Model 378
Incubation Period 386
Duration of Illness 388
Secondary Cases 389
Impact of Immunity 392
Outbreak Detection 393
References 397
CHAPTER 11 RISK CHARACTERIZATION AND DECISION MAKING 399
Introduction 399
Valuing Residual Outcomes 400
Classical Economics 400
DALYs and QALYs 404
Decision Making 407
CostndashBenefit Analysis 408
Multivariate Approaches 411
Other Aspects Entering into a Decision 412
Equity and Justice Aspects 412
References 413
INDEX 415
CONTENTS ix
PREFACE
In the 14 years since we prepared the first edition there has been an explosion inknowledge of and need for quantitative microbial risk assessment (QMRA) Whileour motivation for the first edition stemmed from concerns (principally in water) aboutenteric bacteria viruses and protozoa the motivation has now exploded to newdomains and agents SARS influenza biothreat agents and zoonotic pathogens haveall become of greater concern
The 2001 anthrax letters have highlighted the need for risk assessment ofinhaled agents Both biothreat agents and emergence of new strains of virulentcontagious organisms have raised concern for modeling pathogen dynamics inpopulations
In this edition we have retained the fundamental approach of the riskassessment methodology as a central paradigm We have added new material onmodern pathogen analytical methods predictive microbiology (of pathogen growthand decay) dynamic risk models (explicitly considering incubation time) and diseasepropagation models in populations Of necessity we have removed some materialmdashitis no longer possible to present comprehensive tables of microbial dosendashresponseparameters
In the years since the first edition the authors have gained experience inteaching this material to generations of studentsmdashin the form of formal classestutorials independent studies and short courses We know this book can be valuablein instructing advanced students in environmental sciences environmental engineer-ing public health and microbiology It is also a useful reference for practitionersand regulatory personnel Some prior statistical background would be useful inapproaching the material but not necessary the key requirement for any risk assessoris the absence of fear from mathematical constructs and concepts
The three of us have been on a QMRA journey for almost 30 years We havelearned that doing high-quality risk assessments is of necessity a team sport requiringindividuals with different skills and interests We have learned a tremendous amountfrom each other from our students from our collaborators and from the problems thatwe have sought to approach Practitioners of the art of quantitative microbial riskassessment should be advised to cast a wide net with respect to colleagues andcollaborators to perfect their craft
xi
We encourage comments and feedback from users of this work and look for-ward to observing and participating in developments in coming years and ultimatelyto handing the baton off to our students and their students
Charles N Haas
Joan B Rose
Charles P GerbaNovember 2013
xii PREFACE
CHAPTER1MOTIVATION
THE PREVENTION of infectious disease transmission from human exposure tocontaminated food water soil and air remains a major task of environmental andpublic health professionals There are numerous microbial hazards including expo-sure via food water air and malicious release of pathogens that may arise Indeedsome have argued that the property of virulence of human pathogens is one which isfavored by evolutionary interactions between pathogens and host populations andtherefore will always be of important concern [1] To make rational decisions in pre-paring responding and recovering from exposures to such hazards a quantitativeframework is of high benefit
The objective of this book is to comprehensively set forth the methods forassessment of risk from infectious agents transmitted via these routes in a frameworkthat is compatible with the framework for other risk assessments (eg for chemicalagents) as set forth in standard protocols [2 3]
In this chapter information on the occurrence of infectious disease in broadcategories will be presented along with a historical background on prior methodsfor assessment of microbial safety of food water and air This will be followed byan overview of key issues covered in this book
PREVALENCE OF INFECTIOUS DISEASE
Outbreaks of infectious waterborne illness continue to occur although it remainsimpossible to identify the infectious agent in all cases For example in 1991 a water-borne outbreak in Ireland resulting from sewage contamination of water suppliesinfected about 5000 persons However the infectious agent responsible for thisoutbreak could not be determined [4] In the United States it has been estimated that38 million cases of foodborne infectious disease occur annually with unidentifiedagents [5]
In the United States there have typically been three to five reported outbreaksper year in community drinking water systems involving infectious microorganismswith perhaps up to 10000 annual cases [6] The 1994 Milwaukee Cryptosporidiumoutbreak with over 400000 cases [7 8] was a highly unusual event among thesestatistics As shown in Figure 11 there has been an increasing ability to identify
Quantitative Microbial Risk Assessment Second Edition Charles N Haas Joan B Roseand Charles P Gerbacopy 2014 John Wiley amp Sons Inc Published 2014 by John Wiley amp Sons Inc
1
microorganisms responsible for waterborne diseases and it is expected that withadvances in molecular biology this will increase
There are substantially more outbreaks and cases of foodborne infectiousdiseases than are reported Table 11 summarizes reports of US cases of principalmicrobial infectious foodborne illnesses for two 5-year periods (1988ndash1992 and
1971ndash1982
10
20
30
40
Perc
ent o
f out
brea
ks
50
60
1983ndash1994Period
1995ndash2006
Figure 11 Percentages of outbreaks associated with public water systems (n = 680) by timeperiod 1971ndash2006 that had unknown etiologies based on data from Ref [6]
TABLE 11 Comparison of Five-Year Averages for Common Foodborne Reported Outbreaks
Agent
Annual Average 1988ndash1992 Annual Average 2002ndash2006
Cases Outbreaks Cases Outbreaks
Campylobacter 996 44 624 22
Escherichia coli 488 22 481a 30a
Salmonella 42354 1098 3475 144
Shigella 9576 5 495 12
Staphylococcus aureus 3356 94 554 25
Hepatitis 4218 86 238 1
Listeria monocytogenes 04 02 22 2
Giardia 368 14 2 1
Norovirus 584 04 10854 338
Vibrio (all) 114 18 114 5
Unknown etiologies 40483 1422 4052 30
Source From Refs [9 10]a Include both Shiga toxigenic and enterotoxigenic
2 CHAPTER 1 MOTIVATION
2002ndash2006) There is a mix of causal agents including bacteria virus and protozoaIt is noteworthy that (as in the case of waterborne outbreaks) the frequency ofoutbreaks of unknown etiology has dramatically decreased but the frequency of out-breaks associated with norovirus has dramatically increased These changes are duein part to the ability to better identify causal agents (eg via molecular methods)
It is generally recognized that reported outbreaks either of water- or foodborneinfectious disease represent only a small fractionof the total populationdisease burdenHowever particularly in the United States voluntary reporting systems and theoccurrence of mild cases (for which no medical attention is sought but neverthelessare frank cases of disease) have made it difficult to estimate the total caseload
In the United Kingdom comparisons between the number of confirmed casesin infectious disease outbreaks and total confirmed laboratory illnesses (occurring inEngland and Wales) have been made (Table 12) This suggests that the ratio ofreported outbreak cases to total cases that may seek medical attention may be from10 to 5001 with some dependency on the particular agent
Colford et al [12] developed estimates for the total disease burden associatedwith acute gastroenteritis from drinking water This relies on combining the reportedoutbreak data with interventional epidemiologic studies Based on their analysis thetotal US disease burden is estimated to be 426ndash1169 million cases per year in theUnited States which is substantially in excess of the reported outbreaks In the case offoodborne illness there are an estimated 14 million cases per year [13]
Drinking water and food are by no means the only potential routes of exposureto infectious agents in the environment Recreation in water (either natural or artificialpools) containing pathogens can produce illness [14]
Indoor air transmission can be a vehicle of infection Legionella transmittedthrough indoor environments has been a concern since the 1970s [15] The multina-tional epidemic of severe acute respiratory syndrome (SARS) caused by a coronavi-rus was abetted at least in one location in Hong Kong by indoor aerosol transmissionbetween apartments of infected individuals and susceptible individuals [16] A broadspectrum of other respiratory pathogens including influenza rhinoviruses and myco-bacteria can be transmitted by this route [17]
TABLE 12 Comparison of Laboratory Isolations and Outbreak Cases in Englandand Wales 1992ndash1994
Agent
Cases 1992ndash1994
RatioAll Laboratory Reports Confirmed Outbreak Cases
Campylobacter 122250 240 5094
Rotavirus 47463 127 3737
S sonnei 29080 847 343
Salmonella 92416 5960 155
Cryptosporidium 14454 1066 136
E coli O157 1266 128 99
Source Modified from Ref [11]
PREVALENCE OF INFECTIOUS DISEASE 3
The deliberate release of Bacillus anthracis spores in 2001 (the ldquoAmerithraxrdquoincidents) brought widespread awareness to the potential for indoor releases (as wellas releases in other venues) of bioterrorist agents to cause risk [18] Therefore ofnecessity microbial risk assessors may need to consider the impact of maliciousactivity in certain applications
PRIOR APPROACHES
Concerns for microbial quality of food water and other environmental media havelong existed In the early twentieth century the use of indicator microorganismswas developed for the control and assessment of the hygienic quality of such mediaand the adequacy of disinfection and sterilization processes The coliform group oforganisms was perhaps first employed for this purpose [19ndash21] Indicator techniqueshave also found utility in the food industry such as the total count for milk and othermore recent proposals [22] Other indicator groups for food water or environmentalmedia have been examined such as enterococci [23ndash25] acid-fast bacteria [26]bacteriophage [27ndash29] and Clostridia spores [29ndash31]
The use of indicator organisms was historically justified in because of difficultyin enumerating pathogens However with the increasing availability of modernmicrobial methods for example PCR immunoassay etc for direct pathogen assess-ment this justification has become less persuasive In addition in order to develophealth-based standards from indicators extensive epidemiologic surveillance is oftennecessary The use of epidemiology has limitations with respect to detection limits(for an adverse effect) and is also quite expensive to conduct Indicator methodsare also limited in that many pathogens are more resistant to die off in receiving envir-onments or source waters than indicators or have greater resistance to removal bytreatment processes than indicators [26 28 29 32] Thus the absence of indicatorsmay not suffice to ensure the absence of pathogens Even after a century of use theindicator concept remains imperfect [33]
The use of quantitative microbial risk assessment (QMRA) will enable directmeasurements of pathogens to be used to develop acceptancerejection guidelinesfor food water and other vehicles that may be the source of microbial exposureto human populations The objective of this book is to present these methods in asystematic and unified manner
SCOPE OF COVERAGE
QMRA is the application of principles of risk assessment to the estimate ofconsequences from a planned or actual exposure to infectious microorganismsIn performing a QMRA the risk assessor aims to bring the best available informationto bear in understanding the nature of the potential effects from a microbial exposureSince the information (such as dosendashresponse relationships exposure magnitudes) isalmost invariably incomplete it is also necessary to ascertain the potential error
4 CHAPTER 1 MOTIVATION
involved in the risk assessment With such information necessary steps to mitigatecontrol or defend against such exposures may be developed
At the outset of performing a risk assessment a scoping task should be under-taken This task should set forth the objectives of the analysis and the principal issuesto be addressed Items such as consideration of secondary cases individual versuspopulation risk agent or agents to be examined exposure routes andor accident sce-narios must be stipulated However this scoping may be changed during the course ofa QMRA to reflect the input derived from the risk manager(s) and other stakeholders
POTENTIAL OBJECTIVES OF A QMRA
There may be diverse objectives for a QMRA These objectives relate to the rationalefor the performance of the assessment as well as the methods to be employedBroadly the different objectives reflect different scales at which a risk assessmentmay be performed The step of problem formulation is critical to any risk estimate[34] It is necessary that the problem be formulated to meet the needs of the riskmanagers and stakeholders indeed it is now recognized that the successful practiceof risk analysis requires frequent interchange with manager and stakeholders [3]In general the problems posed are of several types
Site-Specific Assessment
The simplest type of QMRA that may be performed involves one site or exposurescenario The following are typical of the questions that might be asked
1 If a water treatment plant is designed in a certain way (with given removals ofpathogens) then what is the risk that would be placed upon the populationserved
2 A swimming outbreak (in a recreational lake) has just occurred I believe that itresulted from a short-duration contamination event What pathogen levelswould be consistent with the observed attack rate
3 Microbial sampling of a finished food product has found certain pathogensWhat level of risk does this pose to consumers of the product
4 A certain amount of infectious agent has been released into a room What is theimmediate danger to occupants and how stringent should cleanup levels be
Note that there are certain other contrasts in the objectives of the risk assessments tobe posed In (1) and (3) a before-the-fact computation is desired while in (2) and (4)an after-the-fact computation is described Also in (1) (3) and (4) pathogen levelsare available (or somehow are estimated) while in (2) an inverse computation isneeded given an observed attack rate
In performing this risk assessment the relationship between an exposure ortechnological metric and a risk measurement must be ascertained and then theparticular point of correspondence determined (Fig 12) In cases (1) (3) and (4)for a known (or assumed) exposure (on the x-axis) the corresponding range of risks
POTENTIAL OBJECTIVES OF A QMRA 5
on the y-axis is sought In cases (2) for known or assumed risks (on the y-axis)the corresponding range of exposures (or level of technological protection) is to bedetermined (on the x-axis)
Ensemble of Sites
A somewhat more complex situation occurs if the risk for a set of events or sites mustbe estimated Basically this now includes the necessity to incorporate site-to-sitefactors into the assessment Some examples of this are as follows
1 If I desire keeping the risk to a population served by multiple water treatmentplants at a given level (or better) then what criteria should I use (microbiallevels)
2 For a food product subject to contamination by pathogens what would be anacceptable treatment specification (eg heating time holding period) to ensuremicrobial acceptability
3 I am designing a water quality standard for recreational bathing waters If auniform (eg national) standard is to be developed what standard would ensurethat average risk was acceptable with keeping the risk of a large ldquoclusterrdquo ofillnesses low
In addition to incorporating a measure of ensemble average risk in general it is alsodesired to ensure that no single member of the ensemble be unacceptably extreme Forexample consider the evaluation of three options of disease control among three com-munities as indicated in Table 13
This table indicates the number of cases and the rate among the three commu-nities The three policy options yield the same number of expected cases Howeverthere are differences in the allocation of risk among the communities of different sizesIn option A all communities have an identical level of estimated risk In option B therisk increases as community size decreases while in option C the risk increases ascommunity size increases This distribution of risk among affected subsets of the
Exposure
Ris
k
Level of technological protection
Figure 12 Relationship between exposurelevel of technological protection andmicrobial risk The middle curve indicatesthe best estimate The other two curvesindicate the upper and lower confidenceregions
6 CHAPTER 1 MOTIVATION
ensemble being considered adds an additional dimension for consideration by a riskmanagermdashwhich may be termed risk equity
SECONDARY TRANSMISSION
Infectious microbial diseases are different in terms of risk to a population than arechemical agents in that an individual who may become infected (with or withoutillness) can then proceed to infect additional individuals These secondary (tertiaryquaternary etc) cases may be persons who had no direct contact with the initialvehicle of exposure but nevertheless in fairly accounting for the public health impactthey should be considered
Secondary cases may arise by a variety of mechanisms Particularly amongclose family members household secondary cases can arise by direct or indirect(eg surface contamination) contact this is particularly so when the primary caseor one household secondary case is a child [35ndash37] Table 14 summarizes secondarycase statistics obtained from a variety of outbreaks As will be discussed inChapter 10 the secondary case rate is a complex factor involving (among other things)the nature of the venue and contact patterns when infected and susceptible individualsintermingle
Presumably secondary cases may also arise from close contact with anasymptomatic individual (in the ldquocarrierrdquo state) This is well known for highly acuteand (now) uncommon illnesses (such as typhoid) Excretion of Norwalk virusfollowing recovery (and resulting in additional cases) has been documented to occurfor as long as 48 h post recovery [44]
OUTBREAKS VERSUS ENDEMIC CASES
As noted previously there may be a substantial difference between reported outbreakcases and total disease burden in a community In order for a disease case to receiverecognition by the public health authorities the following specific and sequential stepsmust occur [47]
TABLE 13 Effect of Different Hypothetical Policy Options on Distribution of Risk AmongCommunities (for a Fixed Total Risk)
CommunityExposedPopulation
Policy Option A Policy Option B Policy Option C
CasesIncidence(10000) Cases
Incidence(10000) Cases
Incidence(10000)
A 100000 20 2 6 06 24 24
B 50000 10 2 18 36 7 14
C 10000 2 2 8 8 1 1
Total 160000 32 2 32 2 16 2
OUTBREAKS VERSUS ENDEMIC CASES 7
1 An ill person must seek medical care
2 Appropriate clinical tests (eg blood stool) must be ordered by the attendingphysician
3 The patient must comply with obtaining the sample
4 The laboratory must be capable of detecting the relevant pathogens
5 The clinical test must be positive
6 The test result must be reported to the health agency in a timely manner
If any of the links in this sequential chain are broken then a disease case will not enterthe records maintained by health authorities For example with increasing controls on
TABLE 14 Summary of Secondary Case Data in Outbreak Situations
Organism
SecondaryAttackRatioa
SecondaryPrevalence inHouseholdsb Remarks Reference
Cryptosporidiumparvum
033 033 Outbreak in contaminatedapple cider
[38]
C parvum NA 0042 Drinking water outbreak(Milwaukee)
[37]
Shigella 028 026 Day-care center outbreaksin children
[39]
Rotavirus 042 015 Day-care center outbreaksin children
[30]
Giardia lamblia 133 017 Day-care center outbreaksin children
[39]
Viral gastroenteritis 022 011c Drinking waterborneoutbreak
[40]
Viral gastroenteritis 056 NA Drinking water outbreak(Denmark)
[41]
Norovirus 05ndash10 019 Swimming outbreak [42]
Norovirus 11 029 Swimming outbreakin children
[43]
Norovirus NA 044 Foodborne outbreakin children and teachers
[36]
Norovirus 04 NA Foodborne outbreak [44]
E coli O157H7 NA 018c Day-care center outbreakin children
[45]
Unidentifiedday-care diarrhealdiseases
138 009c [46]
NA information not availableaRatio of secondary cases to primary casesb Proportion of households with one or more primary cases who have one or more secondary casesc Proportion of persons in contact with one or more primary cases who have a secondary case
8 CHAPTER 1 MOTIVATION
medical care stool samples may not be obtained from mild cases of illness Someorganisms may only be present sporadically or may be difficult to test in stool orblood sample Patients may not seek medical attention for mild cases of illness Fur-thermore in the United States in particular the surveillance of environmentallyinduced disease is done on a passive basis and hence the number of actual illnessclusters that are actually compiled into recorded statistics is only a small fractionof such clusters of illness that occur [47]
From a more fundamental point of view an outbreak of illness is generallydefined as occurrence of the illness at a level greater than normal or anticipated Thisdefinition recognizes that there is a level of illness (endemic) that may exist underusual circumstances The detection of such outbreaks poses a particular challengeThe problem is illustrated conceptually in Figure 13
Additional complications arise from the different patterns of illness in acommunity including definite periodicities as well as temporal trends and fromthe presence of reporting lags associated with laboratory analysis and time for patientsto seek medical attention Figure 14 illustrates the different patterns of illness inthe case of six pathogens for England and Wales [48]
In the case of waterborne and foodborne illnesses it is highly likely that thelevel of such endemic illnesses is substantially greater than those occurring duringoutbreaks (even accounting for unrecognized outbreaks)
As a result there are often many cases of environmentally caused (water airfood) infectious disease that are unrecognized One example of this isCampylobacterThere has been an average of about 200 cases per year of water- and foodborne illnessin outbreaks of this organism and yet estimates of the disease burden suggest about2100000 cases per year that is approximately 10000 cases per case of detectableoutbreak illness Therefore it will be important to assess the factors that may influenceoutbreak detection These issues will be discussed in subsequent chapters
Detectedoutbreak
Undetectedoutbreak
Threshold of detection
Hyper endemicSporadic
Endemic rate
Time
Num
ber
of c
ases
Figure 13 Schematic of disease occurrence in a hypothetical community (Modified fromRef [47])
OUTBREAKS VERSUS ENDEMIC CASES 9
REFERENCES
1 Levin B R 1996 The Evolution and Maintenance of Virulence in Microparasites Emerging InfectiousDisease 293ndash102
2 National Academy of Sciences 1983 Risk Assessment in the Federal Government Managing theProcess National Academy Press Washington DC
3 National Research Council 2009 Science and Decisions Advancing Risk Assessment NationalAcademies Press Washington DC
10090807060504030201001190 1191 1192 1193 1194 1195
(b)
140
120
100
80
60
40
20
01190 1191 1192 1193 1194 1195
(f)
700
600
500
400
300
200
100
01190 1191 1192 1193 1194 1195
(d)
1200
1000
800
600
400
200
1190 1191 1192 1193 1194 1195
(a)
240
200
160
120
80
40
01190 1191 1192 1193 1194 1195
(e)
7
6
5
4
3
2
1
01190 1191 1192 1193 1194 1195
(c)
Figure 14 Weekly count of reported organism isolations in England andWales (a) rotavirus(b) Clostridium difficile (c) Salmonella derby (d) Shigella sonnei (e) influenza B and (f)Salmonella typhimurium DT 104 (From Ref [48])
10 CHAPTER 1 MOTIVATION
4 Fogarty J L Thornton and R Corcoran 1995 Illness in a Community Associated with an Episode ofWater Contamination with Sewage Epidemiology and Infection 114289ndash295
5 Scallan E 2011 Foodborne Illness Acquired in the United StatesmdashUnspecified Agents EmergingInfectious Diseases 17 16ndash22
6 Craun G F J M Brunkard J S Yoder V A Roberts J Carpenter T Wade R L CalderonJ M Roberts M J Beach and S L Roy 2010 Causes of Outbreaks Associated with Drinking Waterin the United States from 1971 to 2006 Clinical Microbiology Reviews 23507ndash528
7 Edwards D D 1993 Troubled Waters in Milwaukee ASM News 59342ndash3458 MacKenzie W R N J Hoxie M E Proctor M S Gradus K A Blair D E Peterson
J J Kazmierczak K R Fox D G Addias J B Rose and J P Davis 1994 Massive WaterborneOutbreak of Cryptosporidium Infection Associated with a Filtered Public Water Supply MilwaukeeWisconsin March and April 1993 New England Journal of Medicine 331161ndash167
9 Anonymous 2010 Surveillance for Foodborne Disease OutbreaksmdashUnited States 2007 Morbidityand Mortality Weekly Reports 59973ndash979
10 Bean N H J S Goulding C Lau and F J Angulo 1996 Surveillance for Foodborne-DiseaseOutbreaksmdashUnited States 1988ndash1992 Morbidity and Mortality Weekly Reports 451ndash66
11 Wall P G J de Louvois R J Gilbert and B Rowe 1996 Food Poisoning NotificationsLaboratory Reports and OutbreaksmdashWhere do the Statistics Come From and What Do They MeanCommunicable Disease Report Review 6 R93ndashR100
12 Colford J M S Roy M J Beach A Hightower S E Shaw and T J Wade 2006 A Review ofHousehold Drinking Water Intervention Trials and an Approach to the Estimation of EndemicWaterborne Gastroenteritis in the United States Journal of Water and Health 471
13 Mead P S L Slutsker V Dietz L F McCaig J S Bresee C Shapiro P M Griffinand R V Tauxe 1999 Food Related Illness and Death in the United States Emerging InfectiousDisease 5607ndash625
14 Dziuban E J J L Liang G F Craun V Hill P A Yu J Painter M R Moore R L CalderonS L Roy and M J Beach 2006 Surveillance for Waterborne Disease and Outbreaks Associatedwith Recreational WatermdashUnited States 2003ndash2004 and Surveillance for Waterborne Disease andOutbreaks Associated with Drinking Water and Water not Intended for DrinkingmdashUnited States2003ndash2004 Morbidity and Mortality Weekly Reports 551ndash30
15 Fliermans C B 1996 Ecology of Legionella From Data to Knowledge with a Little WisdomMicrobial Ecology 32203ndash228
16 Li Y S Duan I T Yu and T W Wong 2005 Multi-Zone Modeling of Probable SARS VirusTransmission by Airflow Between Flats in Block E Amoy Gardens Indoor Air 1596ndash111
17 Peccia J D K Milton T Reponen and J Hill 2008 A Role for Environmental Engineering andScience in Preventing Bioaerosol-Related Disease Environmental Science amp Technology424631ndash4637
18 Jernigan D B P L Raghunathan B P Bell R Brechner E A Bresnitz J C Butler M CetronM Cohen T Doyle and M Fischer 2002 Investigation of Bioterrorism-Related AnthraxUnited States 2001 Epidemiologic Findings Emerging Infectious Diseases 81019ndash1028
19 Greenwood M and G U Yule 1917 On the Statistical Interpretation of Some BacteriologicalMethods Employed in Water Analysis Journal of Hygiene 1636ndash56
20 Phelps E 1909 The Disinfection of Sewage and Sewage Filter Effluents USGS Water Supply Paper229 GPO Washington DC
21 Rudolfs W and H W Gehm 1935 Multiplication of Total Bacteria and B coli after SewageChlorination Sewage Works Journal 7991ndash996
22 Subcommittee onMicrobiological Criteria 1985 An Evaluation of the Role ofMicrobiological Criteriafor Foods and Food Ingredients National Academy Press Washington DC
23 Cabelli V J A P Dufour L J McCabe and M A Levin 1982 Swimming-AssociatedGastroenteritis and Water Quality American Journal of Epidemiology 115606ndash616
24 Dufour A P 1984 Health Effects Criteria for Fresh Recreational Waters USEPA Research TrianglePark NC
25 Fleisher J M F Jones and D Kay 1993 Water and Non-Water-Related Risk Factors forGastroenteritis among Bathers Exposed to Sewage-Contaminated Marine Waters InternationalJournal of Epidemiology 22698ndash708
REFERENCES 11
26 Engelbrecht R S C N Haas J A Shular D L Dunn D Roy A Lalchandani B F Severin andS Farooq 1979 Acid-Fast Bacteria and Yeasts as Indicators of Disinfection Efficiency EPA-6002-79-091 US Environmental Protection Agency Cincinnati OH
27 Grabow W O K 1983 Inactivation of Hepatitis A Virus and Indicator Organisms in Water by FreeChlorine Residuals Applied and Environmental Microbiology 46619
28 Helmer R D and G R Finch 1993 Use of MS2 Coliphage as a Surrogate for Enteric Viruses inSurface Waters Disinfected with Ozone Ozone Science and Engineering 15279ndash293
29 Payment P and E Franco 1993Clostridium Perfringens and Somatic Coliphages as Indicators of theEfficiency of Drinking Water Treatment for Viruses and Protozoan Cysts Applied and EnvironmentalMicrobiology 592418ndash2424
30 Cabelli V J 1977Clostridium Perfringens as aWater Quality Indicator pp 65ndash79 InA Hoadley andB Dutka (eds) Bacterial IndicatorsHealth Hazards Associated with Water ASTM Philadelphia PA
31 Rice E W K R Fox R J Miltner D A Lytle and C H Johnson 1996 Evaluating PlantPerformance with Endospores Journal of the American Water Works Association 88122ndash130
32 Engelbrecht R S B F Severin M T Masarik S Farooq S H Lee C N Haas and A Lalchandani1977 New Microbial Indicators of Disinfection Efficiency EPA-6002-77-052 US EnvironmentalProtection Agency Cincinnati OH
33 Committee on Indicators for Waterborne Pathogens ndash National Research Council 2004 Indicators forWaterborne Pathogens National Academies Press Washington DC
34 PresidentialCongressional Commission on Risk Assessment and RiskManagement 1997 Frameworkfor Environmental Health Risk Management The Commission Washington DC
35 Griffin P M and R V Tauxe 1991 The Epidemiology of Infections Caused by Escherichiacoli O157H7 Other Enterohemorrhagic E coli and the Associated Hemolytic Uremic SyndromeEpidemiologic Reviews 1360ndash98
36 Heun E M R L Vogt P J Hudson S Parren and G W Gary 1987 Risk Factors for SecondaryTransmission in Households after a Common Source Outbreak of Norwalk Gastroenteritis AmericanJournal of Epidemiology 1261181ndash1186
37 MacKenzie W R W L Schell B A Blair D G Addiss D E Peterson N J HozieJ J Kazmierczak and J P Davis 1995 Massive Outbreak of Waterborne CryptosporidiumInfection in Milwaukee Wisconsin Recurrence of Illness and Risk of Secondary TransmissionClinical Infectious Diseases 2157ndash62
38 Millard P K Gensheimer D G Addiss D M Sosin G A Beckett A Houck-Jankoski andA Hudson 1994 An Outbreak of Cryptosporidiosis from Fresh-Pressed Apple Cider Journal ofthe American Medical Association 2721592ndash1596
39 Pickering L K D G Evans H L DuPont J J Vollet and D J Evans Jr 1981 Diarrhea Caused byShigella Rotavirus and Giardia in Day Care Centers Prospective Study Journal of Pediatrics9951ndash56
40 Morens D M R M Zweighaft T M Vernon G W Gary J J Eslien B T Wood R C Holmanand R Dolin 1979 A Waterborne Outbreak of Gastroenteritis with Secondary Person to PersonSpread Lancet 5964ndash966
41 Laursen E O Mygind B Rasmussen and T Ronne 1994 Gastroenteritis A Waterborne OutbreakAffecting 1600 People in a Small Danish Town Journal of Epidemiology amp Community Health48453ndash458
42 Baron R C F D Murphy H B Greenberg C E Davis D J Bregman G W Gary J M Hughesand L B Schonberger 1982 Norwalk Gastrointestinal Illness An Outbreak Associated withSwimming in a Recreational Lake and Secondary Person to Person Transmission American Journalof Epidemiology 115163ndash172
43 Kappus K D J S Marks R C Holman J K Bryant C Baker G W Gary and H B Greenberg1982 An Outbreak of Norwalk Gastroenteritis Associated with Swimming in a Pool and SecondaryPerson to Person Transmission American Journal of Epidemiology 116834ndash839
44 White K E M T Osterbolm J A Mariotti J A Korlath D H Lawrence T L Ristinen andH B Greenberg 1986 A Foodborne Outbreak of Norwalk Virus Gastroenteritis American Journalof Epidemiology 124120ndash126
45 Spika J S J E Parsons and D Nordenberg 1986 Hemolytic Uremic Syndrome and DiarrheaAssociated with Escherichia coli O157H7 in a Day Care Center Journal of Pediatrics 109287ndash291
12 CHAPTER 1 MOTIVATION
46 Ferguson J K L R Jorm C D Allen P KWhitehead and G L Gilbert 1995 Prospective Study ofDiarrhoeal Outbreaks in Child Long Daycare Centres in Western Sydney Medical Journal of Australia163137ndash140
47 Frost F J G F Craun and R L Calderon 1996 Waterborne Disease Surveillance Journal of theAmerican Water Works Association 8866ndash75
48 Farrington C P N J Andrews A D Beale and M A Catchpole 1996 A Statistical Algorithmfor the Early Detection of Outbreaks of Infectious Disease Journal of the Royal StatisticalSociety A 159547ndash563
REFERENCES 13
CHAPTER2MICROBIAL AGENTS ANDTRANSMISSION
MICROBIAL TAXONOMY
The development of techniques for examining the nucleic acids of microorganisms hasseen major changes in which we classify and group related microorganisms This isespecially true for the study of ribosomal ribonucleic acid (rRNA) which is a highlyconserved sequence involved in the synthesis of proteins in all living organisms Basedon this analysis the classification of living things has been placed into a three-domainsystem consisting of Archaea Eukarya and Bacteria Of these the Bacteria andArchaea are termed prokaryotes (no organized cell nucleus) and the Eukarya areknown as eukaryotes (an organized cell nucleus) Eukaryotic microbes other thanalgae and fungi are collectively calledprotistsWithin theEukarya are fungi protozoahelminth worms algae plants animals and humans Archaea are microbes that looksomewhat similar to bacteria in size and shape under the light microscope but they areactually genetically and biochemically quite different They appear to be a simpler formof life and may in fact be the oldest form of life on earth Viruses are obligate intercel-lular parasites and are not amember of any group They are usually composed only of anucleic acid surrounded by a protein coat Eukaryotes are much more complex thanprokaryotic cells in structure and nutritional requirements Prokaryotes divide by sim-ple binary fissionwhereas eukaryotes divide byamore complexprocess calledmitosis
Eukaryotes
Fungi protozoa and helminth worms are all eukaryotes All contain members that arepathogenic to man and animals While algae do not infect humans they can producetoxins that are harmful to animals and man Fungi obtain nutrients solely by adsorp-tion of organic matter from dead organisms Even when they invade living tissuesthey typically kill cells and then adsorb the nutrients from them Some fungi are capa-ble of developing environmentally resistant spores which can be transported throughthe air Fungal diseases in humans are referred to asmycoses Airborne fungal sporesare responsible for some allergies in humans Yeasts are classified with the fungi and
Quantitative Microbial Risk Assessment Second Edition Charles N Haas Joan B Roseand Charles P Gerbacopy 2014 John Wiley amp Sons Inc Published 2014 by John Wiley amp Sons Inc
15
some are pathogenic to humans (Candida albicans) Certain fungi produce toxins(ie aflatoxins) when growing in foods that are mutagenic and carcinogenic in ani-mals Inhalation is an important route of transmission for some fungal diseases suchas aspergillosis blastomycosis coccidioidomycosis and histoplasmosis These fungiare found growing in animal feces soil or decaying organic matter (compost manure)and may be transmitted through the air when this matter is disturbed Some fungi maybe transmitted by direct contact with the skin Fungi are often found in drinking waterdistribution systems and they have been linked to infections in immunocompromisedindividuals [1] Food is not believed to be a significant route of transmission ofpathogenic fungi
Protozoans are unicellular organisms that are surrounded by a cytoplasmicmembrane that is covered by a protective structure called a pellicle Most are freeliving feeding off of bacteria Some of these can cause disease while others are obli-gate parasites They are capable of forming structures called cysts oocysts or spores(depending on the life cycle of the organism) resistant to adverse environmentalconditions such as desiccation starvation high temperatures and disinfectantsSome pathogenic protozoa are found mainly in the soil (Naegleria) or water(Acanthamoeba) Others such a Giardia and Cryptosporidium whose natural habitatis the intestines of warm-blooded animals are capable of causing disease in bothhumans and animals Others such as Entamoeba histolytica are only capable ofcausing disease in humans
Pathogenic enteric (replicate in the intestines) protozoans are usually excretedin the feces or urine and can be transmitted by fecally contaminated food and waterSome protozoa may be transmitted through the air (Acanthamoeba) or throughfomites (inanimate objects) Some important environmentally transmitted protozoaare listed in Table 21 The clinically important protozoa are divided taxonomicallyinto the amoebas (Entamoeba spp) flagellates (Giardia) and coccidian meaningldquoglobose in shaperdquo (Cryptosporidium and Cyclospora) Microsporidia are alsocapable of causing intestinal infections but their classification is uncertain becausethey have many characteristics associated with fungi They are all obligate parasitesand are transmitted via infectious cysts oocysts or spores by the fecalndashoral routeThe life cycles of these protozoa are similar The initial stage occurs during ingestionof the cyst oocyst or spore After ingestion the body temperature and passagethrough the stomach cause these infective stages to open up in a process calledexcystation
The Giardia cysts house two trophozoites which is the stage that attaches tointestinal cells and grows in the intestinal tract through asexual reproduction As thetrophozoites grow and begin to cover the wall of the intestinal tract diarrhea canresult As the trophozoites are released some form cysts as they pass through thebowels Cryptosporidium and Cyclospora both produce oocysts The life cycle ofCyclospora is still not well known except that its oocysts require some period of timein the environment before they are infective Cryptosporidium oocysts contain foursporozoites which enter the intestinal cells and begin the infection process As morecells become infected the illness begins and oocysts are excreted in high numbers inthe feces (about 100000g)
Worms and helminths are small multicellular animals that are parasiticto humans and animals They include flukes tapeworms and roundworms
16 CHAPTER 2 MICROBIAL AGENTS AND TRANSMISSION
QUANTITATIVEMICROBIAL RISKASSESSMENT
SECOND EDITION
QUANTITATIVEMICROBIAL RISKASSESSMENT
CHARLES N HAAS
JOAN B ROSE
CHARLES P GERBA
Copyright copy 2014 by John Wiley amp Sons Inc All rights reserved
Published by John Wiley amp Sons Inc Hoboken New JerseyPublished simultaneously in Canada
No part of this publication may be reproduced stored in a retrieval system or transmitted in any formor by any means electronic mechanical photocopying recording scanning or otherwise except aspermitted under Section 107 or 108 of the 1976 United States Copyright Act without either the prior writtenpermission of the Publisher or authorization through payment of the appropriate per-copy fee to theCopyright Clearance Center Inc 222 Rosewood Drive Danvers MA 01923 (978) 7508400 fax (978)7504470 or on the web at wwwcopyrightcom Requests to the Publisher for permission should beaddressed to the Permissions Department John Wiley amp Sons Inc 111 River Street Hoboken NJ 07030(201) 748-6011 fax (201) 748-6008 or online at httpwwwwileycomgopermission
Limit of LiabilityDisclaimer of Warranty While the publisher and author have used their best effortsin preparing this book they make no representations or warranties with respect to the accuracy orcompleteness of the contents of this book and specifically disclaim any implied warranties ofmerchantability or fitness for a particular purpose No warranty may be created or extended bysales representatives or written sales materials The advice and strategies contained herein may not besuitable for your situation You should consult with a professional where appropriate Neither thepublisher nor author shall be liable for any loss of profit or any other commercial damages including butnot limited to special incidental consequential or other damages
For general information on our other products and services or for technical support please contactour Customer Care Department within the United States at (800) 7622974 outside the United Statesat (317) 5723993 or fax (317) 5724002
Wiley also publishes its books in a variety of electronic formats Some content that appears in print maynot be available in electronic formats For more information about Wiley products visit our web site atwwwwileycom
Library of Congress Cataloging-in-Publication Data
Haas Charles NQuantitative microbial risk assessment Charles N Haas Joan B Rose Charles P Gerba ndash Second edition
p cmIncludes bibliographical references and indexISBN 978-1-118-14529-6 (cloth alk paper)
1 Communicable diseasesndashEpidemiologyndashMethodology 2 Health risk assessment 3 InfectionndashMathematical models 4 Environmental healthndashMathematical models I Rose Joan B II GerbaCharles P 1945- III Title
RA643H22 2014615902ndashdc23
2014002690
Printed in the United States of America
10 9 8 7 6 5 4 3 2 1
CONTENTS
PREFACE xi
CHAPTER 1 MOTIVATION 1
Prevalence of Infectious Disease 1
Prior Approaches 4
Scope of Coverage 4
Potential Objectives of a QMRA 5
Site-Specific Assessment 5
Ensemble of Sites 6
Secondary Transmission 7
Outbreaks versus Endemic Cases 7
References 10
CHAPTER 2 MICROBIAL AGENTS AND TRANSMISSION 15
Microbial Taxonomy 15
Eukaryotes 15
Prokaryotes 18
Viruses 20
Prions 22
Clinical Characterization 24
Microorganisms of Interest 27
Viruses 27
Bacteria 37
Protozoa 42
Transmission Routes 45
Inhalation 48
Dermal Exposure 50
Oral Ingestion 50
References 55
CHAPTER 3 RISK ASSESSMENT PARADIGMS 63
Chemical Risk Assessment National Academy of Sciences Paradigm 63
Ecological Risk Assessment 67
Approaches for Assessing Microbial Risks 71
Background 71
v
The QMRA Framework 74
Hazard Identification 74
DosendashResponse Assessment 74
Exposure Assessment 76
Risk Characterization 77
Risk Management 79
Development of the QMRA Framework and Processes 79
QMRA and the Safety of Water 82
QMRA Food Safety and the HACCP System 84
References 86
CHAPTER 4 CONDUCTING THE HAZARD IDENTIFICATION (HAZ ID) 91
Identifying and Diagnosing Infectious Disease 92
Health Outcomes Associated with Microbial Infections 95
Sensitive Populations 100
Women during Pregnancy Neonates and Young Babies 101
Diabetes 102
The Elderly 102
The Immunocompromised 104
Databases for Statistical Assessment of Disease 106
ICD Codes 107
Waterborne and Foodborne Outbreaks 111
Epidemiological Methods for Undertaking HAZ ID 117
Controlled Epidemiological Investigations 118
HAZ ID Data Used in the Risk Assessment Process 119
Recommendations for Updating Quantitative Data for HAZ ID Information 121
References 122
CHAPTER 5 ANALYTICAL METHODS AND THE QMRA FRAMEWORKDEVELOPING OCCURRENCE AND EXPOSURE DATABASES 129
Introduction 129
Approaches for Developing Occurrence and Exposure Databases 132
Overview of Methodological Issues 134
Sampling Water 136
Sampling Surfaces and Food 138
Sampling Aerosols 138
Specific Techniques for Bacteria Protozoa and Viruses 140
Bacteria 140
Protozoa 142
Viruses 143
Molecular Techniques 145
Probes (FISH) 146
Typing 146
vi CONTENTS
Metagenomics 147
PCR and Quantitative PCR 147
References 151
CHAPTER 6 EXPOSURE ASSESSMENT 159
Conducting the Exposure Assessment 159
Characterizing ConcentrationDuration Distributions 160
Random (Poisson) Distributions of Organisms 160
Estimation of Poisson Mean in Count Assay (Constant and Variable Volumes) 162
Count Assay with Upper Limits 163
Estimation with Quantal Assay 164
Goodness of Fit to Poisson Plate Assay 168
Goodness of Fit MPN 178
Confidence Limits Likelihood 182
Implications for Risk Assessment 187
Consumption Distributions 214
Systematic Subpopulation Differences 221
Afterword 223
Appendix 224
Microsoft Excel 224
MATLAB 225
R 227
References 230
CHAPTER 7 PREDICTIVE MICROBIOLOGY 235
Objective 235
Basic First-Order Processes and Deviations 236
Biological and Physical Bases for Deviations 236
Physical Removal 238
Types of Decay Processes 238
General Forms of Decay and Reasons for Nonlinearity 238
SpontaneousEndogenous 240
Chemical Agents 241
Thermally Induced 243
Ionizing and Nonionizing Radiation 243
Predation and Antagonism 245
Types of Growth Processes 245
Mathematical Modeling of Growth Curves 246
Substrate Dependency 252
Structured Growth Models 255
Incorporation of Decay into Growth Models 256
Systems Biology Approaches 258
CONTENTS vii
Dependence of Growth Parameters on Other Environmental Variables 258
Interacting Populations 258
Data Sources 260
References 263
CHAPTER 8 CONDUCTING THE DOSEndashRESPONSE ASSESSMENT 267
Plausible DosendashResponse Models 268
Framework for Mechanistic DosendashResponse Relationships 269
Exponential DosendashResponse Model 271
Beta-Poisson DosendashResponse Model 272
Simple Threshold Models 274
Negative Binomial Dose Distributions 277
Variable Threshold Models 278
Other Mixture Models 279
Biological Arguments for One-Hit Models 281
Empirical Models 282
Fitting Available Data 283
Types of Data Sets 284
Potential Impacts of Immune Status 298
Relationship between Dose and Severity (Morbidity and Mortality) 299
Morbidity Ratio (PDI) 299
Mortality Ratio 303
Reality Checking Validation 304
Validation 1993 Milwaukee Outbreak 304
Use of Indicators and Other Proxy Measures in DosendashResponse 305
Indicator Methods 305
Molecular Methods 307
Advanced Topics in DosendashResponse Modeling 308
DosendashResponsendashTime Models 308
Physiological Models 313
Appendix 315
References 317
CHAPTER 9 UNCERTAINTY 323
Point Estimates of Risk 324
Terminology Types of Uncertainty 326
Sources of Uncertainty 327
Sources of Variability 328
Variability that is Uncertain 329
Approaches to Quantify Parametric Uncertainty 329
Likelihood 329
Bootstrap 330
Other Methods 330
viii CONTENTS
Applications 332
Exposure Assessment 332
DosendashResponse Assessment 338
Combining Parametric Uncertainty from Multiple Sources 344
Propagation Methods 344
Monte Carlo Analyses 347
Overall Risk Characterization Example 365
Second-Order Methods 368
Model Uncertainty and Averaging 370
References 373
CHAPTER 10 POPULATION DISEASE TRANSMISSION 377
Introduction Models for Population and Community Illnesses 377
Basic SIR Model 378
Incubation Period 386
Duration of Illness 388
Secondary Cases 389
Impact of Immunity 392
Outbreak Detection 393
References 397
CHAPTER 11 RISK CHARACTERIZATION AND DECISION MAKING 399
Introduction 399
Valuing Residual Outcomes 400
Classical Economics 400
DALYs and QALYs 404
Decision Making 407
CostndashBenefit Analysis 408
Multivariate Approaches 411
Other Aspects Entering into a Decision 412
Equity and Justice Aspects 412
References 413
INDEX 415
CONTENTS ix
PREFACE
In the 14 years since we prepared the first edition there has been an explosion inknowledge of and need for quantitative microbial risk assessment (QMRA) Whileour motivation for the first edition stemmed from concerns (principally in water) aboutenteric bacteria viruses and protozoa the motivation has now exploded to newdomains and agents SARS influenza biothreat agents and zoonotic pathogens haveall become of greater concern
The 2001 anthrax letters have highlighted the need for risk assessment ofinhaled agents Both biothreat agents and emergence of new strains of virulentcontagious organisms have raised concern for modeling pathogen dynamics inpopulations
In this edition we have retained the fundamental approach of the riskassessment methodology as a central paradigm We have added new material onmodern pathogen analytical methods predictive microbiology (of pathogen growthand decay) dynamic risk models (explicitly considering incubation time) and diseasepropagation models in populations Of necessity we have removed some materialmdashitis no longer possible to present comprehensive tables of microbial dosendashresponseparameters
In the years since the first edition the authors have gained experience inteaching this material to generations of studentsmdashin the form of formal classestutorials independent studies and short courses We know this book can be valuablein instructing advanced students in environmental sciences environmental engineer-ing public health and microbiology It is also a useful reference for practitionersand regulatory personnel Some prior statistical background would be useful inapproaching the material but not necessary the key requirement for any risk assessoris the absence of fear from mathematical constructs and concepts
The three of us have been on a QMRA journey for almost 30 years We havelearned that doing high-quality risk assessments is of necessity a team sport requiringindividuals with different skills and interests We have learned a tremendous amountfrom each other from our students from our collaborators and from the problems thatwe have sought to approach Practitioners of the art of quantitative microbial riskassessment should be advised to cast a wide net with respect to colleagues andcollaborators to perfect their craft
xi
We encourage comments and feedback from users of this work and look for-ward to observing and participating in developments in coming years and ultimatelyto handing the baton off to our students and their students
Charles N Haas
Joan B Rose
Charles P GerbaNovember 2013
xii PREFACE
CHAPTER1MOTIVATION
THE PREVENTION of infectious disease transmission from human exposure tocontaminated food water soil and air remains a major task of environmental andpublic health professionals There are numerous microbial hazards including expo-sure via food water air and malicious release of pathogens that may arise Indeedsome have argued that the property of virulence of human pathogens is one which isfavored by evolutionary interactions between pathogens and host populations andtherefore will always be of important concern [1] To make rational decisions in pre-paring responding and recovering from exposures to such hazards a quantitativeframework is of high benefit
The objective of this book is to comprehensively set forth the methods forassessment of risk from infectious agents transmitted via these routes in a frameworkthat is compatible with the framework for other risk assessments (eg for chemicalagents) as set forth in standard protocols [2 3]
In this chapter information on the occurrence of infectious disease in broadcategories will be presented along with a historical background on prior methodsfor assessment of microbial safety of food water and air This will be followed byan overview of key issues covered in this book
PREVALENCE OF INFECTIOUS DISEASE
Outbreaks of infectious waterborne illness continue to occur although it remainsimpossible to identify the infectious agent in all cases For example in 1991 a water-borne outbreak in Ireland resulting from sewage contamination of water suppliesinfected about 5000 persons However the infectious agent responsible for thisoutbreak could not be determined [4] In the United States it has been estimated that38 million cases of foodborne infectious disease occur annually with unidentifiedagents [5]
In the United States there have typically been three to five reported outbreaksper year in community drinking water systems involving infectious microorganismswith perhaps up to 10000 annual cases [6] The 1994 Milwaukee Cryptosporidiumoutbreak with over 400000 cases [7 8] was a highly unusual event among thesestatistics As shown in Figure 11 there has been an increasing ability to identify
Quantitative Microbial Risk Assessment Second Edition Charles N Haas Joan B Roseand Charles P Gerbacopy 2014 John Wiley amp Sons Inc Published 2014 by John Wiley amp Sons Inc
1
microorganisms responsible for waterborne diseases and it is expected that withadvances in molecular biology this will increase
There are substantially more outbreaks and cases of foodborne infectiousdiseases than are reported Table 11 summarizes reports of US cases of principalmicrobial infectious foodborne illnesses for two 5-year periods (1988ndash1992 and
1971ndash1982
10
20
30
40
Perc
ent o
f out
brea
ks
50
60
1983ndash1994Period
1995ndash2006
Figure 11 Percentages of outbreaks associated with public water systems (n = 680) by timeperiod 1971ndash2006 that had unknown etiologies based on data from Ref [6]
TABLE 11 Comparison of Five-Year Averages for Common Foodborne Reported Outbreaks
Agent
Annual Average 1988ndash1992 Annual Average 2002ndash2006
Cases Outbreaks Cases Outbreaks
Campylobacter 996 44 624 22
Escherichia coli 488 22 481a 30a
Salmonella 42354 1098 3475 144
Shigella 9576 5 495 12
Staphylococcus aureus 3356 94 554 25
Hepatitis 4218 86 238 1
Listeria monocytogenes 04 02 22 2
Giardia 368 14 2 1
Norovirus 584 04 10854 338
Vibrio (all) 114 18 114 5
Unknown etiologies 40483 1422 4052 30
Source From Refs [9 10]a Include both Shiga toxigenic and enterotoxigenic
2 CHAPTER 1 MOTIVATION
2002ndash2006) There is a mix of causal agents including bacteria virus and protozoaIt is noteworthy that (as in the case of waterborne outbreaks) the frequency ofoutbreaks of unknown etiology has dramatically decreased but the frequency of out-breaks associated with norovirus has dramatically increased These changes are duein part to the ability to better identify causal agents (eg via molecular methods)
It is generally recognized that reported outbreaks either of water- or foodborneinfectious disease represent only a small fractionof the total populationdisease burdenHowever particularly in the United States voluntary reporting systems and theoccurrence of mild cases (for which no medical attention is sought but neverthelessare frank cases of disease) have made it difficult to estimate the total caseload
In the United Kingdom comparisons between the number of confirmed casesin infectious disease outbreaks and total confirmed laboratory illnesses (occurring inEngland and Wales) have been made (Table 12) This suggests that the ratio ofreported outbreak cases to total cases that may seek medical attention may be from10 to 5001 with some dependency on the particular agent
Colford et al [12] developed estimates for the total disease burden associatedwith acute gastroenteritis from drinking water This relies on combining the reportedoutbreak data with interventional epidemiologic studies Based on their analysis thetotal US disease burden is estimated to be 426ndash1169 million cases per year in theUnited States which is substantially in excess of the reported outbreaks In the case offoodborne illness there are an estimated 14 million cases per year [13]
Drinking water and food are by no means the only potential routes of exposureto infectious agents in the environment Recreation in water (either natural or artificialpools) containing pathogens can produce illness [14]
Indoor air transmission can be a vehicle of infection Legionella transmittedthrough indoor environments has been a concern since the 1970s [15] The multina-tional epidemic of severe acute respiratory syndrome (SARS) caused by a coronavi-rus was abetted at least in one location in Hong Kong by indoor aerosol transmissionbetween apartments of infected individuals and susceptible individuals [16] A broadspectrum of other respiratory pathogens including influenza rhinoviruses and myco-bacteria can be transmitted by this route [17]
TABLE 12 Comparison of Laboratory Isolations and Outbreak Cases in Englandand Wales 1992ndash1994
Agent
Cases 1992ndash1994
RatioAll Laboratory Reports Confirmed Outbreak Cases
Campylobacter 122250 240 5094
Rotavirus 47463 127 3737
S sonnei 29080 847 343
Salmonella 92416 5960 155
Cryptosporidium 14454 1066 136
E coli O157 1266 128 99
Source Modified from Ref [11]
PREVALENCE OF INFECTIOUS DISEASE 3
The deliberate release of Bacillus anthracis spores in 2001 (the ldquoAmerithraxrdquoincidents) brought widespread awareness to the potential for indoor releases (as wellas releases in other venues) of bioterrorist agents to cause risk [18] Therefore ofnecessity microbial risk assessors may need to consider the impact of maliciousactivity in certain applications
PRIOR APPROACHES
Concerns for microbial quality of food water and other environmental media havelong existed In the early twentieth century the use of indicator microorganismswas developed for the control and assessment of the hygienic quality of such mediaand the adequacy of disinfection and sterilization processes The coliform group oforganisms was perhaps first employed for this purpose [19ndash21] Indicator techniqueshave also found utility in the food industry such as the total count for milk and othermore recent proposals [22] Other indicator groups for food water or environmentalmedia have been examined such as enterococci [23ndash25] acid-fast bacteria [26]bacteriophage [27ndash29] and Clostridia spores [29ndash31]
The use of indicator organisms was historically justified in because of difficultyin enumerating pathogens However with the increasing availability of modernmicrobial methods for example PCR immunoassay etc for direct pathogen assess-ment this justification has become less persuasive In addition in order to develophealth-based standards from indicators extensive epidemiologic surveillance is oftennecessary The use of epidemiology has limitations with respect to detection limits(for an adverse effect) and is also quite expensive to conduct Indicator methodsare also limited in that many pathogens are more resistant to die off in receiving envir-onments or source waters than indicators or have greater resistance to removal bytreatment processes than indicators [26 28 29 32] Thus the absence of indicatorsmay not suffice to ensure the absence of pathogens Even after a century of use theindicator concept remains imperfect [33]
The use of quantitative microbial risk assessment (QMRA) will enable directmeasurements of pathogens to be used to develop acceptancerejection guidelinesfor food water and other vehicles that may be the source of microbial exposureto human populations The objective of this book is to present these methods in asystematic and unified manner
SCOPE OF COVERAGE
QMRA is the application of principles of risk assessment to the estimate ofconsequences from a planned or actual exposure to infectious microorganismsIn performing a QMRA the risk assessor aims to bring the best available informationto bear in understanding the nature of the potential effects from a microbial exposureSince the information (such as dosendashresponse relationships exposure magnitudes) isalmost invariably incomplete it is also necessary to ascertain the potential error
4 CHAPTER 1 MOTIVATION
involved in the risk assessment With such information necessary steps to mitigatecontrol or defend against such exposures may be developed
At the outset of performing a risk assessment a scoping task should be under-taken This task should set forth the objectives of the analysis and the principal issuesto be addressed Items such as consideration of secondary cases individual versuspopulation risk agent or agents to be examined exposure routes andor accident sce-narios must be stipulated However this scoping may be changed during the course ofa QMRA to reflect the input derived from the risk manager(s) and other stakeholders
POTENTIAL OBJECTIVES OF A QMRA
There may be diverse objectives for a QMRA These objectives relate to the rationalefor the performance of the assessment as well as the methods to be employedBroadly the different objectives reflect different scales at which a risk assessmentmay be performed The step of problem formulation is critical to any risk estimate[34] It is necessary that the problem be formulated to meet the needs of the riskmanagers and stakeholders indeed it is now recognized that the successful practiceof risk analysis requires frequent interchange with manager and stakeholders [3]In general the problems posed are of several types
Site-Specific Assessment
The simplest type of QMRA that may be performed involves one site or exposurescenario The following are typical of the questions that might be asked
1 If a water treatment plant is designed in a certain way (with given removals ofpathogens) then what is the risk that would be placed upon the populationserved
2 A swimming outbreak (in a recreational lake) has just occurred I believe that itresulted from a short-duration contamination event What pathogen levelswould be consistent with the observed attack rate
3 Microbial sampling of a finished food product has found certain pathogensWhat level of risk does this pose to consumers of the product
4 A certain amount of infectious agent has been released into a room What is theimmediate danger to occupants and how stringent should cleanup levels be
Note that there are certain other contrasts in the objectives of the risk assessments tobe posed In (1) and (3) a before-the-fact computation is desired while in (2) and (4)an after-the-fact computation is described Also in (1) (3) and (4) pathogen levelsare available (or somehow are estimated) while in (2) an inverse computation isneeded given an observed attack rate
In performing this risk assessment the relationship between an exposure ortechnological metric and a risk measurement must be ascertained and then theparticular point of correspondence determined (Fig 12) In cases (1) (3) and (4)for a known (or assumed) exposure (on the x-axis) the corresponding range of risks
POTENTIAL OBJECTIVES OF A QMRA 5
on the y-axis is sought In cases (2) for known or assumed risks (on the y-axis)the corresponding range of exposures (or level of technological protection) is to bedetermined (on the x-axis)
Ensemble of Sites
A somewhat more complex situation occurs if the risk for a set of events or sites mustbe estimated Basically this now includes the necessity to incorporate site-to-sitefactors into the assessment Some examples of this are as follows
1 If I desire keeping the risk to a population served by multiple water treatmentplants at a given level (or better) then what criteria should I use (microbiallevels)
2 For a food product subject to contamination by pathogens what would be anacceptable treatment specification (eg heating time holding period) to ensuremicrobial acceptability
3 I am designing a water quality standard for recreational bathing waters If auniform (eg national) standard is to be developed what standard would ensurethat average risk was acceptable with keeping the risk of a large ldquoclusterrdquo ofillnesses low
In addition to incorporating a measure of ensemble average risk in general it is alsodesired to ensure that no single member of the ensemble be unacceptably extreme Forexample consider the evaluation of three options of disease control among three com-munities as indicated in Table 13
This table indicates the number of cases and the rate among the three commu-nities The three policy options yield the same number of expected cases Howeverthere are differences in the allocation of risk among the communities of different sizesIn option A all communities have an identical level of estimated risk In option B therisk increases as community size decreases while in option C the risk increases ascommunity size increases This distribution of risk among affected subsets of the
Exposure
Ris
k
Level of technological protection
Figure 12 Relationship between exposurelevel of technological protection andmicrobial risk The middle curve indicatesthe best estimate The other two curvesindicate the upper and lower confidenceregions
6 CHAPTER 1 MOTIVATION
ensemble being considered adds an additional dimension for consideration by a riskmanagermdashwhich may be termed risk equity
SECONDARY TRANSMISSION
Infectious microbial diseases are different in terms of risk to a population than arechemical agents in that an individual who may become infected (with or withoutillness) can then proceed to infect additional individuals These secondary (tertiaryquaternary etc) cases may be persons who had no direct contact with the initialvehicle of exposure but nevertheless in fairly accounting for the public health impactthey should be considered
Secondary cases may arise by a variety of mechanisms Particularly amongclose family members household secondary cases can arise by direct or indirect(eg surface contamination) contact this is particularly so when the primary caseor one household secondary case is a child [35ndash37] Table 14 summarizes secondarycase statistics obtained from a variety of outbreaks As will be discussed inChapter 10 the secondary case rate is a complex factor involving (among other things)the nature of the venue and contact patterns when infected and susceptible individualsintermingle
Presumably secondary cases may also arise from close contact with anasymptomatic individual (in the ldquocarrierrdquo state) This is well known for highly acuteand (now) uncommon illnesses (such as typhoid) Excretion of Norwalk virusfollowing recovery (and resulting in additional cases) has been documented to occurfor as long as 48 h post recovery [44]
OUTBREAKS VERSUS ENDEMIC CASES
As noted previously there may be a substantial difference between reported outbreakcases and total disease burden in a community In order for a disease case to receiverecognition by the public health authorities the following specific and sequential stepsmust occur [47]
TABLE 13 Effect of Different Hypothetical Policy Options on Distribution of Risk AmongCommunities (for a Fixed Total Risk)
CommunityExposedPopulation
Policy Option A Policy Option B Policy Option C
CasesIncidence(10000) Cases
Incidence(10000) Cases
Incidence(10000)
A 100000 20 2 6 06 24 24
B 50000 10 2 18 36 7 14
C 10000 2 2 8 8 1 1
Total 160000 32 2 32 2 16 2
OUTBREAKS VERSUS ENDEMIC CASES 7
1 An ill person must seek medical care
2 Appropriate clinical tests (eg blood stool) must be ordered by the attendingphysician
3 The patient must comply with obtaining the sample
4 The laboratory must be capable of detecting the relevant pathogens
5 The clinical test must be positive
6 The test result must be reported to the health agency in a timely manner
If any of the links in this sequential chain are broken then a disease case will not enterthe records maintained by health authorities For example with increasing controls on
TABLE 14 Summary of Secondary Case Data in Outbreak Situations
Organism
SecondaryAttackRatioa
SecondaryPrevalence inHouseholdsb Remarks Reference
Cryptosporidiumparvum
033 033 Outbreak in contaminatedapple cider
[38]
C parvum NA 0042 Drinking water outbreak(Milwaukee)
[37]
Shigella 028 026 Day-care center outbreaksin children
[39]
Rotavirus 042 015 Day-care center outbreaksin children
[30]
Giardia lamblia 133 017 Day-care center outbreaksin children
[39]
Viral gastroenteritis 022 011c Drinking waterborneoutbreak
[40]
Viral gastroenteritis 056 NA Drinking water outbreak(Denmark)
[41]
Norovirus 05ndash10 019 Swimming outbreak [42]
Norovirus 11 029 Swimming outbreakin children
[43]
Norovirus NA 044 Foodborne outbreakin children and teachers
[36]
Norovirus 04 NA Foodborne outbreak [44]
E coli O157H7 NA 018c Day-care center outbreakin children
[45]
Unidentifiedday-care diarrhealdiseases
138 009c [46]
NA information not availableaRatio of secondary cases to primary casesb Proportion of households with one or more primary cases who have one or more secondary casesc Proportion of persons in contact with one or more primary cases who have a secondary case
8 CHAPTER 1 MOTIVATION
medical care stool samples may not be obtained from mild cases of illness Someorganisms may only be present sporadically or may be difficult to test in stool orblood sample Patients may not seek medical attention for mild cases of illness Fur-thermore in the United States in particular the surveillance of environmentallyinduced disease is done on a passive basis and hence the number of actual illnessclusters that are actually compiled into recorded statistics is only a small fractionof such clusters of illness that occur [47]
From a more fundamental point of view an outbreak of illness is generallydefined as occurrence of the illness at a level greater than normal or anticipated Thisdefinition recognizes that there is a level of illness (endemic) that may exist underusual circumstances The detection of such outbreaks poses a particular challengeThe problem is illustrated conceptually in Figure 13
Additional complications arise from the different patterns of illness in acommunity including definite periodicities as well as temporal trends and fromthe presence of reporting lags associated with laboratory analysis and time for patientsto seek medical attention Figure 14 illustrates the different patterns of illness inthe case of six pathogens for England and Wales [48]
In the case of waterborne and foodborne illnesses it is highly likely that thelevel of such endemic illnesses is substantially greater than those occurring duringoutbreaks (even accounting for unrecognized outbreaks)
As a result there are often many cases of environmentally caused (water airfood) infectious disease that are unrecognized One example of this isCampylobacterThere has been an average of about 200 cases per year of water- and foodborne illnessin outbreaks of this organism and yet estimates of the disease burden suggest about2100000 cases per year that is approximately 10000 cases per case of detectableoutbreak illness Therefore it will be important to assess the factors that may influenceoutbreak detection These issues will be discussed in subsequent chapters
Detectedoutbreak
Undetectedoutbreak
Threshold of detection
Hyper endemicSporadic
Endemic rate
Time
Num
ber
of c
ases
Figure 13 Schematic of disease occurrence in a hypothetical community (Modified fromRef [47])
OUTBREAKS VERSUS ENDEMIC CASES 9
REFERENCES
1 Levin B R 1996 The Evolution and Maintenance of Virulence in Microparasites Emerging InfectiousDisease 293ndash102
2 National Academy of Sciences 1983 Risk Assessment in the Federal Government Managing theProcess National Academy Press Washington DC
3 National Research Council 2009 Science and Decisions Advancing Risk Assessment NationalAcademies Press Washington DC
10090807060504030201001190 1191 1192 1193 1194 1195
(b)
140
120
100
80
60
40
20
01190 1191 1192 1193 1194 1195
(f)
700
600
500
400
300
200
100
01190 1191 1192 1193 1194 1195
(d)
1200
1000
800
600
400
200
1190 1191 1192 1193 1194 1195
(a)
240
200
160
120
80
40
01190 1191 1192 1193 1194 1195
(e)
7
6
5
4
3
2
1
01190 1191 1192 1193 1194 1195
(c)
Figure 14 Weekly count of reported organism isolations in England andWales (a) rotavirus(b) Clostridium difficile (c) Salmonella derby (d) Shigella sonnei (e) influenza B and (f)Salmonella typhimurium DT 104 (From Ref [48])
10 CHAPTER 1 MOTIVATION
4 Fogarty J L Thornton and R Corcoran 1995 Illness in a Community Associated with an Episode ofWater Contamination with Sewage Epidemiology and Infection 114289ndash295
5 Scallan E 2011 Foodborne Illness Acquired in the United StatesmdashUnspecified Agents EmergingInfectious Diseases 17 16ndash22
6 Craun G F J M Brunkard J S Yoder V A Roberts J Carpenter T Wade R L CalderonJ M Roberts M J Beach and S L Roy 2010 Causes of Outbreaks Associated with Drinking Waterin the United States from 1971 to 2006 Clinical Microbiology Reviews 23507ndash528
7 Edwards D D 1993 Troubled Waters in Milwaukee ASM News 59342ndash3458 MacKenzie W R N J Hoxie M E Proctor M S Gradus K A Blair D E Peterson
J J Kazmierczak K R Fox D G Addias J B Rose and J P Davis 1994 Massive WaterborneOutbreak of Cryptosporidium Infection Associated with a Filtered Public Water Supply MilwaukeeWisconsin March and April 1993 New England Journal of Medicine 331161ndash167
9 Anonymous 2010 Surveillance for Foodborne Disease OutbreaksmdashUnited States 2007 Morbidityand Mortality Weekly Reports 59973ndash979
10 Bean N H J S Goulding C Lau and F J Angulo 1996 Surveillance for Foodborne-DiseaseOutbreaksmdashUnited States 1988ndash1992 Morbidity and Mortality Weekly Reports 451ndash66
11 Wall P G J de Louvois R J Gilbert and B Rowe 1996 Food Poisoning NotificationsLaboratory Reports and OutbreaksmdashWhere do the Statistics Come From and What Do They MeanCommunicable Disease Report Review 6 R93ndashR100
12 Colford J M S Roy M J Beach A Hightower S E Shaw and T J Wade 2006 A Review ofHousehold Drinking Water Intervention Trials and an Approach to the Estimation of EndemicWaterborne Gastroenteritis in the United States Journal of Water and Health 471
13 Mead P S L Slutsker V Dietz L F McCaig J S Bresee C Shapiro P M Griffinand R V Tauxe 1999 Food Related Illness and Death in the United States Emerging InfectiousDisease 5607ndash625
14 Dziuban E J J L Liang G F Craun V Hill P A Yu J Painter M R Moore R L CalderonS L Roy and M J Beach 2006 Surveillance for Waterborne Disease and Outbreaks Associatedwith Recreational WatermdashUnited States 2003ndash2004 and Surveillance for Waterborne Disease andOutbreaks Associated with Drinking Water and Water not Intended for DrinkingmdashUnited States2003ndash2004 Morbidity and Mortality Weekly Reports 551ndash30
15 Fliermans C B 1996 Ecology of Legionella From Data to Knowledge with a Little WisdomMicrobial Ecology 32203ndash228
16 Li Y S Duan I T Yu and T W Wong 2005 Multi-Zone Modeling of Probable SARS VirusTransmission by Airflow Between Flats in Block E Amoy Gardens Indoor Air 1596ndash111
17 Peccia J D K Milton T Reponen and J Hill 2008 A Role for Environmental Engineering andScience in Preventing Bioaerosol-Related Disease Environmental Science amp Technology424631ndash4637
18 Jernigan D B P L Raghunathan B P Bell R Brechner E A Bresnitz J C Butler M CetronM Cohen T Doyle and M Fischer 2002 Investigation of Bioterrorism-Related AnthraxUnited States 2001 Epidemiologic Findings Emerging Infectious Diseases 81019ndash1028
19 Greenwood M and G U Yule 1917 On the Statistical Interpretation of Some BacteriologicalMethods Employed in Water Analysis Journal of Hygiene 1636ndash56
20 Phelps E 1909 The Disinfection of Sewage and Sewage Filter Effluents USGS Water Supply Paper229 GPO Washington DC
21 Rudolfs W and H W Gehm 1935 Multiplication of Total Bacteria and B coli after SewageChlorination Sewage Works Journal 7991ndash996
22 Subcommittee onMicrobiological Criteria 1985 An Evaluation of the Role ofMicrobiological Criteriafor Foods and Food Ingredients National Academy Press Washington DC
23 Cabelli V J A P Dufour L J McCabe and M A Levin 1982 Swimming-AssociatedGastroenteritis and Water Quality American Journal of Epidemiology 115606ndash616
24 Dufour A P 1984 Health Effects Criteria for Fresh Recreational Waters USEPA Research TrianglePark NC
25 Fleisher J M F Jones and D Kay 1993 Water and Non-Water-Related Risk Factors forGastroenteritis among Bathers Exposed to Sewage-Contaminated Marine Waters InternationalJournal of Epidemiology 22698ndash708
REFERENCES 11
26 Engelbrecht R S C N Haas J A Shular D L Dunn D Roy A Lalchandani B F Severin andS Farooq 1979 Acid-Fast Bacteria and Yeasts as Indicators of Disinfection Efficiency EPA-6002-79-091 US Environmental Protection Agency Cincinnati OH
27 Grabow W O K 1983 Inactivation of Hepatitis A Virus and Indicator Organisms in Water by FreeChlorine Residuals Applied and Environmental Microbiology 46619
28 Helmer R D and G R Finch 1993 Use of MS2 Coliphage as a Surrogate for Enteric Viruses inSurface Waters Disinfected with Ozone Ozone Science and Engineering 15279ndash293
29 Payment P and E Franco 1993Clostridium Perfringens and Somatic Coliphages as Indicators of theEfficiency of Drinking Water Treatment for Viruses and Protozoan Cysts Applied and EnvironmentalMicrobiology 592418ndash2424
30 Cabelli V J 1977Clostridium Perfringens as aWater Quality Indicator pp 65ndash79 InA Hoadley andB Dutka (eds) Bacterial IndicatorsHealth Hazards Associated with Water ASTM Philadelphia PA
31 Rice E W K R Fox R J Miltner D A Lytle and C H Johnson 1996 Evaluating PlantPerformance with Endospores Journal of the American Water Works Association 88122ndash130
32 Engelbrecht R S B F Severin M T Masarik S Farooq S H Lee C N Haas and A Lalchandani1977 New Microbial Indicators of Disinfection Efficiency EPA-6002-77-052 US EnvironmentalProtection Agency Cincinnati OH
33 Committee on Indicators for Waterborne Pathogens ndash National Research Council 2004 Indicators forWaterborne Pathogens National Academies Press Washington DC
34 PresidentialCongressional Commission on Risk Assessment and RiskManagement 1997 Frameworkfor Environmental Health Risk Management The Commission Washington DC
35 Griffin P M and R V Tauxe 1991 The Epidemiology of Infections Caused by Escherichiacoli O157H7 Other Enterohemorrhagic E coli and the Associated Hemolytic Uremic SyndromeEpidemiologic Reviews 1360ndash98
36 Heun E M R L Vogt P J Hudson S Parren and G W Gary 1987 Risk Factors for SecondaryTransmission in Households after a Common Source Outbreak of Norwalk Gastroenteritis AmericanJournal of Epidemiology 1261181ndash1186
37 MacKenzie W R W L Schell B A Blair D G Addiss D E Peterson N J HozieJ J Kazmierczak and J P Davis 1995 Massive Outbreak of Waterborne CryptosporidiumInfection in Milwaukee Wisconsin Recurrence of Illness and Risk of Secondary TransmissionClinical Infectious Diseases 2157ndash62
38 Millard P K Gensheimer D G Addiss D M Sosin G A Beckett A Houck-Jankoski andA Hudson 1994 An Outbreak of Cryptosporidiosis from Fresh-Pressed Apple Cider Journal ofthe American Medical Association 2721592ndash1596
39 Pickering L K D G Evans H L DuPont J J Vollet and D J Evans Jr 1981 Diarrhea Caused byShigella Rotavirus and Giardia in Day Care Centers Prospective Study Journal of Pediatrics9951ndash56
40 Morens D M R M Zweighaft T M Vernon G W Gary J J Eslien B T Wood R C Holmanand R Dolin 1979 A Waterborne Outbreak of Gastroenteritis with Secondary Person to PersonSpread Lancet 5964ndash966
41 Laursen E O Mygind B Rasmussen and T Ronne 1994 Gastroenteritis A Waterborne OutbreakAffecting 1600 People in a Small Danish Town Journal of Epidemiology amp Community Health48453ndash458
42 Baron R C F D Murphy H B Greenberg C E Davis D J Bregman G W Gary J M Hughesand L B Schonberger 1982 Norwalk Gastrointestinal Illness An Outbreak Associated withSwimming in a Recreational Lake and Secondary Person to Person Transmission American Journalof Epidemiology 115163ndash172
43 Kappus K D J S Marks R C Holman J K Bryant C Baker G W Gary and H B Greenberg1982 An Outbreak of Norwalk Gastroenteritis Associated with Swimming in a Pool and SecondaryPerson to Person Transmission American Journal of Epidemiology 116834ndash839
44 White K E M T Osterbolm J A Mariotti J A Korlath D H Lawrence T L Ristinen andH B Greenberg 1986 A Foodborne Outbreak of Norwalk Virus Gastroenteritis American Journalof Epidemiology 124120ndash126
45 Spika J S J E Parsons and D Nordenberg 1986 Hemolytic Uremic Syndrome and DiarrheaAssociated with Escherichia coli O157H7 in a Day Care Center Journal of Pediatrics 109287ndash291
12 CHAPTER 1 MOTIVATION
46 Ferguson J K L R Jorm C D Allen P KWhitehead and G L Gilbert 1995 Prospective Study ofDiarrhoeal Outbreaks in Child Long Daycare Centres in Western Sydney Medical Journal of Australia163137ndash140
47 Frost F J G F Craun and R L Calderon 1996 Waterborne Disease Surveillance Journal of theAmerican Water Works Association 8866ndash75
48 Farrington C P N J Andrews A D Beale and M A Catchpole 1996 A Statistical Algorithmfor the Early Detection of Outbreaks of Infectious Disease Journal of the Royal StatisticalSociety A 159547ndash563
REFERENCES 13
CHAPTER2MICROBIAL AGENTS ANDTRANSMISSION
MICROBIAL TAXONOMY
The development of techniques for examining the nucleic acids of microorganisms hasseen major changes in which we classify and group related microorganisms This isespecially true for the study of ribosomal ribonucleic acid (rRNA) which is a highlyconserved sequence involved in the synthesis of proteins in all living organisms Basedon this analysis the classification of living things has been placed into a three-domainsystem consisting of Archaea Eukarya and Bacteria Of these the Bacteria andArchaea are termed prokaryotes (no organized cell nucleus) and the Eukarya areknown as eukaryotes (an organized cell nucleus) Eukaryotic microbes other thanalgae and fungi are collectively calledprotistsWithin theEukarya are fungi protozoahelminth worms algae plants animals and humans Archaea are microbes that looksomewhat similar to bacteria in size and shape under the light microscope but they areactually genetically and biochemically quite different They appear to be a simpler formof life and may in fact be the oldest form of life on earth Viruses are obligate intercel-lular parasites and are not amember of any group They are usually composed only of anucleic acid surrounded by a protein coat Eukaryotes are much more complex thanprokaryotic cells in structure and nutritional requirements Prokaryotes divide by sim-ple binary fissionwhereas eukaryotes divide byamore complexprocess calledmitosis
Eukaryotes
Fungi protozoa and helminth worms are all eukaryotes All contain members that arepathogenic to man and animals While algae do not infect humans they can producetoxins that are harmful to animals and man Fungi obtain nutrients solely by adsorp-tion of organic matter from dead organisms Even when they invade living tissuesthey typically kill cells and then adsorb the nutrients from them Some fungi are capa-ble of developing environmentally resistant spores which can be transported throughthe air Fungal diseases in humans are referred to asmycoses Airborne fungal sporesare responsible for some allergies in humans Yeasts are classified with the fungi and
Quantitative Microbial Risk Assessment Second Edition Charles N Haas Joan B Roseand Charles P Gerbacopy 2014 John Wiley amp Sons Inc Published 2014 by John Wiley amp Sons Inc
15
some are pathogenic to humans (Candida albicans) Certain fungi produce toxins(ie aflatoxins) when growing in foods that are mutagenic and carcinogenic in ani-mals Inhalation is an important route of transmission for some fungal diseases suchas aspergillosis blastomycosis coccidioidomycosis and histoplasmosis These fungiare found growing in animal feces soil or decaying organic matter (compost manure)and may be transmitted through the air when this matter is disturbed Some fungi maybe transmitted by direct contact with the skin Fungi are often found in drinking waterdistribution systems and they have been linked to infections in immunocompromisedindividuals [1] Food is not believed to be a significant route of transmission ofpathogenic fungi
Protozoans are unicellular organisms that are surrounded by a cytoplasmicmembrane that is covered by a protective structure called a pellicle Most are freeliving feeding off of bacteria Some of these can cause disease while others are obli-gate parasites They are capable of forming structures called cysts oocysts or spores(depending on the life cycle of the organism) resistant to adverse environmentalconditions such as desiccation starvation high temperatures and disinfectantsSome pathogenic protozoa are found mainly in the soil (Naegleria) or water(Acanthamoeba) Others such a Giardia and Cryptosporidium whose natural habitatis the intestines of warm-blooded animals are capable of causing disease in bothhumans and animals Others such as Entamoeba histolytica are only capable ofcausing disease in humans
Pathogenic enteric (replicate in the intestines) protozoans are usually excretedin the feces or urine and can be transmitted by fecally contaminated food and waterSome protozoa may be transmitted through the air (Acanthamoeba) or throughfomites (inanimate objects) Some important environmentally transmitted protozoaare listed in Table 21 The clinically important protozoa are divided taxonomicallyinto the amoebas (Entamoeba spp) flagellates (Giardia) and coccidian meaningldquoglobose in shaperdquo (Cryptosporidium and Cyclospora) Microsporidia are alsocapable of causing intestinal infections but their classification is uncertain becausethey have many characteristics associated with fungi They are all obligate parasitesand are transmitted via infectious cysts oocysts or spores by the fecalndashoral routeThe life cycles of these protozoa are similar The initial stage occurs during ingestionof the cyst oocyst or spore After ingestion the body temperature and passagethrough the stomach cause these infective stages to open up in a process calledexcystation
The Giardia cysts house two trophozoites which is the stage that attaches tointestinal cells and grows in the intestinal tract through asexual reproduction As thetrophozoites grow and begin to cover the wall of the intestinal tract diarrhea canresult As the trophozoites are released some form cysts as they pass through thebowels Cryptosporidium and Cyclospora both produce oocysts The life cycle ofCyclospora is still not well known except that its oocysts require some period of timein the environment before they are infective Cryptosporidium oocysts contain foursporozoites which enter the intestinal cells and begin the infection process As morecells become infected the illness begins and oocysts are excreted in high numbers inthe feces (about 100000g)
Worms and helminths are small multicellular animals that are parasiticto humans and animals They include flukes tapeworms and roundworms
16 CHAPTER 2 MICROBIAL AGENTS AND TRANSMISSION
SECOND EDITION
QUANTITATIVEMICROBIAL RISKASSESSMENT
CHARLES N HAAS
JOAN B ROSE
CHARLES P GERBA
Copyright copy 2014 by John Wiley amp Sons Inc All rights reserved
Published by John Wiley amp Sons Inc Hoboken New JerseyPublished simultaneously in Canada
No part of this publication may be reproduced stored in a retrieval system or transmitted in any formor by any means electronic mechanical photocopying recording scanning or otherwise except aspermitted under Section 107 or 108 of the 1976 United States Copyright Act without either the prior writtenpermission of the Publisher or authorization through payment of the appropriate per-copy fee to theCopyright Clearance Center Inc 222 Rosewood Drive Danvers MA 01923 (978) 7508400 fax (978)7504470 or on the web at wwwcopyrightcom Requests to the Publisher for permission should beaddressed to the Permissions Department John Wiley amp Sons Inc 111 River Street Hoboken NJ 07030(201) 748-6011 fax (201) 748-6008 or online at httpwwwwileycomgopermission
Limit of LiabilityDisclaimer of Warranty While the publisher and author have used their best effortsin preparing this book they make no representations or warranties with respect to the accuracy orcompleteness of the contents of this book and specifically disclaim any implied warranties ofmerchantability or fitness for a particular purpose No warranty may be created or extended bysales representatives or written sales materials The advice and strategies contained herein may not besuitable for your situation You should consult with a professional where appropriate Neither thepublisher nor author shall be liable for any loss of profit or any other commercial damages including butnot limited to special incidental consequential or other damages
For general information on our other products and services or for technical support please contactour Customer Care Department within the United States at (800) 7622974 outside the United Statesat (317) 5723993 or fax (317) 5724002
Wiley also publishes its books in a variety of electronic formats Some content that appears in print maynot be available in electronic formats For more information about Wiley products visit our web site atwwwwileycom
Library of Congress Cataloging-in-Publication Data
Haas Charles NQuantitative microbial risk assessment Charles N Haas Joan B Rose Charles P Gerba ndash Second edition
p cmIncludes bibliographical references and indexISBN 978-1-118-14529-6 (cloth alk paper)
1 Communicable diseasesndashEpidemiologyndashMethodology 2 Health risk assessment 3 InfectionndashMathematical models 4 Environmental healthndashMathematical models I Rose Joan B II GerbaCharles P 1945- III Title
RA643H22 2014615902ndashdc23
2014002690
Printed in the United States of America
10 9 8 7 6 5 4 3 2 1
CONTENTS
PREFACE xi
CHAPTER 1 MOTIVATION 1
Prevalence of Infectious Disease 1
Prior Approaches 4
Scope of Coverage 4
Potential Objectives of a QMRA 5
Site-Specific Assessment 5
Ensemble of Sites 6
Secondary Transmission 7
Outbreaks versus Endemic Cases 7
References 10
CHAPTER 2 MICROBIAL AGENTS AND TRANSMISSION 15
Microbial Taxonomy 15
Eukaryotes 15
Prokaryotes 18
Viruses 20
Prions 22
Clinical Characterization 24
Microorganisms of Interest 27
Viruses 27
Bacteria 37
Protozoa 42
Transmission Routes 45
Inhalation 48
Dermal Exposure 50
Oral Ingestion 50
References 55
CHAPTER 3 RISK ASSESSMENT PARADIGMS 63
Chemical Risk Assessment National Academy of Sciences Paradigm 63
Ecological Risk Assessment 67
Approaches for Assessing Microbial Risks 71
Background 71
v
The QMRA Framework 74
Hazard Identification 74
DosendashResponse Assessment 74
Exposure Assessment 76
Risk Characterization 77
Risk Management 79
Development of the QMRA Framework and Processes 79
QMRA and the Safety of Water 82
QMRA Food Safety and the HACCP System 84
References 86
CHAPTER 4 CONDUCTING THE HAZARD IDENTIFICATION (HAZ ID) 91
Identifying and Diagnosing Infectious Disease 92
Health Outcomes Associated with Microbial Infections 95
Sensitive Populations 100
Women during Pregnancy Neonates and Young Babies 101
Diabetes 102
The Elderly 102
The Immunocompromised 104
Databases for Statistical Assessment of Disease 106
ICD Codes 107
Waterborne and Foodborne Outbreaks 111
Epidemiological Methods for Undertaking HAZ ID 117
Controlled Epidemiological Investigations 118
HAZ ID Data Used in the Risk Assessment Process 119
Recommendations for Updating Quantitative Data for HAZ ID Information 121
References 122
CHAPTER 5 ANALYTICAL METHODS AND THE QMRA FRAMEWORKDEVELOPING OCCURRENCE AND EXPOSURE DATABASES 129
Introduction 129
Approaches for Developing Occurrence and Exposure Databases 132
Overview of Methodological Issues 134
Sampling Water 136
Sampling Surfaces and Food 138
Sampling Aerosols 138
Specific Techniques for Bacteria Protozoa and Viruses 140
Bacteria 140
Protozoa 142
Viruses 143
Molecular Techniques 145
Probes (FISH) 146
Typing 146
vi CONTENTS
Metagenomics 147
PCR and Quantitative PCR 147
References 151
CHAPTER 6 EXPOSURE ASSESSMENT 159
Conducting the Exposure Assessment 159
Characterizing ConcentrationDuration Distributions 160
Random (Poisson) Distributions of Organisms 160
Estimation of Poisson Mean in Count Assay (Constant and Variable Volumes) 162
Count Assay with Upper Limits 163
Estimation with Quantal Assay 164
Goodness of Fit to Poisson Plate Assay 168
Goodness of Fit MPN 178
Confidence Limits Likelihood 182
Implications for Risk Assessment 187
Consumption Distributions 214
Systematic Subpopulation Differences 221
Afterword 223
Appendix 224
Microsoft Excel 224
MATLAB 225
R 227
References 230
CHAPTER 7 PREDICTIVE MICROBIOLOGY 235
Objective 235
Basic First-Order Processes and Deviations 236
Biological and Physical Bases for Deviations 236
Physical Removal 238
Types of Decay Processes 238
General Forms of Decay and Reasons for Nonlinearity 238
SpontaneousEndogenous 240
Chemical Agents 241
Thermally Induced 243
Ionizing and Nonionizing Radiation 243
Predation and Antagonism 245
Types of Growth Processes 245
Mathematical Modeling of Growth Curves 246
Substrate Dependency 252
Structured Growth Models 255
Incorporation of Decay into Growth Models 256
Systems Biology Approaches 258
CONTENTS vii
Dependence of Growth Parameters on Other Environmental Variables 258
Interacting Populations 258
Data Sources 260
References 263
CHAPTER 8 CONDUCTING THE DOSEndashRESPONSE ASSESSMENT 267
Plausible DosendashResponse Models 268
Framework for Mechanistic DosendashResponse Relationships 269
Exponential DosendashResponse Model 271
Beta-Poisson DosendashResponse Model 272
Simple Threshold Models 274
Negative Binomial Dose Distributions 277
Variable Threshold Models 278
Other Mixture Models 279
Biological Arguments for One-Hit Models 281
Empirical Models 282
Fitting Available Data 283
Types of Data Sets 284
Potential Impacts of Immune Status 298
Relationship between Dose and Severity (Morbidity and Mortality) 299
Morbidity Ratio (PDI) 299
Mortality Ratio 303
Reality Checking Validation 304
Validation 1993 Milwaukee Outbreak 304
Use of Indicators and Other Proxy Measures in DosendashResponse 305
Indicator Methods 305
Molecular Methods 307
Advanced Topics in DosendashResponse Modeling 308
DosendashResponsendashTime Models 308
Physiological Models 313
Appendix 315
References 317
CHAPTER 9 UNCERTAINTY 323
Point Estimates of Risk 324
Terminology Types of Uncertainty 326
Sources of Uncertainty 327
Sources of Variability 328
Variability that is Uncertain 329
Approaches to Quantify Parametric Uncertainty 329
Likelihood 329
Bootstrap 330
Other Methods 330
viii CONTENTS
Applications 332
Exposure Assessment 332
DosendashResponse Assessment 338
Combining Parametric Uncertainty from Multiple Sources 344
Propagation Methods 344
Monte Carlo Analyses 347
Overall Risk Characterization Example 365
Second-Order Methods 368
Model Uncertainty and Averaging 370
References 373
CHAPTER 10 POPULATION DISEASE TRANSMISSION 377
Introduction Models for Population and Community Illnesses 377
Basic SIR Model 378
Incubation Period 386
Duration of Illness 388
Secondary Cases 389
Impact of Immunity 392
Outbreak Detection 393
References 397
CHAPTER 11 RISK CHARACTERIZATION AND DECISION MAKING 399
Introduction 399
Valuing Residual Outcomes 400
Classical Economics 400
DALYs and QALYs 404
Decision Making 407
CostndashBenefit Analysis 408
Multivariate Approaches 411
Other Aspects Entering into a Decision 412
Equity and Justice Aspects 412
References 413
INDEX 415
CONTENTS ix
PREFACE
In the 14 years since we prepared the first edition there has been an explosion inknowledge of and need for quantitative microbial risk assessment (QMRA) Whileour motivation for the first edition stemmed from concerns (principally in water) aboutenteric bacteria viruses and protozoa the motivation has now exploded to newdomains and agents SARS influenza biothreat agents and zoonotic pathogens haveall become of greater concern
The 2001 anthrax letters have highlighted the need for risk assessment ofinhaled agents Both biothreat agents and emergence of new strains of virulentcontagious organisms have raised concern for modeling pathogen dynamics inpopulations
In this edition we have retained the fundamental approach of the riskassessment methodology as a central paradigm We have added new material onmodern pathogen analytical methods predictive microbiology (of pathogen growthand decay) dynamic risk models (explicitly considering incubation time) and diseasepropagation models in populations Of necessity we have removed some materialmdashitis no longer possible to present comprehensive tables of microbial dosendashresponseparameters
In the years since the first edition the authors have gained experience inteaching this material to generations of studentsmdashin the form of formal classestutorials independent studies and short courses We know this book can be valuablein instructing advanced students in environmental sciences environmental engineer-ing public health and microbiology It is also a useful reference for practitionersand regulatory personnel Some prior statistical background would be useful inapproaching the material but not necessary the key requirement for any risk assessoris the absence of fear from mathematical constructs and concepts
The three of us have been on a QMRA journey for almost 30 years We havelearned that doing high-quality risk assessments is of necessity a team sport requiringindividuals with different skills and interests We have learned a tremendous amountfrom each other from our students from our collaborators and from the problems thatwe have sought to approach Practitioners of the art of quantitative microbial riskassessment should be advised to cast a wide net with respect to colleagues andcollaborators to perfect their craft
xi
We encourage comments and feedback from users of this work and look for-ward to observing and participating in developments in coming years and ultimatelyto handing the baton off to our students and their students
Charles N Haas
Joan B Rose
Charles P GerbaNovember 2013
xii PREFACE
CHAPTER1MOTIVATION
THE PREVENTION of infectious disease transmission from human exposure tocontaminated food water soil and air remains a major task of environmental andpublic health professionals There are numerous microbial hazards including expo-sure via food water air and malicious release of pathogens that may arise Indeedsome have argued that the property of virulence of human pathogens is one which isfavored by evolutionary interactions between pathogens and host populations andtherefore will always be of important concern [1] To make rational decisions in pre-paring responding and recovering from exposures to such hazards a quantitativeframework is of high benefit
The objective of this book is to comprehensively set forth the methods forassessment of risk from infectious agents transmitted via these routes in a frameworkthat is compatible with the framework for other risk assessments (eg for chemicalagents) as set forth in standard protocols [2 3]
In this chapter information on the occurrence of infectious disease in broadcategories will be presented along with a historical background on prior methodsfor assessment of microbial safety of food water and air This will be followed byan overview of key issues covered in this book
PREVALENCE OF INFECTIOUS DISEASE
Outbreaks of infectious waterborne illness continue to occur although it remainsimpossible to identify the infectious agent in all cases For example in 1991 a water-borne outbreak in Ireland resulting from sewage contamination of water suppliesinfected about 5000 persons However the infectious agent responsible for thisoutbreak could not be determined [4] In the United States it has been estimated that38 million cases of foodborne infectious disease occur annually with unidentifiedagents [5]
In the United States there have typically been three to five reported outbreaksper year in community drinking water systems involving infectious microorganismswith perhaps up to 10000 annual cases [6] The 1994 Milwaukee Cryptosporidiumoutbreak with over 400000 cases [7 8] was a highly unusual event among thesestatistics As shown in Figure 11 there has been an increasing ability to identify
Quantitative Microbial Risk Assessment Second Edition Charles N Haas Joan B Roseand Charles P Gerbacopy 2014 John Wiley amp Sons Inc Published 2014 by John Wiley amp Sons Inc
1
microorganisms responsible for waterborne diseases and it is expected that withadvances in molecular biology this will increase
There are substantially more outbreaks and cases of foodborne infectiousdiseases than are reported Table 11 summarizes reports of US cases of principalmicrobial infectious foodborne illnesses for two 5-year periods (1988ndash1992 and
1971ndash1982
10
20
30
40
Perc
ent o
f out
brea
ks
50
60
1983ndash1994Period
1995ndash2006
Figure 11 Percentages of outbreaks associated with public water systems (n = 680) by timeperiod 1971ndash2006 that had unknown etiologies based on data from Ref [6]
TABLE 11 Comparison of Five-Year Averages for Common Foodborne Reported Outbreaks
Agent
Annual Average 1988ndash1992 Annual Average 2002ndash2006
Cases Outbreaks Cases Outbreaks
Campylobacter 996 44 624 22
Escherichia coli 488 22 481a 30a
Salmonella 42354 1098 3475 144
Shigella 9576 5 495 12
Staphylococcus aureus 3356 94 554 25
Hepatitis 4218 86 238 1
Listeria monocytogenes 04 02 22 2
Giardia 368 14 2 1
Norovirus 584 04 10854 338
Vibrio (all) 114 18 114 5
Unknown etiologies 40483 1422 4052 30
Source From Refs [9 10]a Include both Shiga toxigenic and enterotoxigenic
2 CHAPTER 1 MOTIVATION
2002ndash2006) There is a mix of causal agents including bacteria virus and protozoaIt is noteworthy that (as in the case of waterborne outbreaks) the frequency ofoutbreaks of unknown etiology has dramatically decreased but the frequency of out-breaks associated with norovirus has dramatically increased These changes are duein part to the ability to better identify causal agents (eg via molecular methods)
It is generally recognized that reported outbreaks either of water- or foodborneinfectious disease represent only a small fractionof the total populationdisease burdenHowever particularly in the United States voluntary reporting systems and theoccurrence of mild cases (for which no medical attention is sought but neverthelessare frank cases of disease) have made it difficult to estimate the total caseload
In the United Kingdom comparisons between the number of confirmed casesin infectious disease outbreaks and total confirmed laboratory illnesses (occurring inEngland and Wales) have been made (Table 12) This suggests that the ratio ofreported outbreak cases to total cases that may seek medical attention may be from10 to 5001 with some dependency on the particular agent
Colford et al [12] developed estimates for the total disease burden associatedwith acute gastroenteritis from drinking water This relies on combining the reportedoutbreak data with interventional epidemiologic studies Based on their analysis thetotal US disease burden is estimated to be 426ndash1169 million cases per year in theUnited States which is substantially in excess of the reported outbreaks In the case offoodborne illness there are an estimated 14 million cases per year [13]
Drinking water and food are by no means the only potential routes of exposureto infectious agents in the environment Recreation in water (either natural or artificialpools) containing pathogens can produce illness [14]
Indoor air transmission can be a vehicle of infection Legionella transmittedthrough indoor environments has been a concern since the 1970s [15] The multina-tional epidemic of severe acute respiratory syndrome (SARS) caused by a coronavi-rus was abetted at least in one location in Hong Kong by indoor aerosol transmissionbetween apartments of infected individuals and susceptible individuals [16] A broadspectrum of other respiratory pathogens including influenza rhinoviruses and myco-bacteria can be transmitted by this route [17]
TABLE 12 Comparison of Laboratory Isolations and Outbreak Cases in Englandand Wales 1992ndash1994
Agent
Cases 1992ndash1994
RatioAll Laboratory Reports Confirmed Outbreak Cases
Campylobacter 122250 240 5094
Rotavirus 47463 127 3737
S sonnei 29080 847 343
Salmonella 92416 5960 155
Cryptosporidium 14454 1066 136
E coli O157 1266 128 99
Source Modified from Ref [11]
PREVALENCE OF INFECTIOUS DISEASE 3
The deliberate release of Bacillus anthracis spores in 2001 (the ldquoAmerithraxrdquoincidents) brought widespread awareness to the potential for indoor releases (as wellas releases in other venues) of bioterrorist agents to cause risk [18] Therefore ofnecessity microbial risk assessors may need to consider the impact of maliciousactivity in certain applications
PRIOR APPROACHES
Concerns for microbial quality of food water and other environmental media havelong existed In the early twentieth century the use of indicator microorganismswas developed for the control and assessment of the hygienic quality of such mediaand the adequacy of disinfection and sterilization processes The coliform group oforganisms was perhaps first employed for this purpose [19ndash21] Indicator techniqueshave also found utility in the food industry such as the total count for milk and othermore recent proposals [22] Other indicator groups for food water or environmentalmedia have been examined such as enterococci [23ndash25] acid-fast bacteria [26]bacteriophage [27ndash29] and Clostridia spores [29ndash31]
The use of indicator organisms was historically justified in because of difficultyin enumerating pathogens However with the increasing availability of modernmicrobial methods for example PCR immunoassay etc for direct pathogen assess-ment this justification has become less persuasive In addition in order to develophealth-based standards from indicators extensive epidemiologic surveillance is oftennecessary The use of epidemiology has limitations with respect to detection limits(for an adverse effect) and is also quite expensive to conduct Indicator methodsare also limited in that many pathogens are more resistant to die off in receiving envir-onments or source waters than indicators or have greater resistance to removal bytreatment processes than indicators [26 28 29 32] Thus the absence of indicatorsmay not suffice to ensure the absence of pathogens Even after a century of use theindicator concept remains imperfect [33]
The use of quantitative microbial risk assessment (QMRA) will enable directmeasurements of pathogens to be used to develop acceptancerejection guidelinesfor food water and other vehicles that may be the source of microbial exposureto human populations The objective of this book is to present these methods in asystematic and unified manner
SCOPE OF COVERAGE
QMRA is the application of principles of risk assessment to the estimate ofconsequences from a planned or actual exposure to infectious microorganismsIn performing a QMRA the risk assessor aims to bring the best available informationto bear in understanding the nature of the potential effects from a microbial exposureSince the information (such as dosendashresponse relationships exposure magnitudes) isalmost invariably incomplete it is also necessary to ascertain the potential error
4 CHAPTER 1 MOTIVATION
involved in the risk assessment With such information necessary steps to mitigatecontrol or defend against such exposures may be developed
At the outset of performing a risk assessment a scoping task should be under-taken This task should set forth the objectives of the analysis and the principal issuesto be addressed Items such as consideration of secondary cases individual versuspopulation risk agent or agents to be examined exposure routes andor accident sce-narios must be stipulated However this scoping may be changed during the course ofa QMRA to reflect the input derived from the risk manager(s) and other stakeholders
POTENTIAL OBJECTIVES OF A QMRA
There may be diverse objectives for a QMRA These objectives relate to the rationalefor the performance of the assessment as well as the methods to be employedBroadly the different objectives reflect different scales at which a risk assessmentmay be performed The step of problem formulation is critical to any risk estimate[34] It is necessary that the problem be formulated to meet the needs of the riskmanagers and stakeholders indeed it is now recognized that the successful practiceof risk analysis requires frequent interchange with manager and stakeholders [3]In general the problems posed are of several types
Site-Specific Assessment
The simplest type of QMRA that may be performed involves one site or exposurescenario The following are typical of the questions that might be asked
1 If a water treatment plant is designed in a certain way (with given removals ofpathogens) then what is the risk that would be placed upon the populationserved
2 A swimming outbreak (in a recreational lake) has just occurred I believe that itresulted from a short-duration contamination event What pathogen levelswould be consistent with the observed attack rate
3 Microbial sampling of a finished food product has found certain pathogensWhat level of risk does this pose to consumers of the product
4 A certain amount of infectious agent has been released into a room What is theimmediate danger to occupants and how stringent should cleanup levels be
Note that there are certain other contrasts in the objectives of the risk assessments tobe posed In (1) and (3) a before-the-fact computation is desired while in (2) and (4)an after-the-fact computation is described Also in (1) (3) and (4) pathogen levelsare available (or somehow are estimated) while in (2) an inverse computation isneeded given an observed attack rate
In performing this risk assessment the relationship between an exposure ortechnological metric and a risk measurement must be ascertained and then theparticular point of correspondence determined (Fig 12) In cases (1) (3) and (4)for a known (or assumed) exposure (on the x-axis) the corresponding range of risks
POTENTIAL OBJECTIVES OF A QMRA 5
on the y-axis is sought In cases (2) for known or assumed risks (on the y-axis)the corresponding range of exposures (or level of technological protection) is to bedetermined (on the x-axis)
Ensemble of Sites
A somewhat more complex situation occurs if the risk for a set of events or sites mustbe estimated Basically this now includes the necessity to incorporate site-to-sitefactors into the assessment Some examples of this are as follows
1 If I desire keeping the risk to a population served by multiple water treatmentplants at a given level (or better) then what criteria should I use (microbiallevels)
2 For a food product subject to contamination by pathogens what would be anacceptable treatment specification (eg heating time holding period) to ensuremicrobial acceptability
3 I am designing a water quality standard for recreational bathing waters If auniform (eg national) standard is to be developed what standard would ensurethat average risk was acceptable with keeping the risk of a large ldquoclusterrdquo ofillnesses low
In addition to incorporating a measure of ensemble average risk in general it is alsodesired to ensure that no single member of the ensemble be unacceptably extreme Forexample consider the evaluation of three options of disease control among three com-munities as indicated in Table 13
This table indicates the number of cases and the rate among the three commu-nities The three policy options yield the same number of expected cases Howeverthere are differences in the allocation of risk among the communities of different sizesIn option A all communities have an identical level of estimated risk In option B therisk increases as community size decreases while in option C the risk increases ascommunity size increases This distribution of risk among affected subsets of the
Exposure
Ris
k
Level of technological protection
Figure 12 Relationship between exposurelevel of technological protection andmicrobial risk The middle curve indicatesthe best estimate The other two curvesindicate the upper and lower confidenceregions
6 CHAPTER 1 MOTIVATION
ensemble being considered adds an additional dimension for consideration by a riskmanagermdashwhich may be termed risk equity
SECONDARY TRANSMISSION
Infectious microbial diseases are different in terms of risk to a population than arechemical agents in that an individual who may become infected (with or withoutillness) can then proceed to infect additional individuals These secondary (tertiaryquaternary etc) cases may be persons who had no direct contact with the initialvehicle of exposure but nevertheless in fairly accounting for the public health impactthey should be considered
Secondary cases may arise by a variety of mechanisms Particularly amongclose family members household secondary cases can arise by direct or indirect(eg surface contamination) contact this is particularly so when the primary caseor one household secondary case is a child [35ndash37] Table 14 summarizes secondarycase statistics obtained from a variety of outbreaks As will be discussed inChapter 10 the secondary case rate is a complex factor involving (among other things)the nature of the venue and contact patterns when infected and susceptible individualsintermingle
Presumably secondary cases may also arise from close contact with anasymptomatic individual (in the ldquocarrierrdquo state) This is well known for highly acuteand (now) uncommon illnesses (such as typhoid) Excretion of Norwalk virusfollowing recovery (and resulting in additional cases) has been documented to occurfor as long as 48 h post recovery [44]
OUTBREAKS VERSUS ENDEMIC CASES
As noted previously there may be a substantial difference between reported outbreakcases and total disease burden in a community In order for a disease case to receiverecognition by the public health authorities the following specific and sequential stepsmust occur [47]
TABLE 13 Effect of Different Hypothetical Policy Options on Distribution of Risk AmongCommunities (for a Fixed Total Risk)
CommunityExposedPopulation
Policy Option A Policy Option B Policy Option C
CasesIncidence(10000) Cases
Incidence(10000) Cases
Incidence(10000)
A 100000 20 2 6 06 24 24
B 50000 10 2 18 36 7 14
C 10000 2 2 8 8 1 1
Total 160000 32 2 32 2 16 2
OUTBREAKS VERSUS ENDEMIC CASES 7
1 An ill person must seek medical care
2 Appropriate clinical tests (eg blood stool) must be ordered by the attendingphysician
3 The patient must comply with obtaining the sample
4 The laboratory must be capable of detecting the relevant pathogens
5 The clinical test must be positive
6 The test result must be reported to the health agency in a timely manner
If any of the links in this sequential chain are broken then a disease case will not enterthe records maintained by health authorities For example with increasing controls on
TABLE 14 Summary of Secondary Case Data in Outbreak Situations
Organism
SecondaryAttackRatioa
SecondaryPrevalence inHouseholdsb Remarks Reference
Cryptosporidiumparvum
033 033 Outbreak in contaminatedapple cider
[38]
C parvum NA 0042 Drinking water outbreak(Milwaukee)
[37]
Shigella 028 026 Day-care center outbreaksin children
[39]
Rotavirus 042 015 Day-care center outbreaksin children
[30]
Giardia lamblia 133 017 Day-care center outbreaksin children
[39]
Viral gastroenteritis 022 011c Drinking waterborneoutbreak
[40]
Viral gastroenteritis 056 NA Drinking water outbreak(Denmark)
[41]
Norovirus 05ndash10 019 Swimming outbreak [42]
Norovirus 11 029 Swimming outbreakin children
[43]
Norovirus NA 044 Foodborne outbreakin children and teachers
[36]
Norovirus 04 NA Foodborne outbreak [44]
E coli O157H7 NA 018c Day-care center outbreakin children
[45]
Unidentifiedday-care diarrhealdiseases
138 009c [46]
NA information not availableaRatio of secondary cases to primary casesb Proportion of households with one or more primary cases who have one or more secondary casesc Proportion of persons in contact with one or more primary cases who have a secondary case
8 CHAPTER 1 MOTIVATION
medical care stool samples may not be obtained from mild cases of illness Someorganisms may only be present sporadically or may be difficult to test in stool orblood sample Patients may not seek medical attention for mild cases of illness Fur-thermore in the United States in particular the surveillance of environmentallyinduced disease is done on a passive basis and hence the number of actual illnessclusters that are actually compiled into recorded statistics is only a small fractionof such clusters of illness that occur [47]
From a more fundamental point of view an outbreak of illness is generallydefined as occurrence of the illness at a level greater than normal or anticipated Thisdefinition recognizes that there is a level of illness (endemic) that may exist underusual circumstances The detection of such outbreaks poses a particular challengeThe problem is illustrated conceptually in Figure 13
Additional complications arise from the different patterns of illness in acommunity including definite periodicities as well as temporal trends and fromthe presence of reporting lags associated with laboratory analysis and time for patientsto seek medical attention Figure 14 illustrates the different patterns of illness inthe case of six pathogens for England and Wales [48]
In the case of waterborne and foodborne illnesses it is highly likely that thelevel of such endemic illnesses is substantially greater than those occurring duringoutbreaks (even accounting for unrecognized outbreaks)
As a result there are often many cases of environmentally caused (water airfood) infectious disease that are unrecognized One example of this isCampylobacterThere has been an average of about 200 cases per year of water- and foodborne illnessin outbreaks of this organism and yet estimates of the disease burden suggest about2100000 cases per year that is approximately 10000 cases per case of detectableoutbreak illness Therefore it will be important to assess the factors that may influenceoutbreak detection These issues will be discussed in subsequent chapters
Detectedoutbreak
Undetectedoutbreak
Threshold of detection
Hyper endemicSporadic
Endemic rate
Time
Num
ber
of c
ases
Figure 13 Schematic of disease occurrence in a hypothetical community (Modified fromRef [47])
OUTBREAKS VERSUS ENDEMIC CASES 9
REFERENCES
1 Levin B R 1996 The Evolution and Maintenance of Virulence in Microparasites Emerging InfectiousDisease 293ndash102
2 National Academy of Sciences 1983 Risk Assessment in the Federal Government Managing theProcess National Academy Press Washington DC
3 National Research Council 2009 Science and Decisions Advancing Risk Assessment NationalAcademies Press Washington DC
10090807060504030201001190 1191 1192 1193 1194 1195
(b)
140
120
100
80
60
40
20
01190 1191 1192 1193 1194 1195
(f)
700
600
500
400
300
200
100
01190 1191 1192 1193 1194 1195
(d)
1200
1000
800
600
400
200
1190 1191 1192 1193 1194 1195
(a)
240
200
160
120
80
40
01190 1191 1192 1193 1194 1195
(e)
7
6
5
4
3
2
1
01190 1191 1192 1193 1194 1195
(c)
Figure 14 Weekly count of reported organism isolations in England andWales (a) rotavirus(b) Clostridium difficile (c) Salmonella derby (d) Shigella sonnei (e) influenza B and (f)Salmonella typhimurium DT 104 (From Ref [48])
10 CHAPTER 1 MOTIVATION
4 Fogarty J L Thornton and R Corcoran 1995 Illness in a Community Associated with an Episode ofWater Contamination with Sewage Epidemiology and Infection 114289ndash295
5 Scallan E 2011 Foodborne Illness Acquired in the United StatesmdashUnspecified Agents EmergingInfectious Diseases 17 16ndash22
6 Craun G F J M Brunkard J S Yoder V A Roberts J Carpenter T Wade R L CalderonJ M Roberts M J Beach and S L Roy 2010 Causes of Outbreaks Associated with Drinking Waterin the United States from 1971 to 2006 Clinical Microbiology Reviews 23507ndash528
7 Edwards D D 1993 Troubled Waters in Milwaukee ASM News 59342ndash3458 MacKenzie W R N J Hoxie M E Proctor M S Gradus K A Blair D E Peterson
J J Kazmierczak K R Fox D G Addias J B Rose and J P Davis 1994 Massive WaterborneOutbreak of Cryptosporidium Infection Associated with a Filtered Public Water Supply MilwaukeeWisconsin March and April 1993 New England Journal of Medicine 331161ndash167
9 Anonymous 2010 Surveillance for Foodborne Disease OutbreaksmdashUnited States 2007 Morbidityand Mortality Weekly Reports 59973ndash979
10 Bean N H J S Goulding C Lau and F J Angulo 1996 Surveillance for Foodborne-DiseaseOutbreaksmdashUnited States 1988ndash1992 Morbidity and Mortality Weekly Reports 451ndash66
11 Wall P G J de Louvois R J Gilbert and B Rowe 1996 Food Poisoning NotificationsLaboratory Reports and OutbreaksmdashWhere do the Statistics Come From and What Do They MeanCommunicable Disease Report Review 6 R93ndashR100
12 Colford J M S Roy M J Beach A Hightower S E Shaw and T J Wade 2006 A Review ofHousehold Drinking Water Intervention Trials and an Approach to the Estimation of EndemicWaterborne Gastroenteritis in the United States Journal of Water and Health 471
13 Mead P S L Slutsker V Dietz L F McCaig J S Bresee C Shapiro P M Griffinand R V Tauxe 1999 Food Related Illness and Death in the United States Emerging InfectiousDisease 5607ndash625
14 Dziuban E J J L Liang G F Craun V Hill P A Yu J Painter M R Moore R L CalderonS L Roy and M J Beach 2006 Surveillance for Waterborne Disease and Outbreaks Associatedwith Recreational WatermdashUnited States 2003ndash2004 and Surveillance for Waterborne Disease andOutbreaks Associated with Drinking Water and Water not Intended for DrinkingmdashUnited States2003ndash2004 Morbidity and Mortality Weekly Reports 551ndash30
15 Fliermans C B 1996 Ecology of Legionella From Data to Knowledge with a Little WisdomMicrobial Ecology 32203ndash228
16 Li Y S Duan I T Yu and T W Wong 2005 Multi-Zone Modeling of Probable SARS VirusTransmission by Airflow Between Flats in Block E Amoy Gardens Indoor Air 1596ndash111
17 Peccia J D K Milton T Reponen and J Hill 2008 A Role for Environmental Engineering andScience in Preventing Bioaerosol-Related Disease Environmental Science amp Technology424631ndash4637
18 Jernigan D B P L Raghunathan B P Bell R Brechner E A Bresnitz J C Butler M CetronM Cohen T Doyle and M Fischer 2002 Investigation of Bioterrorism-Related AnthraxUnited States 2001 Epidemiologic Findings Emerging Infectious Diseases 81019ndash1028
19 Greenwood M and G U Yule 1917 On the Statistical Interpretation of Some BacteriologicalMethods Employed in Water Analysis Journal of Hygiene 1636ndash56
20 Phelps E 1909 The Disinfection of Sewage and Sewage Filter Effluents USGS Water Supply Paper229 GPO Washington DC
21 Rudolfs W and H W Gehm 1935 Multiplication of Total Bacteria and B coli after SewageChlorination Sewage Works Journal 7991ndash996
22 Subcommittee onMicrobiological Criteria 1985 An Evaluation of the Role ofMicrobiological Criteriafor Foods and Food Ingredients National Academy Press Washington DC
23 Cabelli V J A P Dufour L J McCabe and M A Levin 1982 Swimming-AssociatedGastroenteritis and Water Quality American Journal of Epidemiology 115606ndash616
24 Dufour A P 1984 Health Effects Criteria for Fresh Recreational Waters USEPA Research TrianglePark NC
25 Fleisher J M F Jones and D Kay 1993 Water and Non-Water-Related Risk Factors forGastroenteritis among Bathers Exposed to Sewage-Contaminated Marine Waters InternationalJournal of Epidemiology 22698ndash708
REFERENCES 11
26 Engelbrecht R S C N Haas J A Shular D L Dunn D Roy A Lalchandani B F Severin andS Farooq 1979 Acid-Fast Bacteria and Yeasts as Indicators of Disinfection Efficiency EPA-6002-79-091 US Environmental Protection Agency Cincinnati OH
27 Grabow W O K 1983 Inactivation of Hepatitis A Virus and Indicator Organisms in Water by FreeChlorine Residuals Applied and Environmental Microbiology 46619
28 Helmer R D and G R Finch 1993 Use of MS2 Coliphage as a Surrogate for Enteric Viruses inSurface Waters Disinfected with Ozone Ozone Science and Engineering 15279ndash293
29 Payment P and E Franco 1993Clostridium Perfringens and Somatic Coliphages as Indicators of theEfficiency of Drinking Water Treatment for Viruses and Protozoan Cysts Applied and EnvironmentalMicrobiology 592418ndash2424
30 Cabelli V J 1977Clostridium Perfringens as aWater Quality Indicator pp 65ndash79 InA Hoadley andB Dutka (eds) Bacterial IndicatorsHealth Hazards Associated with Water ASTM Philadelphia PA
31 Rice E W K R Fox R J Miltner D A Lytle and C H Johnson 1996 Evaluating PlantPerformance with Endospores Journal of the American Water Works Association 88122ndash130
32 Engelbrecht R S B F Severin M T Masarik S Farooq S H Lee C N Haas and A Lalchandani1977 New Microbial Indicators of Disinfection Efficiency EPA-6002-77-052 US EnvironmentalProtection Agency Cincinnati OH
33 Committee on Indicators for Waterborne Pathogens ndash National Research Council 2004 Indicators forWaterborne Pathogens National Academies Press Washington DC
34 PresidentialCongressional Commission on Risk Assessment and RiskManagement 1997 Frameworkfor Environmental Health Risk Management The Commission Washington DC
35 Griffin P M and R V Tauxe 1991 The Epidemiology of Infections Caused by Escherichiacoli O157H7 Other Enterohemorrhagic E coli and the Associated Hemolytic Uremic SyndromeEpidemiologic Reviews 1360ndash98
36 Heun E M R L Vogt P J Hudson S Parren and G W Gary 1987 Risk Factors for SecondaryTransmission in Households after a Common Source Outbreak of Norwalk Gastroenteritis AmericanJournal of Epidemiology 1261181ndash1186
37 MacKenzie W R W L Schell B A Blair D G Addiss D E Peterson N J HozieJ J Kazmierczak and J P Davis 1995 Massive Outbreak of Waterborne CryptosporidiumInfection in Milwaukee Wisconsin Recurrence of Illness and Risk of Secondary TransmissionClinical Infectious Diseases 2157ndash62
38 Millard P K Gensheimer D G Addiss D M Sosin G A Beckett A Houck-Jankoski andA Hudson 1994 An Outbreak of Cryptosporidiosis from Fresh-Pressed Apple Cider Journal ofthe American Medical Association 2721592ndash1596
39 Pickering L K D G Evans H L DuPont J J Vollet and D J Evans Jr 1981 Diarrhea Caused byShigella Rotavirus and Giardia in Day Care Centers Prospective Study Journal of Pediatrics9951ndash56
40 Morens D M R M Zweighaft T M Vernon G W Gary J J Eslien B T Wood R C Holmanand R Dolin 1979 A Waterborne Outbreak of Gastroenteritis with Secondary Person to PersonSpread Lancet 5964ndash966
41 Laursen E O Mygind B Rasmussen and T Ronne 1994 Gastroenteritis A Waterborne OutbreakAffecting 1600 People in a Small Danish Town Journal of Epidemiology amp Community Health48453ndash458
42 Baron R C F D Murphy H B Greenberg C E Davis D J Bregman G W Gary J M Hughesand L B Schonberger 1982 Norwalk Gastrointestinal Illness An Outbreak Associated withSwimming in a Recreational Lake and Secondary Person to Person Transmission American Journalof Epidemiology 115163ndash172
43 Kappus K D J S Marks R C Holman J K Bryant C Baker G W Gary and H B Greenberg1982 An Outbreak of Norwalk Gastroenteritis Associated with Swimming in a Pool and SecondaryPerson to Person Transmission American Journal of Epidemiology 116834ndash839
44 White K E M T Osterbolm J A Mariotti J A Korlath D H Lawrence T L Ristinen andH B Greenberg 1986 A Foodborne Outbreak of Norwalk Virus Gastroenteritis American Journalof Epidemiology 124120ndash126
45 Spika J S J E Parsons and D Nordenberg 1986 Hemolytic Uremic Syndrome and DiarrheaAssociated with Escherichia coli O157H7 in a Day Care Center Journal of Pediatrics 109287ndash291
12 CHAPTER 1 MOTIVATION
46 Ferguson J K L R Jorm C D Allen P KWhitehead and G L Gilbert 1995 Prospective Study ofDiarrhoeal Outbreaks in Child Long Daycare Centres in Western Sydney Medical Journal of Australia163137ndash140
47 Frost F J G F Craun and R L Calderon 1996 Waterborne Disease Surveillance Journal of theAmerican Water Works Association 8866ndash75
48 Farrington C P N J Andrews A D Beale and M A Catchpole 1996 A Statistical Algorithmfor the Early Detection of Outbreaks of Infectious Disease Journal of the Royal StatisticalSociety A 159547ndash563
REFERENCES 13
CHAPTER2MICROBIAL AGENTS ANDTRANSMISSION
MICROBIAL TAXONOMY
The development of techniques for examining the nucleic acids of microorganisms hasseen major changes in which we classify and group related microorganisms This isespecially true for the study of ribosomal ribonucleic acid (rRNA) which is a highlyconserved sequence involved in the synthesis of proteins in all living organisms Basedon this analysis the classification of living things has been placed into a three-domainsystem consisting of Archaea Eukarya and Bacteria Of these the Bacteria andArchaea are termed prokaryotes (no organized cell nucleus) and the Eukarya areknown as eukaryotes (an organized cell nucleus) Eukaryotic microbes other thanalgae and fungi are collectively calledprotistsWithin theEukarya are fungi protozoahelminth worms algae plants animals and humans Archaea are microbes that looksomewhat similar to bacteria in size and shape under the light microscope but they areactually genetically and biochemically quite different They appear to be a simpler formof life and may in fact be the oldest form of life on earth Viruses are obligate intercel-lular parasites and are not amember of any group They are usually composed only of anucleic acid surrounded by a protein coat Eukaryotes are much more complex thanprokaryotic cells in structure and nutritional requirements Prokaryotes divide by sim-ple binary fissionwhereas eukaryotes divide byamore complexprocess calledmitosis
Eukaryotes
Fungi protozoa and helminth worms are all eukaryotes All contain members that arepathogenic to man and animals While algae do not infect humans they can producetoxins that are harmful to animals and man Fungi obtain nutrients solely by adsorp-tion of organic matter from dead organisms Even when they invade living tissuesthey typically kill cells and then adsorb the nutrients from them Some fungi are capa-ble of developing environmentally resistant spores which can be transported throughthe air Fungal diseases in humans are referred to asmycoses Airborne fungal sporesare responsible for some allergies in humans Yeasts are classified with the fungi and
Quantitative Microbial Risk Assessment Second Edition Charles N Haas Joan B Roseand Charles P Gerbacopy 2014 John Wiley amp Sons Inc Published 2014 by John Wiley amp Sons Inc
15
some are pathogenic to humans (Candida albicans) Certain fungi produce toxins(ie aflatoxins) when growing in foods that are mutagenic and carcinogenic in ani-mals Inhalation is an important route of transmission for some fungal diseases suchas aspergillosis blastomycosis coccidioidomycosis and histoplasmosis These fungiare found growing in animal feces soil or decaying organic matter (compost manure)and may be transmitted through the air when this matter is disturbed Some fungi maybe transmitted by direct contact with the skin Fungi are often found in drinking waterdistribution systems and they have been linked to infections in immunocompromisedindividuals [1] Food is not believed to be a significant route of transmission ofpathogenic fungi
Protozoans are unicellular organisms that are surrounded by a cytoplasmicmembrane that is covered by a protective structure called a pellicle Most are freeliving feeding off of bacteria Some of these can cause disease while others are obli-gate parasites They are capable of forming structures called cysts oocysts or spores(depending on the life cycle of the organism) resistant to adverse environmentalconditions such as desiccation starvation high temperatures and disinfectantsSome pathogenic protozoa are found mainly in the soil (Naegleria) or water(Acanthamoeba) Others such a Giardia and Cryptosporidium whose natural habitatis the intestines of warm-blooded animals are capable of causing disease in bothhumans and animals Others such as Entamoeba histolytica are only capable ofcausing disease in humans
Pathogenic enteric (replicate in the intestines) protozoans are usually excretedin the feces or urine and can be transmitted by fecally contaminated food and waterSome protozoa may be transmitted through the air (Acanthamoeba) or throughfomites (inanimate objects) Some important environmentally transmitted protozoaare listed in Table 21 The clinically important protozoa are divided taxonomicallyinto the amoebas (Entamoeba spp) flagellates (Giardia) and coccidian meaningldquoglobose in shaperdquo (Cryptosporidium and Cyclospora) Microsporidia are alsocapable of causing intestinal infections but their classification is uncertain becausethey have many characteristics associated with fungi They are all obligate parasitesand are transmitted via infectious cysts oocysts or spores by the fecalndashoral routeThe life cycles of these protozoa are similar The initial stage occurs during ingestionof the cyst oocyst or spore After ingestion the body temperature and passagethrough the stomach cause these infective stages to open up in a process calledexcystation
The Giardia cysts house two trophozoites which is the stage that attaches tointestinal cells and grows in the intestinal tract through asexual reproduction As thetrophozoites grow and begin to cover the wall of the intestinal tract diarrhea canresult As the trophozoites are released some form cysts as they pass through thebowels Cryptosporidium and Cyclospora both produce oocysts The life cycle ofCyclospora is still not well known except that its oocysts require some period of timein the environment before they are infective Cryptosporidium oocysts contain foursporozoites which enter the intestinal cells and begin the infection process As morecells become infected the illness begins and oocysts are excreted in high numbers inthe feces (about 100000g)
Worms and helminths are small multicellular animals that are parasiticto humans and animals They include flukes tapeworms and roundworms
16 CHAPTER 2 MICROBIAL AGENTS AND TRANSMISSION
Copyright copy 2014 by John Wiley amp Sons Inc All rights reserved
Published by John Wiley amp Sons Inc Hoboken New JerseyPublished simultaneously in Canada
No part of this publication may be reproduced stored in a retrieval system or transmitted in any formor by any means electronic mechanical photocopying recording scanning or otherwise except aspermitted under Section 107 or 108 of the 1976 United States Copyright Act without either the prior writtenpermission of the Publisher or authorization through payment of the appropriate per-copy fee to theCopyright Clearance Center Inc 222 Rosewood Drive Danvers MA 01923 (978) 7508400 fax (978)7504470 or on the web at wwwcopyrightcom Requests to the Publisher for permission should beaddressed to the Permissions Department John Wiley amp Sons Inc 111 River Street Hoboken NJ 07030(201) 748-6011 fax (201) 748-6008 or online at httpwwwwileycomgopermission
Limit of LiabilityDisclaimer of Warranty While the publisher and author have used their best effortsin preparing this book they make no representations or warranties with respect to the accuracy orcompleteness of the contents of this book and specifically disclaim any implied warranties ofmerchantability or fitness for a particular purpose No warranty may be created or extended bysales representatives or written sales materials The advice and strategies contained herein may not besuitable for your situation You should consult with a professional where appropriate Neither thepublisher nor author shall be liable for any loss of profit or any other commercial damages including butnot limited to special incidental consequential or other damages
For general information on our other products and services or for technical support please contactour Customer Care Department within the United States at (800) 7622974 outside the United Statesat (317) 5723993 or fax (317) 5724002
Wiley also publishes its books in a variety of electronic formats Some content that appears in print maynot be available in electronic formats For more information about Wiley products visit our web site atwwwwileycom
Library of Congress Cataloging-in-Publication Data
Haas Charles NQuantitative microbial risk assessment Charles N Haas Joan B Rose Charles P Gerba ndash Second edition
p cmIncludes bibliographical references and indexISBN 978-1-118-14529-6 (cloth alk paper)
1 Communicable diseasesndashEpidemiologyndashMethodology 2 Health risk assessment 3 InfectionndashMathematical models 4 Environmental healthndashMathematical models I Rose Joan B II GerbaCharles P 1945- III Title
RA643H22 2014615902ndashdc23
2014002690
Printed in the United States of America
10 9 8 7 6 5 4 3 2 1
CONTENTS
PREFACE xi
CHAPTER 1 MOTIVATION 1
Prevalence of Infectious Disease 1
Prior Approaches 4
Scope of Coverage 4
Potential Objectives of a QMRA 5
Site-Specific Assessment 5
Ensemble of Sites 6
Secondary Transmission 7
Outbreaks versus Endemic Cases 7
References 10
CHAPTER 2 MICROBIAL AGENTS AND TRANSMISSION 15
Microbial Taxonomy 15
Eukaryotes 15
Prokaryotes 18
Viruses 20
Prions 22
Clinical Characterization 24
Microorganisms of Interest 27
Viruses 27
Bacteria 37
Protozoa 42
Transmission Routes 45
Inhalation 48
Dermal Exposure 50
Oral Ingestion 50
References 55
CHAPTER 3 RISK ASSESSMENT PARADIGMS 63
Chemical Risk Assessment National Academy of Sciences Paradigm 63
Ecological Risk Assessment 67
Approaches for Assessing Microbial Risks 71
Background 71
v
The QMRA Framework 74
Hazard Identification 74
DosendashResponse Assessment 74
Exposure Assessment 76
Risk Characterization 77
Risk Management 79
Development of the QMRA Framework and Processes 79
QMRA and the Safety of Water 82
QMRA Food Safety and the HACCP System 84
References 86
CHAPTER 4 CONDUCTING THE HAZARD IDENTIFICATION (HAZ ID) 91
Identifying and Diagnosing Infectious Disease 92
Health Outcomes Associated with Microbial Infections 95
Sensitive Populations 100
Women during Pregnancy Neonates and Young Babies 101
Diabetes 102
The Elderly 102
The Immunocompromised 104
Databases for Statistical Assessment of Disease 106
ICD Codes 107
Waterborne and Foodborne Outbreaks 111
Epidemiological Methods for Undertaking HAZ ID 117
Controlled Epidemiological Investigations 118
HAZ ID Data Used in the Risk Assessment Process 119
Recommendations for Updating Quantitative Data for HAZ ID Information 121
References 122
CHAPTER 5 ANALYTICAL METHODS AND THE QMRA FRAMEWORKDEVELOPING OCCURRENCE AND EXPOSURE DATABASES 129
Introduction 129
Approaches for Developing Occurrence and Exposure Databases 132
Overview of Methodological Issues 134
Sampling Water 136
Sampling Surfaces and Food 138
Sampling Aerosols 138
Specific Techniques for Bacteria Protozoa and Viruses 140
Bacteria 140
Protozoa 142
Viruses 143
Molecular Techniques 145
Probes (FISH) 146
Typing 146
vi CONTENTS
Metagenomics 147
PCR and Quantitative PCR 147
References 151
CHAPTER 6 EXPOSURE ASSESSMENT 159
Conducting the Exposure Assessment 159
Characterizing ConcentrationDuration Distributions 160
Random (Poisson) Distributions of Organisms 160
Estimation of Poisson Mean in Count Assay (Constant and Variable Volumes) 162
Count Assay with Upper Limits 163
Estimation with Quantal Assay 164
Goodness of Fit to Poisson Plate Assay 168
Goodness of Fit MPN 178
Confidence Limits Likelihood 182
Implications for Risk Assessment 187
Consumption Distributions 214
Systematic Subpopulation Differences 221
Afterword 223
Appendix 224
Microsoft Excel 224
MATLAB 225
R 227
References 230
CHAPTER 7 PREDICTIVE MICROBIOLOGY 235
Objective 235
Basic First-Order Processes and Deviations 236
Biological and Physical Bases for Deviations 236
Physical Removal 238
Types of Decay Processes 238
General Forms of Decay and Reasons for Nonlinearity 238
SpontaneousEndogenous 240
Chemical Agents 241
Thermally Induced 243
Ionizing and Nonionizing Radiation 243
Predation and Antagonism 245
Types of Growth Processes 245
Mathematical Modeling of Growth Curves 246
Substrate Dependency 252
Structured Growth Models 255
Incorporation of Decay into Growth Models 256
Systems Biology Approaches 258
CONTENTS vii
Dependence of Growth Parameters on Other Environmental Variables 258
Interacting Populations 258
Data Sources 260
References 263
CHAPTER 8 CONDUCTING THE DOSEndashRESPONSE ASSESSMENT 267
Plausible DosendashResponse Models 268
Framework for Mechanistic DosendashResponse Relationships 269
Exponential DosendashResponse Model 271
Beta-Poisson DosendashResponse Model 272
Simple Threshold Models 274
Negative Binomial Dose Distributions 277
Variable Threshold Models 278
Other Mixture Models 279
Biological Arguments for One-Hit Models 281
Empirical Models 282
Fitting Available Data 283
Types of Data Sets 284
Potential Impacts of Immune Status 298
Relationship between Dose and Severity (Morbidity and Mortality) 299
Morbidity Ratio (PDI) 299
Mortality Ratio 303
Reality Checking Validation 304
Validation 1993 Milwaukee Outbreak 304
Use of Indicators and Other Proxy Measures in DosendashResponse 305
Indicator Methods 305
Molecular Methods 307
Advanced Topics in DosendashResponse Modeling 308
DosendashResponsendashTime Models 308
Physiological Models 313
Appendix 315
References 317
CHAPTER 9 UNCERTAINTY 323
Point Estimates of Risk 324
Terminology Types of Uncertainty 326
Sources of Uncertainty 327
Sources of Variability 328
Variability that is Uncertain 329
Approaches to Quantify Parametric Uncertainty 329
Likelihood 329
Bootstrap 330
Other Methods 330
viii CONTENTS
Applications 332
Exposure Assessment 332
DosendashResponse Assessment 338
Combining Parametric Uncertainty from Multiple Sources 344
Propagation Methods 344
Monte Carlo Analyses 347
Overall Risk Characterization Example 365
Second-Order Methods 368
Model Uncertainty and Averaging 370
References 373
CHAPTER 10 POPULATION DISEASE TRANSMISSION 377
Introduction Models for Population and Community Illnesses 377
Basic SIR Model 378
Incubation Period 386
Duration of Illness 388
Secondary Cases 389
Impact of Immunity 392
Outbreak Detection 393
References 397
CHAPTER 11 RISK CHARACTERIZATION AND DECISION MAKING 399
Introduction 399
Valuing Residual Outcomes 400
Classical Economics 400
DALYs and QALYs 404
Decision Making 407
CostndashBenefit Analysis 408
Multivariate Approaches 411
Other Aspects Entering into a Decision 412
Equity and Justice Aspects 412
References 413
INDEX 415
CONTENTS ix
PREFACE
In the 14 years since we prepared the first edition there has been an explosion inknowledge of and need for quantitative microbial risk assessment (QMRA) Whileour motivation for the first edition stemmed from concerns (principally in water) aboutenteric bacteria viruses and protozoa the motivation has now exploded to newdomains and agents SARS influenza biothreat agents and zoonotic pathogens haveall become of greater concern
The 2001 anthrax letters have highlighted the need for risk assessment ofinhaled agents Both biothreat agents and emergence of new strains of virulentcontagious organisms have raised concern for modeling pathogen dynamics inpopulations
In this edition we have retained the fundamental approach of the riskassessment methodology as a central paradigm We have added new material onmodern pathogen analytical methods predictive microbiology (of pathogen growthand decay) dynamic risk models (explicitly considering incubation time) and diseasepropagation models in populations Of necessity we have removed some materialmdashitis no longer possible to present comprehensive tables of microbial dosendashresponseparameters
In the years since the first edition the authors have gained experience inteaching this material to generations of studentsmdashin the form of formal classestutorials independent studies and short courses We know this book can be valuablein instructing advanced students in environmental sciences environmental engineer-ing public health and microbiology It is also a useful reference for practitionersand regulatory personnel Some prior statistical background would be useful inapproaching the material but not necessary the key requirement for any risk assessoris the absence of fear from mathematical constructs and concepts
The three of us have been on a QMRA journey for almost 30 years We havelearned that doing high-quality risk assessments is of necessity a team sport requiringindividuals with different skills and interests We have learned a tremendous amountfrom each other from our students from our collaborators and from the problems thatwe have sought to approach Practitioners of the art of quantitative microbial riskassessment should be advised to cast a wide net with respect to colleagues andcollaborators to perfect their craft
xi
We encourage comments and feedback from users of this work and look for-ward to observing and participating in developments in coming years and ultimatelyto handing the baton off to our students and their students
Charles N Haas
Joan B Rose
Charles P GerbaNovember 2013
xii PREFACE
CHAPTER1MOTIVATION
THE PREVENTION of infectious disease transmission from human exposure tocontaminated food water soil and air remains a major task of environmental andpublic health professionals There are numerous microbial hazards including expo-sure via food water air and malicious release of pathogens that may arise Indeedsome have argued that the property of virulence of human pathogens is one which isfavored by evolutionary interactions between pathogens and host populations andtherefore will always be of important concern [1] To make rational decisions in pre-paring responding and recovering from exposures to such hazards a quantitativeframework is of high benefit
The objective of this book is to comprehensively set forth the methods forassessment of risk from infectious agents transmitted via these routes in a frameworkthat is compatible with the framework for other risk assessments (eg for chemicalagents) as set forth in standard protocols [2 3]
In this chapter information on the occurrence of infectious disease in broadcategories will be presented along with a historical background on prior methodsfor assessment of microbial safety of food water and air This will be followed byan overview of key issues covered in this book
PREVALENCE OF INFECTIOUS DISEASE
Outbreaks of infectious waterborne illness continue to occur although it remainsimpossible to identify the infectious agent in all cases For example in 1991 a water-borne outbreak in Ireland resulting from sewage contamination of water suppliesinfected about 5000 persons However the infectious agent responsible for thisoutbreak could not be determined [4] In the United States it has been estimated that38 million cases of foodborne infectious disease occur annually with unidentifiedagents [5]
In the United States there have typically been three to five reported outbreaksper year in community drinking water systems involving infectious microorganismswith perhaps up to 10000 annual cases [6] The 1994 Milwaukee Cryptosporidiumoutbreak with over 400000 cases [7 8] was a highly unusual event among thesestatistics As shown in Figure 11 there has been an increasing ability to identify
Quantitative Microbial Risk Assessment Second Edition Charles N Haas Joan B Roseand Charles P Gerbacopy 2014 John Wiley amp Sons Inc Published 2014 by John Wiley amp Sons Inc
1
microorganisms responsible for waterborne diseases and it is expected that withadvances in molecular biology this will increase
There are substantially more outbreaks and cases of foodborne infectiousdiseases than are reported Table 11 summarizes reports of US cases of principalmicrobial infectious foodborne illnesses for two 5-year periods (1988ndash1992 and
1971ndash1982
10
20
30
40
Perc
ent o
f out
brea
ks
50
60
1983ndash1994Period
1995ndash2006
Figure 11 Percentages of outbreaks associated with public water systems (n = 680) by timeperiod 1971ndash2006 that had unknown etiologies based on data from Ref [6]
TABLE 11 Comparison of Five-Year Averages for Common Foodborne Reported Outbreaks
Agent
Annual Average 1988ndash1992 Annual Average 2002ndash2006
Cases Outbreaks Cases Outbreaks
Campylobacter 996 44 624 22
Escherichia coli 488 22 481a 30a
Salmonella 42354 1098 3475 144
Shigella 9576 5 495 12
Staphylococcus aureus 3356 94 554 25
Hepatitis 4218 86 238 1
Listeria monocytogenes 04 02 22 2
Giardia 368 14 2 1
Norovirus 584 04 10854 338
Vibrio (all) 114 18 114 5
Unknown etiologies 40483 1422 4052 30
Source From Refs [9 10]a Include both Shiga toxigenic and enterotoxigenic
2 CHAPTER 1 MOTIVATION
2002ndash2006) There is a mix of causal agents including bacteria virus and protozoaIt is noteworthy that (as in the case of waterborne outbreaks) the frequency ofoutbreaks of unknown etiology has dramatically decreased but the frequency of out-breaks associated with norovirus has dramatically increased These changes are duein part to the ability to better identify causal agents (eg via molecular methods)
It is generally recognized that reported outbreaks either of water- or foodborneinfectious disease represent only a small fractionof the total populationdisease burdenHowever particularly in the United States voluntary reporting systems and theoccurrence of mild cases (for which no medical attention is sought but neverthelessare frank cases of disease) have made it difficult to estimate the total caseload
In the United Kingdom comparisons between the number of confirmed casesin infectious disease outbreaks and total confirmed laboratory illnesses (occurring inEngland and Wales) have been made (Table 12) This suggests that the ratio ofreported outbreak cases to total cases that may seek medical attention may be from10 to 5001 with some dependency on the particular agent
Colford et al [12] developed estimates for the total disease burden associatedwith acute gastroenteritis from drinking water This relies on combining the reportedoutbreak data with interventional epidemiologic studies Based on their analysis thetotal US disease burden is estimated to be 426ndash1169 million cases per year in theUnited States which is substantially in excess of the reported outbreaks In the case offoodborne illness there are an estimated 14 million cases per year [13]
Drinking water and food are by no means the only potential routes of exposureto infectious agents in the environment Recreation in water (either natural or artificialpools) containing pathogens can produce illness [14]
Indoor air transmission can be a vehicle of infection Legionella transmittedthrough indoor environments has been a concern since the 1970s [15] The multina-tional epidemic of severe acute respiratory syndrome (SARS) caused by a coronavi-rus was abetted at least in one location in Hong Kong by indoor aerosol transmissionbetween apartments of infected individuals and susceptible individuals [16] A broadspectrum of other respiratory pathogens including influenza rhinoviruses and myco-bacteria can be transmitted by this route [17]
TABLE 12 Comparison of Laboratory Isolations and Outbreak Cases in Englandand Wales 1992ndash1994
Agent
Cases 1992ndash1994
RatioAll Laboratory Reports Confirmed Outbreak Cases
Campylobacter 122250 240 5094
Rotavirus 47463 127 3737
S sonnei 29080 847 343
Salmonella 92416 5960 155
Cryptosporidium 14454 1066 136
E coli O157 1266 128 99
Source Modified from Ref [11]
PREVALENCE OF INFECTIOUS DISEASE 3
The deliberate release of Bacillus anthracis spores in 2001 (the ldquoAmerithraxrdquoincidents) brought widespread awareness to the potential for indoor releases (as wellas releases in other venues) of bioterrorist agents to cause risk [18] Therefore ofnecessity microbial risk assessors may need to consider the impact of maliciousactivity in certain applications
PRIOR APPROACHES
Concerns for microbial quality of food water and other environmental media havelong existed In the early twentieth century the use of indicator microorganismswas developed for the control and assessment of the hygienic quality of such mediaand the adequacy of disinfection and sterilization processes The coliform group oforganisms was perhaps first employed for this purpose [19ndash21] Indicator techniqueshave also found utility in the food industry such as the total count for milk and othermore recent proposals [22] Other indicator groups for food water or environmentalmedia have been examined such as enterococci [23ndash25] acid-fast bacteria [26]bacteriophage [27ndash29] and Clostridia spores [29ndash31]
The use of indicator organisms was historically justified in because of difficultyin enumerating pathogens However with the increasing availability of modernmicrobial methods for example PCR immunoassay etc for direct pathogen assess-ment this justification has become less persuasive In addition in order to develophealth-based standards from indicators extensive epidemiologic surveillance is oftennecessary The use of epidemiology has limitations with respect to detection limits(for an adverse effect) and is also quite expensive to conduct Indicator methodsare also limited in that many pathogens are more resistant to die off in receiving envir-onments or source waters than indicators or have greater resistance to removal bytreatment processes than indicators [26 28 29 32] Thus the absence of indicatorsmay not suffice to ensure the absence of pathogens Even after a century of use theindicator concept remains imperfect [33]
The use of quantitative microbial risk assessment (QMRA) will enable directmeasurements of pathogens to be used to develop acceptancerejection guidelinesfor food water and other vehicles that may be the source of microbial exposureto human populations The objective of this book is to present these methods in asystematic and unified manner
SCOPE OF COVERAGE
QMRA is the application of principles of risk assessment to the estimate ofconsequences from a planned or actual exposure to infectious microorganismsIn performing a QMRA the risk assessor aims to bring the best available informationto bear in understanding the nature of the potential effects from a microbial exposureSince the information (such as dosendashresponse relationships exposure magnitudes) isalmost invariably incomplete it is also necessary to ascertain the potential error
4 CHAPTER 1 MOTIVATION
involved in the risk assessment With such information necessary steps to mitigatecontrol or defend against such exposures may be developed
At the outset of performing a risk assessment a scoping task should be under-taken This task should set forth the objectives of the analysis and the principal issuesto be addressed Items such as consideration of secondary cases individual versuspopulation risk agent or agents to be examined exposure routes andor accident sce-narios must be stipulated However this scoping may be changed during the course ofa QMRA to reflect the input derived from the risk manager(s) and other stakeholders
POTENTIAL OBJECTIVES OF A QMRA
There may be diverse objectives for a QMRA These objectives relate to the rationalefor the performance of the assessment as well as the methods to be employedBroadly the different objectives reflect different scales at which a risk assessmentmay be performed The step of problem formulation is critical to any risk estimate[34] It is necessary that the problem be formulated to meet the needs of the riskmanagers and stakeholders indeed it is now recognized that the successful practiceof risk analysis requires frequent interchange with manager and stakeholders [3]In general the problems posed are of several types
Site-Specific Assessment
The simplest type of QMRA that may be performed involves one site or exposurescenario The following are typical of the questions that might be asked
1 If a water treatment plant is designed in a certain way (with given removals ofpathogens) then what is the risk that would be placed upon the populationserved
2 A swimming outbreak (in a recreational lake) has just occurred I believe that itresulted from a short-duration contamination event What pathogen levelswould be consistent with the observed attack rate
3 Microbial sampling of a finished food product has found certain pathogensWhat level of risk does this pose to consumers of the product
4 A certain amount of infectious agent has been released into a room What is theimmediate danger to occupants and how stringent should cleanup levels be
Note that there are certain other contrasts in the objectives of the risk assessments tobe posed In (1) and (3) a before-the-fact computation is desired while in (2) and (4)an after-the-fact computation is described Also in (1) (3) and (4) pathogen levelsare available (or somehow are estimated) while in (2) an inverse computation isneeded given an observed attack rate
In performing this risk assessment the relationship between an exposure ortechnological metric and a risk measurement must be ascertained and then theparticular point of correspondence determined (Fig 12) In cases (1) (3) and (4)for a known (or assumed) exposure (on the x-axis) the corresponding range of risks
POTENTIAL OBJECTIVES OF A QMRA 5
on the y-axis is sought In cases (2) for known or assumed risks (on the y-axis)the corresponding range of exposures (or level of technological protection) is to bedetermined (on the x-axis)
Ensemble of Sites
A somewhat more complex situation occurs if the risk for a set of events or sites mustbe estimated Basically this now includes the necessity to incorporate site-to-sitefactors into the assessment Some examples of this are as follows
1 If I desire keeping the risk to a population served by multiple water treatmentplants at a given level (or better) then what criteria should I use (microbiallevels)
2 For a food product subject to contamination by pathogens what would be anacceptable treatment specification (eg heating time holding period) to ensuremicrobial acceptability
3 I am designing a water quality standard for recreational bathing waters If auniform (eg national) standard is to be developed what standard would ensurethat average risk was acceptable with keeping the risk of a large ldquoclusterrdquo ofillnesses low
In addition to incorporating a measure of ensemble average risk in general it is alsodesired to ensure that no single member of the ensemble be unacceptably extreme Forexample consider the evaluation of three options of disease control among three com-munities as indicated in Table 13
This table indicates the number of cases and the rate among the three commu-nities The three policy options yield the same number of expected cases Howeverthere are differences in the allocation of risk among the communities of different sizesIn option A all communities have an identical level of estimated risk In option B therisk increases as community size decreases while in option C the risk increases ascommunity size increases This distribution of risk among affected subsets of the
Exposure
Ris
k
Level of technological protection
Figure 12 Relationship between exposurelevel of technological protection andmicrobial risk The middle curve indicatesthe best estimate The other two curvesindicate the upper and lower confidenceregions
6 CHAPTER 1 MOTIVATION
ensemble being considered adds an additional dimension for consideration by a riskmanagermdashwhich may be termed risk equity
SECONDARY TRANSMISSION
Infectious microbial diseases are different in terms of risk to a population than arechemical agents in that an individual who may become infected (with or withoutillness) can then proceed to infect additional individuals These secondary (tertiaryquaternary etc) cases may be persons who had no direct contact with the initialvehicle of exposure but nevertheless in fairly accounting for the public health impactthey should be considered
Secondary cases may arise by a variety of mechanisms Particularly amongclose family members household secondary cases can arise by direct or indirect(eg surface contamination) contact this is particularly so when the primary caseor one household secondary case is a child [35ndash37] Table 14 summarizes secondarycase statistics obtained from a variety of outbreaks As will be discussed inChapter 10 the secondary case rate is a complex factor involving (among other things)the nature of the venue and contact patterns when infected and susceptible individualsintermingle
Presumably secondary cases may also arise from close contact with anasymptomatic individual (in the ldquocarrierrdquo state) This is well known for highly acuteand (now) uncommon illnesses (such as typhoid) Excretion of Norwalk virusfollowing recovery (and resulting in additional cases) has been documented to occurfor as long as 48 h post recovery [44]
OUTBREAKS VERSUS ENDEMIC CASES
As noted previously there may be a substantial difference between reported outbreakcases and total disease burden in a community In order for a disease case to receiverecognition by the public health authorities the following specific and sequential stepsmust occur [47]
TABLE 13 Effect of Different Hypothetical Policy Options on Distribution of Risk AmongCommunities (for a Fixed Total Risk)
CommunityExposedPopulation
Policy Option A Policy Option B Policy Option C
CasesIncidence(10000) Cases
Incidence(10000) Cases
Incidence(10000)
A 100000 20 2 6 06 24 24
B 50000 10 2 18 36 7 14
C 10000 2 2 8 8 1 1
Total 160000 32 2 32 2 16 2
OUTBREAKS VERSUS ENDEMIC CASES 7
1 An ill person must seek medical care
2 Appropriate clinical tests (eg blood stool) must be ordered by the attendingphysician
3 The patient must comply with obtaining the sample
4 The laboratory must be capable of detecting the relevant pathogens
5 The clinical test must be positive
6 The test result must be reported to the health agency in a timely manner
If any of the links in this sequential chain are broken then a disease case will not enterthe records maintained by health authorities For example with increasing controls on
TABLE 14 Summary of Secondary Case Data in Outbreak Situations
Organism
SecondaryAttackRatioa
SecondaryPrevalence inHouseholdsb Remarks Reference
Cryptosporidiumparvum
033 033 Outbreak in contaminatedapple cider
[38]
C parvum NA 0042 Drinking water outbreak(Milwaukee)
[37]
Shigella 028 026 Day-care center outbreaksin children
[39]
Rotavirus 042 015 Day-care center outbreaksin children
[30]
Giardia lamblia 133 017 Day-care center outbreaksin children
[39]
Viral gastroenteritis 022 011c Drinking waterborneoutbreak
[40]
Viral gastroenteritis 056 NA Drinking water outbreak(Denmark)
[41]
Norovirus 05ndash10 019 Swimming outbreak [42]
Norovirus 11 029 Swimming outbreakin children
[43]
Norovirus NA 044 Foodborne outbreakin children and teachers
[36]
Norovirus 04 NA Foodborne outbreak [44]
E coli O157H7 NA 018c Day-care center outbreakin children
[45]
Unidentifiedday-care diarrhealdiseases
138 009c [46]
NA information not availableaRatio of secondary cases to primary casesb Proportion of households with one or more primary cases who have one or more secondary casesc Proportion of persons in contact with one or more primary cases who have a secondary case
8 CHAPTER 1 MOTIVATION
medical care stool samples may not be obtained from mild cases of illness Someorganisms may only be present sporadically or may be difficult to test in stool orblood sample Patients may not seek medical attention for mild cases of illness Fur-thermore in the United States in particular the surveillance of environmentallyinduced disease is done on a passive basis and hence the number of actual illnessclusters that are actually compiled into recorded statistics is only a small fractionof such clusters of illness that occur [47]
From a more fundamental point of view an outbreak of illness is generallydefined as occurrence of the illness at a level greater than normal or anticipated Thisdefinition recognizes that there is a level of illness (endemic) that may exist underusual circumstances The detection of such outbreaks poses a particular challengeThe problem is illustrated conceptually in Figure 13
Additional complications arise from the different patterns of illness in acommunity including definite periodicities as well as temporal trends and fromthe presence of reporting lags associated with laboratory analysis and time for patientsto seek medical attention Figure 14 illustrates the different patterns of illness inthe case of six pathogens for England and Wales [48]
In the case of waterborne and foodborne illnesses it is highly likely that thelevel of such endemic illnesses is substantially greater than those occurring duringoutbreaks (even accounting for unrecognized outbreaks)
As a result there are often many cases of environmentally caused (water airfood) infectious disease that are unrecognized One example of this isCampylobacterThere has been an average of about 200 cases per year of water- and foodborne illnessin outbreaks of this organism and yet estimates of the disease burden suggest about2100000 cases per year that is approximately 10000 cases per case of detectableoutbreak illness Therefore it will be important to assess the factors that may influenceoutbreak detection These issues will be discussed in subsequent chapters
Detectedoutbreak
Undetectedoutbreak
Threshold of detection
Hyper endemicSporadic
Endemic rate
Time
Num
ber
of c
ases
Figure 13 Schematic of disease occurrence in a hypothetical community (Modified fromRef [47])
OUTBREAKS VERSUS ENDEMIC CASES 9
REFERENCES
1 Levin B R 1996 The Evolution and Maintenance of Virulence in Microparasites Emerging InfectiousDisease 293ndash102
2 National Academy of Sciences 1983 Risk Assessment in the Federal Government Managing theProcess National Academy Press Washington DC
3 National Research Council 2009 Science and Decisions Advancing Risk Assessment NationalAcademies Press Washington DC
10090807060504030201001190 1191 1192 1193 1194 1195
(b)
140
120
100
80
60
40
20
01190 1191 1192 1193 1194 1195
(f)
700
600
500
400
300
200
100
01190 1191 1192 1193 1194 1195
(d)
1200
1000
800
600
400
200
1190 1191 1192 1193 1194 1195
(a)
240
200
160
120
80
40
01190 1191 1192 1193 1194 1195
(e)
7
6
5
4
3
2
1
01190 1191 1192 1193 1194 1195
(c)
Figure 14 Weekly count of reported organism isolations in England andWales (a) rotavirus(b) Clostridium difficile (c) Salmonella derby (d) Shigella sonnei (e) influenza B and (f)Salmonella typhimurium DT 104 (From Ref [48])
10 CHAPTER 1 MOTIVATION
4 Fogarty J L Thornton and R Corcoran 1995 Illness in a Community Associated with an Episode ofWater Contamination with Sewage Epidemiology and Infection 114289ndash295
5 Scallan E 2011 Foodborne Illness Acquired in the United StatesmdashUnspecified Agents EmergingInfectious Diseases 17 16ndash22
6 Craun G F J M Brunkard J S Yoder V A Roberts J Carpenter T Wade R L CalderonJ M Roberts M J Beach and S L Roy 2010 Causes of Outbreaks Associated with Drinking Waterin the United States from 1971 to 2006 Clinical Microbiology Reviews 23507ndash528
7 Edwards D D 1993 Troubled Waters in Milwaukee ASM News 59342ndash3458 MacKenzie W R N J Hoxie M E Proctor M S Gradus K A Blair D E Peterson
J J Kazmierczak K R Fox D G Addias J B Rose and J P Davis 1994 Massive WaterborneOutbreak of Cryptosporidium Infection Associated with a Filtered Public Water Supply MilwaukeeWisconsin March and April 1993 New England Journal of Medicine 331161ndash167
9 Anonymous 2010 Surveillance for Foodborne Disease OutbreaksmdashUnited States 2007 Morbidityand Mortality Weekly Reports 59973ndash979
10 Bean N H J S Goulding C Lau and F J Angulo 1996 Surveillance for Foodborne-DiseaseOutbreaksmdashUnited States 1988ndash1992 Morbidity and Mortality Weekly Reports 451ndash66
11 Wall P G J de Louvois R J Gilbert and B Rowe 1996 Food Poisoning NotificationsLaboratory Reports and OutbreaksmdashWhere do the Statistics Come From and What Do They MeanCommunicable Disease Report Review 6 R93ndashR100
12 Colford J M S Roy M J Beach A Hightower S E Shaw and T J Wade 2006 A Review ofHousehold Drinking Water Intervention Trials and an Approach to the Estimation of EndemicWaterborne Gastroenteritis in the United States Journal of Water and Health 471
13 Mead P S L Slutsker V Dietz L F McCaig J S Bresee C Shapiro P M Griffinand R V Tauxe 1999 Food Related Illness and Death in the United States Emerging InfectiousDisease 5607ndash625
14 Dziuban E J J L Liang G F Craun V Hill P A Yu J Painter M R Moore R L CalderonS L Roy and M J Beach 2006 Surveillance for Waterborne Disease and Outbreaks Associatedwith Recreational WatermdashUnited States 2003ndash2004 and Surveillance for Waterborne Disease andOutbreaks Associated with Drinking Water and Water not Intended for DrinkingmdashUnited States2003ndash2004 Morbidity and Mortality Weekly Reports 551ndash30
15 Fliermans C B 1996 Ecology of Legionella From Data to Knowledge with a Little WisdomMicrobial Ecology 32203ndash228
16 Li Y S Duan I T Yu and T W Wong 2005 Multi-Zone Modeling of Probable SARS VirusTransmission by Airflow Between Flats in Block E Amoy Gardens Indoor Air 1596ndash111
17 Peccia J D K Milton T Reponen and J Hill 2008 A Role for Environmental Engineering andScience in Preventing Bioaerosol-Related Disease Environmental Science amp Technology424631ndash4637
18 Jernigan D B P L Raghunathan B P Bell R Brechner E A Bresnitz J C Butler M CetronM Cohen T Doyle and M Fischer 2002 Investigation of Bioterrorism-Related AnthraxUnited States 2001 Epidemiologic Findings Emerging Infectious Diseases 81019ndash1028
19 Greenwood M and G U Yule 1917 On the Statistical Interpretation of Some BacteriologicalMethods Employed in Water Analysis Journal of Hygiene 1636ndash56
20 Phelps E 1909 The Disinfection of Sewage and Sewage Filter Effluents USGS Water Supply Paper229 GPO Washington DC
21 Rudolfs W and H W Gehm 1935 Multiplication of Total Bacteria and B coli after SewageChlorination Sewage Works Journal 7991ndash996
22 Subcommittee onMicrobiological Criteria 1985 An Evaluation of the Role ofMicrobiological Criteriafor Foods and Food Ingredients National Academy Press Washington DC
23 Cabelli V J A P Dufour L J McCabe and M A Levin 1982 Swimming-AssociatedGastroenteritis and Water Quality American Journal of Epidemiology 115606ndash616
24 Dufour A P 1984 Health Effects Criteria for Fresh Recreational Waters USEPA Research TrianglePark NC
25 Fleisher J M F Jones and D Kay 1993 Water and Non-Water-Related Risk Factors forGastroenteritis among Bathers Exposed to Sewage-Contaminated Marine Waters InternationalJournal of Epidemiology 22698ndash708
REFERENCES 11
26 Engelbrecht R S C N Haas J A Shular D L Dunn D Roy A Lalchandani B F Severin andS Farooq 1979 Acid-Fast Bacteria and Yeasts as Indicators of Disinfection Efficiency EPA-6002-79-091 US Environmental Protection Agency Cincinnati OH
27 Grabow W O K 1983 Inactivation of Hepatitis A Virus and Indicator Organisms in Water by FreeChlorine Residuals Applied and Environmental Microbiology 46619
28 Helmer R D and G R Finch 1993 Use of MS2 Coliphage as a Surrogate for Enteric Viruses inSurface Waters Disinfected with Ozone Ozone Science and Engineering 15279ndash293
29 Payment P and E Franco 1993Clostridium Perfringens and Somatic Coliphages as Indicators of theEfficiency of Drinking Water Treatment for Viruses and Protozoan Cysts Applied and EnvironmentalMicrobiology 592418ndash2424
30 Cabelli V J 1977Clostridium Perfringens as aWater Quality Indicator pp 65ndash79 InA Hoadley andB Dutka (eds) Bacterial IndicatorsHealth Hazards Associated with Water ASTM Philadelphia PA
31 Rice E W K R Fox R J Miltner D A Lytle and C H Johnson 1996 Evaluating PlantPerformance with Endospores Journal of the American Water Works Association 88122ndash130
32 Engelbrecht R S B F Severin M T Masarik S Farooq S H Lee C N Haas and A Lalchandani1977 New Microbial Indicators of Disinfection Efficiency EPA-6002-77-052 US EnvironmentalProtection Agency Cincinnati OH
33 Committee on Indicators for Waterborne Pathogens ndash National Research Council 2004 Indicators forWaterborne Pathogens National Academies Press Washington DC
34 PresidentialCongressional Commission on Risk Assessment and RiskManagement 1997 Frameworkfor Environmental Health Risk Management The Commission Washington DC
35 Griffin P M and R V Tauxe 1991 The Epidemiology of Infections Caused by Escherichiacoli O157H7 Other Enterohemorrhagic E coli and the Associated Hemolytic Uremic SyndromeEpidemiologic Reviews 1360ndash98
36 Heun E M R L Vogt P J Hudson S Parren and G W Gary 1987 Risk Factors for SecondaryTransmission in Households after a Common Source Outbreak of Norwalk Gastroenteritis AmericanJournal of Epidemiology 1261181ndash1186
37 MacKenzie W R W L Schell B A Blair D G Addiss D E Peterson N J HozieJ J Kazmierczak and J P Davis 1995 Massive Outbreak of Waterborne CryptosporidiumInfection in Milwaukee Wisconsin Recurrence of Illness and Risk of Secondary TransmissionClinical Infectious Diseases 2157ndash62
38 Millard P K Gensheimer D G Addiss D M Sosin G A Beckett A Houck-Jankoski andA Hudson 1994 An Outbreak of Cryptosporidiosis from Fresh-Pressed Apple Cider Journal ofthe American Medical Association 2721592ndash1596
39 Pickering L K D G Evans H L DuPont J J Vollet and D J Evans Jr 1981 Diarrhea Caused byShigella Rotavirus and Giardia in Day Care Centers Prospective Study Journal of Pediatrics9951ndash56
40 Morens D M R M Zweighaft T M Vernon G W Gary J J Eslien B T Wood R C Holmanand R Dolin 1979 A Waterborne Outbreak of Gastroenteritis with Secondary Person to PersonSpread Lancet 5964ndash966
41 Laursen E O Mygind B Rasmussen and T Ronne 1994 Gastroenteritis A Waterborne OutbreakAffecting 1600 People in a Small Danish Town Journal of Epidemiology amp Community Health48453ndash458
42 Baron R C F D Murphy H B Greenberg C E Davis D J Bregman G W Gary J M Hughesand L B Schonberger 1982 Norwalk Gastrointestinal Illness An Outbreak Associated withSwimming in a Recreational Lake and Secondary Person to Person Transmission American Journalof Epidemiology 115163ndash172
43 Kappus K D J S Marks R C Holman J K Bryant C Baker G W Gary and H B Greenberg1982 An Outbreak of Norwalk Gastroenteritis Associated with Swimming in a Pool and SecondaryPerson to Person Transmission American Journal of Epidemiology 116834ndash839
44 White K E M T Osterbolm J A Mariotti J A Korlath D H Lawrence T L Ristinen andH B Greenberg 1986 A Foodborne Outbreak of Norwalk Virus Gastroenteritis American Journalof Epidemiology 124120ndash126
45 Spika J S J E Parsons and D Nordenberg 1986 Hemolytic Uremic Syndrome and DiarrheaAssociated with Escherichia coli O157H7 in a Day Care Center Journal of Pediatrics 109287ndash291
12 CHAPTER 1 MOTIVATION
46 Ferguson J K L R Jorm C D Allen P KWhitehead and G L Gilbert 1995 Prospective Study ofDiarrhoeal Outbreaks in Child Long Daycare Centres in Western Sydney Medical Journal of Australia163137ndash140
47 Frost F J G F Craun and R L Calderon 1996 Waterborne Disease Surveillance Journal of theAmerican Water Works Association 8866ndash75
48 Farrington C P N J Andrews A D Beale and M A Catchpole 1996 A Statistical Algorithmfor the Early Detection of Outbreaks of Infectious Disease Journal of the Royal StatisticalSociety A 159547ndash563
REFERENCES 13
CHAPTER2MICROBIAL AGENTS ANDTRANSMISSION
MICROBIAL TAXONOMY
The development of techniques for examining the nucleic acids of microorganisms hasseen major changes in which we classify and group related microorganisms This isespecially true for the study of ribosomal ribonucleic acid (rRNA) which is a highlyconserved sequence involved in the synthesis of proteins in all living organisms Basedon this analysis the classification of living things has been placed into a three-domainsystem consisting of Archaea Eukarya and Bacteria Of these the Bacteria andArchaea are termed prokaryotes (no organized cell nucleus) and the Eukarya areknown as eukaryotes (an organized cell nucleus) Eukaryotic microbes other thanalgae and fungi are collectively calledprotistsWithin theEukarya are fungi protozoahelminth worms algae plants animals and humans Archaea are microbes that looksomewhat similar to bacteria in size and shape under the light microscope but they areactually genetically and biochemically quite different They appear to be a simpler formof life and may in fact be the oldest form of life on earth Viruses are obligate intercel-lular parasites and are not amember of any group They are usually composed only of anucleic acid surrounded by a protein coat Eukaryotes are much more complex thanprokaryotic cells in structure and nutritional requirements Prokaryotes divide by sim-ple binary fissionwhereas eukaryotes divide byamore complexprocess calledmitosis
Eukaryotes
Fungi protozoa and helminth worms are all eukaryotes All contain members that arepathogenic to man and animals While algae do not infect humans they can producetoxins that are harmful to animals and man Fungi obtain nutrients solely by adsorp-tion of organic matter from dead organisms Even when they invade living tissuesthey typically kill cells and then adsorb the nutrients from them Some fungi are capa-ble of developing environmentally resistant spores which can be transported throughthe air Fungal diseases in humans are referred to asmycoses Airborne fungal sporesare responsible for some allergies in humans Yeasts are classified with the fungi and
Quantitative Microbial Risk Assessment Second Edition Charles N Haas Joan B Roseand Charles P Gerbacopy 2014 John Wiley amp Sons Inc Published 2014 by John Wiley amp Sons Inc
15
some are pathogenic to humans (Candida albicans) Certain fungi produce toxins(ie aflatoxins) when growing in foods that are mutagenic and carcinogenic in ani-mals Inhalation is an important route of transmission for some fungal diseases suchas aspergillosis blastomycosis coccidioidomycosis and histoplasmosis These fungiare found growing in animal feces soil or decaying organic matter (compost manure)and may be transmitted through the air when this matter is disturbed Some fungi maybe transmitted by direct contact with the skin Fungi are often found in drinking waterdistribution systems and they have been linked to infections in immunocompromisedindividuals [1] Food is not believed to be a significant route of transmission ofpathogenic fungi
Protozoans are unicellular organisms that are surrounded by a cytoplasmicmembrane that is covered by a protective structure called a pellicle Most are freeliving feeding off of bacteria Some of these can cause disease while others are obli-gate parasites They are capable of forming structures called cysts oocysts or spores(depending on the life cycle of the organism) resistant to adverse environmentalconditions such as desiccation starvation high temperatures and disinfectantsSome pathogenic protozoa are found mainly in the soil (Naegleria) or water(Acanthamoeba) Others such a Giardia and Cryptosporidium whose natural habitatis the intestines of warm-blooded animals are capable of causing disease in bothhumans and animals Others such as Entamoeba histolytica are only capable ofcausing disease in humans
Pathogenic enteric (replicate in the intestines) protozoans are usually excretedin the feces or urine and can be transmitted by fecally contaminated food and waterSome protozoa may be transmitted through the air (Acanthamoeba) or throughfomites (inanimate objects) Some important environmentally transmitted protozoaare listed in Table 21 The clinically important protozoa are divided taxonomicallyinto the amoebas (Entamoeba spp) flagellates (Giardia) and coccidian meaningldquoglobose in shaperdquo (Cryptosporidium and Cyclospora) Microsporidia are alsocapable of causing intestinal infections but their classification is uncertain becausethey have many characteristics associated with fungi They are all obligate parasitesand are transmitted via infectious cysts oocysts or spores by the fecalndashoral routeThe life cycles of these protozoa are similar The initial stage occurs during ingestionof the cyst oocyst or spore After ingestion the body temperature and passagethrough the stomach cause these infective stages to open up in a process calledexcystation
The Giardia cysts house two trophozoites which is the stage that attaches tointestinal cells and grows in the intestinal tract through asexual reproduction As thetrophozoites grow and begin to cover the wall of the intestinal tract diarrhea canresult As the trophozoites are released some form cysts as they pass through thebowels Cryptosporidium and Cyclospora both produce oocysts The life cycle ofCyclospora is still not well known except that its oocysts require some period of timein the environment before they are infective Cryptosporidium oocysts contain foursporozoites which enter the intestinal cells and begin the infection process As morecells become infected the illness begins and oocysts are excreted in high numbers inthe feces (about 100000g)
Worms and helminths are small multicellular animals that are parasiticto humans and animals They include flukes tapeworms and roundworms
16 CHAPTER 2 MICROBIAL AGENTS AND TRANSMISSION
CONTENTS
PREFACE xi
CHAPTER 1 MOTIVATION 1
Prevalence of Infectious Disease 1
Prior Approaches 4
Scope of Coverage 4
Potential Objectives of a QMRA 5
Site-Specific Assessment 5
Ensemble of Sites 6
Secondary Transmission 7
Outbreaks versus Endemic Cases 7
References 10
CHAPTER 2 MICROBIAL AGENTS AND TRANSMISSION 15
Microbial Taxonomy 15
Eukaryotes 15
Prokaryotes 18
Viruses 20
Prions 22
Clinical Characterization 24
Microorganisms of Interest 27
Viruses 27
Bacteria 37
Protozoa 42
Transmission Routes 45
Inhalation 48
Dermal Exposure 50
Oral Ingestion 50
References 55
CHAPTER 3 RISK ASSESSMENT PARADIGMS 63
Chemical Risk Assessment National Academy of Sciences Paradigm 63
Ecological Risk Assessment 67
Approaches for Assessing Microbial Risks 71
Background 71
v
The QMRA Framework 74
Hazard Identification 74
DosendashResponse Assessment 74
Exposure Assessment 76
Risk Characterization 77
Risk Management 79
Development of the QMRA Framework and Processes 79
QMRA and the Safety of Water 82
QMRA Food Safety and the HACCP System 84
References 86
CHAPTER 4 CONDUCTING THE HAZARD IDENTIFICATION (HAZ ID) 91
Identifying and Diagnosing Infectious Disease 92
Health Outcomes Associated with Microbial Infections 95
Sensitive Populations 100
Women during Pregnancy Neonates and Young Babies 101
Diabetes 102
The Elderly 102
The Immunocompromised 104
Databases for Statistical Assessment of Disease 106
ICD Codes 107
Waterborne and Foodborne Outbreaks 111
Epidemiological Methods for Undertaking HAZ ID 117
Controlled Epidemiological Investigations 118
HAZ ID Data Used in the Risk Assessment Process 119
Recommendations for Updating Quantitative Data for HAZ ID Information 121
References 122
CHAPTER 5 ANALYTICAL METHODS AND THE QMRA FRAMEWORKDEVELOPING OCCURRENCE AND EXPOSURE DATABASES 129
Introduction 129
Approaches for Developing Occurrence and Exposure Databases 132
Overview of Methodological Issues 134
Sampling Water 136
Sampling Surfaces and Food 138
Sampling Aerosols 138
Specific Techniques for Bacteria Protozoa and Viruses 140
Bacteria 140
Protozoa 142
Viruses 143
Molecular Techniques 145
Probes (FISH) 146
Typing 146
vi CONTENTS
Metagenomics 147
PCR and Quantitative PCR 147
References 151
CHAPTER 6 EXPOSURE ASSESSMENT 159
Conducting the Exposure Assessment 159
Characterizing ConcentrationDuration Distributions 160
Random (Poisson) Distributions of Organisms 160
Estimation of Poisson Mean in Count Assay (Constant and Variable Volumes) 162
Count Assay with Upper Limits 163
Estimation with Quantal Assay 164
Goodness of Fit to Poisson Plate Assay 168
Goodness of Fit MPN 178
Confidence Limits Likelihood 182
Implications for Risk Assessment 187
Consumption Distributions 214
Systematic Subpopulation Differences 221
Afterword 223
Appendix 224
Microsoft Excel 224
MATLAB 225
R 227
References 230
CHAPTER 7 PREDICTIVE MICROBIOLOGY 235
Objective 235
Basic First-Order Processes and Deviations 236
Biological and Physical Bases for Deviations 236
Physical Removal 238
Types of Decay Processes 238
General Forms of Decay and Reasons for Nonlinearity 238
SpontaneousEndogenous 240
Chemical Agents 241
Thermally Induced 243
Ionizing and Nonionizing Radiation 243
Predation and Antagonism 245
Types of Growth Processes 245
Mathematical Modeling of Growth Curves 246
Substrate Dependency 252
Structured Growth Models 255
Incorporation of Decay into Growth Models 256
Systems Biology Approaches 258
CONTENTS vii
Dependence of Growth Parameters on Other Environmental Variables 258
Interacting Populations 258
Data Sources 260
References 263
CHAPTER 8 CONDUCTING THE DOSEndashRESPONSE ASSESSMENT 267
Plausible DosendashResponse Models 268
Framework for Mechanistic DosendashResponse Relationships 269
Exponential DosendashResponse Model 271
Beta-Poisson DosendashResponse Model 272
Simple Threshold Models 274
Negative Binomial Dose Distributions 277
Variable Threshold Models 278
Other Mixture Models 279
Biological Arguments for One-Hit Models 281
Empirical Models 282
Fitting Available Data 283
Types of Data Sets 284
Potential Impacts of Immune Status 298
Relationship between Dose and Severity (Morbidity and Mortality) 299
Morbidity Ratio (PDI) 299
Mortality Ratio 303
Reality Checking Validation 304
Validation 1993 Milwaukee Outbreak 304
Use of Indicators and Other Proxy Measures in DosendashResponse 305
Indicator Methods 305
Molecular Methods 307
Advanced Topics in DosendashResponse Modeling 308
DosendashResponsendashTime Models 308
Physiological Models 313
Appendix 315
References 317
CHAPTER 9 UNCERTAINTY 323
Point Estimates of Risk 324
Terminology Types of Uncertainty 326
Sources of Uncertainty 327
Sources of Variability 328
Variability that is Uncertain 329
Approaches to Quantify Parametric Uncertainty 329
Likelihood 329
Bootstrap 330
Other Methods 330
viii CONTENTS
Applications 332
Exposure Assessment 332
DosendashResponse Assessment 338
Combining Parametric Uncertainty from Multiple Sources 344
Propagation Methods 344
Monte Carlo Analyses 347
Overall Risk Characterization Example 365
Second-Order Methods 368
Model Uncertainty and Averaging 370
References 373
CHAPTER 10 POPULATION DISEASE TRANSMISSION 377
Introduction Models for Population and Community Illnesses 377
Basic SIR Model 378
Incubation Period 386
Duration of Illness 388
Secondary Cases 389
Impact of Immunity 392
Outbreak Detection 393
References 397
CHAPTER 11 RISK CHARACTERIZATION AND DECISION MAKING 399
Introduction 399
Valuing Residual Outcomes 400
Classical Economics 400
DALYs and QALYs 404
Decision Making 407
CostndashBenefit Analysis 408
Multivariate Approaches 411
Other Aspects Entering into a Decision 412
Equity and Justice Aspects 412
References 413
INDEX 415
CONTENTS ix
PREFACE
In the 14 years since we prepared the first edition there has been an explosion inknowledge of and need for quantitative microbial risk assessment (QMRA) Whileour motivation for the first edition stemmed from concerns (principally in water) aboutenteric bacteria viruses and protozoa the motivation has now exploded to newdomains and agents SARS influenza biothreat agents and zoonotic pathogens haveall become of greater concern
The 2001 anthrax letters have highlighted the need for risk assessment ofinhaled agents Both biothreat agents and emergence of new strains of virulentcontagious organisms have raised concern for modeling pathogen dynamics inpopulations
In this edition we have retained the fundamental approach of the riskassessment methodology as a central paradigm We have added new material onmodern pathogen analytical methods predictive microbiology (of pathogen growthand decay) dynamic risk models (explicitly considering incubation time) and diseasepropagation models in populations Of necessity we have removed some materialmdashitis no longer possible to present comprehensive tables of microbial dosendashresponseparameters
In the years since the first edition the authors have gained experience inteaching this material to generations of studentsmdashin the form of formal classestutorials independent studies and short courses We know this book can be valuablein instructing advanced students in environmental sciences environmental engineer-ing public health and microbiology It is also a useful reference for practitionersand regulatory personnel Some prior statistical background would be useful inapproaching the material but not necessary the key requirement for any risk assessoris the absence of fear from mathematical constructs and concepts
The three of us have been on a QMRA journey for almost 30 years We havelearned that doing high-quality risk assessments is of necessity a team sport requiringindividuals with different skills and interests We have learned a tremendous amountfrom each other from our students from our collaborators and from the problems thatwe have sought to approach Practitioners of the art of quantitative microbial riskassessment should be advised to cast a wide net with respect to colleagues andcollaborators to perfect their craft
xi
We encourage comments and feedback from users of this work and look for-ward to observing and participating in developments in coming years and ultimatelyto handing the baton off to our students and their students
Charles N Haas
Joan B Rose
Charles P GerbaNovember 2013
xii PREFACE
CHAPTER1MOTIVATION
THE PREVENTION of infectious disease transmission from human exposure tocontaminated food water soil and air remains a major task of environmental andpublic health professionals There are numerous microbial hazards including expo-sure via food water air and malicious release of pathogens that may arise Indeedsome have argued that the property of virulence of human pathogens is one which isfavored by evolutionary interactions between pathogens and host populations andtherefore will always be of important concern [1] To make rational decisions in pre-paring responding and recovering from exposures to such hazards a quantitativeframework is of high benefit
The objective of this book is to comprehensively set forth the methods forassessment of risk from infectious agents transmitted via these routes in a frameworkthat is compatible with the framework for other risk assessments (eg for chemicalagents) as set forth in standard protocols [2 3]
In this chapter information on the occurrence of infectious disease in broadcategories will be presented along with a historical background on prior methodsfor assessment of microbial safety of food water and air This will be followed byan overview of key issues covered in this book
PREVALENCE OF INFECTIOUS DISEASE
Outbreaks of infectious waterborne illness continue to occur although it remainsimpossible to identify the infectious agent in all cases For example in 1991 a water-borne outbreak in Ireland resulting from sewage contamination of water suppliesinfected about 5000 persons However the infectious agent responsible for thisoutbreak could not be determined [4] In the United States it has been estimated that38 million cases of foodborne infectious disease occur annually with unidentifiedagents [5]
In the United States there have typically been three to five reported outbreaksper year in community drinking water systems involving infectious microorganismswith perhaps up to 10000 annual cases [6] The 1994 Milwaukee Cryptosporidiumoutbreak with over 400000 cases [7 8] was a highly unusual event among thesestatistics As shown in Figure 11 there has been an increasing ability to identify
Quantitative Microbial Risk Assessment Second Edition Charles N Haas Joan B Roseand Charles P Gerbacopy 2014 John Wiley amp Sons Inc Published 2014 by John Wiley amp Sons Inc
1
microorganisms responsible for waterborne diseases and it is expected that withadvances in molecular biology this will increase
There are substantially more outbreaks and cases of foodborne infectiousdiseases than are reported Table 11 summarizes reports of US cases of principalmicrobial infectious foodborne illnesses for two 5-year periods (1988ndash1992 and
1971ndash1982
10
20
30
40
Perc
ent o
f out
brea
ks
50
60
1983ndash1994Period
1995ndash2006
Figure 11 Percentages of outbreaks associated with public water systems (n = 680) by timeperiod 1971ndash2006 that had unknown etiologies based on data from Ref [6]
TABLE 11 Comparison of Five-Year Averages for Common Foodborne Reported Outbreaks
Agent
Annual Average 1988ndash1992 Annual Average 2002ndash2006
Cases Outbreaks Cases Outbreaks
Campylobacter 996 44 624 22
Escherichia coli 488 22 481a 30a
Salmonella 42354 1098 3475 144
Shigella 9576 5 495 12
Staphylococcus aureus 3356 94 554 25
Hepatitis 4218 86 238 1
Listeria monocytogenes 04 02 22 2
Giardia 368 14 2 1
Norovirus 584 04 10854 338
Vibrio (all) 114 18 114 5
Unknown etiologies 40483 1422 4052 30
Source From Refs [9 10]a Include both Shiga toxigenic and enterotoxigenic
2 CHAPTER 1 MOTIVATION
2002ndash2006) There is a mix of causal agents including bacteria virus and protozoaIt is noteworthy that (as in the case of waterborne outbreaks) the frequency ofoutbreaks of unknown etiology has dramatically decreased but the frequency of out-breaks associated with norovirus has dramatically increased These changes are duein part to the ability to better identify causal agents (eg via molecular methods)
It is generally recognized that reported outbreaks either of water- or foodborneinfectious disease represent only a small fractionof the total populationdisease burdenHowever particularly in the United States voluntary reporting systems and theoccurrence of mild cases (for which no medical attention is sought but neverthelessare frank cases of disease) have made it difficult to estimate the total caseload
In the United Kingdom comparisons between the number of confirmed casesin infectious disease outbreaks and total confirmed laboratory illnesses (occurring inEngland and Wales) have been made (Table 12) This suggests that the ratio ofreported outbreak cases to total cases that may seek medical attention may be from10 to 5001 with some dependency on the particular agent
Colford et al [12] developed estimates for the total disease burden associatedwith acute gastroenteritis from drinking water This relies on combining the reportedoutbreak data with interventional epidemiologic studies Based on their analysis thetotal US disease burden is estimated to be 426ndash1169 million cases per year in theUnited States which is substantially in excess of the reported outbreaks In the case offoodborne illness there are an estimated 14 million cases per year [13]
Drinking water and food are by no means the only potential routes of exposureto infectious agents in the environment Recreation in water (either natural or artificialpools) containing pathogens can produce illness [14]
Indoor air transmission can be a vehicle of infection Legionella transmittedthrough indoor environments has been a concern since the 1970s [15] The multina-tional epidemic of severe acute respiratory syndrome (SARS) caused by a coronavi-rus was abetted at least in one location in Hong Kong by indoor aerosol transmissionbetween apartments of infected individuals and susceptible individuals [16] A broadspectrum of other respiratory pathogens including influenza rhinoviruses and myco-bacteria can be transmitted by this route [17]
TABLE 12 Comparison of Laboratory Isolations and Outbreak Cases in Englandand Wales 1992ndash1994
Agent
Cases 1992ndash1994
RatioAll Laboratory Reports Confirmed Outbreak Cases
Campylobacter 122250 240 5094
Rotavirus 47463 127 3737
S sonnei 29080 847 343
Salmonella 92416 5960 155
Cryptosporidium 14454 1066 136
E coli O157 1266 128 99
Source Modified from Ref [11]
PREVALENCE OF INFECTIOUS DISEASE 3
The deliberate release of Bacillus anthracis spores in 2001 (the ldquoAmerithraxrdquoincidents) brought widespread awareness to the potential for indoor releases (as wellas releases in other venues) of bioterrorist agents to cause risk [18] Therefore ofnecessity microbial risk assessors may need to consider the impact of maliciousactivity in certain applications
PRIOR APPROACHES
Concerns for microbial quality of food water and other environmental media havelong existed In the early twentieth century the use of indicator microorganismswas developed for the control and assessment of the hygienic quality of such mediaand the adequacy of disinfection and sterilization processes The coliform group oforganisms was perhaps first employed for this purpose [19ndash21] Indicator techniqueshave also found utility in the food industry such as the total count for milk and othermore recent proposals [22] Other indicator groups for food water or environmentalmedia have been examined such as enterococci [23ndash25] acid-fast bacteria [26]bacteriophage [27ndash29] and Clostridia spores [29ndash31]
The use of indicator organisms was historically justified in because of difficultyin enumerating pathogens However with the increasing availability of modernmicrobial methods for example PCR immunoassay etc for direct pathogen assess-ment this justification has become less persuasive In addition in order to develophealth-based standards from indicators extensive epidemiologic surveillance is oftennecessary The use of epidemiology has limitations with respect to detection limits(for an adverse effect) and is also quite expensive to conduct Indicator methodsare also limited in that many pathogens are more resistant to die off in receiving envir-onments or source waters than indicators or have greater resistance to removal bytreatment processes than indicators [26 28 29 32] Thus the absence of indicatorsmay not suffice to ensure the absence of pathogens Even after a century of use theindicator concept remains imperfect [33]
The use of quantitative microbial risk assessment (QMRA) will enable directmeasurements of pathogens to be used to develop acceptancerejection guidelinesfor food water and other vehicles that may be the source of microbial exposureto human populations The objective of this book is to present these methods in asystematic and unified manner
SCOPE OF COVERAGE
QMRA is the application of principles of risk assessment to the estimate ofconsequences from a planned or actual exposure to infectious microorganismsIn performing a QMRA the risk assessor aims to bring the best available informationto bear in understanding the nature of the potential effects from a microbial exposureSince the information (such as dosendashresponse relationships exposure magnitudes) isalmost invariably incomplete it is also necessary to ascertain the potential error
4 CHAPTER 1 MOTIVATION
involved in the risk assessment With such information necessary steps to mitigatecontrol or defend against such exposures may be developed
At the outset of performing a risk assessment a scoping task should be under-taken This task should set forth the objectives of the analysis and the principal issuesto be addressed Items such as consideration of secondary cases individual versuspopulation risk agent or agents to be examined exposure routes andor accident sce-narios must be stipulated However this scoping may be changed during the course ofa QMRA to reflect the input derived from the risk manager(s) and other stakeholders
POTENTIAL OBJECTIVES OF A QMRA
There may be diverse objectives for a QMRA These objectives relate to the rationalefor the performance of the assessment as well as the methods to be employedBroadly the different objectives reflect different scales at which a risk assessmentmay be performed The step of problem formulation is critical to any risk estimate[34] It is necessary that the problem be formulated to meet the needs of the riskmanagers and stakeholders indeed it is now recognized that the successful practiceof risk analysis requires frequent interchange with manager and stakeholders [3]In general the problems posed are of several types
Site-Specific Assessment
The simplest type of QMRA that may be performed involves one site or exposurescenario The following are typical of the questions that might be asked
1 If a water treatment plant is designed in a certain way (with given removals ofpathogens) then what is the risk that would be placed upon the populationserved
2 A swimming outbreak (in a recreational lake) has just occurred I believe that itresulted from a short-duration contamination event What pathogen levelswould be consistent with the observed attack rate
3 Microbial sampling of a finished food product has found certain pathogensWhat level of risk does this pose to consumers of the product
4 A certain amount of infectious agent has been released into a room What is theimmediate danger to occupants and how stringent should cleanup levels be
Note that there are certain other contrasts in the objectives of the risk assessments tobe posed In (1) and (3) a before-the-fact computation is desired while in (2) and (4)an after-the-fact computation is described Also in (1) (3) and (4) pathogen levelsare available (or somehow are estimated) while in (2) an inverse computation isneeded given an observed attack rate
In performing this risk assessment the relationship between an exposure ortechnological metric and a risk measurement must be ascertained and then theparticular point of correspondence determined (Fig 12) In cases (1) (3) and (4)for a known (or assumed) exposure (on the x-axis) the corresponding range of risks
POTENTIAL OBJECTIVES OF A QMRA 5
on the y-axis is sought In cases (2) for known or assumed risks (on the y-axis)the corresponding range of exposures (or level of technological protection) is to bedetermined (on the x-axis)
Ensemble of Sites
A somewhat more complex situation occurs if the risk for a set of events or sites mustbe estimated Basically this now includes the necessity to incorporate site-to-sitefactors into the assessment Some examples of this are as follows
1 If I desire keeping the risk to a population served by multiple water treatmentplants at a given level (or better) then what criteria should I use (microbiallevels)
2 For a food product subject to contamination by pathogens what would be anacceptable treatment specification (eg heating time holding period) to ensuremicrobial acceptability
3 I am designing a water quality standard for recreational bathing waters If auniform (eg national) standard is to be developed what standard would ensurethat average risk was acceptable with keeping the risk of a large ldquoclusterrdquo ofillnesses low
In addition to incorporating a measure of ensemble average risk in general it is alsodesired to ensure that no single member of the ensemble be unacceptably extreme Forexample consider the evaluation of three options of disease control among three com-munities as indicated in Table 13
This table indicates the number of cases and the rate among the three commu-nities The three policy options yield the same number of expected cases Howeverthere are differences in the allocation of risk among the communities of different sizesIn option A all communities have an identical level of estimated risk In option B therisk increases as community size decreases while in option C the risk increases ascommunity size increases This distribution of risk among affected subsets of the
Exposure
Ris
k
Level of technological protection
Figure 12 Relationship between exposurelevel of technological protection andmicrobial risk The middle curve indicatesthe best estimate The other two curvesindicate the upper and lower confidenceregions
6 CHAPTER 1 MOTIVATION
ensemble being considered adds an additional dimension for consideration by a riskmanagermdashwhich may be termed risk equity
SECONDARY TRANSMISSION
Infectious microbial diseases are different in terms of risk to a population than arechemical agents in that an individual who may become infected (with or withoutillness) can then proceed to infect additional individuals These secondary (tertiaryquaternary etc) cases may be persons who had no direct contact with the initialvehicle of exposure but nevertheless in fairly accounting for the public health impactthey should be considered
Secondary cases may arise by a variety of mechanisms Particularly amongclose family members household secondary cases can arise by direct or indirect(eg surface contamination) contact this is particularly so when the primary caseor one household secondary case is a child [35ndash37] Table 14 summarizes secondarycase statistics obtained from a variety of outbreaks As will be discussed inChapter 10 the secondary case rate is a complex factor involving (among other things)the nature of the venue and contact patterns when infected and susceptible individualsintermingle
Presumably secondary cases may also arise from close contact with anasymptomatic individual (in the ldquocarrierrdquo state) This is well known for highly acuteand (now) uncommon illnesses (such as typhoid) Excretion of Norwalk virusfollowing recovery (and resulting in additional cases) has been documented to occurfor as long as 48 h post recovery [44]
OUTBREAKS VERSUS ENDEMIC CASES
As noted previously there may be a substantial difference between reported outbreakcases and total disease burden in a community In order for a disease case to receiverecognition by the public health authorities the following specific and sequential stepsmust occur [47]
TABLE 13 Effect of Different Hypothetical Policy Options on Distribution of Risk AmongCommunities (for a Fixed Total Risk)
CommunityExposedPopulation
Policy Option A Policy Option B Policy Option C
CasesIncidence(10000) Cases
Incidence(10000) Cases
Incidence(10000)
A 100000 20 2 6 06 24 24
B 50000 10 2 18 36 7 14
C 10000 2 2 8 8 1 1
Total 160000 32 2 32 2 16 2
OUTBREAKS VERSUS ENDEMIC CASES 7
1 An ill person must seek medical care
2 Appropriate clinical tests (eg blood stool) must be ordered by the attendingphysician
3 The patient must comply with obtaining the sample
4 The laboratory must be capable of detecting the relevant pathogens
5 The clinical test must be positive
6 The test result must be reported to the health agency in a timely manner
If any of the links in this sequential chain are broken then a disease case will not enterthe records maintained by health authorities For example with increasing controls on
TABLE 14 Summary of Secondary Case Data in Outbreak Situations
Organism
SecondaryAttackRatioa
SecondaryPrevalence inHouseholdsb Remarks Reference
Cryptosporidiumparvum
033 033 Outbreak in contaminatedapple cider
[38]
C parvum NA 0042 Drinking water outbreak(Milwaukee)
[37]
Shigella 028 026 Day-care center outbreaksin children
[39]
Rotavirus 042 015 Day-care center outbreaksin children
[30]
Giardia lamblia 133 017 Day-care center outbreaksin children
[39]
Viral gastroenteritis 022 011c Drinking waterborneoutbreak
[40]
Viral gastroenteritis 056 NA Drinking water outbreak(Denmark)
[41]
Norovirus 05ndash10 019 Swimming outbreak [42]
Norovirus 11 029 Swimming outbreakin children
[43]
Norovirus NA 044 Foodborne outbreakin children and teachers
[36]
Norovirus 04 NA Foodborne outbreak [44]
E coli O157H7 NA 018c Day-care center outbreakin children
[45]
Unidentifiedday-care diarrhealdiseases
138 009c [46]
NA information not availableaRatio of secondary cases to primary casesb Proportion of households with one or more primary cases who have one or more secondary casesc Proportion of persons in contact with one or more primary cases who have a secondary case
8 CHAPTER 1 MOTIVATION
medical care stool samples may not be obtained from mild cases of illness Someorganisms may only be present sporadically or may be difficult to test in stool orblood sample Patients may not seek medical attention for mild cases of illness Fur-thermore in the United States in particular the surveillance of environmentallyinduced disease is done on a passive basis and hence the number of actual illnessclusters that are actually compiled into recorded statistics is only a small fractionof such clusters of illness that occur [47]
From a more fundamental point of view an outbreak of illness is generallydefined as occurrence of the illness at a level greater than normal or anticipated Thisdefinition recognizes that there is a level of illness (endemic) that may exist underusual circumstances The detection of such outbreaks poses a particular challengeThe problem is illustrated conceptually in Figure 13
Additional complications arise from the different patterns of illness in acommunity including definite periodicities as well as temporal trends and fromthe presence of reporting lags associated with laboratory analysis and time for patientsto seek medical attention Figure 14 illustrates the different patterns of illness inthe case of six pathogens for England and Wales [48]
In the case of waterborne and foodborne illnesses it is highly likely that thelevel of such endemic illnesses is substantially greater than those occurring duringoutbreaks (even accounting for unrecognized outbreaks)
As a result there are often many cases of environmentally caused (water airfood) infectious disease that are unrecognized One example of this isCampylobacterThere has been an average of about 200 cases per year of water- and foodborne illnessin outbreaks of this organism and yet estimates of the disease burden suggest about2100000 cases per year that is approximately 10000 cases per case of detectableoutbreak illness Therefore it will be important to assess the factors that may influenceoutbreak detection These issues will be discussed in subsequent chapters
Detectedoutbreak
Undetectedoutbreak
Threshold of detection
Hyper endemicSporadic
Endemic rate
Time
Num
ber
of c
ases
Figure 13 Schematic of disease occurrence in a hypothetical community (Modified fromRef [47])
OUTBREAKS VERSUS ENDEMIC CASES 9
REFERENCES
1 Levin B R 1996 The Evolution and Maintenance of Virulence in Microparasites Emerging InfectiousDisease 293ndash102
2 National Academy of Sciences 1983 Risk Assessment in the Federal Government Managing theProcess National Academy Press Washington DC
3 National Research Council 2009 Science and Decisions Advancing Risk Assessment NationalAcademies Press Washington DC
10090807060504030201001190 1191 1192 1193 1194 1195
(b)
140
120
100
80
60
40
20
01190 1191 1192 1193 1194 1195
(f)
700
600
500
400
300
200
100
01190 1191 1192 1193 1194 1195
(d)
1200
1000
800
600
400
200
1190 1191 1192 1193 1194 1195
(a)
240
200
160
120
80
40
01190 1191 1192 1193 1194 1195
(e)
7
6
5
4
3
2
1
01190 1191 1192 1193 1194 1195
(c)
Figure 14 Weekly count of reported organism isolations in England andWales (a) rotavirus(b) Clostridium difficile (c) Salmonella derby (d) Shigella sonnei (e) influenza B and (f)Salmonella typhimurium DT 104 (From Ref [48])
10 CHAPTER 1 MOTIVATION
4 Fogarty J L Thornton and R Corcoran 1995 Illness in a Community Associated with an Episode ofWater Contamination with Sewage Epidemiology and Infection 114289ndash295
5 Scallan E 2011 Foodborne Illness Acquired in the United StatesmdashUnspecified Agents EmergingInfectious Diseases 17 16ndash22
6 Craun G F J M Brunkard J S Yoder V A Roberts J Carpenter T Wade R L CalderonJ M Roberts M J Beach and S L Roy 2010 Causes of Outbreaks Associated with Drinking Waterin the United States from 1971 to 2006 Clinical Microbiology Reviews 23507ndash528
7 Edwards D D 1993 Troubled Waters in Milwaukee ASM News 59342ndash3458 MacKenzie W R N J Hoxie M E Proctor M S Gradus K A Blair D E Peterson
J J Kazmierczak K R Fox D G Addias J B Rose and J P Davis 1994 Massive WaterborneOutbreak of Cryptosporidium Infection Associated with a Filtered Public Water Supply MilwaukeeWisconsin March and April 1993 New England Journal of Medicine 331161ndash167
9 Anonymous 2010 Surveillance for Foodborne Disease OutbreaksmdashUnited States 2007 Morbidityand Mortality Weekly Reports 59973ndash979
10 Bean N H J S Goulding C Lau and F J Angulo 1996 Surveillance for Foodborne-DiseaseOutbreaksmdashUnited States 1988ndash1992 Morbidity and Mortality Weekly Reports 451ndash66
11 Wall P G J de Louvois R J Gilbert and B Rowe 1996 Food Poisoning NotificationsLaboratory Reports and OutbreaksmdashWhere do the Statistics Come From and What Do They MeanCommunicable Disease Report Review 6 R93ndashR100
12 Colford J M S Roy M J Beach A Hightower S E Shaw and T J Wade 2006 A Review ofHousehold Drinking Water Intervention Trials and an Approach to the Estimation of EndemicWaterborne Gastroenteritis in the United States Journal of Water and Health 471
13 Mead P S L Slutsker V Dietz L F McCaig J S Bresee C Shapiro P M Griffinand R V Tauxe 1999 Food Related Illness and Death in the United States Emerging InfectiousDisease 5607ndash625
14 Dziuban E J J L Liang G F Craun V Hill P A Yu J Painter M R Moore R L CalderonS L Roy and M J Beach 2006 Surveillance for Waterborne Disease and Outbreaks Associatedwith Recreational WatermdashUnited States 2003ndash2004 and Surveillance for Waterborne Disease andOutbreaks Associated with Drinking Water and Water not Intended for DrinkingmdashUnited States2003ndash2004 Morbidity and Mortality Weekly Reports 551ndash30
15 Fliermans C B 1996 Ecology of Legionella From Data to Knowledge with a Little WisdomMicrobial Ecology 32203ndash228
16 Li Y S Duan I T Yu and T W Wong 2005 Multi-Zone Modeling of Probable SARS VirusTransmission by Airflow Between Flats in Block E Amoy Gardens Indoor Air 1596ndash111
17 Peccia J D K Milton T Reponen and J Hill 2008 A Role for Environmental Engineering andScience in Preventing Bioaerosol-Related Disease Environmental Science amp Technology424631ndash4637
18 Jernigan D B P L Raghunathan B P Bell R Brechner E A Bresnitz J C Butler M CetronM Cohen T Doyle and M Fischer 2002 Investigation of Bioterrorism-Related AnthraxUnited States 2001 Epidemiologic Findings Emerging Infectious Diseases 81019ndash1028
19 Greenwood M and G U Yule 1917 On the Statistical Interpretation of Some BacteriologicalMethods Employed in Water Analysis Journal of Hygiene 1636ndash56
20 Phelps E 1909 The Disinfection of Sewage and Sewage Filter Effluents USGS Water Supply Paper229 GPO Washington DC
21 Rudolfs W and H W Gehm 1935 Multiplication of Total Bacteria and B coli after SewageChlorination Sewage Works Journal 7991ndash996
22 Subcommittee onMicrobiological Criteria 1985 An Evaluation of the Role ofMicrobiological Criteriafor Foods and Food Ingredients National Academy Press Washington DC
23 Cabelli V J A P Dufour L J McCabe and M A Levin 1982 Swimming-AssociatedGastroenteritis and Water Quality American Journal of Epidemiology 115606ndash616
24 Dufour A P 1984 Health Effects Criteria for Fresh Recreational Waters USEPA Research TrianglePark NC
25 Fleisher J M F Jones and D Kay 1993 Water and Non-Water-Related Risk Factors forGastroenteritis among Bathers Exposed to Sewage-Contaminated Marine Waters InternationalJournal of Epidemiology 22698ndash708
REFERENCES 11
26 Engelbrecht R S C N Haas J A Shular D L Dunn D Roy A Lalchandani B F Severin andS Farooq 1979 Acid-Fast Bacteria and Yeasts as Indicators of Disinfection Efficiency EPA-6002-79-091 US Environmental Protection Agency Cincinnati OH
27 Grabow W O K 1983 Inactivation of Hepatitis A Virus and Indicator Organisms in Water by FreeChlorine Residuals Applied and Environmental Microbiology 46619
28 Helmer R D and G R Finch 1993 Use of MS2 Coliphage as a Surrogate for Enteric Viruses inSurface Waters Disinfected with Ozone Ozone Science and Engineering 15279ndash293
29 Payment P and E Franco 1993Clostridium Perfringens and Somatic Coliphages as Indicators of theEfficiency of Drinking Water Treatment for Viruses and Protozoan Cysts Applied and EnvironmentalMicrobiology 592418ndash2424
30 Cabelli V J 1977Clostridium Perfringens as aWater Quality Indicator pp 65ndash79 InA Hoadley andB Dutka (eds) Bacterial IndicatorsHealth Hazards Associated with Water ASTM Philadelphia PA
31 Rice E W K R Fox R J Miltner D A Lytle and C H Johnson 1996 Evaluating PlantPerformance with Endospores Journal of the American Water Works Association 88122ndash130
32 Engelbrecht R S B F Severin M T Masarik S Farooq S H Lee C N Haas and A Lalchandani1977 New Microbial Indicators of Disinfection Efficiency EPA-6002-77-052 US EnvironmentalProtection Agency Cincinnati OH
33 Committee on Indicators for Waterborne Pathogens ndash National Research Council 2004 Indicators forWaterborne Pathogens National Academies Press Washington DC
34 PresidentialCongressional Commission on Risk Assessment and RiskManagement 1997 Frameworkfor Environmental Health Risk Management The Commission Washington DC
35 Griffin P M and R V Tauxe 1991 The Epidemiology of Infections Caused by Escherichiacoli O157H7 Other Enterohemorrhagic E coli and the Associated Hemolytic Uremic SyndromeEpidemiologic Reviews 1360ndash98
36 Heun E M R L Vogt P J Hudson S Parren and G W Gary 1987 Risk Factors for SecondaryTransmission in Households after a Common Source Outbreak of Norwalk Gastroenteritis AmericanJournal of Epidemiology 1261181ndash1186
37 MacKenzie W R W L Schell B A Blair D G Addiss D E Peterson N J HozieJ J Kazmierczak and J P Davis 1995 Massive Outbreak of Waterborne CryptosporidiumInfection in Milwaukee Wisconsin Recurrence of Illness and Risk of Secondary TransmissionClinical Infectious Diseases 2157ndash62
38 Millard P K Gensheimer D G Addiss D M Sosin G A Beckett A Houck-Jankoski andA Hudson 1994 An Outbreak of Cryptosporidiosis from Fresh-Pressed Apple Cider Journal ofthe American Medical Association 2721592ndash1596
39 Pickering L K D G Evans H L DuPont J J Vollet and D J Evans Jr 1981 Diarrhea Caused byShigella Rotavirus and Giardia in Day Care Centers Prospective Study Journal of Pediatrics9951ndash56
40 Morens D M R M Zweighaft T M Vernon G W Gary J J Eslien B T Wood R C Holmanand R Dolin 1979 A Waterborne Outbreak of Gastroenteritis with Secondary Person to PersonSpread Lancet 5964ndash966
41 Laursen E O Mygind B Rasmussen and T Ronne 1994 Gastroenteritis A Waterborne OutbreakAffecting 1600 People in a Small Danish Town Journal of Epidemiology amp Community Health48453ndash458
42 Baron R C F D Murphy H B Greenberg C E Davis D J Bregman G W Gary J M Hughesand L B Schonberger 1982 Norwalk Gastrointestinal Illness An Outbreak Associated withSwimming in a Recreational Lake and Secondary Person to Person Transmission American Journalof Epidemiology 115163ndash172
43 Kappus K D J S Marks R C Holman J K Bryant C Baker G W Gary and H B Greenberg1982 An Outbreak of Norwalk Gastroenteritis Associated with Swimming in a Pool and SecondaryPerson to Person Transmission American Journal of Epidemiology 116834ndash839
44 White K E M T Osterbolm J A Mariotti J A Korlath D H Lawrence T L Ristinen andH B Greenberg 1986 A Foodborne Outbreak of Norwalk Virus Gastroenteritis American Journalof Epidemiology 124120ndash126
45 Spika J S J E Parsons and D Nordenberg 1986 Hemolytic Uremic Syndrome and DiarrheaAssociated with Escherichia coli O157H7 in a Day Care Center Journal of Pediatrics 109287ndash291
12 CHAPTER 1 MOTIVATION
46 Ferguson J K L R Jorm C D Allen P KWhitehead and G L Gilbert 1995 Prospective Study ofDiarrhoeal Outbreaks in Child Long Daycare Centres in Western Sydney Medical Journal of Australia163137ndash140
47 Frost F J G F Craun and R L Calderon 1996 Waterborne Disease Surveillance Journal of theAmerican Water Works Association 8866ndash75
48 Farrington C P N J Andrews A D Beale and M A Catchpole 1996 A Statistical Algorithmfor the Early Detection of Outbreaks of Infectious Disease Journal of the Royal StatisticalSociety A 159547ndash563
REFERENCES 13
CHAPTER2MICROBIAL AGENTS ANDTRANSMISSION
MICROBIAL TAXONOMY
The development of techniques for examining the nucleic acids of microorganisms hasseen major changes in which we classify and group related microorganisms This isespecially true for the study of ribosomal ribonucleic acid (rRNA) which is a highlyconserved sequence involved in the synthesis of proteins in all living organisms Basedon this analysis the classification of living things has been placed into a three-domainsystem consisting of Archaea Eukarya and Bacteria Of these the Bacteria andArchaea are termed prokaryotes (no organized cell nucleus) and the Eukarya areknown as eukaryotes (an organized cell nucleus) Eukaryotic microbes other thanalgae and fungi are collectively calledprotistsWithin theEukarya are fungi protozoahelminth worms algae plants animals and humans Archaea are microbes that looksomewhat similar to bacteria in size and shape under the light microscope but they areactually genetically and biochemically quite different They appear to be a simpler formof life and may in fact be the oldest form of life on earth Viruses are obligate intercel-lular parasites and are not amember of any group They are usually composed only of anucleic acid surrounded by a protein coat Eukaryotes are much more complex thanprokaryotic cells in structure and nutritional requirements Prokaryotes divide by sim-ple binary fissionwhereas eukaryotes divide byamore complexprocess calledmitosis
Eukaryotes
Fungi protozoa and helminth worms are all eukaryotes All contain members that arepathogenic to man and animals While algae do not infect humans they can producetoxins that are harmful to animals and man Fungi obtain nutrients solely by adsorp-tion of organic matter from dead organisms Even when they invade living tissuesthey typically kill cells and then adsorb the nutrients from them Some fungi are capa-ble of developing environmentally resistant spores which can be transported throughthe air Fungal diseases in humans are referred to asmycoses Airborne fungal sporesare responsible for some allergies in humans Yeasts are classified with the fungi and
Quantitative Microbial Risk Assessment Second Edition Charles N Haas Joan B Roseand Charles P Gerbacopy 2014 John Wiley amp Sons Inc Published 2014 by John Wiley amp Sons Inc
15
some are pathogenic to humans (Candida albicans) Certain fungi produce toxins(ie aflatoxins) when growing in foods that are mutagenic and carcinogenic in ani-mals Inhalation is an important route of transmission for some fungal diseases suchas aspergillosis blastomycosis coccidioidomycosis and histoplasmosis These fungiare found growing in animal feces soil or decaying organic matter (compost manure)and may be transmitted through the air when this matter is disturbed Some fungi maybe transmitted by direct contact with the skin Fungi are often found in drinking waterdistribution systems and they have been linked to infections in immunocompromisedindividuals [1] Food is not believed to be a significant route of transmission ofpathogenic fungi
Protozoans are unicellular organisms that are surrounded by a cytoplasmicmembrane that is covered by a protective structure called a pellicle Most are freeliving feeding off of bacteria Some of these can cause disease while others are obli-gate parasites They are capable of forming structures called cysts oocysts or spores(depending on the life cycle of the organism) resistant to adverse environmentalconditions such as desiccation starvation high temperatures and disinfectantsSome pathogenic protozoa are found mainly in the soil (Naegleria) or water(Acanthamoeba) Others such a Giardia and Cryptosporidium whose natural habitatis the intestines of warm-blooded animals are capable of causing disease in bothhumans and animals Others such as Entamoeba histolytica are only capable ofcausing disease in humans
Pathogenic enteric (replicate in the intestines) protozoans are usually excretedin the feces or urine and can be transmitted by fecally contaminated food and waterSome protozoa may be transmitted through the air (Acanthamoeba) or throughfomites (inanimate objects) Some important environmentally transmitted protozoaare listed in Table 21 The clinically important protozoa are divided taxonomicallyinto the amoebas (Entamoeba spp) flagellates (Giardia) and coccidian meaningldquoglobose in shaperdquo (Cryptosporidium and Cyclospora) Microsporidia are alsocapable of causing intestinal infections but their classification is uncertain becausethey have many characteristics associated with fungi They are all obligate parasitesand are transmitted via infectious cysts oocysts or spores by the fecalndashoral routeThe life cycles of these protozoa are similar The initial stage occurs during ingestionof the cyst oocyst or spore After ingestion the body temperature and passagethrough the stomach cause these infective stages to open up in a process calledexcystation
The Giardia cysts house two trophozoites which is the stage that attaches tointestinal cells and grows in the intestinal tract through asexual reproduction As thetrophozoites grow and begin to cover the wall of the intestinal tract diarrhea canresult As the trophozoites are released some form cysts as they pass through thebowels Cryptosporidium and Cyclospora both produce oocysts The life cycle ofCyclospora is still not well known except that its oocysts require some period of timein the environment before they are infective Cryptosporidium oocysts contain foursporozoites which enter the intestinal cells and begin the infection process As morecells become infected the illness begins and oocysts are excreted in high numbers inthe feces (about 100000g)
Worms and helminths are small multicellular animals that are parasiticto humans and animals They include flukes tapeworms and roundworms
16 CHAPTER 2 MICROBIAL AGENTS AND TRANSMISSION
The QMRA Framework 74
Hazard Identification 74
DosendashResponse Assessment 74
Exposure Assessment 76
Risk Characterization 77
Risk Management 79
Development of the QMRA Framework and Processes 79
QMRA and the Safety of Water 82
QMRA Food Safety and the HACCP System 84
References 86
CHAPTER 4 CONDUCTING THE HAZARD IDENTIFICATION (HAZ ID) 91
Identifying and Diagnosing Infectious Disease 92
Health Outcomes Associated with Microbial Infections 95
Sensitive Populations 100
Women during Pregnancy Neonates and Young Babies 101
Diabetes 102
The Elderly 102
The Immunocompromised 104
Databases for Statistical Assessment of Disease 106
ICD Codes 107
Waterborne and Foodborne Outbreaks 111
Epidemiological Methods for Undertaking HAZ ID 117
Controlled Epidemiological Investigations 118
HAZ ID Data Used in the Risk Assessment Process 119
Recommendations for Updating Quantitative Data for HAZ ID Information 121
References 122
CHAPTER 5 ANALYTICAL METHODS AND THE QMRA FRAMEWORKDEVELOPING OCCURRENCE AND EXPOSURE DATABASES 129
Introduction 129
Approaches for Developing Occurrence and Exposure Databases 132
Overview of Methodological Issues 134
Sampling Water 136
Sampling Surfaces and Food 138
Sampling Aerosols 138
Specific Techniques for Bacteria Protozoa and Viruses 140
Bacteria 140
Protozoa 142
Viruses 143
Molecular Techniques 145
Probes (FISH) 146
Typing 146
vi CONTENTS
Metagenomics 147
PCR and Quantitative PCR 147
References 151
CHAPTER 6 EXPOSURE ASSESSMENT 159
Conducting the Exposure Assessment 159
Characterizing ConcentrationDuration Distributions 160
Random (Poisson) Distributions of Organisms 160
Estimation of Poisson Mean in Count Assay (Constant and Variable Volumes) 162
Count Assay with Upper Limits 163
Estimation with Quantal Assay 164
Goodness of Fit to Poisson Plate Assay 168
Goodness of Fit MPN 178
Confidence Limits Likelihood 182
Implications for Risk Assessment 187
Consumption Distributions 214
Systematic Subpopulation Differences 221
Afterword 223
Appendix 224
Microsoft Excel 224
MATLAB 225
R 227
References 230
CHAPTER 7 PREDICTIVE MICROBIOLOGY 235
Objective 235
Basic First-Order Processes and Deviations 236
Biological and Physical Bases for Deviations 236
Physical Removal 238
Types of Decay Processes 238
General Forms of Decay and Reasons for Nonlinearity 238
SpontaneousEndogenous 240
Chemical Agents 241
Thermally Induced 243
Ionizing and Nonionizing Radiation 243
Predation and Antagonism 245
Types of Growth Processes 245
Mathematical Modeling of Growth Curves 246
Substrate Dependency 252
Structured Growth Models 255
Incorporation of Decay into Growth Models 256
Systems Biology Approaches 258
CONTENTS vii
Dependence of Growth Parameters on Other Environmental Variables 258
Interacting Populations 258
Data Sources 260
References 263
CHAPTER 8 CONDUCTING THE DOSEndashRESPONSE ASSESSMENT 267
Plausible DosendashResponse Models 268
Framework for Mechanistic DosendashResponse Relationships 269
Exponential DosendashResponse Model 271
Beta-Poisson DosendashResponse Model 272
Simple Threshold Models 274
Negative Binomial Dose Distributions 277
Variable Threshold Models 278
Other Mixture Models 279
Biological Arguments for One-Hit Models 281
Empirical Models 282
Fitting Available Data 283
Types of Data Sets 284
Potential Impacts of Immune Status 298
Relationship between Dose and Severity (Morbidity and Mortality) 299
Morbidity Ratio (PDI) 299
Mortality Ratio 303
Reality Checking Validation 304
Validation 1993 Milwaukee Outbreak 304
Use of Indicators and Other Proxy Measures in DosendashResponse 305
Indicator Methods 305
Molecular Methods 307
Advanced Topics in DosendashResponse Modeling 308
DosendashResponsendashTime Models 308
Physiological Models 313
Appendix 315
References 317
CHAPTER 9 UNCERTAINTY 323
Point Estimates of Risk 324
Terminology Types of Uncertainty 326
Sources of Uncertainty 327
Sources of Variability 328
Variability that is Uncertain 329
Approaches to Quantify Parametric Uncertainty 329
Likelihood 329
Bootstrap 330
Other Methods 330
viii CONTENTS
Applications 332
Exposure Assessment 332
DosendashResponse Assessment 338
Combining Parametric Uncertainty from Multiple Sources 344
Propagation Methods 344
Monte Carlo Analyses 347
Overall Risk Characterization Example 365
Second-Order Methods 368
Model Uncertainty and Averaging 370
References 373
CHAPTER 10 POPULATION DISEASE TRANSMISSION 377
Introduction Models for Population and Community Illnesses 377
Basic SIR Model 378
Incubation Period 386
Duration of Illness 388
Secondary Cases 389
Impact of Immunity 392
Outbreak Detection 393
References 397
CHAPTER 11 RISK CHARACTERIZATION AND DECISION MAKING 399
Introduction 399
Valuing Residual Outcomes 400
Classical Economics 400
DALYs and QALYs 404
Decision Making 407
CostndashBenefit Analysis 408
Multivariate Approaches 411
Other Aspects Entering into a Decision 412
Equity and Justice Aspects 412
References 413
INDEX 415
CONTENTS ix
PREFACE
In the 14 years since we prepared the first edition there has been an explosion inknowledge of and need for quantitative microbial risk assessment (QMRA) Whileour motivation for the first edition stemmed from concerns (principally in water) aboutenteric bacteria viruses and protozoa the motivation has now exploded to newdomains and agents SARS influenza biothreat agents and zoonotic pathogens haveall become of greater concern
The 2001 anthrax letters have highlighted the need for risk assessment ofinhaled agents Both biothreat agents and emergence of new strains of virulentcontagious organisms have raised concern for modeling pathogen dynamics inpopulations
In this edition we have retained the fundamental approach of the riskassessment methodology as a central paradigm We have added new material onmodern pathogen analytical methods predictive microbiology (of pathogen growthand decay) dynamic risk models (explicitly considering incubation time) and diseasepropagation models in populations Of necessity we have removed some materialmdashitis no longer possible to present comprehensive tables of microbial dosendashresponseparameters
In the years since the first edition the authors have gained experience inteaching this material to generations of studentsmdashin the form of formal classestutorials independent studies and short courses We know this book can be valuablein instructing advanced students in environmental sciences environmental engineer-ing public health and microbiology It is also a useful reference for practitionersand regulatory personnel Some prior statistical background would be useful inapproaching the material but not necessary the key requirement for any risk assessoris the absence of fear from mathematical constructs and concepts
The three of us have been on a QMRA journey for almost 30 years We havelearned that doing high-quality risk assessments is of necessity a team sport requiringindividuals with different skills and interests We have learned a tremendous amountfrom each other from our students from our collaborators and from the problems thatwe have sought to approach Practitioners of the art of quantitative microbial riskassessment should be advised to cast a wide net with respect to colleagues andcollaborators to perfect their craft
xi
We encourage comments and feedback from users of this work and look for-ward to observing and participating in developments in coming years and ultimatelyto handing the baton off to our students and their students
Charles N Haas
Joan B Rose
Charles P GerbaNovember 2013
xii PREFACE
CHAPTER1MOTIVATION
THE PREVENTION of infectious disease transmission from human exposure tocontaminated food water soil and air remains a major task of environmental andpublic health professionals There are numerous microbial hazards including expo-sure via food water air and malicious release of pathogens that may arise Indeedsome have argued that the property of virulence of human pathogens is one which isfavored by evolutionary interactions between pathogens and host populations andtherefore will always be of important concern [1] To make rational decisions in pre-paring responding and recovering from exposures to such hazards a quantitativeframework is of high benefit
The objective of this book is to comprehensively set forth the methods forassessment of risk from infectious agents transmitted via these routes in a frameworkthat is compatible with the framework for other risk assessments (eg for chemicalagents) as set forth in standard protocols [2 3]
In this chapter information on the occurrence of infectious disease in broadcategories will be presented along with a historical background on prior methodsfor assessment of microbial safety of food water and air This will be followed byan overview of key issues covered in this book
PREVALENCE OF INFECTIOUS DISEASE
Outbreaks of infectious waterborne illness continue to occur although it remainsimpossible to identify the infectious agent in all cases For example in 1991 a water-borne outbreak in Ireland resulting from sewage contamination of water suppliesinfected about 5000 persons However the infectious agent responsible for thisoutbreak could not be determined [4] In the United States it has been estimated that38 million cases of foodborne infectious disease occur annually with unidentifiedagents [5]
In the United States there have typically been three to five reported outbreaksper year in community drinking water systems involving infectious microorganismswith perhaps up to 10000 annual cases [6] The 1994 Milwaukee Cryptosporidiumoutbreak with over 400000 cases [7 8] was a highly unusual event among thesestatistics As shown in Figure 11 there has been an increasing ability to identify
Quantitative Microbial Risk Assessment Second Edition Charles N Haas Joan B Roseand Charles P Gerbacopy 2014 John Wiley amp Sons Inc Published 2014 by John Wiley amp Sons Inc
1
microorganisms responsible for waterborne diseases and it is expected that withadvances in molecular biology this will increase
There are substantially more outbreaks and cases of foodborne infectiousdiseases than are reported Table 11 summarizes reports of US cases of principalmicrobial infectious foodborne illnesses for two 5-year periods (1988ndash1992 and
1971ndash1982
10
20
30
40
Perc
ent o
f out
brea
ks
50
60
1983ndash1994Period
1995ndash2006
Figure 11 Percentages of outbreaks associated with public water systems (n = 680) by timeperiod 1971ndash2006 that had unknown etiologies based on data from Ref [6]
TABLE 11 Comparison of Five-Year Averages for Common Foodborne Reported Outbreaks
Agent
Annual Average 1988ndash1992 Annual Average 2002ndash2006
Cases Outbreaks Cases Outbreaks
Campylobacter 996 44 624 22
Escherichia coli 488 22 481a 30a
Salmonella 42354 1098 3475 144
Shigella 9576 5 495 12
Staphylococcus aureus 3356 94 554 25
Hepatitis 4218 86 238 1
Listeria monocytogenes 04 02 22 2
Giardia 368 14 2 1
Norovirus 584 04 10854 338
Vibrio (all) 114 18 114 5
Unknown etiologies 40483 1422 4052 30
Source From Refs [9 10]a Include both Shiga toxigenic and enterotoxigenic
2 CHAPTER 1 MOTIVATION
2002ndash2006) There is a mix of causal agents including bacteria virus and protozoaIt is noteworthy that (as in the case of waterborne outbreaks) the frequency ofoutbreaks of unknown etiology has dramatically decreased but the frequency of out-breaks associated with norovirus has dramatically increased These changes are duein part to the ability to better identify causal agents (eg via molecular methods)
It is generally recognized that reported outbreaks either of water- or foodborneinfectious disease represent only a small fractionof the total populationdisease burdenHowever particularly in the United States voluntary reporting systems and theoccurrence of mild cases (for which no medical attention is sought but neverthelessare frank cases of disease) have made it difficult to estimate the total caseload
In the United Kingdom comparisons between the number of confirmed casesin infectious disease outbreaks and total confirmed laboratory illnesses (occurring inEngland and Wales) have been made (Table 12) This suggests that the ratio ofreported outbreak cases to total cases that may seek medical attention may be from10 to 5001 with some dependency on the particular agent
Colford et al [12] developed estimates for the total disease burden associatedwith acute gastroenteritis from drinking water This relies on combining the reportedoutbreak data with interventional epidemiologic studies Based on their analysis thetotal US disease burden is estimated to be 426ndash1169 million cases per year in theUnited States which is substantially in excess of the reported outbreaks In the case offoodborne illness there are an estimated 14 million cases per year [13]
Drinking water and food are by no means the only potential routes of exposureto infectious agents in the environment Recreation in water (either natural or artificialpools) containing pathogens can produce illness [14]
Indoor air transmission can be a vehicle of infection Legionella transmittedthrough indoor environments has been a concern since the 1970s [15] The multina-tional epidemic of severe acute respiratory syndrome (SARS) caused by a coronavi-rus was abetted at least in one location in Hong Kong by indoor aerosol transmissionbetween apartments of infected individuals and susceptible individuals [16] A broadspectrum of other respiratory pathogens including influenza rhinoviruses and myco-bacteria can be transmitted by this route [17]
TABLE 12 Comparison of Laboratory Isolations and Outbreak Cases in Englandand Wales 1992ndash1994
Agent
Cases 1992ndash1994
RatioAll Laboratory Reports Confirmed Outbreak Cases
Campylobacter 122250 240 5094
Rotavirus 47463 127 3737
S sonnei 29080 847 343
Salmonella 92416 5960 155
Cryptosporidium 14454 1066 136
E coli O157 1266 128 99
Source Modified from Ref [11]
PREVALENCE OF INFECTIOUS DISEASE 3
The deliberate release of Bacillus anthracis spores in 2001 (the ldquoAmerithraxrdquoincidents) brought widespread awareness to the potential for indoor releases (as wellas releases in other venues) of bioterrorist agents to cause risk [18] Therefore ofnecessity microbial risk assessors may need to consider the impact of maliciousactivity in certain applications
PRIOR APPROACHES
Concerns for microbial quality of food water and other environmental media havelong existed In the early twentieth century the use of indicator microorganismswas developed for the control and assessment of the hygienic quality of such mediaand the adequacy of disinfection and sterilization processes The coliform group oforganisms was perhaps first employed for this purpose [19ndash21] Indicator techniqueshave also found utility in the food industry such as the total count for milk and othermore recent proposals [22] Other indicator groups for food water or environmentalmedia have been examined such as enterococci [23ndash25] acid-fast bacteria [26]bacteriophage [27ndash29] and Clostridia spores [29ndash31]
The use of indicator organisms was historically justified in because of difficultyin enumerating pathogens However with the increasing availability of modernmicrobial methods for example PCR immunoassay etc for direct pathogen assess-ment this justification has become less persuasive In addition in order to develophealth-based standards from indicators extensive epidemiologic surveillance is oftennecessary The use of epidemiology has limitations with respect to detection limits(for an adverse effect) and is also quite expensive to conduct Indicator methodsare also limited in that many pathogens are more resistant to die off in receiving envir-onments or source waters than indicators or have greater resistance to removal bytreatment processes than indicators [26 28 29 32] Thus the absence of indicatorsmay not suffice to ensure the absence of pathogens Even after a century of use theindicator concept remains imperfect [33]
The use of quantitative microbial risk assessment (QMRA) will enable directmeasurements of pathogens to be used to develop acceptancerejection guidelinesfor food water and other vehicles that may be the source of microbial exposureto human populations The objective of this book is to present these methods in asystematic and unified manner
SCOPE OF COVERAGE
QMRA is the application of principles of risk assessment to the estimate ofconsequences from a planned or actual exposure to infectious microorganismsIn performing a QMRA the risk assessor aims to bring the best available informationto bear in understanding the nature of the potential effects from a microbial exposureSince the information (such as dosendashresponse relationships exposure magnitudes) isalmost invariably incomplete it is also necessary to ascertain the potential error
4 CHAPTER 1 MOTIVATION
involved in the risk assessment With such information necessary steps to mitigatecontrol or defend against such exposures may be developed
At the outset of performing a risk assessment a scoping task should be under-taken This task should set forth the objectives of the analysis and the principal issuesto be addressed Items such as consideration of secondary cases individual versuspopulation risk agent or agents to be examined exposure routes andor accident sce-narios must be stipulated However this scoping may be changed during the course ofa QMRA to reflect the input derived from the risk manager(s) and other stakeholders
POTENTIAL OBJECTIVES OF A QMRA
There may be diverse objectives for a QMRA These objectives relate to the rationalefor the performance of the assessment as well as the methods to be employedBroadly the different objectives reflect different scales at which a risk assessmentmay be performed The step of problem formulation is critical to any risk estimate[34] It is necessary that the problem be formulated to meet the needs of the riskmanagers and stakeholders indeed it is now recognized that the successful practiceof risk analysis requires frequent interchange with manager and stakeholders [3]In general the problems posed are of several types
Site-Specific Assessment
The simplest type of QMRA that may be performed involves one site or exposurescenario The following are typical of the questions that might be asked
1 If a water treatment plant is designed in a certain way (with given removals ofpathogens) then what is the risk that would be placed upon the populationserved
2 A swimming outbreak (in a recreational lake) has just occurred I believe that itresulted from a short-duration contamination event What pathogen levelswould be consistent with the observed attack rate
3 Microbial sampling of a finished food product has found certain pathogensWhat level of risk does this pose to consumers of the product
4 A certain amount of infectious agent has been released into a room What is theimmediate danger to occupants and how stringent should cleanup levels be
Note that there are certain other contrasts in the objectives of the risk assessments tobe posed In (1) and (3) a before-the-fact computation is desired while in (2) and (4)an after-the-fact computation is described Also in (1) (3) and (4) pathogen levelsare available (or somehow are estimated) while in (2) an inverse computation isneeded given an observed attack rate
In performing this risk assessment the relationship between an exposure ortechnological metric and a risk measurement must be ascertained and then theparticular point of correspondence determined (Fig 12) In cases (1) (3) and (4)for a known (or assumed) exposure (on the x-axis) the corresponding range of risks
POTENTIAL OBJECTIVES OF A QMRA 5
on the y-axis is sought In cases (2) for known or assumed risks (on the y-axis)the corresponding range of exposures (or level of technological protection) is to bedetermined (on the x-axis)
Ensemble of Sites
A somewhat more complex situation occurs if the risk for a set of events or sites mustbe estimated Basically this now includes the necessity to incorporate site-to-sitefactors into the assessment Some examples of this are as follows
1 If I desire keeping the risk to a population served by multiple water treatmentplants at a given level (or better) then what criteria should I use (microbiallevels)
2 For a food product subject to contamination by pathogens what would be anacceptable treatment specification (eg heating time holding period) to ensuremicrobial acceptability
3 I am designing a water quality standard for recreational bathing waters If auniform (eg national) standard is to be developed what standard would ensurethat average risk was acceptable with keeping the risk of a large ldquoclusterrdquo ofillnesses low
In addition to incorporating a measure of ensemble average risk in general it is alsodesired to ensure that no single member of the ensemble be unacceptably extreme Forexample consider the evaluation of three options of disease control among three com-munities as indicated in Table 13
This table indicates the number of cases and the rate among the three commu-nities The three policy options yield the same number of expected cases Howeverthere are differences in the allocation of risk among the communities of different sizesIn option A all communities have an identical level of estimated risk In option B therisk increases as community size decreases while in option C the risk increases ascommunity size increases This distribution of risk among affected subsets of the
Exposure
Ris
k
Level of technological protection
Figure 12 Relationship between exposurelevel of technological protection andmicrobial risk The middle curve indicatesthe best estimate The other two curvesindicate the upper and lower confidenceregions
6 CHAPTER 1 MOTIVATION
ensemble being considered adds an additional dimension for consideration by a riskmanagermdashwhich may be termed risk equity
SECONDARY TRANSMISSION
Infectious microbial diseases are different in terms of risk to a population than arechemical agents in that an individual who may become infected (with or withoutillness) can then proceed to infect additional individuals These secondary (tertiaryquaternary etc) cases may be persons who had no direct contact with the initialvehicle of exposure but nevertheless in fairly accounting for the public health impactthey should be considered
Secondary cases may arise by a variety of mechanisms Particularly amongclose family members household secondary cases can arise by direct or indirect(eg surface contamination) contact this is particularly so when the primary caseor one household secondary case is a child [35ndash37] Table 14 summarizes secondarycase statistics obtained from a variety of outbreaks As will be discussed inChapter 10 the secondary case rate is a complex factor involving (among other things)the nature of the venue and contact patterns when infected and susceptible individualsintermingle
Presumably secondary cases may also arise from close contact with anasymptomatic individual (in the ldquocarrierrdquo state) This is well known for highly acuteand (now) uncommon illnesses (such as typhoid) Excretion of Norwalk virusfollowing recovery (and resulting in additional cases) has been documented to occurfor as long as 48 h post recovery [44]
OUTBREAKS VERSUS ENDEMIC CASES
As noted previously there may be a substantial difference between reported outbreakcases and total disease burden in a community In order for a disease case to receiverecognition by the public health authorities the following specific and sequential stepsmust occur [47]
TABLE 13 Effect of Different Hypothetical Policy Options on Distribution of Risk AmongCommunities (for a Fixed Total Risk)
CommunityExposedPopulation
Policy Option A Policy Option B Policy Option C
CasesIncidence(10000) Cases
Incidence(10000) Cases
Incidence(10000)
A 100000 20 2 6 06 24 24
B 50000 10 2 18 36 7 14
C 10000 2 2 8 8 1 1
Total 160000 32 2 32 2 16 2
OUTBREAKS VERSUS ENDEMIC CASES 7
1 An ill person must seek medical care
2 Appropriate clinical tests (eg blood stool) must be ordered by the attendingphysician
3 The patient must comply with obtaining the sample
4 The laboratory must be capable of detecting the relevant pathogens
5 The clinical test must be positive
6 The test result must be reported to the health agency in a timely manner
If any of the links in this sequential chain are broken then a disease case will not enterthe records maintained by health authorities For example with increasing controls on
TABLE 14 Summary of Secondary Case Data in Outbreak Situations
Organism
SecondaryAttackRatioa
SecondaryPrevalence inHouseholdsb Remarks Reference
Cryptosporidiumparvum
033 033 Outbreak in contaminatedapple cider
[38]
C parvum NA 0042 Drinking water outbreak(Milwaukee)
[37]
Shigella 028 026 Day-care center outbreaksin children
[39]
Rotavirus 042 015 Day-care center outbreaksin children
[30]
Giardia lamblia 133 017 Day-care center outbreaksin children
[39]
Viral gastroenteritis 022 011c Drinking waterborneoutbreak
[40]
Viral gastroenteritis 056 NA Drinking water outbreak(Denmark)
[41]
Norovirus 05ndash10 019 Swimming outbreak [42]
Norovirus 11 029 Swimming outbreakin children
[43]
Norovirus NA 044 Foodborne outbreakin children and teachers
[36]
Norovirus 04 NA Foodborne outbreak [44]
E coli O157H7 NA 018c Day-care center outbreakin children
[45]
Unidentifiedday-care diarrhealdiseases
138 009c [46]
NA information not availableaRatio of secondary cases to primary casesb Proportion of households with one or more primary cases who have one or more secondary casesc Proportion of persons in contact with one or more primary cases who have a secondary case
8 CHAPTER 1 MOTIVATION
medical care stool samples may not be obtained from mild cases of illness Someorganisms may only be present sporadically or may be difficult to test in stool orblood sample Patients may not seek medical attention for mild cases of illness Fur-thermore in the United States in particular the surveillance of environmentallyinduced disease is done on a passive basis and hence the number of actual illnessclusters that are actually compiled into recorded statistics is only a small fractionof such clusters of illness that occur [47]
From a more fundamental point of view an outbreak of illness is generallydefined as occurrence of the illness at a level greater than normal or anticipated Thisdefinition recognizes that there is a level of illness (endemic) that may exist underusual circumstances The detection of such outbreaks poses a particular challengeThe problem is illustrated conceptually in Figure 13
Additional complications arise from the different patterns of illness in acommunity including definite periodicities as well as temporal trends and fromthe presence of reporting lags associated with laboratory analysis and time for patientsto seek medical attention Figure 14 illustrates the different patterns of illness inthe case of six pathogens for England and Wales [48]
In the case of waterborne and foodborne illnesses it is highly likely that thelevel of such endemic illnesses is substantially greater than those occurring duringoutbreaks (even accounting for unrecognized outbreaks)
As a result there are often many cases of environmentally caused (water airfood) infectious disease that are unrecognized One example of this isCampylobacterThere has been an average of about 200 cases per year of water- and foodborne illnessin outbreaks of this organism and yet estimates of the disease burden suggest about2100000 cases per year that is approximately 10000 cases per case of detectableoutbreak illness Therefore it will be important to assess the factors that may influenceoutbreak detection These issues will be discussed in subsequent chapters
Detectedoutbreak
Undetectedoutbreak
Threshold of detection
Hyper endemicSporadic
Endemic rate
Time
Num
ber
of c
ases
Figure 13 Schematic of disease occurrence in a hypothetical community (Modified fromRef [47])
OUTBREAKS VERSUS ENDEMIC CASES 9
REFERENCES
1 Levin B R 1996 The Evolution and Maintenance of Virulence in Microparasites Emerging InfectiousDisease 293ndash102
2 National Academy of Sciences 1983 Risk Assessment in the Federal Government Managing theProcess National Academy Press Washington DC
3 National Research Council 2009 Science and Decisions Advancing Risk Assessment NationalAcademies Press Washington DC
10090807060504030201001190 1191 1192 1193 1194 1195
(b)
140
120
100
80
60
40
20
01190 1191 1192 1193 1194 1195
(f)
700
600
500
400
300
200
100
01190 1191 1192 1193 1194 1195
(d)
1200
1000
800
600
400
200
1190 1191 1192 1193 1194 1195
(a)
240
200
160
120
80
40
01190 1191 1192 1193 1194 1195
(e)
7
6
5
4
3
2
1
01190 1191 1192 1193 1194 1195
(c)
Figure 14 Weekly count of reported organism isolations in England andWales (a) rotavirus(b) Clostridium difficile (c) Salmonella derby (d) Shigella sonnei (e) influenza B and (f)Salmonella typhimurium DT 104 (From Ref [48])
10 CHAPTER 1 MOTIVATION
4 Fogarty J L Thornton and R Corcoran 1995 Illness in a Community Associated with an Episode ofWater Contamination with Sewage Epidemiology and Infection 114289ndash295
5 Scallan E 2011 Foodborne Illness Acquired in the United StatesmdashUnspecified Agents EmergingInfectious Diseases 17 16ndash22
6 Craun G F J M Brunkard J S Yoder V A Roberts J Carpenter T Wade R L CalderonJ M Roberts M J Beach and S L Roy 2010 Causes of Outbreaks Associated with Drinking Waterin the United States from 1971 to 2006 Clinical Microbiology Reviews 23507ndash528
7 Edwards D D 1993 Troubled Waters in Milwaukee ASM News 59342ndash3458 MacKenzie W R N J Hoxie M E Proctor M S Gradus K A Blair D E Peterson
J J Kazmierczak K R Fox D G Addias J B Rose and J P Davis 1994 Massive WaterborneOutbreak of Cryptosporidium Infection Associated with a Filtered Public Water Supply MilwaukeeWisconsin March and April 1993 New England Journal of Medicine 331161ndash167
9 Anonymous 2010 Surveillance for Foodborne Disease OutbreaksmdashUnited States 2007 Morbidityand Mortality Weekly Reports 59973ndash979
10 Bean N H J S Goulding C Lau and F J Angulo 1996 Surveillance for Foodborne-DiseaseOutbreaksmdashUnited States 1988ndash1992 Morbidity and Mortality Weekly Reports 451ndash66
11 Wall P G J de Louvois R J Gilbert and B Rowe 1996 Food Poisoning NotificationsLaboratory Reports and OutbreaksmdashWhere do the Statistics Come From and What Do They MeanCommunicable Disease Report Review 6 R93ndashR100
12 Colford J M S Roy M J Beach A Hightower S E Shaw and T J Wade 2006 A Review ofHousehold Drinking Water Intervention Trials and an Approach to the Estimation of EndemicWaterborne Gastroenteritis in the United States Journal of Water and Health 471
13 Mead P S L Slutsker V Dietz L F McCaig J S Bresee C Shapiro P M Griffinand R V Tauxe 1999 Food Related Illness and Death in the United States Emerging InfectiousDisease 5607ndash625
14 Dziuban E J J L Liang G F Craun V Hill P A Yu J Painter M R Moore R L CalderonS L Roy and M J Beach 2006 Surveillance for Waterborne Disease and Outbreaks Associatedwith Recreational WatermdashUnited States 2003ndash2004 and Surveillance for Waterborne Disease andOutbreaks Associated with Drinking Water and Water not Intended for DrinkingmdashUnited States2003ndash2004 Morbidity and Mortality Weekly Reports 551ndash30
15 Fliermans C B 1996 Ecology of Legionella From Data to Knowledge with a Little WisdomMicrobial Ecology 32203ndash228
16 Li Y S Duan I T Yu and T W Wong 2005 Multi-Zone Modeling of Probable SARS VirusTransmission by Airflow Between Flats in Block E Amoy Gardens Indoor Air 1596ndash111
17 Peccia J D K Milton T Reponen and J Hill 2008 A Role for Environmental Engineering andScience in Preventing Bioaerosol-Related Disease Environmental Science amp Technology424631ndash4637
18 Jernigan D B P L Raghunathan B P Bell R Brechner E A Bresnitz J C Butler M CetronM Cohen T Doyle and M Fischer 2002 Investigation of Bioterrorism-Related AnthraxUnited States 2001 Epidemiologic Findings Emerging Infectious Diseases 81019ndash1028
19 Greenwood M and G U Yule 1917 On the Statistical Interpretation of Some BacteriologicalMethods Employed in Water Analysis Journal of Hygiene 1636ndash56
20 Phelps E 1909 The Disinfection of Sewage and Sewage Filter Effluents USGS Water Supply Paper229 GPO Washington DC
21 Rudolfs W and H W Gehm 1935 Multiplication of Total Bacteria and B coli after SewageChlorination Sewage Works Journal 7991ndash996
22 Subcommittee onMicrobiological Criteria 1985 An Evaluation of the Role ofMicrobiological Criteriafor Foods and Food Ingredients National Academy Press Washington DC
23 Cabelli V J A P Dufour L J McCabe and M A Levin 1982 Swimming-AssociatedGastroenteritis and Water Quality American Journal of Epidemiology 115606ndash616
24 Dufour A P 1984 Health Effects Criteria for Fresh Recreational Waters USEPA Research TrianglePark NC
25 Fleisher J M F Jones and D Kay 1993 Water and Non-Water-Related Risk Factors forGastroenteritis among Bathers Exposed to Sewage-Contaminated Marine Waters InternationalJournal of Epidemiology 22698ndash708
REFERENCES 11
26 Engelbrecht R S C N Haas J A Shular D L Dunn D Roy A Lalchandani B F Severin andS Farooq 1979 Acid-Fast Bacteria and Yeasts as Indicators of Disinfection Efficiency EPA-6002-79-091 US Environmental Protection Agency Cincinnati OH
27 Grabow W O K 1983 Inactivation of Hepatitis A Virus and Indicator Organisms in Water by FreeChlorine Residuals Applied and Environmental Microbiology 46619
28 Helmer R D and G R Finch 1993 Use of MS2 Coliphage as a Surrogate for Enteric Viruses inSurface Waters Disinfected with Ozone Ozone Science and Engineering 15279ndash293
29 Payment P and E Franco 1993Clostridium Perfringens and Somatic Coliphages as Indicators of theEfficiency of Drinking Water Treatment for Viruses and Protozoan Cysts Applied and EnvironmentalMicrobiology 592418ndash2424
30 Cabelli V J 1977Clostridium Perfringens as aWater Quality Indicator pp 65ndash79 InA Hoadley andB Dutka (eds) Bacterial IndicatorsHealth Hazards Associated with Water ASTM Philadelphia PA
31 Rice E W K R Fox R J Miltner D A Lytle and C H Johnson 1996 Evaluating PlantPerformance with Endospores Journal of the American Water Works Association 88122ndash130
32 Engelbrecht R S B F Severin M T Masarik S Farooq S H Lee C N Haas and A Lalchandani1977 New Microbial Indicators of Disinfection Efficiency EPA-6002-77-052 US EnvironmentalProtection Agency Cincinnati OH
33 Committee on Indicators for Waterborne Pathogens ndash National Research Council 2004 Indicators forWaterborne Pathogens National Academies Press Washington DC
34 PresidentialCongressional Commission on Risk Assessment and RiskManagement 1997 Frameworkfor Environmental Health Risk Management The Commission Washington DC
35 Griffin P M and R V Tauxe 1991 The Epidemiology of Infections Caused by Escherichiacoli O157H7 Other Enterohemorrhagic E coli and the Associated Hemolytic Uremic SyndromeEpidemiologic Reviews 1360ndash98
36 Heun E M R L Vogt P J Hudson S Parren and G W Gary 1987 Risk Factors for SecondaryTransmission in Households after a Common Source Outbreak of Norwalk Gastroenteritis AmericanJournal of Epidemiology 1261181ndash1186
37 MacKenzie W R W L Schell B A Blair D G Addiss D E Peterson N J HozieJ J Kazmierczak and J P Davis 1995 Massive Outbreak of Waterborne CryptosporidiumInfection in Milwaukee Wisconsin Recurrence of Illness and Risk of Secondary TransmissionClinical Infectious Diseases 2157ndash62
38 Millard P K Gensheimer D G Addiss D M Sosin G A Beckett A Houck-Jankoski andA Hudson 1994 An Outbreak of Cryptosporidiosis from Fresh-Pressed Apple Cider Journal ofthe American Medical Association 2721592ndash1596
39 Pickering L K D G Evans H L DuPont J J Vollet and D J Evans Jr 1981 Diarrhea Caused byShigella Rotavirus and Giardia in Day Care Centers Prospective Study Journal of Pediatrics9951ndash56
40 Morens D M R M Zweighaft T M Vernon G W Gary J J Eslien B T Wood R C Holmanand R Dolin 1979 A Waterborne Outbreak of Gastroenteritis with Secondary Person to PersonSpread Lancet 5964ndash966
41 Laursen E O Mygind B Rasmussen and T Ronne 1994 Gastroenteritis A Waterborne OutbreakAffecting 1600 People in a Small Danish Town Journal of Epidemiology amp Community Health48453ndash458
42 Baron R C F D Murphy H B Greenberg C E Davis D J Bregman G W Gary J M Hughesand L B Schonberger 1982 Norwalk Gastrointestinal Illness An Outbreak Associated withSwimming in a Recreational Lake and Secondary Person to Person Transmission American Journalof Epidemiology 115163ndash172
43 Kappus K D J S Marks R C Holman J K Bryant C Baker G W Gary and H B Greenberg1982 An Outbreak of Norwalk Gastroenteritis Associated with Swimming in a Pool and SecondaryPerson to Person Transmission American Journal of Epidemiology 116834ndash839
44 White K E M T Osterbolm J A Mariotti J A Korlath D H Lawrence T L Ristinen andH B Greenberg 1986 A Foodborne Outbreak of Norwalk Virus Gastroenteritis American Journalof Epidemiology 124120ndash126
45 Spika J S J E Parsons and D Nordenberg 1986 Hemolytic Uremic Syndrome and DiarrheaAssociated with Escherichia coli O157H7 in a Day Care Center Journal of Pediatrics 109287ndash291
12 CHAPTER 1 MOTIVATION
46 Ferguson J K L R Jorm C D Allen P KWhitehead and G L Gilbert 1995 Prospective Study ofDiarrhoeal Outbreaks in Child Long Daycare Centres in Western Sydney Medical Journal of Australia163137ndash140
47 Frost F J G F Craun and R L Calderon 1996 Waterborne Disease Surveillance Journal of theAmerican Water Works Association 8866ndash75
48 Farrington C P N J Andrews A D Beale and M A Catchpole 1996 A Statistical Algorithmfor the Early Detection of Outbreaks of Infectious Disease Journal of the Royal StatisticalSociety A 159547ndash563
REFERENCES 13
CHAPTER2MICROBIAL AGENTS ANDTRANSMISSION
MICROBIAL TAXONOMY
The development of techniques for examining the nucleic acids of microorganisms hasseen major changes in which we classify and group related microorganisms This isespecially true for the study of ribosomal ribonucleic acid (rRNA) which is a highlyconserved sequence involved in the synthesis of proteins in all living organisms Basedon this analysis the classification of living things has been placed into a three-domainsystem consisting of Archaea Eukarya and Bacteria Of these the Bacteria andArchaea are termed prokaryotes (no organized cell nucleus) and the Eukarya areknown as eukaryotes (an organized cell nucleus) Eukaryotic microbes other thanalgae and fungi are collectively calledprotistsWithin theEukarya are fungi protozoahelminth worms algae plants animals and humans Archaea are microbes that looksomewhat similar to bacteria in size and shape under the light microscope but they areactually genetically and biochemically quite different They appear to be a simpler formof life and may in fact be the oldest form of life on earth Viruses are obligate intercel-lular parasites and are not amember of any group They are usually composed only of anucleic acid surrounded by a protein coat Eukaryotes are much more complex thanprokaryotic cells in structure and nutritional requirements Prokaryotes divide by sim-ple binary fissionwhereas eukaryotes divide byamore complexprocess calledmitosis
Eukaryotes
Fungi protozoa and helminth worms are all eukaryotes All contain members that arepathogenic to man and animals While algae do not infect humans they can producetoxins that are harmful to animals and man Fungi obtain nutrients solely by adsorp-tion of organic matter from dead organisms Even when they invade living tissuesthey typically kill cells and then adsorb the nutrients from them Some fungi are capa-ble of developing environmentally resistant spores which can be transported throughthe air Fungal diseases in humans are referred to asmycoses Airborne fungal sporesare responsible for some allergies in humans Yeasts are classified with the fungi and
Quantitative Microbial Risk Assessment Second Edition Charles N Haas Joan B Roseand Charles P Gerbacopy 2014 John Wiley amp Sons Inc Published 2014 by John Wiley amp Sons Inc
15
some are pathogenic to humans (Candida albicans) Certain fungi produce toxins(ie aflatoxins) when growing in foods that are mutagenic and carcinogenic in ani-mals Inhalation is an important route of transmission for some fungal diseases suchas aspergillosis blastomycosis coccidioidomycosis and histoplasmosis These fungiare found growing in animal feces soil or decaying organic matter (compost manure)and may be transmitted through the air when this matter is disturbed Some fungi maybe transmitted by direct contact with the skin Fungi are often found in drinking waterdistribution systems and they have been linked to infections in immunocompromisedindividuals [1] Food is not believed to be a significant route of transmission ofpathogenic fungi
Protozoans are unicellular organisms that are surrounded by a cytoplasmicmembrane that is covered by a protective structure called a pellicle Most are freeliving feeding off of bacteria Some of these can cause disease while others are obli-gate parasites They are capable of forming structures called cysts oocysts or spores(depending on the life cycle of the organism) resistant to adverse environmentalconditions such as desiccation starvation high temperatures and disinfectantsSome pathogenic protozoa are found mainly in the soil (Naegleria) or water(Acanthamoeba) Others such a Giardia and Cryptosporidium whose natural habitatis the intestines of warm-blooded animals are capable of causing disease in bothhumans and animals Others such as Entamoeba histolytica are only capable ofcausing disease in humans
Pathogenic enteric (replicate in the intestines) protozoans are usually excretedin the feces or urine and can be transmitted by fecally contaminated food and waterSome protozoa may be transmitted through the air (Acanthamoeba) or throughfomites (inanimate objects) Some important environmentally transmitted protozoaare listed in Table 21 The clinically important protozoa are divided taxonomicallyinto the amoebas (Entamoeba spp) flagellates (Giardia) and coccidian meaningldquoglobose in shaperdquo (Cryptosporidium and Cyclospora) Microsporidia are alsocapable of causing intestinal infections but their classification is uncertain becausethey have many characteristics associated with fungi They are all obligate parasitesand are transmitted via infectious cysts oocysts or spores by the fecalndashoral routeThe life cycles of these protozoa are similar The initial stage occurs during ingestionof the cyst oocyst or spore After ingestion the body temperature and passagethrough the stomach cause these infective stages to open up in a process calledexcystation
The Giardia cysts house two trophozoites which is the stage that attaches tointestinal cells and grows in the intestinal tract through asexual reproduction As thetrophozoites grow and begin to cover the wall of the intestinal tract diarrhea canresult As the trophozoites are released some form cysts as they pass through thebowels Cryptosporidium and Cyclospora both produce oocysts The life cycle ofCyclospora is still not well known except that its oocysts require some period of timein the environment before they are infective Cryptosporidium oocysts contain foursporozoites which enter the intestinal cells and begin the infection process As morecells become infected the illness begins and oocysts are excreted in high numbers inthe feces (about 100000g)
Worms and helminths are small multicellular animals that are parasiticto humans and animals They include flukes tapeworms and roundworms
16 CHAPTER 2 MICROBIAL AGENTS AND TRANSMISSION
Metagenomics 147
PCR and Quantitative PCR 147
References 151
CHAPTER 6 EXPOSURE ASSESSMENT 159
Conducting the Exposure Assessment 159
Characterizing ConcentrationDuration Distributions 160
Random (Poisson) Distributions of Organisms 160
Estimation of Poisson Mean in Count Assay (Constant and Variable Volumes) 162
Count Assay with Upper Limits 163
Estimation with Quantal Assay 164
Goodness of Fit to Poisson Plate Assay 168
Goodness of Fit MPN 178
Confidence Limits Likelihood 182
Implications for Risk Assessment 187
Consumption Distributions 214
Systematic Subpopulation Differences 221
Afterword 223
Appendix 224
Microsoft Excel 224
MATLAB 225
R 227
References 230
CHAPTER 7 PREDICTIVE MICROBIOLOGY 235
Objective 235
Basic First-Order Processes and Deviations 236
Biological and Physical Bases for Deviations 236
Physical Removal 238
Types of Decay Processes 238
General Forms of Decay and Reasons for Nonlinearity 238
SpontaneousEndogenous 240
Chemical Agents 241
Thermally Induced 243
Ionizing and Nonionizing Radiation 243
Predation and Antagonism 245
Types of Growth Processes 245
Mathematical Modeling of Growth Curves 246
Substrate Dependency 252
Structured Growth Models 255
Incorporation of Decay into Growth Models 256
Systems Biology Approaches 258
CONTENTS vii
Dependence of Growth Parameters on Other Environmental Variables 258
Interacting Populations 258
Data Sources 260
References 263
CHAPTER 8 CONDUCTING THE DOSEndashRESPONSE ASSESSMENT 267
Plausible DosendashResponse Models 268
Framework for Mechanistic DosendashResponse Relationships 269
Exponential DosendashResponse Model 271
Beta-Poisson DosendashResponse Model 272
Simple Threshold Models 274
Negative Binomial Dose Distributions 277
Variable Threshold Models 278
Other Mixture Models 279
Biological Arguments for One-Hit Models 281
Empirical Models 282
Fitting Available Data 283
Types of Data Sets 284
Potential Impacts of Immune Status 298
Relationship between Dose and Severity (Morbidity and Mortality) 299
Morbidity Ratio (PDI) 299
Mortality Ratio 303
Reality Checking Validation 304
Validation 1993 Milwaukee Outbreak 304
Use of Indicators and Other Proxy Measures in DosendashResponse 305
Indicator Methods 305
Molecular Methods 307
Advanced Topics in DosendashResponse Modeling 308
DosendashResponsendashTime Models 308
Physiological Models 313
Appendix 315
References 317
CHAPTER 9 UNCERTAINTY 323
Point Estimates of Risk 324
Terminology Types of Uncertainty 326
Sources of Uncertainty 327
Sources of Variability 328
Variability that is Uncertain 329
Approaches to Quantify Parametric Uncertainty 329
Likelihood 329
Bootstrap 330
Other Methods 330
viii CONTENTS
Applications 332
Exposure Assessment 332
DosendashResponse Assessment 338
Combining Parametric Uncertainty from Multiple Sources 344
Propagation Methods 344
Monte Carlo Analyses 347
Overall Risk Characterization Example 365
Second-Order Methods 368
Model Uncertainty and Averaging 370
References 373
CHAPTER 10 POPULATION DISEASE TRANSMISSION 377
Introduction Models for Population and Community Illnesses 377
Basic SIR Model 378
Incubation Period 386
Duration of Illness 388
Secondary Cases 389
Impact of Immunity 392
Outbreak Detection 393
References 397
CHAPTER 11 RISK CHARACTERIZATION AND DECISION MAKING 399
Introduction 399
Valuing Residual Outcomes 400
Classical Economics 400
DALYs and QALYs 404
Decision Making 407
CostndashBenefit Analysis 408
Multivariate Approaches 411
Other Aspects Entering into a Decision 412
Equity and Justice Aspects 412
References 413
INDEX 415
CONTENTS ix
PREFACE
In the 14 years since we prepared the first edition there has been an explosion inknowledge of and need for quantitative microbial risk assessment (QMRA) Whileour motivation for the first edition stemmed from concerns (principally in water) aboutenteric bacteria viruses and protozoa the motivation has now exploded to newdomains and agents SARS influenza biothreat agents and zoonotic pathogens haveall become of greater concern
The 2001 anthrax letters have highlighted the need for risk assessment ofinhaled agents Both biothreat agents and emergence of new strains of virulentcontagious organisms have raised concern for modeling pathogen dynamics inpopulations
In this edition we have retained the fundamental approach of the riskassessment methodology as a central paradigm We have added new material onmodern pathogen analytical methods predictive microbiology (of pathogen growthand decay) dynamic risk models (explicitly considering incubation time) and diseasepropagation models in populations Of necessity we have removed some materialmdashitis no longer possible to present comprehensive tables of microbial dosendashresponseparameters
In the years since the first edition the authors have gained experience inteaching this material to generations of studentsmdashin the form of formal classestutorials independent studies and short courses We know this book can be valuablein instructing advanced students in environmental sciences environmental engineer-ing public health and microbiology It is also a useful reference for practitionersand regulatory personnel Some prior statistical background would be useful inapproaching the material but not necessary the key requirement for any risk assessoris the absence of fear from mathematical constructs and concepts
The three of us have been on a QMRA journey for almost 30 years We havelearned that doing high-quality risk assessments is of necessity a team sport requiringindividuals with different skills and interests We have learned a tremendous amountfrom each other from our students from our collaborators and from the problems thatwe have sought to approach Practitioners of the art of quantitative microbial riskassessment should be advised to cast a wide net with respect to colleagues andcollaborators to perfect their craft
xi
We encourage comments and feedback from users of this work and look for-ward to observing and participating in developments in coming years and ultimatelyto handing the baton off to our students and their students
Charles N Haas
Joan B Rose
Charles P GerbaNovember 2013
xii PREFACE
CHAPTER1MOTIVATION
THE PREVENTION of infectious disease transmission from human exposure tocontaminated food water soil and air remains a major task of environmental andpublic health professionals There are numerous microbial hazards including expo-sure via food water air and malicious release of pathogens that may arise Indeedsome have argued that the property of virulence of human pathogens is one which isfavored by evolutionary interactions between pathogens and host populations andtherefore will always be of important concern [1] To make rational decisions in pre-paring responding and recovering from exposures to such hazards a quantitativeframework is of high benefit
The objective of this book is to comprehensively set forth the methods forassessment of risk from infectious agents transmitted via these routes in a frameworkthat is compatible with the framework for other risk assessments (eg for chemicalagents) as set forth in standard protocols [2 3]
In this chapter information on the occurrence of infectious disease in broadcategories will be presented along with a historical background on prior methodsfor assessment of microbial safety of food water and air This will be followed byan overview of key issues covered in this book
PREVALENCE OF INFECTIOUS DISEASE
Outbreaks of infectious waterborne illness continue to occur although it remainsimpossible to identify the infectious agent in all cases For example in 1991 a water-borne outbreak in Ireland resulting from sewage contamination of water suppliesinfected about 5000 persons However the infectious agent responsible for thisoutbreak could not be determined [4] In the United States it has been estimated that38 million cases of foodborne infectious disease occur annually with unidentifiedagents [5]
In the United States there have typically been three to five reported outbreaksper year in community drinking water systems involving infectious microorganismswith perhaps up to 10000 annual cases [6] The 1994 Milwaukee Cryptosporidiumoutbreak with over 400000 cases [7 8] was a highly unusual event among thesestatistics As shown in Figure 11 there has been an increasing ability to identify
Quantitative Microbial Risk Assessment Second Edition Charles N Haas Joan B Roseand Charles P Gerbacopy 2014 John Wiley amp Sons Inc Published 2014 by John Wiley amp Sons Inc
1
microorganisms responsible for waterborne diseases and it is expected that withadvances in molecular biology this will increase
There are substantially more outbreaks and cases of foodborne infectiousdiseases than are reported Table 11 summarizes reports of US cases of principalmicrobial infectious foodborne illnesses for two 5-year periods (1988ndash1992 and
1971ndash1982
10
20
30
40
Perc
ent o
f out
brea
ks
50
60
1983ndash1994Period
1995ndash2006
Figure 11 Percentages of outbreaks associated with public water systems (n = 680) by timeperiod 1971ndash2006 that had unknown etiologies based on data from Ref [6]
TABLE 11 Comparison of Five-Year Averages for Common Foodborne Reported Outbreaks
Agent
Annual Average 1988ndash1992 Annual Average 2002ndash2006
Cases Outbreaks Cases Outbreaks
Campylobacter 996 44 624 22
Escherichia coli 488 22 481a 30a
Salmonella 42354 1098 3475 144
Shigella 9576 5 495 12
Staphylococcus aureus 3356 94 554 25
Hepatitis 4218 86 238 1
Listeria monocytogenes 04 02 22 2
Giardia 368 14 2 1
Norovirus 584 04 10854 338
Vibrio (all) 114 18 114 5
Unknown etiologies 40483 1422 4052 30
Source From Refs [9 10]a Include both Shiga toxigenic and enterotoxigenic
2 CHAPTER 1 MOTIVATION
2002ndash2006) There is a mix of causal agents including bacteria virus and protozoaIt is noteworthy that (as in the case of waterborne outbreaks) the frequency ofoutbreaks of unknown etiology has dramatically decreased but the frequency of out-breaks associated with norovirus has dramatically increased These changes are duein part to the ability to better identify causal agents (eg via molecular methods)
It is generally recognized that reported outbreaks either of water- or foodborneinfectious disease represent only a small fractionof the total populationdisease burdenHowever particularly in the United States voluntary reporting systems and theoccurrence of mild cases (for which no medical attention is sought but neverthelessare frank cases of disease) have made it difficult to estimate the total caseload
In the United Kingdom comparisons between the number of confirmed casesin infectious disease outbreaks and total confirmed laboratory illnesses (occurring inEngland and Wales) have been made (Table 12) This suggests that the ratio ofreported outbreak cases to total cases that may seek medical attention may be from10 to 5001 with some dependency on the particular agent
Colford et al [12] developed estimates for the total disease burden associatedwith acute gastroenteritis from drinking water This relies on combining the reportedoutbreak data with interventional epidemiologic studies Based on their analysis thetotal US disease burden is estimated to be 426ndash1169 million cases per year in theUnited States which is substantially in excess of the reported outbreaks In the case offoodborne illness there are an estimated 14 million cases per year [13]
Drinking water and food are by no means the only potential routes of exposureto infectious agents in the environment Recreation in water (either natural or artificialpools) containing pathogens can produce illness [14]
Indoor air transmission can be a vehicle of infection Legionella transmittedthrough indoor environments has been a concern since the 1970s [15] The multina-tional epidemic of severe acute respiratory syndrome (SARS) caused by a coronavi-rus was abetted at least in one location in Hong Kong by indoor aerosol transmissionbetween apartments of infected individuals and susceptible individuals [16] A broadspectrum of other respiratory pathogens including influenza rhinoviruses and myco-bacteria can be transmitted by this route [17]
TABLE 12 Comparison of Laboratory Isolations and Outbreak Cases in Englandand Wales 1992ndash1994
Agent
Cases 1992ndash1994
RatioAll Laboratory Reports Confirmed Outbreak Cases
Campylobacter 122250 240 5094
Rotavirus 47463 127 3737
S sonnei 29080 847 343
Salmonella 92416 5960 155
Cryptosporidium 14454 1066 136
E coli O157 1266 128 99
Source Modified from Ref [11]
PREVALENCE OF INFECTIOUS DISEASE 3
The deliberate release of Bacillus anthracis spores in 2001 (the ldquoAmerithraxrdquoincidents) brought widespread awareness to the potential for indoor releases (as wellas releases in other venues) of bioterrorist agents to cause risk [18] Therefore ofnecessity microbial risk assessors may need to consider the impact of maliciousactivity in certain applications
PRIOR APPROACHES
Concerns for microbial quality of food water and other environmental media havelong existed In the early twentieth century the use of indicator microorganismswas developed for the control and assessment of the hygienic quality of such mediaand the adequacy of disinfection and sterilization processes The coliform group oforganisms was perhaps first employed for this purpose [19ndash21] Indicator techniqueshave also found utility in the food industry such as the total count for milk and othermore recent proposals [22] Other indicator groups for food water or environmentalmedia have been examined such as enterococci [23ndash25] acid-fast bacteria [26]bacteriophage [27ndash29] and Clostridia spores [29ndash31]
The use of indicator organisms was historically justified in because of difficultyin enumerating pathogens However with the increasing availability of modernmicrobial methods for example PCR immunoassay etc for direct pathogen assess-ment this justification has become less persuasive In addition in order to develophealth-based standards from indicators extensive epidemiologic surveillance is oftennecessary The use of epidemiology has limitations with respect to detection limits(for an adverse effect) and is also quite expensive to conduct Indicator methodsare also limited in that many pathogens are more resistant to die off in receiving envir-onments or source waters than indicators or have greater resistance to removal bytreatment processes than indicators [26 28 29 32] Thus the absence of indicatorsmay not suffice to ensure the absence of pathogens Even after a century of use theindicator concept remains imperfect [33]
The use of quantitative microbial risk assessment (QMRA) will enable directmeasurements of pathogens to be used to develop acceptancerejection guidelinesfor food water and other vehicles that may be the source of microbial exposureto human populations The objective of this book is to present these methods in asystematic and unified manner
SCOPE OF COVERAGE
QMRA is the application of principles of risk assessment to the estimate ofconsequences from a planned or actual exposure to infectious microorganismsIn performing a QMRA the risk assessor aims to bring the best available informationto bear in understanding the nature of the potential effects from a microbial exposureSince the information (such as dosendashresponse relationships exposure magnitudes) isalmost invariably incomplete it is also necessary to ascertain the potential error
4 CHAPTER 1 MOTIVATION
involved in the risk assessment With such information necessary steps to mitigatecontrol or defend against such exposures may be developed
At the outset of performing a risk assessment a scoping task should be under-taken This task should set forth the objectives of the analysis and the principal issuesto be addressed Items such as consideration of secondary cases individual versuspopulation risk agent or agents to be examined exposure routes andor accident sce-narios must be stipulated However this scoping may be changed during the course ofa QMRA to reflect the input derived from the risk manager(s) and other stakeholders
POTENTIAL OBJECTIVES OF A QMRA
There may be diverse objectives for a QMRA These objectives relate to the rationalefor the performance of the assessment as well as the methods to be employedBroadly the different objectives reflect different scales at which a risk assessmentmay be performed The step of problem formulation is critical to any risk estimate[34] It is necessary that the problem be formulated to meet the needs of the riskmanagers and stakeholders indeed it is now recognized that the successful practiceof risk analysis requires frequent interchange with manager and stakeholders [3]In general the problems posed are of several types
Site-Specific Assessment
The simplest type of QMRA that may be performed involves one site or exposurescenario The following are typical of the questions that might be asked
1 If a water treatment plant is designed in a certain way (with given removals ofpathogens) then what is the risk that would be placed upon the populationserved
2 A swimming outbreak (in a recreational lake) has just occurred I believe that itresulted from a short-duration contamination event What pathogen levelswould be consistent with the observed attack rate
3 Microbial sampling of a finished food product has found certain pathogensWhat level of risk does this pose to consumers of the product
4 A certain amount of infectious agent has been released into a room What is theimmediate danger to occupants and how stringent should cleanup levels be
Note that there are certain other contrasts in the objectives of the risk assessments tobe posed In (1) and (3) a before-the-fact computation is desired while in (2) and (4)an after-the-fact computation is described Also in (1) (3) and (4) pathogen levelsare available (or somehow are estimated) while in (2) an inverse computation isneeded given an observed attack rate
In performing this risk assessment the relationship between an exposure ortechnological metric and a risk measurement must be ascertained and then theparticular point of correspondence determined (Fig 12) In cases (1) (3) and (4)for a known (or assumed) exposure (on the x-axis) the corresponding range of risks
POTENTIAL OBJECTIVES OF A QMRA 5
on the y-axis is sought In cases (2) for known or assumed risks (on the y-axis)the corresponding range of exposures (or level of technological protection) is to bedetermined (on the x-axis)
Ensemble of Sites
A somewhat more complex situation occurs if the risk for a set of events or sites mustbe estimated Basically this now includes the necessity to incorporate site-to-sitefactors into the assessment Some examples of this are as follows
1 If I desire keeping the risk to a population served by multiple water treatmentplants at a given level (or better) then what criteria should I use (microbiallevels)
2 For a food product subject to contamination by pathogens what would be anacceptable treatment specification (eg heating time holding period) to ensuremicrobial acceptability
3 I am designing a water quality standard for recreational bathing waters If auniform (eg national) standard is to be developed what standard would ensurethat average risk was acceptable with keeping the risk of a large ldquoclusterrdquo ofillnesses low
In addition to incorporating a measure of ensemble average risk in general it is alsodesired to ensure that no single member of the ensemble be unacceptably extreme Forexample consider the evaluation of three options of disease control among three com-munities as indicated in Table 13
This table indicates the number of cases and the rate among the three commu-nities The three policy options yield the same number of expected cases Howeverthere are differences in the allocation of risk among the communities of different sizesIn option A all communities have an identical level of estimated risk In option B therisk increases as community size decreases while in option C the risk increases ascommunity size increases This distribution of risk among affected subsets of the
Exposure
Ris
k
Level of technological protection
Figure 12 Relationship between exposurelevel of technological protection andmicrobial risk The middle curve indicatesthe best estimate The other two curvesindicate the upper and lower confidenceregions
6 CHAPTER 1 MOTIVATION
ensemble being considered adds an additional dimension for consideration by a riskmanagermdashwhich may be termed risk equity
SECONDARY TRANSMISSION
Infectious microbial diseases are different in terms of risk to a population than arechemical agents in that an individual who may become infected (with or withoutillness) can then proceed to infect additional individuals These secondary (tertiaryquaternary etc) cases may be persons who had no direct contact with the initialvehicle of exposure but nevertheless in fairly accounting for the public health impactthey should be considered
Secondary cases may arise by a variety of mechanisms Particularly amongclose family members household secondary cases can arise by direct or indirect(eg surface contamination) contact this is particularly so when the primary caseor one household secondary case is a child [35ndash37] Table 14 summarizes secondarycase statistics obtained from a variety of outbreaks As will be discussed inChapter 10 the secondary case rate is a complex factor involving (among other things)the nature of the venue and contact patterns when infected and susceptible individualsintermingle
Presumably secondary cases may also arise from close contact with anasymptomatic individual (in the ldquocarrierrdquo state) This is well known for highly acuteand (now) uncommon illnesses (such as typhoid) Excretion of Norwalk virusfollowing recovery (and resulting in additional cases) has been documented to occurfor as long as 48 h post recovery [44]
OUTBREAKS VERSUS ENDEMIC CASES
As noted previously there may be a substantial difference between reported outbreakcases and total disease burden in a community In order for a disease case to receiverecognition by the public health authorities the following specific and sequential stepsmust occur [47]
TABLE 13 Effect of Different Hypothetical Policy Options on Distribution of Risk AmongCommunities (for a Fixed Total Risk)
CommunityExposedPopulation
Policy Option A Policy Option B Policy Option C
CasesIncidence(10000) Cases
Incidence(10000) Cases
Incidence(10000)
A 100000 20 2 6 06 24 24
B 50000 10 2 18 36 7 14
C 10000 2 2 8 8 1 1
Total 160000 32 2 32 2 16 2
OUTBREAKS VERSUS ENDEMIC CASES 7
1 An ill person must seek medical care
2 Appropriate clinical tests (eg blood stool) must be ordered by the attendingphysician
3 The patient must comply with obtaining the sample
4 The laboratory must be capable of detecting the relevant pathogens
5 The clinical test must be positive
6 The test result must be reported to the health agency in a timely manner
If any of the links in this sequential chain are broken then a disease case will not enterthe records maintained by health authorities For example with increasing controls on
TABLE 14 Summary of Secondary Case Data in Outbreak Situations
Organism
SecondaryAttackRatioa
SecondaryPrevalence inHouseholdsb Remarks Reference
Cryptosporidiumparvum
033 033 Outbreak in contaminatedapple cider
[38]
C parvum NA 0042 Drinking water outbreak(Milwaukee)
[37]
Shigella 028 026 Day-care center outbreaksin children
[39]
Rotavirus 042 015 Day-care center outbreaksin children
[30]
Giardia lamblia 133 017 Day-care center outbreaksin children
[39]
Viral gastroenteritis 022 011c Drinking waterborneoutbreak
[40]
Viral gastroenteritis 056 NA Drinking water outbreak(Denmark)
[41]
Norovirus 05ndash10 019 Swimming outbreak [42]
Norovirus 11 029 Swimming outbreakin children
[43]
Norovirus NA 044 Foodborne outbreakin children and teachers
[36]
Norovirus 04 NA Foodborne outbreak [44]
E coli O157H7 NA 018c Day-care center outbreakin children
[45]
Unidentifiedday-care diarrhealdiseases
138 009c [46]
NA information not availableaRatio of secondary cases to primary casesb Proportion of households with one or more primary cases who have one or more secondary casesc Proportion of persons in contact with one or more primary cases who have a secondary case
8 CHAPTER 1 MOTIVATION
medical care stool samples may not be obtained from mild cases of illness Someorganisms may only be present sporadically or may be difficult to test in stool orblood sample Patients may not seek medical attention for mild cases of illness Fur-thermore in the United States in particular the surveillance of environmentallyinduced disease is done on a passive basis and hence the number of actual illnessclusters that are actually compiled into recorded statistics is only a small fractionof such clusters of illness that occur [47]
From a more fundamental point of view an outbreak of illness is generallydefined as occurrence of the illness at a level greater than normal or anticipated Thisdefinition recognizes that there is a level of illness (endemic) that may exist underusual circumstances The detection of such outbreaks poses a particular challengeThe problem is illustrated conceptually in Figure 13
Additional complications arise from the different patterns of illness in acommunity including definite periodicities as well as temporal trends and fromthe presence of reporting lags associated with laboratory analysis and time for patientsto seek medical attention Figure 14 illustrates the different patterns of illness inthe case of six pathogens for England and Wales [48]
In the case of waterborne and foodborne illnesses it is highly likely that thelevel of such endemic illnesses is substantially greater than those occurring duringoutbreaks (even accounting for unrecognized outbreaks)
As a result there are often many cases of environmentally caused (water airfood) infectious disease that are unrecognized One example of this isCampylobacterThere has been an average of about 200 cases per year of water- and foodborne illnessin outbreaks of this organism and yet estimates of the disease burden suggest about2100000 cases per year that is approximately 10000 cases per case of detectableoutbreak illness Therefore it will be important to assess the factors that may influenceoutbreak detection These issues will be discussed in subsequent chapters
Detectedoutbreak
Undetectedoutbreak
Threshold of detection
Hyper endemicSporadic
Endemic rate
Time
Num
ber
of c
ases
Figure 13 Schematic of disease occurrence in a hypothetical community (Modified fromRef [47])
OUTBREAKS VERSUS ENDEMIC CASES 9
REFERENCES
1 Levin B R 1996 The Evolution and Maintenance of Virulence in Microparasites Emerging InfectiousDisease 293ndash102
2 National Academy of Sciences 1983 Risk Assessment in the Federal Government Managing theProcess National Academy Press Washington DC
3 National Research Council 2009 Science and Decisions Advancing Risk Assessment NationalAcademies Press Washington DC
10090807060504030201001190 1191 1192 1193 1194 1195
(b)
140
120
100
80
60
40
20
01190 1191 1192 1193 1194 1195
(f)
700
600
500
400
300
200
100
01190 1191 1192 1193 1194 1195
(d)
1200
1000
800
600
400
200
1190 1191 1192 1193 1194 1195
(a)
240
200
160
120
80
40
01190 1191 1192 1193 1194 1195
(e)
7
6
5
4
3
2
1
01190 1191 1192 1193 1194 1195
(c)
Figure 14 Weekly count of reported organism isolations in England andWales (a) rotavirus(b) Clostridium difficile (c) Salmonella derby (d) Shigella sonnei (e) influenza B and (f)Salmonella typhimurium DT 104 (From Ref [48])
10 CHAPTER 1 MOTIVATION
4 Fogarty J L Thornton and R Corcoran 1995 Illness in a Community Associated with an Episode ofWater Contamination with Sewage Epidemiology and Infection 114289ndash295
5 Scallan E 2011 Foodborne Illness Acquired in the United StatesmdashUnspecified Agents EmergingInfectious Diseases 17 16ndash22
6 Craun G F J M Brunkard J S Yoder V A Roberts J Carpenter T Wade R L CalderonJ M Roberts M J Beach and S L Roy 2010 Causes of Outbreaks Associated with Drinking Waterin the United States from 1971 to 2006 Clinical Microbiology Reviews 23507ndash528
7 Edwards D D 1993 Troubled Waters in Milwaukee ASM News 59342ndash3458 MacKenzie W R N J Hoxie M E Proctor M S Gradus K A Blair D E Peterson
J J Kazmierczak K R Fox D G Addias J B Rose and J P Davis 1994 Massive WaterborneOutbreak of Cryptosporidium Infection Associated with a Filtered Public Water Supply MilwaukeeWisconsin March and April 1993 New England Journal of Medicine 331161ndash167
9 Anonymous 2010 Surveillance for Foodborne Disease OutbreaksmdashUnited States 2007 Morbidityand Mortality Weekly Reports 59973ndash979
10 Bean N H J S Goulding C Lau and F J Angulo 1996 Surveillance for Foodborne-DiseaseOutbreaksmdashUnited States 1988ndash1992 Morbidity and Mortality Weekly Reports 451ndash66
11 Wall P G J de Louvois R J Gilbert and B Rowe 1996 Food Poisoning NotificationsLaboratory Reports and OutbreaksmdashWhere do the Statistics Come From and What Do They MeanCommunicable Disease Report Review 6 R93ndashR100
12 Colford J M S Roy M J Beach A Hightower S E Shaw and T J Wade 2006 A Review ofHousehold Drinking Water Intervention Trials and an Approach to the Estimation of EndemicWaterborne Gastroenteritis in the United States Journal of Water and Health 471
13 Mead P S L Slutsker V Dietz L F McCaig J S Bresee C Shapiro P M Griffinand R V Tauxe 1999 Food Related Illness and Death in the United States Emerging InfectiousDisease 5607ndash625
14 Dziuban E J J L Liang G F Craun V Hill P A Yu J Painter M R Moore R L CalderonS L Roy and M J Beach 2006 Surveillance for Waterborne Disease and Outbreaks Associatedwith Recreational WatermdashUnited States 2003ndash2004 and Surveillance for Waterborne Disease andOutbreaks Associated with Drinking Water and Water not Intended for DrinkingmdashUnited States2003ndash2004 Morbidity and Mortality Weekly Reports 551ndash30
15 Fliermans C B 1996 Ecology of Legionella From Data to Knowledge with a Little WisdomMicrobial Ecology 32203ndash228
16 Li Y S Duan I T Yu and T W Wong 2005 Multi-Zone Modeling of Probable SARS VirusTransmission by Airflow Between Flats in Block E Amoy Gardens Indoor Air 1596ndash111
17 Peccia J D K Milton T Reponen and J Hill 2008 A Role for Environmental Engineering andScience in Preventing Bioaerosol-Related Disease Environmental Science amp Technology424631ndash4637
18 Jernigan D B P L Raghunathan B P Bell R Brechner E A Bresnitz J C Butler M CetronM Cohen T Doyle and M Fischer 2002 Investigation of Bioterrorism-Related AnthraxUnited States 2001 Epidemiologic Findings Emerging Infectious Diseases 81019ndash1028
19 Greenwood M and G U Yule 1917 On the Statistical Interpretation of Some BacteriologicalMethods Employed in Water Analysis Journal of Hygiene 1636ndash56
20 Phelps E 1909 The Disinfection of Sewage and Sewage Filter Effluents USGS Water Supply Paper229 GPO Washington DC
21 Rudolfs W and H W Gehm 1935 Multiplication of Total Bacteria and B coli after SewageChlorination Sewage Works Journal 7991ndash996
22 Subcommittee onMicrobiological Criteria 1985 An Evaluation of the Role ofMicrobiological Criteriafor Foods and Food Ingredients National Academy Press Washington DC
23 Cabelli V J A P Dufour L J McCabe and M A Levin 1982 Swimming-AssociatedGastroenteritis and Water Quality American Journal of Epidemiology 115606ndash616
24 Dufour A P 1984 Health Effects Criteria for Fresh Recreational Waters USEPA Research TrianglePark NC
25 Fleisher J M F Jones and D Kay 1993 Water and Non-Water-Related Risk Factors forGastroenteritis among Bathers Exposed to Sewage-Contaminated Marine Waters InternationalJournal of Epidemiology 22698ndash708
REFERENCES 11
26 Engelbrecht R S C N Haas J A Shular D L Dunn D Roy A Lalchandani B F Severin andS Farooq 1979 Acid-Fast Bacteria and Yeasts as Indicators of Disinfection Efficiency EPA-6002-79-091 US Environmental Protection Agency Cincinnati OH
27 Grabow W O K 1983 Inactivation of Hepatitis A Virus and Indicator Organisms in Water by FreeChlorine Residuals Applied and Environmental Microbiology 46619
28 Helmer R D and G R Finch 1993 Use of MS2 Coliphage as a Surrogate for Enteric Viruses inSurface Waters Disinfected with Ozone Ozone Science and Engineering 15279ndash293
29 Payment P and E Franco 1993Clostridium Perfringens and Somatic Coliphages as Indicators of theEfficiency of Drinking Water Treatment for Viruses and Protozoan Cysts Applied and EnvironmentalMicrobiology 592418ndash2424
30 Cabelli V J 1977Clostridium Perfringens as aWater Quality Indicator pp 65ndash79 InA Hoadley andB Dutka (eds) Bacterial IndicatorsHealth Hazards Associated with Water ASTM Philadelphia PA
31 Rice E W K R Fox R J Miltner D A Lytle and C H Johnson 1996 Evaluating PlantPerformance with Endospores Journal of the American Water Works Association 88122ndash130
32 Engelbrecht R S B F Severin M T Masarik S Farooq S H Lee C N Haas and A Lalchandani1977 New Microbial Indicators of Disinfection Efficiency EPA-6002-77-052 US EnvironmentalProtection Agency Cincinnati OH
33 Committee on Indicators for Waterborne Pathogens ndash National Research Council 2004 Indicators forWaterborne Pathogens National Academies Press Washington DC
34 PresidentialCongressional Commission on Risk Assessment and RiskManagement 1997 Frameworkfor Environmental Health Risk Management The Commission Washington DC
35 Griffin P M and R V Tauxe 1991 The Epidemiology of Infections Caused by Escherichiacoli O157H7 Other Enterohemorrhagic E coli and the Associated Hemolytic Uremic SyndromeEpidemiologic Reviews 1360ndash98
36 Heun E M R L Vogt P J Hudson S Parren and G W Gary 1987 Risk Factors for SecondaryTransmission in Households after a Common Source Outbreak of Norwalk Gastroenteritis AmericanJournal of Epidemiology 1261181ndash1186
37 MacKenzie W R W L Schell B A Blair D G Addiss D E Peterson N J HozieJ J Kazmierczak and J P Davis 1995 Massive Outbreak of Waterborne CryptosporidiumInfection in Milwaukee Wisconsin Recurrence of Illness and Risk of Secondary TransmissionClinical Infectious Diseases 2157ndash62
38 Millard P K Gensheimer D G Addiss D M Sosin G A Beckett A Houck-Jankoski andA Hudson 1994 An Outbreak of Cryptosporidiosis from Fresh-Pressed Apple Cider Journal ofthe American Medical Association 2721592ndash1596
39 Pickering L K D G Evans H L DuPont J J Vollet and D J Evans Jr 1981 Diarrhea Caused byShigella Rotavirus and Giardia in Day Care Centers Prospective Study Journal of Pediatrics9951ndash56
40 Morens D M R M Zweighaft T M Vernon G W Gary J J Eslien B T Wood R C Holmanand R Dolin 1979 A Waterborne Outbreak of Gastroenteritis with Secondary Person to PersonSpread Lancet 5964ndash966
41 Laursen E O Mygind B Rasmussen and T Ronne 1994 Gastroenteritis A Waterborne OutbreakAffecting 1600 People in a Small Danish Town Journal of Epidemiology amp Community Health48453ndash458
42 Baron R C F D Murphy H B Greenberg C E Davis D J Bregman G W Gary J M Hughesand L B Schonberger 1982 Norwalk Gastrointestinal Illness An Outbreak Associated withSwimming in a Recreational Lake and Secondary Person to Person Transmission American Journalof Epidemiology 115163ndash172
43 Kappus K D J S Marks R C Holman J K Bryant C Baker G W Gary and H B Greenberg1982 An Outbreak of Norwalk Gastroenteritis Associated with Swimming in a Pool and SecondaryPerson to Person Transmission American Journal of Epidemiology 116834ndash839
44 White K E M T Osterbolm J A Mariotti J A Korlath D H Lawrence T L Ristinen andH B Greenberg 1986 A Foodborne Outbreak of Norwalk Virus Gastroenteritis American Journalof Epidemiology 124120ndash126
45 Spika J S J E Parsons and D Nordenberg 1986 Hemolytic Uremic Syndrome and DiarrheaAssociated with Escherichia coli O157H7 in a Day Care Center Journal of Pediatrics 109287ndash291
12 CHAPTER 1 MOTIVATION
46 Ferguson J K L R Jorm C D Allen P KWhitehead and G L Gilbert 1995 Prospective Study ofDiarrhoeal Outbreaks in Child Long Daycare Centres in Western Sydney Medical Journal of Australia163137ndash140
47 Frost F J G F Craun and R L Calderon 1996 Waterborne Disease Surveillance Journal of theAmerican Water Works Association 8866ndash75
48 Farrington C P N J Andrews A D Beale and M A Catchpole 1996 A Statistical Algorithmfor the Early Detection of Outbreaks of Infectious Disease Journal of the Royal StatisticalSociety A 159547ndash563
REFERENCES 13
CHAPTER2MICROBIAL AGENTS ANDTRANSMISSION
MICROBIAL TAXONOMY
The development of techniques for examining the nucleic acids of microorganisms hasseen major changes in which we classify and group related microorganisms This isespecially true for the study of ribosomal ribonucleic acid (rRNA) which is a highlyconserved sequence involved in the synthesis of proteins in all living organisms Basedon this analysis the classification of living things has been placed into a three-domainsystem consisting of Archaea Eukarya and Bacteria Of these the Bacteria andArchaea are termed prokaryotes (no organized cell nucleus) and the Eukarya areknown as eukaryotes (an organized cell nucleus) Eukaryotic microbes other thanalgae and fungi are collectively calledprotistsWithin theEukarya are fungi protozoahelminth worms algae plants animals and humans Archaea are microbes that looksomewhat similar to bacteria in size and shape under the light microscope but they areactually genetically and biochemically quite different They appear to be a simpler formof life and may in fact be the oldest form of life on earth Viruses are obligate intercel-lular parasites and are not amember of any group They are usually composed only of anucleic acid surrounded by a protein coat Eukaryotes are much more complex thanprokaryotic cells in structure and nutritional requirements Prokaryotes divide by sim-ple binary fissionwhereas eukaryotes divide byamore complexprocess calledmitosis
Eukaryotes
Fungi protozoa and helminth worms are all eukaryotes All contain members that arepathogenic to man and animals While algae do not infect humans they can producetoxins that are harmful to animals and man Fungi obtain nutrients solely by adsorp-tion of organic matter from dead organisms Even when they invade living tissuesthey typically kill cells and then adsorb the nutrients from them Some fungi are capa-ble of developing environmentally resistant spores which can be transported throughthe air Fungal diseases in humans are referred to asmycoses Airborne fungal sporesare responsible for some allergies in humans Yeasts are classified with the fungi and
Quantitative Microbial Risk Assessment Second Edition Charles N Haas Joan B Roseand Charles P Gerbacopy 2014 John Wiley amp Sons Inc Published 2014 by John Wiley amp Sons Inc
15
some are pathogenic to humans (Candida albicans) Certain fungi produce toxins(ie aflatoxins) when growing in foods that are mutagenic and carcinogenic in ani-mals Inhalation is an important route of transmission for some fungal diseases suchas aspergillosis blastomycosis coccidioidomycosis and histoplasmosis These fungiare found growing in animal feces soil or decaying organic matter (compost manure)and may be transmitted through the air when this matter is disturbed Some fungi maybe transmitted by direct contact with the skin Fungi are often found in drinking waterdistribution systems and they have been linked to infections in immunocompromisedindividuals [1] Food is not believed to be a significant route of transmission ofpathogenic fungi
Protozoans are unicellular organisms that are surrounded by a cytoplasmicmembrane that is covered by a protective structure called a pellicle Most are freeliving feeding off of bacteria Some of these can cause disease while others are obli-gate parasites They are capable of forming structures called cysts oocysts or spores(depending on the life cycle of the organism) resistant to adverse environmentalconditions such as desiccation starvation high temperatures and disinfectantsSome pathogenic protozoa are found mainly in the soil (Naegleria) or water(Acanthamoeba) Others such a Giardia and Cryptosporidium whose natural habitatis the intestines of warm-blooded animals are capable of causing disease in bothhumans and animals Others such as Entamoeba histolytica are only capable ofcausing disease in humans
Pathogenic enteric (replicate in the intestines) protozoans are usually excretedin the feces or urine and can be transmitted by fecally contaminated food and waterSome protozoa may be transmitted through the air (Acanthamoeba) or throughfomites (inanimate objects) Some important environmentally transmitted protozoaare listed in Table 21 The clinically important protozoa are divided taxonomicallyinto the amoebas (Entamoeba spp) flagellates (Giardia) and coccidian meaningldquoglobose in shaperdquo (Cryptosporidium and Cyclospora) Microsporidia are alsocapable of causing intestinal infections but their classification is uncertain becausethey have many characteristics associated with fungi They are all obligate parasitesand are transmitted via infectious cysts oocysts or spores by the fecalndashoral routeThe life cycles of these protozoa are similar The initial stage occurs during ingestionof the cyst oocyst or spore After ingestion the body temperature and passagethrough the stomach cause these infective stages to open up in a process calledexcystation
The Giardia cysts house two trophozoites which is the stage that attaches tointestinal cells and grows in the intestinal tract through asexual reproduction As thetrophozoites grow and begin to cover the wall of the intestinal tract diarrhea canresult As the trophozoites are released some form cysts as they pass through thebowels Cryptosporidium and Cyclospora both produce oocysts The life cycle ofCyclospora is still not well known except that its oocysts require some period of timein the environment before they are infective Cryptosporidium oocysts contain foursporozoites which enter the intestinal cells and begin the infection process As morecells become infected the illness begins and oocysts are excreted in high numbers inthe feces (about 100000g)
Worms and helminths are small multicellular animals that are parasiticto humans and animals They include flukes tapeworms and roundworms
16 CHAPTER 2 MICROBIAL AGENTS AND TRANSMISSION
Dependence of Growth Parameters on Other Environmental Variables 258
Interacting Populations 258
Data Sources 260
References 263
CHAPTER 8 CONDUCTING THE DOSEndashRESPONSE ASSESSMENT 267
Plausible DosendashResponse Models 268
Framework for Mechanistic DosendashResponse Relationships 269
Exponential DosendashResponse Model 271
Beta-Poisson DosendashResponse Model 272
Simple Threshold Models 274
Negative Binomial Dose Distributions 277
Variable Threshold Models 278
Other Mixture Models 279
Biological Arguments for One-Hit Models 281
Empirical Models 282
Fitting Available Data 283
Types of Data Sets 284
Potential Impacts of Immune Status 298
Relationship between Dose and Severity (Morbidity and Mortality) 299
Morbidity Ratio (PDI) 299
Mortality Ratio 303
Reality Checking Validation 304
Validation 1993 Milwaukee Outbreak 304
Use of Indicators and Other Proxy Measures in DosendashResponse 305
Indicator Methods 305
Molecular Methods 307
Advanced Topics in DosendashResponse Modeling 308
DosendashResponsendashTime Models 308
Physiological Models 313
Appendix 315
References 317
CHAPTER 9 UNCERTAINTY 323
Point Estimates of Risk 324
Terminology Types of Uncertainty 326
Sources of Uncertainty 327
Sources of Variability 328
Variability that is Uncertain 329
Approaches to Quantify Parametric Uncertainty 329
Likelihood 329
Bootstrap 330
Other Methods 330
viii CONTENTS
Applications 332
Exposure Assessment 332
DosendashResponse Assessment 338
Combining Parametric Uncertainty from Multiple Sources 344
Propagation Methods 344
Monte Carlo Analyses 347
Overall Risk Characterization Example 365
Second-Order Methods 368
Model Uncertainty and Averaging 370
References 373
CHAPTER 10 POPULATION DISEASE TRANSMISSION 377
Introduction Models for Population and Community Illnesses 377
Basic SIR Model 378
Incubation Period 386
Duration of Illness 388
Secondary Cases 389
Impact of Immunity 392
Outbreak Detection 393
References 397
CHAPTER 11 RISK CHARACTERIZATION AND DECISION MAKING 399
Introduction 399
Valuing Residual Outcomes 400
Classical Economics 400
DALYs and QALYs 404
Decision Making 407
CostndashBenefit Analysis 408
Multivariate Approaches 411
Other Aspects Entering into a Decision 412
Equity and Justice Aspects 412
References 413
INDEX 415
CONTENTS ix
PREFACE
In the 14 years since we prepared the first edition there has been an explosion inknowledge of and need for quantitative microbial risk assessment (QMRA) Whileour motivation for the first edition stemmed from concerns (principally in water) aboutenteric bacteria viruses and protozoa the motivation has now exploded to newdomains and agents SARS influenza biothreat agents and zoonotic pathogens haveall become of greater concern
The 2001 anthrax letters have highlighted the need for risk assessment ofinhaled agents Both biothreat agents and emergence of new strains of virulentcontagious organisms have raised concern for modeling pathogen dynamics inpopulations
In this edition we have retained the fundamental approach of the riskassessment methodology as a central paradigm We have added new material onmodern pathogen analytical methods predictive microbiology (of pathogen growthand decay) dynamic risk models (explicitly considering incubation time) and diseasepropagation models in populations Of necessity we have removed some materialmdashitis no longer possible to present comprehensive tables of microbial dosendashresponseparameters
In the years since the first edition the authors have gained experience inteaching this material to generations of studentsmdashin the form of formal classestutorials independent studies and short courses We know this book can be valuablein instructing advanced students in environmental sciences environmental engineer-ing public health and microbiology It is also a useful reference for practitionersand regulatory personnel Some prior statistical background would be useful inapproaching the material but not necessary the key requirement for any risk assessoris the absence of fear from mathematical constructs and concepts
The three of us have been on a QMRA journey for almost 30 years We havelearned that doing high-quality risk assessments is of necessity a team sport requiringindividuals with different skills and interests We have learned a tremendous amountfrom each other from our students from our collaborators and from the problems thatwe have sought to approach Practitioners of the art of quantitative microbial riskassessment should be advised to cast a wide net with respect to colleagues andcollaborators to perfect their craft
xi
We encourage comments and feedback from users of this work and look for-ward to observing and participating in developments in coming years and ultimatelyto handing the baton off to our students and their students
Charles N Haas
Joan B Rose
Charles P GerbaNovember 2013
xii PREFACE
CHAPTER1MOTIVATION
THE PREVENTION of infectious disease transmission from human exposure tocontaminated food water soil and air remains a major task of environmental andpublic health professionals There are numerous microbial hazards including expo-sure via food water air and malicious release of pathogens that may arise Indeedsome have argued that the property of virulence of human pathogens is one which isfavored by evolutionary interactions between pathogens and host populations andtherefore will always be of important concern [1] To make rational decisions in pre-paring responding and recovering from exposures to such hazards a quantitativeframework is of high benefit
The objective of this book is to comprehensively set forth the methods forassessment of risk from infectious agents transmitted via these routes in a frameworkthat is compatible with the framework for other risk assessments (eg for chemicalagents) as set forth in standard protocols [2 3]
In this chapter information on the occurrence of infectious disease in broadcategories will be presented along with a historical background on prior methodsfor assessment of microbial safety of food water and air This will be followed byan overview of key issues covered in this book
PREVALENCE OF INFECTIOUS DISEASE
Outbreaks of infectious waterborne illness continue to occur although it remainsimpossible to identify the infectious agent in all cases For example in 1991 a water-borne outbreak in Ireland resulting from sewage contamination of water suppliesinfected about 5000 persons However the infectious agent responsible for thisoutbreak could not be determined [4] In the United States it has been estimated that38 million cases of foodborne infectious disease occur annually with unidentifiedagents [5]
In the United States there have typically been three to five reported outbreaksper year in community drinking water systems involving infectious microorganismswith perhaps up to 10000 annual cases [6] The 1994 Milwaukee Cryptosporidiumoutbreak with over 400000 cases [7 8] was a highly unusual event among thesestatistics As shown in Figure 11 there has been an increasing ability to identify
Quantitative Microbial Risk Assessment Second Edition Charles N Haas Joan B Roseand Charles P Gerbacopy 2014 John Wiley amp Sons Inc Published 2014 by John Wiley amp Sons Inc
1
microorganisms responsible for waterborne diseases and it is expected that withadvances in molecular biology this will increase
There are substantially more outbreaks and cases of foodborne infectiousdiseases than are reported Table 11 summarizes reports of US cases of principalmicrobial infectious foodborne illnesses for two 5-year periods (1988ndash1992 and
1971ndash1982
10
20
30
40
Perc
ent o
f out
brea
ks
50
60
1983ndash1994Period
1995ndash2006
Figure 11 Percentages of outbreaks associated with public water systems (n = 680) by timeperiod 1971ndash2006 that had unknown etiologies based on data from Ref [6]
TABLE 11 Comparison of Five-Year Averages for Common Foodborne Reported Outbreaks
Agent
Annual Average 1988ndash1992 Annual Average 2002ndash2006
Cases Outbreaks Cases Outbreaks
Campylobacter 996 44 624 22
Escherichia coli 488 22 481a 30a
Salmonella 42354 1098 3475 144
Shigella 9576 5 495 12
Staphylococcus aureus 3356 94 554 25
Hepatitis 4218 86 238 1
Listeria monocytogenes 04 02 22 2
Giardia 368 14 2 1
Norovirus 584 04 10854 338
Vibrio (all) 114 18 114 5
Unknown etiologies 40483 1422 4052 30
Source From Refs [9 10]a Include both Shiga toxigenic and enterotoxigenic
2 CHAPTER 1 MOTIVATION
2002ndash2006) There is a mix of causal agents including bacteria virus and protozoaIt is noteworthy that (as in the case of waterborne outbreaks) the frequency ofoutbreaks of unknown etiology has dramatically decreased but the frequency of out-breaks associated with norovirus has dramatically increased These changes are duein part to the ability to better identify causal agents (eg via molecular methods)
It is generally recognized that reported outbreaks either of water- or foodborneinfectious disease represent only a small fractionof the total populationdisease burdenHowever particularly in the United States voluntary reporting systems and theoccurrence of mild cases (for which no medical attention is sought but neverthelessare frank cases of disease) have made it difficult to estimate the total caseload
In the United Kingdom comparisons between the number of confirmed casesin infectious disease outbreaks and total confirmed laboratory illnesses (occurring inEngland and Wales) have been made (Table 12) This suggests that the ratio ofreported outbreak cases to total cases that may seek medical attention may be from10 to 5001 with some dependency on the particular agent
Colford et al [12] developed estimates for the total disease burden associatedwith acute gastroenteritis from drinking water This relies on combining the reportedoutbreak data with interventional epidemiologic studies Based on their analysis thetotal US disease burden is estimated to be 426ndash1169 million cases per year in theUnited States which is substantially in excess of the reported outbreaks In the case offoodborne illness there are an estimated 14 million cases per year [13]
Drinking water and food are by no means the only potential routes of exposureto infectious agents in the environment Recreation in water (either natural or artificialpools) containing pathogens can produce illness [14]
Indoor air transmission can be a vehicle of infection Legionella transmittedthrough indoor environments has been a concern since the 1970s [15] The multina-tional epidemic of severe acute respiratory syndrome (SARS) caused by a coronavi-rus was abetted at least in one location in Hong Kong by indoor aerosol transmissionbetween apartments of infected individuals and susceptible individuals [16] A broadspectrum of other respiratory pathogens including influenza rhinoviruses and myco-bacteria can be transmitted by this route [17]
TABLE 12 Comparison of Laboratory Isolations and Outbreak Cases in Englandand Wales 1992ndash1994
Agent
Cases 1992ndash1994
RatioAll Laboratory Reports Confirmed Outbreak Cases
Campylobacter 122250 240 5094
Rotavirus 47463 127 3737
S sonnei 29080 847 343
Salmonella 92416 5960 155
Cryptosporidium 14454 1066 136
E coli O157 1266 128 99
Source Modified from Ref [11]
PREVALENCE OF INFECTIOUS DISEASE 3
The deliberate release of Bacillus anthracis spores in 2001 (the ldquoAmerithraxrdquoincidents) brought widespread awareness to the potential for indoor releases (as wellas releases in other venues) of bioterrorist agents to cause risk [18] Therefore ofnecessity microbial risk assessors may need to consider the impact of maliciousactivity in certain applications
PRIOR APPROACHES
Concerns for microbial quality of food water and other environmental media havelong existed In the early twentieth century the use of indicator microorganismswas developed for the control and assessment of the hygienic quality of such mediaand the adequacy of disinfection and sterilization processes The coliform group oforganisms was perhaps first employed for this purpose [19ndash21] Indicator techniqueshave also found utility in the food industry such as the total count for milk and othermore recent proposals [22] Other indicator groups for food water or environmentalmedia have been examined such as enterococci [23ndash25] acid-fast bacteria [26]bacteriophage [27ndash29] and Clostridia spores [29ndash31]
The use of indicator organisms was historically justified in because of difficultyin enumerating pathogens However with the increasing availability of modernmicrobial methods for example PCR immunoassay etc for direct pathogen assess-ment this justification has become less persuasive In addition in order to develophealth-based standards from indicators extensive epidemiologic surveillance is oftennecessary The use of epidemiology has limitations with respect to detection limits(for an adverse effect) and is also quite expensive to conduct Indicator methodsare also limited in that many pathogens are more resistant to die off in receiving envir-onments or source waters than indicators or have greater resistance to removal bytreatment processes than indicators [26 28 29 32] Thus the absence of indicatorsmay not suffice to ensure the absence of pathogens Even after a century of use theindicator concept remains imperfect [33]
The use of quantitative microbial risk assessment (QMRA) will enable directmeasurements of pathogens to be used to develop acceptancerejection guidelinesfor food water and other vehicles that may be the source of microbial exposureto human populations The objective of this book is to present these methods in asystematic and unified manner
SCOPE OF COVERAGE
QMRA is the application of principles of risk assessment to the estimate ofconsequences from a planned or actual exposure to infectious microorganismsIn performing a QMRA the risk assessor aims to bring the best available informationto bear in understanding the nature of the potential effects from a microbial exposureSince the information (such as dosendashresponse relationships exposure magnitudes) isalmost invariably incomplete it is also necessary to ascertain the potential error
4 CHAPTER 1 MOTIVATION
involved in the risk assessment With such information necessary steps to mitigatecontrol or defend against such exposures may be developed
At the outset of performing a risk assessment a scoping task should be under-taken This task should set forth the objectives of the analysis and the principal issuesto be addressed Items such as consideration of secondary cases individual versuspopulation risk agent or agents to be examined exposure routes andor accident sce-narios must be stipulated However this scoping may be changed during the course ofa QMRA to reflect the input derived from the risk manager(s) and other stakeholders
POTENTIAL OBJECTIVES OF A QMRA
There may be diverse objectives for a QMRA These objectives relate to the rationalefor the performance of the assessment as well as the methods to be employedBroadly the different objectives reflect different scales at which a risk assessmentmay be performed The step of problem formulation is critical to any risk estimate[34] It is necessary that the problem be formulated to meet the needs of the riskmanagers and stakeholders indeed it is now recognized that the successful practiceof risk analysis requires frequent interchange with manager and stakeholders [3]In general the problems posed are of several types
Site-Specific Assessment
The simplest type of QMRA that may be performed involves one site or exposurescenario The following are typical of the questions that might be asked
1 If a water treatment plant is designed in a certain way (with given removals ofpathogens) then what is the risk that would be placed upon the populationserved
2 A swimming outbreak (in a recreational lake) has just occurred I believe that itresulted from a short-duration contamination event What pathogen levelswould be consistent with the observed attack rate
3 Microbial sampling of a finished food product has found certain pathogensWhat level of risk does this pose to consumers of the product
4 A certain amount of infectious agent has been released into a room What is theimmediate danger to occupants and how stringent should cleanup levels be
Note that there are certain other contrasts in the objectives of the risk assessments tobe posed In (1) and (3) a before-the-fact computation is desired while in (2) and (4)an after-the-fact computation is described Also in (1) (3) and (4) pathogen levelsare available (or somehow are estimated) while in (2) an inverse computation isneeded given an observed attack rate
In performing this risk assessment the relationship between an exposure ortechnological metric and a risk measurement must be ascertained and then theparticular point of correspondence determined (Fig 12) In cases (1) (3) and (4)for a known (or assumed) exposure (on the x-axis) the corresponding range of risks
POTENTIAL OBJECTIVES OF A QMRA 5
on the y-axis is sought In cases (2) for known or assumed risks (on the y-axis)the corresponding range of exposures (or level of technological protection) is to bedetermined (on the x-axis)
Ensemble of Sites
A somewhat more complex situation occurs if the risk for a set of events or sites mustbe estimated Basically this now includes the necessity to incorporate site-to-sitefactors into the assessment Some examples of this are as follows
1 If I desire keeping the risk to a population served by multiple water treatmentplants at a given level (or better) then what criteria should I use (microbiallevels)
2 For a food product subject to contamination by pathogens what would be anacceptable treatment specification (eg heating time holding period) to ensuremicrobial acceptability
3 I am designing a water quality standard for recreational bathing waters If auniform (eg national) standard is to be developed what standard would ensurethat average risk was acceptable with keeping the risk of a large ldquoclusterrdquo ofillnesses low
In addition to incorporating a measure of ensemble average risk in general it is alsodesired to ensure that no single member of the ensemble be unacceptably extreme Forexample consider the evaluation of three options of disease control among three com-munities as indicated in Table 13
This table indicates the number of cases and the rate among the three commu-nities The three policy options yield the same number of expected cases Howeverthere are differences in the allocation of risk among the communities of different sizesIn option A all communities have an identical level of estimated risk In option B therisk increases as community size decreases while in option C the risk increases ascommunity size increases This distribution of risk among affected subsets of the
Exposure
Ris
k
Level of technological protection
Figure 12 Relationship between exposurelevel of technological protection andmicrobial risk The middle curve indicatesthe best estimate The other two curvesindicate the upper and lower confidenceregions
6 CHAPTER 1 MOTIVATION
ensemble being considered adds an additional dimension for consideration by a riskmanagermdashwhich may be termed risk equity
SECONDARY TRANSMISSION
Infectious microbial diseases are different in terms of risk to a population than arechemical agents in that an individual who may become infected (with or withoutillness) can then proceed to infect additional individuals These secondary (tertiaryquaternary etc) cases may be persons who had no direct contact with the initialvehicle of exposure but nevertheless in fairly accounting for the public health impactthey should be considered
Secondary cases may arise by a variety of mechanisms Particularly amongclose family members household secondary cases can arise by direct or indirect(eg surface contamination) contact this is particularly so when the primary caseor one household secondary case is a child [35ndash37] Table 14 summarizes secondarycase statistics obtained from a variety of outbreaks As will be discussed inChapter 10 the secondary case rate is a complex factor involving (among other things)the nature of the venue and contact patterns when infected and susceptible individualsintermingle
Presumably secondary cases may also arise from close contact with anasymptomatic individual (in the ldquocarrierrdquo state) This is well known for highly acuteand (now) uncommon illnesses (such as typhoid) Excretion of Norwalk virusfollowing recovery (and resulting in additional cases) has been documented to occurfor as long as 48 h post recovery [44]
OUTBREAKS VERSUS ENDEMIC CASES
As noted previously there may be a substantial difference between reported outbreakcases and total disease burden in a community In order for a disease case to receiverecognition by the public health authorities the following specific and sequential stepsmust occur [47]
TABLE 13 Effect of Different Hypothetical Policy Options on Distribution of Risk AmongCommunities (for a Fixed Total Risk)
CommunityExposedPopulation
Policy Option A Policy Option B Policy Option C
CasesIncidence(10000) Cases
Incidence(10000) Cases
Incidence(10000)
A 100000 20 2 6 06 24 24
B 50000 10 2 18 36 7 14
C 10000 2 2 8 8 1 1
Total 160000 32 2 32 2 16 2
OUTBREAKS VERSUS ENDEMIC CASES 7
1 An ill person must seek medical care
2 Appropriate clinical tests (eg blood stool) must be ordered by the attendingphysician
3 The patient must comply with obtaining the sample
4 The laboratory must be capable of detecting the relevant pathogens
5 The clinical test must be positive
6 The test result must be reported to the health agency in a timely manner
If any of the links in this sequential chain are broken then a disease case will not enterthe records maintained by health authorities For example with increasing controls on
TABLE 14 Summary of Secondary Case Data in Outbreak Situations
Organism
SecondaryAttackRatioa
SecondaryPrevalence inHouseholdsb Remarks Reference
Cryptosporidiumparvum
033 033 Outbreak in contaminatedapple cider
[38]
C parvum NA 0042 Drinking water outbreak(Milwaukee)
[37]
Shigella 028 026 Day-care center outbreaksin children
[39]
Rotavirus 042 015 Day-care center outbreaksin children
[30]
Giardia lamblia 133 017 Day-care center outbreaksin children
[39]
Viral gastroenteritis 022 011c Drinking waterborneoutbreak
[40]
Viral gastroenteritis 056 NA Drinking water outbreak(Denmark)
[41]
Norovirus 05ndash10 019 Swimming outbreak [42]
Norovirus 11 029 Swimming outbreakin children
[43]
Norovirus NA 044 Foodborne outbreakin children and teachers
[36]
Norovirus 04 NA Foodborne outbreak [44]
E coli O157H7 NA 018c Day-care center outbreakin children
[45]
Unidentifiedday-care diarrhealdiseases
138 009c [46]
NA information not availableaRatio of secondary cases to primary casesb Proportion of households with one or more primary cases who have one or more secondary casesc Proportion of persons in contact with one or more primary cases who have a secondary case
8 CHAPTER 1 MOTIVATION
medical care stool samples may not be obtained from mild cases of illness Someorganisms may only be present sporadically or may be difficult to test in stool orblood sample Patients may not seek medical attention for mild cases of illness Fur-thermore in the United States in particular the surveillance of environmentallyinduced disease is done on a passive basis and hence the number of actual illnessclusters that are actually compiled into recorded statistics is only a small fractionof such clusters of illness that occur [47]
From a more fundamental point of view an outbreak of illness is generallydefined as occurrence of the illness at a level greater than normal or anticipated Thisdefinition recognizes that there is a level of illness (endemic) that may exist underusual circumstances The detection of such outbreaks poses a particular challengeThe problem is illustrated conceptually in Figure 13
Additional complications arise from the different patterns of illness in acommunity including definite periodicities as well as temporal trends and fromthe presence of reporting lags associated with laboratory analysis and time for patientsto seek medical attention Figure 14 illustrates the different patterns of illness inthe case of six pathogens for England and Wales [48]
In the case of waterborne and foodborne illnesses it is highly likely that thelevel of such endemic illnesses is substantially greater than those occurring duringoutbreaks (even accounting for unrecognized outbreaks)
As a result there are often many cases of environmentally caused (water airfood) infectious disease that are unrecognized One example of this isCampylobacterThere has been an average of about 200 cases per year of water- and foodborne illnessin outbreaks of this organism and yet estimates of the disease burden suggest about2100000 cases per year that is approximately 10000 cases per case of detectableoutbreak illness Therefore it will be important to assess the factors that may influenceoutbreak detection These issues will be discussed in subsequent chapters
Detectedoutbreak
Undetectedoutbreak
Threshold of detection
Hyper endemicSporadic
Endemic rate
Time
Num
ber
of c
ases
Figure 13 Schematic of disease occurrence in a hypothetical community (Modified fromRef [47])
OUTBREAKS VERSUS ENDEMIC CASES 9
REFERENCES
1 Levin B R 1996 The Evolution and Maintenance of Virulence in Microparasites Emerging InfectiousDisease 293ndash102
2 National Academy of Sciences 1983 Risk Assessment in the Federal Government Managing theProcess National Academy Press Washington DC
3 National Research Council 2009 Science and Decisions Advancing Risk Assessment NationalAcademies Press Washington DC
10090807060504030201001190 1191 1192 1193 1194 1195
(b)
140
120
100
80
60
40
20
01190 1191 1192 1193 1194 1195
(f)
700
600
500
400
300
200
100
01190 1191 1192 1193 1194 1195
(d)
1200
1000
800
600
400
200
1190 1191 1192 1193 1194 1195
(a)
240
200
160
120
80
40
01190 1191 1192 1193 1194 1195
(e)
7
6
5
4
3
2
1
01190 1191 1192 1193 1194 1195
(c)
Figure 14 Weekly count of reported organism isolations in England andWales (a) rotavirus(b) Clostridium difficile (c) Salmonella derby (d) Shigella sonnei (e) influenza B and (f)Salmonella typhimurium DT 104 (From Ref [48])
10 CHAPTER 1 MOTIVATION
4 Fogarty J L Thornton and R Corcoran 1995 Illness in a Community Associated with an Episode ofWater Contamination with Sewage Epidemiology and Infection 114289ndash295
5 Scallan E 2011 Foodborne Illness Acquired in the United StatesmdashUnspecified Agents EmergingInfectious Diseases 17 16ndash22
6 Craun G F J M Brunkard J S Yoder V A Roberts J Carpenter T Wade R L CalderonJ M Roberts M J Beach and S L Roy 2010 Causes of Outbreaks Associated with Drinking Waterin the United States from 1971 to 2006 Clinical Microbiology Reviews 23507ndash528
7 Edwards D D 1993 Troubled Waters in Milwaukee ASM News 59342ndash3458 MacKenzie W R N J Hoxie M E Proctor M S Gradus K A Blair D E Peterson
J J Kazmierczak K R Fox D G Addias J B Rose and J P Davis 1994 Massive WaterborneOutbreak of Cryptosporidium Infection Associated with a Filtered Public Water Supply MilwaukeeWisconsin March and April 1993 New England Journal of Medicine 331161ndash167
9 Anonymous 2010 Surveillance for Foodborne Disease OutbreaksmdashUnited States 2007 Morbidityand Mortality Weekly Reports 59973ndash979
10 Bean N H J S Goulding C Lau and F J Angulo 1996 Surveillance for Foodborne-DiseaseOutbreaksmdashUnited States 1988ndash1992 Morbidity and Mortality Weekly Reports 451ndash66
11 Wall P G J de Louvois R J Gilbert and B Rowe 1996 Food Poisoning NotificationsLaboratory Reports and OutbreaksmdashWhere do the Statistics Come From and What Do They MeanCommunicable Disease Report Review 6 R93ndashR100
12 Colford J M S Roy M J Beach A Hightower S E Shaw and T J Wade 2006 A Review ofHousehold Drinking Water Intervention Trials and an Approach to the Estimation of EndemicWaterborne Gastroenteritis in the United States Journal of Water and Health 471
13 Mead P S L Slutsker V Dietz L F McCaig J S Bresee C Shapiro P M Griffinand R V Tauxe 1999 Food Related Illness and Death in the United States Emerging InfectiousDisease 5607ndash625
14 Dziuban E J J L Liang G F Craun V Hill P A Yu J Painter M R Moore R L CalderonS L Roy and M J Beach 2006 Surveillance for Waterborne Disease and Outbreaks Associatedwith Recreational WatermdashUnited States 2003ndash2004 and Surveillance for Waterborne Disease andOutbreaks Associated with Drinking Water and Water not Intended for DrinkingmdashUnited States2003ndash2004 Morbidity and Mortality Weekly Reports 551ndash30
15 Fliermans C B 1996 Ecology of Legionella From Data to Knowledge with a Little WisdomMicrobial Ecology 32203ndash228
16 Li Y S Duan I T Yu and T W Wong 2005 Multi-Zone Modeling of Probable SARS VirusTransmission by Airflow Between Flats in Block E Amoy Gardens Indoor Air 1596ndash111
17 Peccia J D K Milton T Reponen and J Hill 2008 A Role for Environmental Engineering andScience in Preventing Bioaerosol-Related Disease Environmental Science amp Technology424631ndash4637
18 Jernigan D B P L Raghunathan B P Bell R Brechner E A Bresnitz J C Butler M CetronM Cohen T Doyle and M Fischer 2002 Investigation of Bioterrorism-Related AnthraxUnited States 2001 Epidemiologic Findings Emerging Infectious Diseases 81019ndash1028
19 Greenwood M and G U Yule 1917 On the Statistical Interpretation of Some BacteriologicalMethods Employed in Water Analysis Journal of Hygiene 1636ndash56
20 Phelps E 1909 The Disinfection of Sewage and Sewage Filter Effluents USGS Water Supply Paper229 GPO Washington DC
21 Rudolfs W and H W Gehm 1935 Multiplication of Total Bacteria and B coli after SewageChlorination Sewage Works Journal 7991ndash996
22 Subcommittee onMicrobiological Criteria 1985 An Evaluation of the Role ofMicrobiological Criteriafor Foods and Food Ingredients National Academy Press Washington DC
23 Cabelli V J A P Dufour L J McCabe and M A Levin 1982 Swimming-AssociatedGastroenteritis and Water Quality American Journal of Epidemiology 115606ndash616
24 Dufour A P 1984 Health Effects Criteria for Fresh Recreational Waters USEPA Research TrianglePark NC
25 Fleisher J M F Jones and D Kay 1993 Water and Non-Water-Related Risk Factors forGastroenteritis among Bathers Exposed to Sewage-Contaminated Marine Waters InternationalJournal of Epidemiology 22698ndash708
REFERENCES 11
26 Engelbrecht R S C N Haas J A Shular D L Dunn D Roy A Lalchandani B F Severin andS Farooq 1979 Acid-Fast Bacteria and Yeasts as Indicators of Disinfection Efficiency EPA-6002-79-091 US Environmental Protection Agency Cincinnati OH
27 Grabow W O K 1983 Inactivation of Hepatitis A Virus and Indicator Organisms in Water by FreeChlorine Residuals Applied and Environmental Microbiology 46619
28 Helmer R D and G R Finch 1993 Use of MS2 Coliphage as a Surrogate for Enteric Viruses inSurface Waters Disinfected with Ozone Ozone Science and Engineering 15279ndash293
29 Payment P and E Franco 1993Clostridium Perfringens and Somatic Coliphages as Indicators of theEfficiency of Drinking Water Treatment for Viruses and Protozoan Cysts Applied and EnvironmentalMicrobiology 592418ndash2424
30 Cabelli V J 1977Clostridium Perfringens as aWater Quality Indicator pp 65ndash79 InA Hoadley andB Dutka (eds) Bacterial IndicatorsHealth Hazards Associated with Water ASTM Philadelphia PA
31 Rice E W K R Fox R J Miltner D A Lytle and C H Johnson 1996 Evaluating PlantPerformance with Endospores Journal of the American Water Works Association 88122ndash130
32 Engelbrecht R S B F Severin M T Masarik S Farooq S H Lee C N Haas and A Lalchandani1977 New Microbial Indicators of Disinfection Efficiency EPA-6002-77-052 US EnvironmentalProtection Agency Cincinnati OH
33 Committee on Indicators for Waterborne Pathogens ndash National Research Council 2004 Indicators forWaterborne Pathogens National Academies Press Washington DC
34 PresidentialCongressional Commission on Risk Assessment and RiskManagement 1997 Frameworkfor Environmental Health Risk Management The Commission Washington DC
35 Griffin P M and R V Tauxe 1991 The Epidemiology of Infections Caused by Escherichiacoli O157H7 Other Enterohemorrhagic E coli and the Associated Hemolytic Uremic SyndromeEpidemiologic Reviews 1360ndash98
36 Heun E M R L Vogt P J Hudson S Parren and G W Gary 1987 Risk Factors for SecondaryTransmission in Households after a Common Source Outbreak of Norwalk Gastroenteritis AmericanJournal of Epidemiology 1261181ndash1186
37 MacKenzie W R W L Schell B A Blair D G Addiss D E Peterson N J HozieJ J Kazmierczak and J P Davis 1995 Massive Outbreak of Waterborne CryptosporidiumInfection in Milwaukee Wisconsin Recurrence of Illness and Risk of Secondary TransmissionClinical Infectious Diseases 2157ndash62
38 Millard P K Gensheimer D G Addiss D M Sosin G A Beckett A Houck-Jankoski andA Hudson 1994 An Outbreak of Cryptosporidiosis from Fresh-Pressed Apple Cider Journal ofthe American Medical Association 2721592ndash1596
39 Pickering L K D G Evans H L DuPont J J Vollet and D J Evans Jr 1981 Diarrhea Caused byShigella Rotavirus and Giardia in Day Care Centers Prospective Study Journal of Pediatrics9951ndash56
40 Morens D M R M Zweighaft T M Vernon G W Gary J J Eslien B T Wood R C Holmanand R Dolin 1979 A Waterborne Outbreak of Gastroenteritis with Secondary Person to PersonSpread Lancet 5964ndash966
41 Laursen E O Mygind B Rasmussen and T Ronne 1994 Gastroenteritis A Waterborne OutbreakAffecting 1600 People in a Small Danish Town Journal of Epidemiology amp Community Health48453ndash458
42 Baron R C F D Murphy H B Greenberg C E Davis D J Bregman G W Gary J M Hughesand L B Schonberger 1982 Norwalk Gastrointestinal Illness An Outbreak Associated withSwimming in a Recreational Lake and Secondary Person to Person Transmission American Journalof Epidemiology 115163ndash172
43 Kappus K D J S Marks R C Holman J K Bryant C Baker G W Gary and H B Greenberg1982 An Outbreak of Norwalk Gastroenteritis Associated with Swimming in a Pool and SecondaryPerson to Person Transmission American Journal of Epidemiology 116834ndash839
44 White K E M T Osterbolm J A Mariotti J A Korlath D H Lawrence T L Ristinen andH B Greenberg 1986 A Foodborne Outbreak of Norwalk Virus Gastroenteritis American Journalof Epidemiology 124120ndash126
45 Spika J S J E Parsons and D Nordenberg 1986 Hemolytic Uremic Syndrome and DiarrheaAssociated with Escherichia coli O157H7 in a Day Care Center Journal of Pediatrics 109287ndash291
12 CHAPTER 1 MOTIVATION
46 Ferguson J K L R Jorm C D Allen P KWhitehead and G L Gilbert 1995 Prospective Study ofDiarrhoeal Outbreaks in Child Long Daycare Centres in Western Sydney Medical Journal of Australia163137ndash140
47 Frost F J G F Craun and R L Calderon 1996 Waterborne Disease Surveillance Journal of theAmerican Water Works Association 8866ndash75
48 Farrington C P N J Andrews A D Beale and M A Catchpole 1996 A Statistical Algorithmfor the Early Detection of Outbreaks of Infectious Disease Journal of the Royal StatisticalSociety A 159547ndash563
REFERENCES 13
CHAPTER2MICROBIAL AGENTS ANDTRANSMISSION
MICROBIAL TAXONOMY
The development of techniques for examining the nucleic acids of microorganisms hasseen major changes in which we classify and group related microorganisms This isespecially true for the study of ribosomal ribonucleic acid (rRNA) which is a highlyconserved sequence involved in the synthesis of proteins in all living organisms Basedon this analysis the classification of living things has been placed into a three-domainsystem consisting of Archaea Eukarya and Bacteria Of these the Bacteria andArchaea are termed prokaryotes (no organized cell nucleus) and the Eukarya areknown as eukaryotes (an organized cell nucleus) Eukaryotic microbes other thanalgae and fungi are collectively calledprotistsWithin theEukarya are fungi protozoahelminth worms algae plants animals and humans Archaea are microbes that looksomewhat similar to bacteria in size and shape under the light microscope but they areactually genetically and biochemically quite different They appear to be a simpler formof life and may in fact be the oldest form of life on earth Viruses are obligate intercel-lular parasites and are not amember of any group They are usually composed only of anucleic acid surrounded by a protein coat Eukaryotes are much more complex thanprokaryotic cells in structure and nutritional requirements Prokaryotes divide by sim-ple binary fissionwhereas eukaryotes divide byamore complexprocess calledmitosis
Eukaryotes
Fungi protozoa and helminth worms are all eukaryotes All contain members that arepathogenic to man and animals While algae do not infect humans they can producetoxins that are harmful to animals and man Fungi obtain nutrients solely by adsorp-tion of organic matter from dead organisms Even when they invade living tissuesthey typically kill cells and then adsorb the nutrients from them Some fungi are capa-ble of developing environmentally resistant spores which can be transported throughthe air Fungal diseases in humans are referred to asmycoses Airborne fungal sporesare responsible for some allergies in humans Yeasts are classified with the fungi and
Quantitative Microbial Risk Assessment Second Edition Charles N Haas Joan B Roseand Charles P Gerbacopy 2014 John Wiley amp Sons Inc Published 2014 by John Wiley amp Sons Inc
15
some are pathogenic to humans (Candida albicans) Certain fungi produce toxins(ie aflatoxins) when growing in foods that are mutagenic and carcinogenic in ani-mals Inhalation is an important route of transmission for some fungal diseases suchas aspergillosis blastomycosis coccidioidomycosis and histoplasmosis These fungiare found growing in animal feces soil or decaying organic matter (compost manure)and may be transmitted through the air when this matter is disturbed Some fungi maybe transmitted by direct contact with the skin Fungi are often found in drinking waterdistribution systems and they have been linked to infections in immunocompromisedindividuals [1] Food is not believed to be a significant route of transmission ofpathogenic fungi
Protozoans are unicellular organisms that are surrounded by a cytoplasmicmembrane that is covered by a protective structure called a pellicle Most are freeliving feeding off of bacteria Some of these can cause disease while others are obli-gate parasites They are capable of forming structures called cysts oocysts or spores(depending on the life cycle of the organism) resistant to adverse environmentalconditions such as desiccation starvation high temperatures and disinfectantsSome pathogenic protozoa are found mainly in the soil (Naegleria) or water(Acanthamoeba) Others such a Giardia and Cryptosporidium whose natural habitatis the intestines of warm-blooded animals are capable of causing disease in bothhumans and animals Others such as Entamoeba histolytica are only capable ofcausing disease in humans
Pathogenic enteric (replicate in the intestines) protozoans are usually excretedin the feces or urine and can be transmitted by fecally contaminated food and waterSome protozoa may be transmitted through the air (Acanthamoeba) or throughfomites (inanimate objects) Some important environmentally transmitted protozoaare listed in Table 21 The clinically important protozoa are divided taxonomicallyinto the amoebas (Entamoeba spp) flagellates (Giardia) and coccidian meaningldquoglobose in shaperdquo (Cryptosporidium and Cyclospora) Microsporidia are alsocapable of causing intestinal infections but their classification is uncertain becausethey have many characteristics associated with fungi They are all obligate parasitesand are transmitted via infectious cysts oocysts or spores by the fecalndashoral routeThe life cycles of these protozoa are similar The initial stage occurs during ingestionof the cyst oocyst or spore After ingestion the body temperature and passagethrough the stomach cause these infective stages to open up in a process calledexcystation
The Giardia cysts house two trophozoites which is the stage that attaches tointestinal cells and grows in the intestinal tract through asexual reproduction As thetrophozoites grow and begin to cover the wall of the intestinal tract diarrhea canresult As the trophozoites are released some form cysts as they pass through thebowels Cryptosporidium and Cyclospora both produce oocysts The life cycle ofCyclospora is still not well known except that its oocysts require some period of timein the environment before they are infective Cryptosporidium oocysts contain foursporozoites which enter the intestinal cells and begin the infection process As morecells become infected the illness begins and oocysts are excreted in high numbers inthe feces (about 100000g)
Worms and helminths are small multicellular animals that are parasiticto humans and animals They include flukes tapeworms and roundworms
16 CHAPTER 2 MICROBIAL AGENTS AND TRANSMISSION
Applications 332
Exposure Assessment 332
DosendashResponse Assessment 338
Combining Parametric Uncertainty from Multiple Sources 344
Propagation Methods 344
Monte Carlo Analyses 347
Overall Risk Characterization Example 365
Second-Order Methods 368
Model Uncertainty and Averaging 370
References 373
CHAPTER 10 POPULATION DISEASE TRANSMISSION 377
Introduction Models for Population and Community Illnesses 377
Basic SIR Model 378
Incubation Period 386
Duration of Illness 388
Secondary Cases 389
Impact of Immunity 392
Outbreak Detection 393
References 397
CHAPTER 11 RISK CHARACTERIZATION AND DECISION MAKING 399
Introduction 399
Valuing Residual Outcomes 400
Classical Economics 400
DALYs and QALYs 404
Decision Making 407
CostndashBenefit Analysis 408
Multivariate Approaches 411
Other Aspects Entering into a Decision 412
Equity and Justice Aspects 412
References 413
INDEX 415
CONTENTS ix
PREFACE
In the 14 years since we prepared the first edition there has been an explosion inknowledge of and need for quantitative microbial risk assessment (QMRA) Whileour motivation for the first edition stemmed from concerns (principally in water) aboutenteric bacteria viruses and protozoa the motivation has now exploded to newdomains and agents SARS influenza biothreat agents and zoonotic pathogens haveall become of greater concern
The 2001 anthrax letters have highlighted the need for risk assessment ofinhaled agents Both biothreat agents and emergence of new strains of virulentcontagious organisms have raised concern for modeling pathogen dynamics inpopulations
In this edition we have retained the fundamental approach of the riskassessment methodology as a central paradigm We have added new material onmodern pathogen analytical methods predictive microbiology (of pathogen growthand decay) dynamic risk models (explicitly considering incubation time) and diseasepropagation models in populations Of necessity we have removed some materialmdashitis no longer possible to present comprehensive tables of microbial dosendashresponseparameters
In the years since the first edition the authors have gained experience inteaching this material to generations of studentsmdashin the form of formal classestutorials independent studies and short courses We know this book can be valuablein instructing advanced students in environmental sciences environmental engineer-ing public health and microbiology It is also a useful reference for practitionersand regulatory personnel Some prior statistical background would be useful inapproaching the material but not necessary the key requirement for any risk assessoris the absence of fear from mathematical constructs and concepts
The three of us have been on a QMRA journey for almost 30 years We havelearned that doing high-quality risk assessments is of necessity a team sport requiringindividuals with different skills and interests We have learned a tremendous amountfrom each other from our students from our collaborators and from the problems thatwe have sought to approach Practitioners of the art of quantitative microbial riskassessment should be advised to cast a wide net with respect to colleagues andcollaborators to perfect their craft
xi
We encourage comments and feedback from users of this work and look for-ward to observing and participating in developments in coming years and ultimatelyto handing the baton off to our students and their students
Charles N Haas
Joan B Rose
Charles P GerbaNovember 2013
xii PREFACE
CHAPTER1MOTIVATION
THE PREVENTION of infectious disease transmission from human exposure tocontaminated food water soil and air remains a major task of environmental andpublic health professionals There are numerous microbial hazards including expo-sure via food water air and malicious release of pathogens that may arise Indeedsome have argued that the property of virulence of human pathogens is one which isfavored by evolutionary interactions between pathogens and host populations andtherefore will always be of important concern [1] To make rational decisions in pre-paring responding and recovering from exposures to such hazards a quantitativeframework is of high benefit
The objective of this book is to comprehensively set forth the methods forassessment of risk from infectious agents transmitted via these routes in a frameworkthat is compatible with the framework for other risk assessments (eg for chemicalagents) as set forth in standard protocols [2 3]
In this chapter information on the occurrence of infectious disease in broadcategories will be presented along with a historical background on prior methodsfor assessment of microbial safety of food water and air This will be followed byan overview of key issues covered in this book
PREVALENCE OF INFECTIOUS DISEASE
Outbreaks of infectious waterborne illness continue to occur although it remainsimpossible to identify the infectious agent in all cases For example in 1991 a water-borne outbreak in Ireland resulting from sewage contamination of water suppliesinfected about 5000 persons However the infectious agent responsible for thisoutbreak could not be determined [4] In the United States it has been estimated that38 million cases of foodborne infectious disease occur annually with unidentifiedagents [5]
In the United States there have typically been three to five reported outbreaksper year in community drinking water systems involving infectious microorganismswith perhaps up to 10000 annual cases [6] The 1994 Milwaukee Cryptosporidiumoutbreak with over 400000 cases [7 8] was a highly unusual event among thesestatistics As shown in Figure 11 there has been an increasing ability to identify
Quantitative Microbial Risk Assessment Second Edition Charles N Haas Joan B Roseand Charles P Gerbacopy 2014 John Wiley amp Sons Inc Published 2014 by John Wiley amp Sons Inc
1
microorganisms responsible for waterborne diseases and it is expected that withadvances in molecular biology this will increase
There are substantially more outbreaks and cases of foodborne infectiousdiseases than are reported Table 11 summarizes reports of US cases of principalmicrobial infectious foodborne illnesses for two 5-year periods (1988ndash1992 and
1971ndash1982
10
20
30
40
Perc
ent o
f out
brea
ks
50
60
1983ndash1994Period
1995ndash2006
Figure 11 Percentages of outbreaks associated with public water systems (n = 680) by timeperiod 1971ndash2006 that had unknown etiologies based on data from Ref [6]
TABLE 11 Comparison of Five-Year Averages for Common Foodborne Reported Outbreaks
Agent
Annual Average 1988ndash1992 Annual Average 2002ndash2006
Cases Outbreaks Cases Outbreaks
Campylobacter 996 44 624 22
Escherichia coli 488 22 481a 30a
Salmonella 42354 1098 3475 144
Shigella 9576 5 495 12
Staphylococcus aureus 3356 94 554 25
Hepatitis 4218 86 238 1
Listeria monocytogenes 04 02 22 2
Giardia 368 14 2 1
Norovirus 584 04 10854 338
Vibrio (all) 114 18 114 5
Unknown etiologies 40483 1422 4052 30
Source From Refs [9 10]a Include both Shiga toxigenic and enterotoxigenic
2 CHAPTER 1 MOTIVATION
2002ndash2006) There is a mix of causal agents including bacteria virus and protozoaIt is noteworthy that (as in the case of waterborne outbreaks) the frequency ofoutbreaks of unknown etiology has dramatically decreased but the frequency of out-breaks associated with norovirus has dramatically increased These changes are duein part to the ability to better identify causal agents (eg via molecular methods)
It is generally recognized that reported outbreaks either of water- or foodborneinfectious disease represent only a small fractionof the total populationdisease burdenHowever particularly in the United States voluntary reporting systems and theoccurrence of mild cases (for which no medical attention is sought but neverthelessare frank cases of disease) have made it difficult to estimate the total caseload
In the United Kingdom comparisons between the number of confirmed casesin infectious disease outbreaks and total confirmed laboratory illnesses (occurring inEngland and Wales) have been made (Table 12) This suggests that the ratio ofreported outbreak cases to total cases that may seek medical attention may be from10 to 5001 with some dependency on the particular agent
Colford et al [12] developed estimates for the total disease burden associatedwith acute gastroenteritis from drinking water This relies on combining the reportedoutbreak data with interventional epidemiologic studies Based on their analysis thetotal US disease burden is estimated to be 426ndash1169 million cases per year in theUnited States which is substantially in excess of the reported outbreaks In the case offoodborne illness there are an estimated 14 million cases per year [13]
Drinking water and food are by no means the only potential routes of exposureto infectious agents in the environment Recreation in water (either natural or artificialpools) containing pathogens can produce illness [14]
Indoor air transmission can be a vehicle of infection Legionella transmittedthrough indoor environments has been a concern since the 1970s [15] The multina-tional epidemic of severe acute respiratory syndrome (SARS) caused by a coronavi-rus was abetted at least in one location in Hong Kong by indoor aerosol transmissionbetween apartments of infected individuals and susceptible individuals [16] A broadspectrum of other respiratory pathogens including influenza rhinoviruses and myco-bacteria can be transmitted by this route [17]
TABLE 12 Comparison of Laboratory Isolations and Outbreak Cases in Englandand Wales 1992ndash1994
Agent
Cases 1992ndash1994
RatioAll Laboratory Reports Confirmed Outbreak Cases
Campylobacter 122250 240 5094
Rotavirus 47463 127 3737
S sonnei 29080 847 343
Salmonella 92416 5960 155
Cryptosporidium 14454 1066 136
E coli O157 1266 128 99
Source Modified from Ref [11]
PREVALENCE OF INFECTIOUS DISEASE 3
The deliberate release of Bacillus anthracis spores in 2001 (the ldquoAmerithraxrdquoincidents) brought widespread awareness to the potential for indoor releases (as wellas releases in other venues) of bioterrorist agents to cause risk [18] Therefore ofnecessity microbial risk assessors may need to consider the impact of maliciousactivity in certain applications
PRIOR APPROACHES
Concerns for microbial quality of food water and other environmental media havelong existed In the early twentieth century the use of indicator microorganismswas developed for the control and assessment of the hygienic quality of such mediaand the adequacy of disinfection and sterilization processes The coliform group oforganisms was perhaps first employed for this purpose [19ndash21] Indicator techniqueshave also found utility in the food industry such as the total count for milk and othermore recent proposals [22] Other indicator groups for food water or environmentalmedia have been examined such as enterococci [23ndash25] acid-fast bacteria [26]bacteriophage [27ndash29] and Clostridia spores [29ndash31]
The use of indicator organisms was historically justified in because of difficultyin enumerating pathogens However with the increasing availability of modernmicrobial methods for example PCR immunoassay etc for direct pathogen assess-ment this justification has become less persuasive In addition in order to develophealth-based standards from indicators extensive epidemiologic surveillance is oftennecessary The use of epidemiology has limitations with respect to detection limits(for an adverse effect) and is also quite expensive to conduct Indicator methodsare also limited in that many pathogens are more resistant to die off in receiving envir-onments or source waters than indicators or have greater resistance to removal bytreatment processes than indicators [26 28 29 32] Thus the absence of indicatorsmay not suffice to ensure the absence of pathogens Even after a century of use theindicator concept remains imperfect [33]
The use of quantitative microbial risk assessment (QMRA) will enable directmeasurements of pathogens to be used to develop acceptancerejection guidelinesfor food water and other vehicles that may be the source of microbial exposureto human populations The objective of this book is to present these methods in asystematic and unified manner
SCOPE OF COVERAGE
QMRA is the application of principles of risk assessment to the estimate ofconsequences from a planned or actual exposure to infectious microorganismsIn performing a QMRA the risk assessor aims to bring the best available informationto bear in understanding the nature of the potential effects from a microbial exposureSince the information (such as dosendashresponse relationships exposure magnitudes) isalmost invariably incomplete it is also necessary to ascertain the potential error
4 CHAPTER 1 MOTIVATION
involved in the risk assessment With such information necessary steps to mitigatecontrol or defend against such exposures may be developed
At the outset of performing a risk assessment a scoping task should be under-taken This task should set forth the objectives of the analysis and the principal issuesto be addressed Items such as consideration of secondary cases individual versuspopulation risk agent or agents to be examined exposure routes andor accident sce-narios must be stipulated However this scoping may be changed during the course ofa QMRA to reflect the input derived from the risk manager(s) and other stakeholders
POTENTIAL OBJECTIVES OF A QMRA
There may be diverse objectives for a QMRA These objectives relate to the rationalefor the performance of the assessment as well as the methods to be employedBroadly the different objectives reflect different scales at which a risk assessmentmay be performed The step of problem formulation is critical to any risk estimate[34] It is necessary that the problem be formulated to meet the needs of the riskmanagers and stakeholders indeed it is now recognized that the successful practiceof risk analysis requires frequent interchange with manager and stakeholders [3]In general the problems posed are of several types
Site-Specific Assessment
The simplest type of QMRA that may be performed involves one site or exposurescenario The following are typical of the questions that might be asked
1 If a water treatment plant is designed in a certain way (with given removals ofpathogens) then what is the risk that would be placed upon the populationserved
2 A swimming outbreak (in a recreational lake) has just occurred I believe that itresulted from a short-duration contamination event What pathogen levelswould be consistent with the observed attack rate
3 Microbial sampling of a finished food product has found certain pathogensWhat level of risk does this pose to consumers of the product
4 A certain amount of infectious agent has been released into a room What is theimmediate danger to occupants and how stringent should cleanup levels be
Note that there are certain other contrasts in the objectives of the risk assessments tobe posed In (1) and (3) a before-the-fact computation is desired while in (2) and (4)an after-the-fact computation is described Also in (1) (3) and (4) pathogen levelsare available (or somehow are estimated) while in (2) an inverse computation isneeded given an observed attack rate
In performing this risk assessment the relationship between an exposure ortechnological metric and a risk measurement must be ascertained and then theparticular point of correspondence determined (Fig 12) In cases (1) (3) and (4)for a known (or assumed) exposure (on the x-axis) the corresponding range of risks
POTENTIAL OBJECTIVES OF A QMRA 5
on the y-axis is sought In cases (2) for known or assumed risks (on the y-axis)the corresponding range of exposures (or level of technological protection) is to bedetermined (on the x-axis)
Ensemble of Sites
A somewhat more complex situation occurs if the risk for a set of events or sites mustbe estimated Basically this now includes the necessity to incorporate site-to-sitefactors into the assessment Some examples of this are as follows
1 If I desire keeping the risk to a population served by multiple water treatmentplants at a given level (or better) then what criteria should I use (microbiallevels)
2 For a food product subject to contamination by pathogens what would be anacceptable treatment specification (eg heating time holding period) to ensuremicrobial acceptability
3 I am designing a water quality standard for recreational bathing waters If auniform (eg national) standard is to be developed what standard would ensurethat average risk was acceptable with keeping the risk of a large ldquoclusterrdquo ofillnesses low
In addition to incorporating a measure of ensemble average risk in general it is alsodesired to ensure that no single member of the ensemble be unacceptably extreme Forexample consider the evaluation of three options of disease control among three com-munities as indicated in Table 13
This table indicates the number of cases and the rate among the three commu-nities The three policy options yield the same number of expected cases Howeverthere are differences in the allocation of risk among the communities of different sizesIn option A all communities have an identical level of estimated risk In option B therisk increases as community size decreases while in option C the risk increases ascommunity size increases This distribution of risk among affected subsets of the
Exposure
Ris
k
Level of technological protection
Figure 12 Relationship between exposurelevel of technological protection andmicrobial risk The middle curve indicatesthe best estimate The other two curvesindicate the upper and lower confidenceregions
6 CHAPTER 1 MOTIVATION
ensemble being considered adds an additional dimension for consideration by a riskmanagermdashwhich may be termed risk equity
SECONDARY TRANSMISSION
Infectious microbial diseases are different in terms of risk to a population than arechemical agents in that an individual who may become infected (with or withoutillness) can then proceed to infect additional individuals These secondary (tertiaryquaternary etc) cases may be persons who had no direct contact with the initialvehicle of exposure but nevertheless in fairly accounting for the public health impactthey should be considered
Secondary cases may arise by a variety of mechanisms Particularly amongclose family members household secondary cases can arise by direct or indirect(eg surface contamination) contact this is particularly so when the primary caseor one household secondary case is a child [35ndash37] Table 14 summarizes secondarycase statistics obtained from a variety of outbreaks As will be discussed inChapter 10 the secondary case rate is a complex factor involving (among other things)the nature of the venue and contact patterns when infected and susceptible individualsintermingle
Presumably secondary cases may also arise from close contact with anasymptomatic individual (in the ldquocarrierrdquo state) This is well known for highly acuteand (now) uncommon illnesses (such as typhoid) Excretion of Norwalk virusfollowing recovery (and resulting in additional cases) has been documented to occurfor as long as 48 h post recovery [44]
OUTBREAKS VERSUS ENDEMIC CASES
As noted previously there may be a substantial difference between reported outbreakcases and total disease burden in a community In order for a disease case to receiverecognition by the public health authorities the following specific and sequential stepsmust occur [47]
TABLE 13 Effect of Different Hypothetical Policy Options on Distribution of Risk AmongCommunities (for a Fixed Total Risk)
CommunityExposedPopulation
Policy Option A Policy Option B Policy Option C
CasesIncidence(10000) Cases
Incidence(10000) Cases
Incidence(10000)
A 100000 20 2 6 06 24 24
B 50000 10 2 18 36 7 14
C 10000 2 2 8 8 1 1
Total 160000 32 2 32 2 16 2
OUTBREAKS VERSUS ENDEMIC CASES 7
1 An ill person must seek medical care
2 Appropriate clinical tests (eg blood stool) must be ordered by the attendingphysician
3 The patient must comply with obtaining the sample
4 The laboratory must be capable of detecting the relevant pathogens
5 The clinical test must be positive
6 The test result must be reported to the health agency in a timely manner
If any of the links in this sequential chain are broken then a disease case will not enterthe records maintained by health authorities For example with increasing controls on
TABLE 14 Summary of Secondary Case Data in Outbreak Situations
Organism
SecondaryAttackRatioa
SecondaryPrevalence inHouseholdsb Remarks Reference
Cryptosporidiumparvum
033 033 Outbreak in contaminatedapple cider
[38]
C parvum NA 0042 Drinking water outbreak(Milwaukee)
[37]
Shigella 028 026 Day-care center outbreaksin children
[39]
Rotavirus 042 015 Day-care center outbreaksin children
[30]
Giardia lamblia 133 017 Day-care center outbreaksin children
[39]
Viral gastroenteritis 022 011c Drinking waterborneoutbreak
[40]
Viral gastroenteritis 056 NA Drinking water outbreak(Denmark)
[41]
Norovirus 05ndash10 019 Swimming outbreak [42]
Norovirus 11 029 Swimming outbreakin children
[43]
Norovirus NA 044 Foodborne outbreakin children and teachers
[36]
Norovirus 04 NA Foodborne outbreak [44]
E coli O157H7 NA 018c Day-care center outbreakin children
[45]
Unidentifiedday-care diarrhealdiseases
138 009c [46]
NA information not availableaRatio of secondary cases to primary casesb Proportion of households with one or more primary cases who have one or more secondary casesc Proportion of persons in contact with one or more primary cases who have a secondary case
8 CHAPTER 1 MOTIVATION
medical care stool samples may not be obtained from mild cases of illness Someorganisms may only be present sporadically or may be difficult to test in stool orblood sample Patients may not seek medical attention for mild cases of illness Fur-thermore in the United States in particular the surveillance of environmentallyinduced disease is done on a passive basis and hence the number of actual illnessclusters that are actually compiled into recorded statistics is only a small fractionof such clusters of illness that occur [47]
From a more fundamental point of view an outbreak of illness is generallydefined as occurrence of the illness at a level greater than normal or anticipated Thisdefinition recognizes that there is a level of illness (endemic) that may exist underusual circumstances The detection of such outbreaks poses a particular challengeThe problem is illustrated conceptually in Figure 13
Additional complications arise from the different patterns of illness in acommunity including definite periodicities as well as temporal trends and fromthe presence of reporting lags associated with laboratory analysis and time for patientsto seek medical attention Figure 14 illustrates the different patterns of illness inthe case of six pathogens for England and Wales [48]
In the case of waterborne and foodborne illnesses it is highly likely that thelevel of such endemic illnesses is substantially greater than those occurring duringoutbreaks (even accounting for unrecognized outbreaks)
As a result there are often many cases of environmentally caused (water airfood) infectious disease that are unrecognized One example of this isCampylobacterThere has been an average of about 200 cases per year of water- and foodborne illnessin outbreaks of this organism and yet estimates of the disease burden suggest about2100000 cases per year that is approximately 10000 cases per case of detectableoutbreak illness Therefore it will be important to assess the factors that may influenceoutbreak detection These issues will be discussed in subsequent chapters
Detectedoutbreak
Undetectedoutbreak
Threshold of detection
Hyper endemicSporadic
Endemic rate
Time
Num
ber
of c
ases
Figure 13 Schematic of disease occurrence in a hypothetical community (Modified fromRef [47])
OUTBREAKS VERSUS ENDEMIC CASES 9
REFERENCES
1 Levin B R 1996 The Evolution and Maintenance of Virulence in Microparasites Emerging InfectiousDisease 293ndash102
2 National Academy of Sciences 1983 Risk Assessment in the Federal Government Managing theProcess National Academy Press Washington DC
3 National Research Council 2009 Science and Decisions Advancing Risk Assessment NationalAcademies Press Washington DC
10090807060504030201001190 1191 1192 1193 1194 1195
(b)
140
120
100
80
60
40
20
01190 1191 1192 1193 1194 1195
(f)
700
600
500
400
300
200
100
01190 1191 1192 1193 1194 1195
(d)
1200
1000
800
600
400
200
1190 1191 1192 1193 1194 1195
(a)
240
200
160
120
80
40
01190 1191 1192 1193 1194 1195
(e)
7
6
5
4
3
2
1
01190 1191 1192 1193 1194 1195
(c)
Figure 14 Weekly count of reported organism isolations in England andWales (a) rotavirus(b) Clostridium difficile (c) Salmonella derby (d) Shigella sonnei (e) influenza B and (f)Salmonella typhimurium DT 104 (From Ref [48])
10 CHAPTER 1 MOTIVATION
4 Fogarty J L Thornton and R Corcoran 1995 Illness in a Community Associated with an Episode ofWater Contamination with Sewage Epidemiology and Infection 114289ndash295
5 Scallan E 2011 Foodborne Illness Acquired in the United StatesmdashUnspecified Agents EmergingInfectious Diseases 17 16ndash22
6 Craun G F J M Brunkard J S Yoder V A Roberts J Carpenter T Wade R L CalderonJ M Roberts M J Beach and S L Roy 2010 Causes of Outbreaks Associated with Drinking Waterin the United States from 1971 to 2006 Clinical Microbiology Reviews 23507ndash528
7 Edwards D D 1993 Troubled Waters in Milwaukee ASM News 59342ndash3458 MacKenzie W R N J Hoxie M E Proctor M S Gradus K A Blair D E Peterson
J J Kazmierczak K R Fox D G Addias J B Rose and J P Davis 1994 Massive WaterborneOutbreak of Cryptosporidium Infection Associated with a Filtered Public Water Supply MilwaukeeWisconsin March and April 1993 New England Journal of Medicine 331161ndash167
9 Anonymous 2010 Surveillance for Foodborne Disease OutbreaksmdashUnited States 2007 Morbidityand Mortality Weekly Reports 59973ndash979
10 Bean N H J S Goulding C Lau and F J Angulo 1996 Surveillance for Foodborne-DiseaseOutbreaksmdashUnited States 1988ndash1992 Morbidity and Mortality Weekly Reports 451ndash66
11 Wall P G J de Louvois R J Gilbert and B Rowe 1996 Food Poisoning NotificationsLaboratory Reports and OutbreaksmdashWhere do the Statistics Come From and What Do They MeanCommunicable Disease Report Review 6 R93ndashR100
12 Colford J M S Roy M J Beach A Hightower S E Shaw and T J Wade 2006 A Review ofHousehold Drinking Water Intervention Trials and an Approach to the Estimation of EndemicWaterborne Gastroenteritis in the United States Journal of Water and Health 471
13 Mead P S L Slutsker V Dietz L F McCaig J S Bresee C Shapiro P M Griffinand R V Tauxe 1999 Food Related Illness and Death in the United States Emerging InfectiousDisease 5607ndash625
14 Dziuban E J J L Liang G F Craun V Hill P A Yu J Painter M R Moore R L CalderonS L Roy and M J Beach 2006 Surveillance for Waterborne Disease and Outbreaks Associatedwith Recreational WatermdashUnited States 2003ndash2004 and Surveillance for Waterborne Disease andOutbreaks Associated with Drinking Water and Water not Intended for DrinkingmdashUnited States2003ndash2004 Morbidity and Mortality Weekly Reports 551ndash30
15 Fliermans C B 1996 Ecology of Legionella From Data to Knowledge with a Little WisdomMicrobial Ecology 32203ndash228
16 Li Y S Duan I T Yu and T W Wong 2005 Multi-Zone Modeling of Probable SARS VirusTransmission by Airflow Between Flats in Block E Amoy Gardens Indoor Air 1596ndash111
17 Peccia J D K Milton T Reponen and J Hill 2008 A Role for Environmental Engineering andScience in Preventing Bioaerosol-Related Disease Environmental Science amp Technology424631ndash4637
18 Jernigan D B P L Raghunathan B P Bell R Brechner E A Bresnitz J C Butler M CetronM Cohen T Doyle and M Fischer 2002 Investigation of Bioterrorism-Related AnthraxUnited States 2001 Epidemiologic Findings Emerging Infectious Diseases 81019ndash1028
19 Greenwood M and G U Yule 1917 On the Statistical Interpretation of Some BacteriologicalMethods Employed in Water Analysis Journal of Hygiene 1636ndash56
20 Phelps E 1909 The Disinfection of Sewage and Sewage Filter Effluents USGS Water Supply Paper229 GPO Washington DC
21 Rudolfs W and H W Gehm 1935 Multiplication of Total Bacteria and B coli after SewageChlorination Sewage Works Journal 7991ndash996
22 Subcommittee onMicrobiological Criteria 1985 An Evaluation of the Role ofMicrobiological Criteriafor Foods and Food Ingredients National Academy Press Washington DC
23 Cabelli V J A P Dufour L J McCabe and M A Levin 1982 Swimming-AssociatedGastroenteritis and Water Quality American Journal of Epidemiology 115606ndash616
24 Dufour A P 1984 Health Effects Criteria for Fresh Recreational Waters USEPA Research TrianglePark NC
25 Fleisher J M F Jones and D Kay 1993 Water and Non-Water-Related Risk Factors forGastroenteritis among Bathers Exposed to Sewage-Contaminated Marine Waters InternationalJournal of Epidemiology 22698ndash708
REFERENCES 11
26 Engelbrecht R S C N Haas J A Shular D L Dunn D Roy A Lalchandani B F Severin andS Farooq 1979 Acid-Fast Bacteria and Yeasts as Indicators of Disinfection Efficiency EPA-6002-79-091 US Environmental Protection Agency Cincinnati OH
27 Grabow W O K 1983 Inactivation of Hepatitis A Virus and Indicator Organisms in Water by FreeChlorine Residuals Applied and Environmental Microbiology 46619
28 Helmer R D and G R Finch 1993 Use of MS2 Coliphage as a Surrogate for Enteric Viruses inSurface Waters Disinfected with Ozone Ozone Science and Engineering 15279ndash293
29 Payment P and E Franco 1993Clostridium Perfringens and Somatic Coliphages as Indicators of theEfficiency of Drinking Water Treatment for Viruses and Protozoan Cysts Applied and EnvironmentalMicrobiology 592418ndash2424
30 Cabelli V J 1977Clostridium Perfringens as aWater Quality Indicator pp 65ndash79 InA Hoadley andB Dutka (eds) Bacterial IndicatorsHealth Hazards Associated with Water ASTM Philadelphia PA
31 Rice E W K R Fox R J Miltner D A Lytle and C H Johnson 1996 Evaluating PlantPerformance with Endospores Journal of the American Water Works Association 88122ndash130
32 Engelbrecht R S B F Severin M T Masarik S Farooq S H Lee C N Haas and A Lalchandani1977 New Microbial Indicators of Disinfection Efficiency EPA-6002-77-052 US EnvironmentalProtection Agency Cincinnati OH
33 Committee on Indicators for Waterborne Pathogens ndash National Research Council 2004 Indicators forWaterborne Pathogens National Academies Press Washington DC
34 PresidentialCongressional Commission on Risk Assessment and RiskManagement 1997 Frameworkfor Environmental Health Risk Management The Commission Washington DC
35 Griffin P M and R V Tauxe 1991 The Epidemiology of Infections Caused by Escherichiacoli O157H7 Other Enterohemorrhagic E coli and the Associated Hemolytic Uremic SyndromeEpidemiologic Reviews 1360ndash98
36 Heun E M R L Vogt P J Hudson S Parren and G W Gary 1987 Risk Factors for SecondaryTransmission in Households after a Common Source Outbreak of Norwalk Gastroenteritis AmericanJournal of Epidemiology 1261181ndash1186
37 MacKenzie W R W L Schell B A Blair D G Addiss D E Peterson N J HozieJ J Kazmierczak and J P Davis 1995 Massive Outbreak of Waterborne CryptosporidiumInfection in Milwaukee Wisconsin Recurrence of Illness and Risk of Secondary TransmissionClinical Infectious Diseases 2157ndash62
38 Millard P K Gensheimer D G Addiss D M Sosin G A Beckett A Houck-Jankoski andA Hudson 1994 An Outbreak of Cryptosporidiosis from Fresh-Pressed Apple Cider Journal ofthe American Medical Association 2721592ndash1596
39 Pickering L K D G Evans H L DuPont J J Vollet and D J Evans Jr 1981 Diarrhea Caused byShigella Rotavirus and Giardia in Day Care Centers Prospective Study Journal of Pediatrics9951ndash56
40 Morens D M R M Zweighaft T M Vernon G W Gary J J Eslien B T Wood R C Holmanand R Dolin 1979 A Waterborne Outbreak of Gastroenteritis with Secondary Person to PersonSpread Lancet 5964ndash966
41 Laursen E O Mygind B Rasmussen and T Ronne 1994 Gastroenteritis A Waterborne OutbreakAffecting 1600 People in a Small Danish Town Journal of Epidemiology amp Community Health48453ndash458
42 Baron R C F D Murphy H B Greenberg C E Davis D J Bregman G W Gary J M Hughesand L B Schonberger 1982 Norwalk Gastrointestinal Illness An Outbreak Associated withSwimming in a Recreational Lake and Secondary Person to Person Transmission American Journalof Epidemiology 115163ndash172
43 Kappus K D J S Marks R C Holman J K Bryant C Baker G W Gary and H B Greenberg1982 An Outbreak of Norwalk Gastroenteritis Associated with Swimming in a Pool and SecondaryPerson to Person Transmission American Journal of Epidemiology 116834ndash839
44 White K E M T Osterbolm J A Mariotti J A Korlath D H Lawrence T L Ristinen andH B Greenberg 1986 A Foodborne Outbreak of Norwalk Virus Gastroenteritis American Journalof Epidemiology 124120ndash126
45 Spika J S J E Parsons and D Nordenberg 1986 Hemolytic Uremic Syndrome and DiarrheaAssociated with Escherichia coli O157H7 in a Day Care Center Journal of Pediatrics 109287ndash291
12 CHAPTER 1 MOTIVATION
46 Ferguson J K L R Jorm C D Allen P KWhitehead and G L Gilbert 1995 Prospective Study ofDiarrhoeal Outbreaks in Child Long Daycare Centres in Western Sydney Medical Journal of Australia163137ndash140
47 Frost F J G F Craun and R L Calderon 1996 Waterborne Disease Surveillance Journal of theAmerican Water Works Association 8866ndash75
48 Farrington C P N J Andrews A D Beale and M A Catchpole 1996 A Statistical Algorithmfor the Early Detection of Outbreaks of Infectious Disease Journal of the Royal StatisticalSociety A 159547ndash563
REFERENCES 13
CHAPTER2MICROBIAL AGENTS ANDTRANSMISSION
MICROBIAL TAXONOMY
The development of techniques for examining the nucleic acids of microorganisms hasseen major changes in which we classify and group related microorganisms This isespecially true for the study of ribosomal ribonucleic acid (rRNA) which is a highlyconserved sequence involved in the synthesis of proteins in all living organisms Basedon this analysis the classification of living things has been placed into a three-domainsystem consisting of Archaea Eukarya and Bacteria Of these the Bacteria andArchaea are termed prokaryotes (no organized cell nucleus) and the Eukarya areknown as eukaryotes (an organized cell nucleus) Eukaryotic microbes other thanalgae and fungi are collectively calledprotistsWithin theEukarya are fungi protozoahelminth worms algae plants animals and humans Archaea are microbes that looksomewhat similar to bacteria in size and shape under the light microscope but they areactually genetically and biochemically quite different They appear to be a simpler formof life and may in fact be the oldest form of life on earth Viruses are obligate intercel-lular parasites and are not amember of any group They are usually composed only of anucleic acid surrounded by a protein coat Eukaryotes are much more complex thanprokaryotic cells in structure and nutritional requirements Prokaryotes divide by sim-ple binary fissionwhereas eukaryotes divide byamore complexprocess calledmitosis
Eukaryotes
Fungi protozoa and helminth worms are all eukaryotes All contain members that arepathogenic to man and animals While algae do not infect humans they can producetoxins that are harmful to animals and man Fungi obtain nutrients solely by adsorp-tion of organic matter from dead organisms Even when they invade living tissuesthey typically kill cells and then adsorb the nutrients from them Some fungi are capa-ble of developing environmentally resistant spores which can be transported throughthe air Fungal diseases in humans are referred to asmycoses Airborne fungal sporesare responsible for some allergies in humans Yeasts are classified with the fungi and
Quantitative Microbial Risk Assessment Second Edition Charles N Haas Joan B Roseand Charles P Gerbacopy 2014 John Wiley amp Sons Inc Published 2014 by John Wiley amp Sons Inc
15
some are pathogenic to humans (Candida albicans) Certain fungi produce toxins(ie aflatoxins) when growing in foods that are mutagenic and carcinogenic in ani-mals Inhalation is an important route of transmission for some fungal diseases suchas aspergillosis blastomycosis coccidioidomycosis and histoplasmosis These fungiare found growing in animal feces soil or decaying organic matter (compost manure)and may be transmitted through the air when this matter is disturbed Some fungi maybe transmitted by direct contact with the skin Fungi are often found in drinking waterdistribution systems and they have been linked to infections in immunocompromisedindividuals [1] Food is not believed to be a significant route of transmission ofpathogenic fungi
Protozoans are unicellular organisms that are surrounded by a cytoplasmicmembrane that is covered by a protective structure called a pellicle Most are freeliving feeding off of bacteria Some of these can cause disease while others are obli-gate parasites They are capable of forming structures called cysts oocysts or spores(depending on the life cycle of the organism) resistant to adverse environmentalconditions such as desiccation starvation high temperatures and disinfectantsSome pathogenic protozoa are found mainly in the soil (Naegleria) or water(Acanthamoeba) Others such a Giardia and Cryptosporidium whose natural habitatis the intestines of warm-blooded animals are capable of causing disease in bothhumans and animals Others such as Entamoeba histolytica are only capable ofcausing disease in humans
Pathogenic enteric (replicate in the intestines) protozoans are usually excretedin the feces or urine and can be transmitted by fecally contaminated food and waterSome protozoa may be transmitted through the air (Acanthamoeba) or throughfomites (inanimate objects) Some important environmentally transmitted protozoaare listed in Table 21 The clinically important protozoa are divided taxonomicallyinto the amoebas (Entamoeba spp) flagellates (Giardia) and coccidian meaningldquoglobose in shaperdquo (Cryptosporidium and Cyclospora) Microsporidia are alsocapable of causing intestinal infections but their classification is uncertain becausethey have many characteristics associated with fungi They are all obligate parasitesand are transmitted via infectious cysts oocysts or spores by the fecalndashoral routeThe life cycles of these protozoa are similar The initial stage occurs during ingestionof the cyst oocyst or spore After ingestion the body temperature and passagethrough the stomach cause these infective stages to open up in a process calledexcystation
The Giardia cysts house two trophozoites which is the stage that attaches tointestinal cells and grows in the intestinal tract through asexual reproduction As thetrophozoites grow and begin to cover the wall of the intestinal tract diarrhea canresult As the trophozoites are released some form cysts as they pass through thebowels Cryptosporidium and Cyclospora both produce oocysts The life cycle ofCyclospora is still not well known except that its oocysts require some period of timein the environment before they are infective Cryptosporidium oocysts contain foursporozoites which enter the intestinal cells and begin the infection process As morecells become infected the illness begins and oocysts are excreted in high numbers inthe feces (about 100000g)
Worms and helminths are small multicellular animals that are parasiticto humans and animals They include flukes tapeworms and roundworms
16 CHAPTER 2 MICROBIAL AGENTS AND TRANSMISSION
PREFACE
In the 14 years since we prepared the first edition there has been an explosion inknowledge of and need for quantitative microbial risk assessment (QMRA) Whileour motivation for the first edition stemmed from concerns (principally in water) aboutenteric bacteria viruses and protozoa the motivation has now exploded to newdomains and agents SARS influenza biothreat agents and zoonotic pathogens haveall become of greater concern
The 2001 anthrax letters have highlighted the need for risk assessment ofinhaled agents Both biothreat agents and emergence of new strains of virulentcontagious organisms have raised concern for modeling pathogen dynamics inpopulations
In this edition we have retained the fundamental approach of the riskassessment methodology as a central paradigm We have added new material onmodern pathogen analytical methods predictive microbiology (of pathogen growthand decay) dynamic risk models (explicitly considering incubation time) and diseasepropagation models in populations Of necessity we have removed some materialmdashitis no longer possible to present comprehensive tables of microbial dosendashresponseparameters
In the years since the first edition the authors have gained experience inteaching this material to generations of studentsmdashin the form of formal classestutorials independent studies and short courses We know this book can be valuablein instructing advanced students in environmental sciences environmental engineer-ing public health and microbiology It is also a useful reference for practitionersand regulatory personnel Some prior statistical background would be useful inapproaching the material but not necessary the key requirement for any risk assessoris the absence of fear from mathematical constructs and concepts
The three of us have been on a QMRA journey for almost 30 years We havelearned that doing high-quality risk assessments is of necessity a team sport requiringindividuals with different skills and interests We have learned a tremendous amountfrom each other from our students from our collaborators and from the problems thatwe have sought to approach Practitioners of the art of quantitative microbial riskassessment should be advised to cast a wide net with respect to colleagues andcollaborators to perfect their craft
xi
We encourage comments and feedback from users of this work and look for-ward to observing and participating in developments in coming years and ultimatelyto handing the baton off to our students and their students
Charles N Haas
Joan B Rose
Charles P GerbaNovember 2013
xii PREFACE
CHAPTER1MOTIVATION
THE PREVENTION of infectious disease transmission from human exposure tocontaminated food water soil and air remains a major task of environmental andpublic health professionals There are numerous microbial hazards including expo-sure via food water air and malicious release of pathogens that may arise Indeedsome have argued that the property of virulence of human pathogens is one which isfavored by evolutionary interactions between pathogens and host populations andtherefore will always be of important concern [1] To make rational decisions in pre-paring responding and recovering from exposures to such hazards a quantitativeframework is of high benefit
The objective of this book is to comprehensively set forth the methods forassessment of risk from infectious agents transmitted via these routes in a frameworkthat is compatible with the framework for other risk assessments (eg for chemicalagents) as set forth in standard protocols [2 3]
In this chapter information on the occurrence of infectious disease in broadcategories will be presented along with a historical background on prior methodsfor assessment of microbial safety of food water and air This will be followed byan overview of key issues covered in this book
PREVALENCE OF INFECTIOUS DISEASE
Outbreaks of infectious waterborne illness continue to occur although it remainsimpossible to identify the infectious agent in all cases For example in 1991 a water-borne outbreak in Ireland resulting from sewage contamination of water suppliesinfected about 5000 persons However the infectious agent responsible for thisoutbreak could not be determined [4] In the United States it has been estimated that38 million cases of foodborne infectious disease occur annually with unidentifiedagents [5]
In the United States there have typically been three to five reported outbreaksper year in community drinking water systems involving infectious microorganismswith perhaps up to 10000 annual cases [6] The 1994 Milwaukee Cryptosporidiumoutbreak with over 400000 cases [7 8] was a highly unusual event among thesestatistics As shown in Figure 11 there has been an increasing ability to identify
Quantitative Microbial Risk Assessment Second Edition Charles N Haas Joan B Roseand Charles P Gerbacopy 2014 John Wiley amp Sons Inc Published 2014 by John Wiley amp Sons Inc
1
microorganisms responsible for waterborne diseases and it is expected that withadvances in molecular biology this will increase
There are substantially more outbreaks and cases of foodborne infectiousdiseases than are reported Table 11 summarizes reports of US cases of principalmicrobial infectious foodborne illnesses for two 5-year periods (1988ndash1992 and
1971ndash1982
10
20
30
40
Perc
ent o
f out
brea
ks
50
60
1983ndash1994Period
1995ndash2006
Figure 11 Percentages of outbreaks associated with public water systems (n = 680) by timeperiod 1971ndash2006 that had unknown etiologies based on data from Ref [6]
TABLE 11 Comparison of Five-Year Averages for Common Foodborne Reported Outbreaks
Agent
Annual Average 1988ndash1992 Annual Average 2002ndash2006
Cases Outbreaks Cases Outbreaks
Campylobacter 996 44 624 22
Escherichia coli 488 22 481a 30a
Salmonella 42354 1098 3475 144
Shigella 9576 5 495 12
Staphylococcus aureus 3356 94 554 25
Hepatitis 4218 86 238 1
Listeria monocytogenes 04 02 22 2
Giardia 368 14 2 1
Norovirus 584 04 10854 338
Vibrio (all) 114 18 114 5
Unknown etiologies 40483 1422 4052 30
Source From Refs [9 10]a Include both Shiga toxigenic and enterotoxigenic
2 CHAPTER 1 MOTIVATION
2002ndash2006) There is a mix of causal agents including bacteria virus and protozoaIt is noteworthy that (as in the case of waterborne outbreaks) the frequency ofoutbreaks of unknown etiology has dramatically decreased but the frequency of out-breaks associated with norovirus has dramatically increased These changes are duein part to the ability to better identify causal agents (eg via molecular methods)
It is generally recognized that reported outbreaks either of water- or foodborneinfectious disease represent only a small fractionof the total populationdisease burdenHowever particularly in the United States voluntary reporting systems and theoccurrence of mild cases (for which no medical attention is sought but neverthelessare frank cases of disease) have made it difficult to estimate the total caseload
In the United Kingdom comparisons between the number of confirmed casesin infectious disease outbreaks and total confirmed laboratory illnesses (occurring inEngland and Wales) have been made (Table 12) This suggests that the ratio ofreported outbreak cases to total cases that may seek medical attention may be from10 to 5001 with some dependency on the particular agent
Colford et al [12] developed estimates for the total disease burden associatedwith acute gastroenteritis from drinking water This relies on combining the reportedoutbreak data with interventional epidemiologic studies Based on their analysis thetotal US disease burden is estimated to be 426ndash1169 million cases per year in theUnited States which is substantially in excess of the reported outbreaks In the case offoodborne illness there are an estimated 14 million cases per year [13]
Drinking water and food are by no means the only potential routes of exposureto infectious agents in the environment Recreation in water (either natural or artificialpools) containing pathogens can produce illness [14]
Indoor air transmission can be a vehicle of infection Legionella transmittedthrough indoor environments has been a concern since the 1970s [15] The multina-tional epidemic of severe acute respiratory syndrome (SARS) caused by a coronavi-rus was abetted at least in one location in Hong Kong by indoor aerosol transmissionbetween apartments of infected individuals and susceptible individuals [16] A broadspectrum of other respiratory pathogens including influenza rhinoviruses and myco-bacteria can be transmitted by this route [17]
TABLE 12 Comparison of Laboratory Isolations and Outbreak Cases in Englandand Wales 1992ndash1994
Agent
Cases 1992ndash1994
RatioAll Laboratory Reports Confirmed Outbreak Cases
Campylobacter 122250 240 5094
Rotavirus 47463 127 3737
S sonnei 29080 847 343
Salmonella 92416 5960 155
Cryptosporidium 14454 1066 136
E coli O157 1266 128 99
Source Modified from Ref [11]
PREVALENCE OF INFECTIOUS DISEASE 3
The deliberate release of Bacillus anthracis spores in 2001 (the ldquoAmerithraxrdquoincidents) brought widespread awareness to the potential for indoor releases (as wellas releases in other venues) of bioterrorist agents to cause risk [18] Therefore ofnecessity microbial risk assessors may need to consider the impact of maliciousactivity in certain applications
PRIOR APPROACHES
Concerns for microbial quality of food water and other environmental media havelong existed In the early twentieth century the use of indicator microorganismswas developed for the control and assessment of the hygienic quality of such mediaand the adequacy of disinfection and sterilization processes The coliform group oforganisms was perhaps first employed for this purpose [19ndash21] Indicator techniqueshave also found utility in the food industry such as the total count for milk and othermore recent proposals [22] Other indicator groups for food water or environmentalmedia have been examined such as enterococci [23ndash25] acid-fast bacteria [26]bacteriophage [27ndash29] and Clostridia spores [29ndash31]
The use of indicator organisms was historically justified in because of difficultyin enumerating pathogens However with the increasing availability of modernmicrobial methods for example PCR immunoassay etc for direct pathogen assess-ment this justification has become less persuasive In addition in order to develophealth-based standards from indicators extensive epidemiologic surveillance is oftennecessary The use of epidemiology has limitations with respect to detection limits(for an adverse effect) and is also quite expensive to conduct Indicator methodsare also limited in that many pathogens are more resistant to die off in receiving envir-onments or source waters than indicators or have greater resistance to removal bytreatment processes than indicators [26 28 29 32] Thus the absence of indicatorsmay not suffice to ensure the absence of pathogens Even after a century of use theindicator concept remains imperfect [33]
The use of quantitative microbial risk assessment (QMRA) will enable directmeasurements of pathogens to be used to develop acceptancerejection guidelinesfor food water and other vehicles that may be the source of microbial exposureto human populations The objective of this book is to present these methods in asystematic and unified manner
SCOPE OF COVERAGE
QMRA is the application of principles of risk assessment to the estimate ofconsequences from a planned or actual exposure to infectious microorganismsIn performing a QMRA the risk assessor aims to bring the best available informationto bear in understanding the nature of the potential effects from a microbial exposureSince the information (such as dosendashresponse relationships exposure magnitudes) isalmost invariably incomplete it is also necessary to ascertain the potential error
4 CHAPTER 1 MOTIVATION
involved in the risk assessment With such information necessary steps to mitigatecontrol or defend against such exposures may be developed
At the outset of performing a risk assessment a scoping task should be under-taken This task should set forth the objectives of the analysis and the principal issuesto be addressed Items such as consideration of secondary cases individual versuspopulation risk agent or agents to be examined exposure routes andor accident sce-narios must be stipulated However this scoping may be changed during the course ofa QMRA to reflect the input derived from the risk manager(s) and other stakeholders
POTENTIAL OBJECTIVES OF A QMRA
There may be diverse objectives for a QMRA These objectives relate to the rationalefor the performance of the assessment as well as the methods to be employedBroadly the different objectives reflect different scales at which a risk assessmentmay be performed The step of problem formulation is critical to any risk estimate[34] It is necessary that the problem be formulated to meet the needs of the riskmanagers and stakeholders indeed it is now recognized that the successful practiceof risk analysis requires frequent interchange with manager and stakeholders [3]In general the problems posed are of several types
Site-Specific Assessment
The simplest type of QMRA that may be performed involves one site or exposurescenario The following are typical of the questions that might be asked
1 If a water treatment plant is designed in a certain way (with given removals ofpathogens) then what is the risk that would be placed upon the populationserved
2 A swimming outbreak (in a recreational lake) has just occurred I believe that itresulted from a short-duration contamination event What pathogen levelswould be consistent with the observed attack rate
3 Microbial sampling of a finished food product has found certain pathogensWhat level of risk does this pose to consumers of the product
4 A certain amount of infectious agent has been released into a room What is theimmediate danger to occupants and how stringent should cleanup levels be
Note that there are certain other contrasts in the objectives of the risk assessments tobe posed In (1) and (3) a before-the-fact computation is desired while in (2) and (4)an after-the-fact computation is described Also in (1) (3) and (4) pathogen levelsare available (or somehow are estimated) while in (2) an inverse computation isneeded given an observed attack rate
In performing this risk assessment the relationship between an exposure ortechnological metric and a risk measurement must be ascertained and then theparticular point of correspondence determined (Fig 12) In cases (1) (3) and (4)for a known (or assumed) exposure (on the x-axis) the corresponding range of risks
POTENTIAL OBJECTIVES OF A QMRA 5
on the y-axis is sought In cases (2) for known or assumed risks (on the y-axis)the corresponding range of exposures (or level of technological protection) is to bedetermined (on the x-axis)
Ensemble of Sites
A somewhat more complex situation occurs if the risk for a set of events or sites mustbe estimated Basically this now includes the necessity to incorporate site-to-sitefactors into the assessment Some examples of this are as follows
1 If I desire keeping the risk to a population served by multiple water treatmentplants at a given level (or better) then what criteria should I use (microbiallevels)
2 For a food product subject to contamination by pathogens what would be anacceptable treatment specification (eg heating time holding period) to ensuremicrobial acceptability
3 I am designing a water quality standard for recreational bathing waters If auniform (eg national) standard is to be developed what standard would ensurethat average risk was acceptable with keeping the risk of a large ldquoclusterrdquo ofillnesses low
In addition to incorporating a measure of ensemble average risk in general it is alsodesired to ensure that no single member of the ensemble be unacceptably extreme Forexample consider the evaluation of three options of disease control among three com-munities as indicated in Table 13
This table indicates the number of cases and the rate among the three commu-nities The three policy options yield the same number of expected cases Howeverthere are differences in the allocation of risk among the communities of different sizesIn option A all communities have an identical level of estimated risk In option B therisk increases as community size decreases while in option C the risk increases ascommunity size increases This distribution of risk among affected subsets of the
Exposure
Ris
k
Level of technological protection
Figure 12 Relationship between exposurelevel of technological protection andmicrobial risk The middle curve indicatesthe best estimate The other two curvesindicate the upper and lower confidenceregions
6 CHAPTER 1 MOTIVATION
ensemble being considered adds an additional dimension for consideration by a riskmanagermdashwhich may be termed risk equity
SECONDARY TRANSMISSION
Infectious microbial diseases are different in terms of risk to a population than arechemical agents in that an individual who may become infected (with or withoutillness) can then proceed to infect additional individuals These secondary (tertiaryquaternary etc) cases may be persons who had no direct contact with the initialvehicle of exposure but nevertheless in fairly accounting for the public health impactthey should be considered
Secondary cases may arise by a variety of mechanisms Particularly amongclose family members household secondary cases can arise by direct or indirect(eg surface contamination) contact this is particularly so when the primary caseor one household secondary case is a child [35ndash37] Table 14 summarizes secondarycase statistics obtained from a variety of outbreaks As will be discussed inChapter 10 the secondary case rate is a complex factor involving (among other things)the nature of the venue and contact patterns when infected and susceptible individualsintermingle
Presumably secondary cases may also arise from close contact with anasymptomatic individual (in the ldquocarrierrdquo state) This is well known for highly acuteand (now) uncommon illnesses (such as typhoid) Excretion of Norwalk virusfollowing recovery (and resulting in additional cases) has been documented to occurfor as long as 48 h post recovery [44]
OUTBREAKS VERSUS ENDEMIC CASES
As noted previously there may be a substantial difference between reported outbreakcases and total disease burden in a community In order for a disease case to receiverecognition by the public health authorities the following specific and sequential stepsmust occur [47]
TABLE 13 Effect of Different Hypothetical Policy Options on Distribution of Risk AmongCommunities (for a Fixed Total Risk)
CommunityExposedPopulation
Policy Option A Policy Option B Policy Option C
CasesIncidence(10000) Cases
Incidence(10000) Cases
Incidence(10000)
A 100000 20 2 6 06 24 24
B 50000 10 2 18 36 7 14
C 10000 2 2 8 8 1 1
Total 160000 32 2 32 2 16 2
OUTBREAKS VERSUS ENDEMIC CASES 7
1 An ill person must seek medical care
2 Appropriate clinical tests (eg blood stool) must be ordered by the attendingphysician
3 The patient must comply with obtaining the sample
4 The laboratory must be capable of detecting the relevant pathogens
5 The clinical test must be positive
6 The test result must be reported to the health agency in a timely manner
If any of the links in this sequential chain are broken then a disease case will not enterthe records maintained by health authorities For example with increasing controls on
TABLE 14 Summary of Secondary Case Data in Outbreak Situations
Organism
SecondaryAttackRatioa
SecondaryPrevalence inHouseholdsb Remarks Reference
Cryptosporidiumparvum
033 033 Outbreak in contaminatedapple cider
[38]
C parvum NA 0042 Drinking water outbreak(Milwaukee)
[37]
Shigella 028 026 Day-care center outbreaksin children
[39]
Rotavirus 042 015 Day-care center outbreaksin children
[30]
Giardia lamblia 133 017 Day-care center outbreaksin children
[39]
Viral gastroenteritis 022 011c Drinking waterborneoutbreak
[40]
Viral gastroenteritis 056 NA Drinking water outbreak(Denmark)
[41]
Norovirus 05ndash10 019 Swimming outbreak [42]
Norovirus 11 029 Swimming outbreakin children
[43]
Norovirus NA 044 Foodborne outbreakin children and teachers
[36]
Norovirus 04 NA Foodborne outbreak [44]
E coli O157H7 NA 018c Day-care center outbreakin children
[45]
Unidentifiedday-care diarrhealdiseases
138 009c [46]
NA information not availableaRatio of secondary cases to primary casesb Proportion of households with one or more primary cases who have one or more secondary casesc Proportion of persons in contact with one or more primary cases who have a secondary case
8 CHAPTER 1 MOTIVATION
medical care stool samples may not be obtained from mild cases of illness Someorganisms may only be present sporadically or may be difficult to test in stool orblood sample Patients may not seek medical attention for mild cases of illness Fur-thermore in the United States in particular the surveillance of environmentallyinduced disease is done on a passive basis and hence the number of actual illnessclusters that are actually compiled into recorded statistics is only a small fractionof such clusters of illness that occur [47]
From a more fundamental point of view an outbreak of illness is generallydefined as occurrence of the illness at a level greater than normal or anticipated Thisdefinition recognizes that there is a level of illness (endemic) that may exist underusual circumstances The detection of such outbreaks poses a particular challengeThe problem is illustrated conceptually in Figure 13
Additional complications arise from the different patterns of illness in acommunity including definite periodicities as well as temporal trends and fromthe presence of reporting lags associated with laboratory analysis and time for patientsto seek medical attention Figure 14 illustrates the different patterns of illness inthe case of six pathogens for England and Wales [48]
In the case of waterborne and foodborne illnesses it is highly likely that thelevel of such endemic illnesses is substantially greater than those occurring duringoutbreaks (even accounting for unrecognized outbreaks)
As a result there are often many cases of environmentally caused (water airfood) infectious disease that are unrecognized One example of this isCampylobacterThere has been an average of about 200 cases per year of water- and foodborne illnessin outbreaks of this organism and yet estimates of the disease burden suggest about2100000 cases per year that is approximately 10000 cases per case of detectableoutbreak illness Therefore it will be important to assess the factors that may influenceoutbreak detection These issues will be discussed in subsequent chapters
Detectedoutbreak
Undetectedoutbreak
Threshold of detection
Hyper endemicSporadic
Endemic rate
Time
Num
ber
of c
ases
Figure 13 Schematic of disease occurrence in a hypothetical community (Modified fromRef [47])
OUTBREAKS VERSUS ENDEMIC CASES 9
REFERENCES
1 Levin B R 1996 The Evolution and Maintenance of Virulence in Microparasites Emerging InfectiousDisease 293ndash102
2 National Academy of Sciences 1983 Risk Assessment in the Federal Government Managing theProcess National Academy Press Washington DC
3 National Research Council 2009 Science and Decisions Advancing Risk Assessment NationalAcademies Press Washington DC
10090807060504030201001190 1191 1192 1193 1194 1195
(b)
140
120
100
80
60
40
20
01190 1191 1192 1193 1194 1195
(f)
700
600
500
400
300
200
100
01190 1191 1192 1193 1194 1195
(d)
1200
1000
800
600
400
200
1190 1191 1192 1193 1194 1195
(a)
240
200
160
120
80
40
01190 1191 1192 1193 1194 1195
(e)
7
6
5
4
3
2
1
01190 1191 1192 1193 1194 1195
(c)
Figure 14 Weekly count of reported organism isolations in England andWales (a) rotavirus(b) Clostridium difficile (c) Salmonella derby (d) Shigella sonnei (e) influenza B and (f)Salmonella typhimurium DT 104 (From Ref [48])
10 CHAPTER 1 MOTIVATION
4 Fogarty J L Thornton and R Corcoran 1995 Illness in a Community Associated with an Episode ofWater Contamination with Sewage Epidemiology and Infection 114289ndash295
5 Scallan E 2011 Foodborne Illness Acquired in the United StatesmdashUnspecified Agents EmergingInfectious Diseases 17 16ndash22
6 Craun G F J M Brunkard J S Yoder V A Roberts J Carpenter T Wade R L CalderonJ M Roberts M J Beach and S L Roy 2010 Causes of Outbreaks Associated with Drinking Waterin the United States from 1971 to 2006 Clinical Microbiology Reviews 23507ndash528
7 Edwards D D 1993 Troubled Waters in Milwaukee ASM News 59342ndash3458 MacKenzie W R N J Hoxie M E Proctor M S Gradus K A Blair D E Peterson
J J Kazmierczak K R Fox D G Addias J B Rose and J P Davis 1994 Massive WaterborneOutbreak of Cryptosporidium Infection Associated with a Filtered Public Water Supply MilwaukeeWisconsin March and April 1993 New England Journal of Medicine 331161ndash167
9 Anonymous 2010 Surveillance for Foodborne Disease OutbreaksmdashUnited States 2007 Morbidityand Mortality Weekly Reports 59973ndash979
10 Bean N H J S Goulding C Lau and F J Angulo 1996 Surveillance for Foodborne-DiseaseOutbreaksmdashUnited States 1988ndash1992 Morbidity and Mortality Weekly Reports 451ndash66
11 Wall P G J de Louvois R J Gilbert and B Rowe 1996 Food Poisoning NotificationsLaboratory Reports and OutbreaksmdashWhere do the Statistics Come From and What Do They MeanCommunicable Disease Report Review 6 R93ndashR100
12 Colford J M S Roy M J Beach A Hightower S E Shaw and T J Wade 2006 A Review ofHousehold Drinking Water Intervention Trials and an Approach to the Estimation of EndemicWaterborne Gastroenteritis in the United States Journal of Water and Health 471
13 Mead P S L Slutsker V Dietz L F McCaig J S Bresee C Shapiro P M Griffinand R V Tauxe 1999 Food Related Illness and Death in the United States Emerging InfectiousDisease 5607ndash625
14 Dziuban E J J L Liang G F Craun V Hill P A Yu J Painter M R Moore R L CalderonS L Roy and M J Beach 2006 Surveillance for Waterborne Disease and Outbreaks Associatedwith Recreational WatermdashUnited States 2003ndash2004 and Surveillance for Waterborne Disease andOutbreaks Associated with Drinking Water and Water not Intended for DrinkingmdashUnited States2003ndash2004 Morbidity and Mortality Weekly Reports 551ndash30
15 Fliermans C B 1996 Ecology of Legionella From Data to Knowledge with a Little WisdomMicrobial Ecology 32203ndash228
16 Li Y S Duan I T Yu and T W Wong 2005 Multi-Zone Modeling of Probable SARS VirusTransmission by Airflow Between Flats in Block E Amoy Gardens Indoor Air 1596ndash111
17 Peccia J D K Milton T Reponen and J Hill 2008 A Role for Environmental Engineering andScience in Preventing Bioaerosol-Related Disease Environmental Science amp Technology424631ndash4637
18 Jernigan D B P L Raghunathan B P Bell R Brechner E A Bresnitz J C Butler M CetronM Cohen T Doyle and M Fischer 2002 Investigation of Bioterrorism-Related AnthraxUnited States 2001 Epidemiologic Findings Emerging Infectious Diseases 81019ndash1028
19 Greenwood M and G U Yule 1917 On the Statistical Interpretation of Some BacteriologicalMethods Employed in Water Analysis Journal of Hygiene 1636ndash56
20 Phelps E 1909 The Disinfection of Sewage and Sewage Filter Effluents USGS Water Supply Paper229 GPO Washington DC
21 Rudolfs W and H W Gehm 1935 Multiplication of Total Bacteria and B coli after SewageChlorination Sewage Works Journal 7991ndash996
22 Subcommittee onMicrobiological Criteria 1985 An Evaluation of the Role ofMicrobiological Criteriafor Foods and Food Ingredients National Academy Press Washington DC
23 Cabelli V J A P Dufour L J McCabe and M A Levin 1982 Swimming-AssociatedGastroenteritis and Water Quality American Journal of Epidemiology 115606ndash616
24 Dufour A P 1984 Health Effects Criteria for Fresh Recreational Waters USEPA Research TrianglePark NC
25 Fleisher J M F Jones and D Kay 1993 Water and Non-Water-Related Risk Factors forGastroenteritis among Bathers Exposed to Sewage-Contaminated Marine Waters InternationalJournal of Epidemiology 22698ndash708
REFERENCES 11
26 Engelbrecht R S C N Haas J A Shular D L Dunn D Roy A Lalchandani B F Severin andS Farooq 1979 Acid-Fast Bacteria and Yeasts as Indicators of Disinfection Efficiency EPA-6002-79-091 US Environmental Protection Agency Cincinnati OH
27 Grabow W O K 1983 Inactivation of Hepatitis A Virus and Indicator Organisms in Water by FreeChlorine Residuals Applied and Environmental Microbiology 46619
28 Helmer R D and G R Finch 1993 Use of MS2 Coliphage as a Surrogate for Enteric Viruses inSurface Waters Disinfected with Ozone Ozone Science and Engineering 15279ndash293
29 Payment P and E Franco 1993Clostridium Perfringens and Somatic Coliphages as Indicators of theEfficiency of Drinking Water Treatment for Viruses and Protozoan Cysts Applied and EnvironmentalMicrobiology 592418ndash2424
30 Cabelli V J 1977Clostridium Perfringens as aWater Quality Indicator pp 65ndash79 InA Hoadley andB Dutka (eds) Bacterial IndicatorsHealth Hazards Associated with Water ASTM Philadelphia PA
31 Rice E W K R Fox R J Miltner D A Lytle and C H Johnson 1996 Evaluating PlantPerformance with Endospores Journal of the American Water Works Association 88122ndash130
32 Engelbrecht R S B F Severin M T Masarik S Farooq S H Lee C N Haas and A Lalchandani1977 New Microbial Indicators of Disinfection Efficiency EPA-6002-77-052 US EnvironmentalProtection Agency Cincinnati OH
33 Committee on Indicators for Waterborne Pathogens ndash National Research Council 2004 Indicators forWaterborne Pathogens National Academies Press Washington DC
34 PresidentialCongressional Commission on Risk Assessment and RiskManagement 1997 Frameworkfor Environmental Health Risk Management The Commission Washington DC
35 Griffin P M and R V Tauxe 1991 The Epidemiology of Infections Caused by Escherichiacoli O157H7 Other Enterohemorrhagic E coli and the Associated Hemolytic Uremic SyndromeEpidemiologic Reviews 1360ndash98
36 Heun E M R L Vogt P J Hudson S Parren and G W Gary 1987 Risk Factors for SecondaryTransmission in Households after a Common Source Outbreak of Norwalk Gastroenteritis AmericanJournal of Epidemiology 1261181ndash1186
37 MacKenzie W R W L Schell B A Blair D G Addiss D E Peterson N J HozieJ J Kazmierczak and J P Davis 1995 Massive Outbreak of Waterborne CryptosporidiumInfection in Milwaukee Wisconsin Recurrence of Illness and Risk of Secondary TransmissionClinical Infectious Diseases 2157ndash62
38 Millard P K Gensheimer D G Addiss D M Sosin G A Beckett A Houck-Jankoski andA Hudson 1994 An Outbreak of Cryptosporidiosis from Fresh-Pressed Apple Cider Journal ofthe American Medical Association 2721592ndash1596
39 Pickering L K D G Evans H L DuPont J J Vollet and D J Evans Jr 1981 Diarrhea Caused byShigella Rotavirus and Giardia in Day Care Centers Prospective Study Journal of Pediatrics9951ndash56
40 Morens D M R M Zweighaft T M Vernon G W Gary J J Eslien B T Wood R C Holmanand R Dolin 1979 A Waterborne Outbreak of Gastroenteritis with Secondary Person to PersonSpread Lancet 5964ndash966
41 Laursen E O Mygind B Rasmussen and T Ronne 1994 Gastroenteritis A Waterborne OutbreakAffecting 1600 People in a Small Danish Town Journal of Epidemiology amp Community Health48453ndash458
42 Baron R C F D Murphy H B Greenberg C E Davis D J Bregman G W Gary J M Hughesand L B Schonberger 1982 Norwalk Gastrointestinal Illness An Outbreak Associated withSwimming in a Recreational Lake and Secondary Person to Person Transmission American Journalof Epidemiology 115163ndash172
43 Kappus K D J S Marks R C Holman J K Bryant C Baker G W Gary and H B Greenberg1982 An Outbreak of Norwalk Gastroenteritis Associated with Swimming in a Pool and SecondaryPerson to Person Transmission American Journal of Epidemiology 116834ndash839
44 White K E M T Osterbolm J A Mariotti J A Korlath D H Lawrence T L Ristinen andH B Greenberg 1986 A Foodborne Outbreak of Norwalk Virus Gastroenteritis American Journalof Epidemiology 124120ndash126
45 Spika J S J E Parsons and D Nordenberg 1986 Hemolytic Uremic Syndrome and DiarrheaAssociated with Escherichia coli O157H7 in a Day Care Center Journal of Pediatrics 109287ndash291
12 CHAPTER 1 MOTIVATION
46 Ferguson J K L R Jorm C D Allen P KWhitehead and G L Gilbert 1995 Prospective Study ofDiarrhoeal Outbreaks in Child Long Daycare Centres in Western Sydney Medical Journal of Australia163137ndash140
47 Frost F J G F Craun and R L Calderon 1996 Waterborne Disease Surveillance Journal of theAmerican Water Works Association 8866ndash75
48 Farrington C P N J Andrews A D Beale and M A Catchpole 1996 A Statistical Algorithmfor the Early Detection of Outbreaks of Infectious Disease Journal of the Royal StatisticalSociety A 159547ndash563
REFERENCES 13
CHAPTER2MICROBIAL AGENTS ANDTRANSMISSION
MICROBIAL TAXONOMY
The development of techniques for examining the nucleic acids of microorganisms hasseen major changes in which we classify and group related microorganisms This isespecially true for the study of ribosomal ribonucleic acid (rRNA) which is a highlyconserved sequence involved in the synthesis of proteins in all living organisms Basedon this analysis the classification of living things has been placed into a three-domainsystem consisting of Archaea Eukarya and Bacteria Of these the Bacteria andArchaea are termed prokaryotes (no organized cell nucleus) and the Eukarya areknown as eukaryotes (an organized cell nucleus) Eukaryotic microbes other thanalgae and fungi are collectively calledprotistsWithin theEukarya are fungi protozoahelminth worms algae plants animals and humans Archaea are microbes that looksomewhat similar to bacteria in size and shape under the light microscope but they areactually genetically and biochemically quite different They appear to be a simpler formof life and may in fact be the oldest form of life on earth Viruses are obligate intercel-lular parasites and are not amember of any group They are usually composed only of anucleic acid surrounded by a protein coat Eukaryotes are much more complex thanprokaryotic cells in structure and nutritional requirements Prokaryotes divide by sim-ple binary fissionwhereas eukaryotes divide byamore complexprocess calledmitosis
Eukaryotes
Fungi protozoa and helminth worms are all eukaryotes All contain members that arepathogenic to man and animals While algae do not infect humans they can producetoxins that are harmful to animals and man Fungi obtain nutrients solely by adsorp-tion of organic matter from dead organisms Even when they invade living tissuesthey typically kill cells and then adsorb the nutrients from them Some fungi are capa-ble of developing environmentally resistant spores which can be transported throughthe air Fungal diseases in humans are referred to asmycoses Airborne fungal sporesare responsible for some allergies in humans Yeasts are classified with the fungi and
Quantitative Microbial Risk Assessment Second Edition Charles N Haas Joan B Roseand Charles P Gerbacopy 2014 John Wiley amp Sons Inc Published 2014 by John Wiley amp Sons Inc
15
some are pathogenic to humans (Candida albicans) Certain fungi produce toxins(ie aflatoxins) when growing in foods that are mutagenic and carcinogenic in ani-mals Inhalation is an important route of transmission for some fungal diseases suchas aspergillosis blastomycosis coccidioidomycosis and histoplasmosis These fungiare found growing in animal feces soil or decaying organic matter (compost manure)and may be transmitted through the air when this matter is disturbed Some fungi maybe transmitted by direct contact with the skin Fungi are often found in drinking waterdistribution systems and they have been linked to infections in immunocompromisedindividuals [1] Food is not believed to be a significant route of transmission ofpathogenic fungi
Protozoans are unicellular organisms that are surrounded by a cytoplasmicmembrane that is covered by a protective structure called a pellicle Most are freeliving feeding off of bacteria Some of these can cause disease while others are obli-gate parasites They are capable of forming structures called cysts oocysts or spores(depending on the life cycle of the organism) resistant to adverse environmentalconditions such as desiccation starvation high temperatures and disinfectantsSome pathogenic protozoa are found mainly in the soil (Naegleria) or water(Acanthamoeba) Others such a Giardia and Cryptosporidium whose natural habitatis the intestines of warm-blooded animals are capable of causing disease in bothhumans and animals Others such as Entamoeba histolytica are only capable ofcausing disease in humans
Pathogenic enteric (replicate in the intestines) protozoans are usually excretedin the feces or urine and can be transmitted by fecally contaminated food and waterSome protozoa may be transmitted through the air (Acanthamoeba) or throughfomites (inanimate objects) Some important environmentally transmitted protozoaare listed in Table 21 The clinically important protozoa are divided taxonomicallyinto the amoebas (Entamoeba spp) flagellates (Giardia) and coccidian meaningldquoglobose in shaperdquo (Cryptosporidium and Cyclospora) Microsporidia are alsocapable of causing intestinal infections but their classification is uncertain becausethey have many characteristics associated with fungi They are all obligate parasitesand are transmitted via infectious cysts oocysts or spores by the fecalndashoral routeThe life cycles of these protozoa are similar The initial stage occurs during ingestionof the cyst oocyst or spore After ingestion the body temperature and passagethrough the stomach cause these infective stages to open up in a process calledexcystation
The Giardia cysts house two trophozoites which is the stage that attaches tointestinal cells and grows in the intestinal tract through asexual reproduction As thetrophozoites grow and begin to cover the wall of the intestinal tract diarrhea canresult As the trophozoites are released some form cysts as they pass through thebowels Cryptosporidium and Cyclospora both produce oocysts The life cycle ofCyclospora is still not well known except that its oocysts require some period of timein the environment before they are infective Cryptosporidium oocysts contain foursporozoites which enter the intestinal cells and begin the infection process As morecells become infected the illness begins and oocysts are excreted in high numbers inthe feces (about 100000g)
Worms and helminths are small multicellular animals that are parasiticto humans and animals They include flukes tapeworms and roundworms
16 CHAPTER 2 MICROBIAL AGENTS AND TRANSMISSION
We encourage comments and feedback from users of this work and look for-ward to observing and participating in developments in coming years and ultimatelyto handing the baton off to our students and their students
Charles N Haas
Joan B Rose
Charles P GerbaNovember 2013
xii PREFACE
CHAPTER1MOTIVATION
THE PREVENTION of infectious disease transmission from human exposure tocontaminated food water soil and air remains a major task of environmental andpublic health professionals There are numerous microbial hazards including expo-sure via food water air and malicious release of pathogens that may arise Indeedsome have argued that the property of virulence of human pathogens is one which isfavored by evolutionary interactions between pathogens and host populations andtherefore will always be of important concern [1] To make rational decisions in pre-paring responding and recovering from exposures to such hazards a quantitativeframework is of high benefit
The objective of this book is to comprehensively set forth the methods forassessment of risk from infectious agents transmitted via these routes in a frameworkthat is compatible with the framework for other risk assessments (eg for chemicalagents) as set forth in standard protocols [2 3]
In this chapter information on the occurrence of infectious disease in broadcategories will be presented along with a historical background on prior methodsfor assessment of microbial safety of food water and air This will be followed byan overview of key issues covered in this book
PREVALENCE OF INFECTIOUS DISEASE
Outbreaks of infectious waterborne illness continue to occur although it remainsimpossible to identify the infectious agent in all cases For example in 1991 a water-borne outbreak in Ireland resulting from sewage contamination of water suppliesinfected about 5000 persons However the infectious agent responsible for thisoutbreak could not be determined [4] In the United States it has been estimated that38 million cases of foodborne infectious disease occur annually with unidentifiedagents [5]
In the United States there have typically been three to five reported outbreaksper year in community drinking water systems involving infectious microorganismswith perhaps up to 10000 annual cases [6] The 1994 Milwaukee Cryptosporidiumoutbreak with over 400000 cases [7 8] was a highly unusual event among thesestatistics As shown in Figure 11 there has been an increasing ability to identify
Quantitative Microbial Risk Assessment Second Edition Charles N Haas Joan B Roseand Charles P Gerbacopy 2014 John Wiley amp Sons Inc Published 2014 by John Wiley amp Sons Inc
1
microorganisms responsible for waterborne diseases and it is expected that withadvances in molecular biology this will increase
There are substantially more outbreaks and cases of foodborne infectiousdiseases than are reported Table 11 summarizes reports of US cases of principalmicrobial infectious foodborne illnesses for two 5-year periods (1988ndash1992 and
1971ndash1982
10
20
30
40
Perc
ent o
f out
brea
ks
50
60
1983ndash1994Period
1995ndash2006
Figure 11 Percentages of outbreaks associated with public water systems (n = 680) by timeperiod 1971ndash2006 that had unknown etiologies based on data from Ref [6]
TABLE 11 Comparison of Five-Year Averages for Common Foodborne Reported Outbreaks
Agent
Annual Average 1988ndash1992 Annual Average 2002ndash2006
Cases Outbreaks Cases Outbreaks
Campylobacter 996 44 624 22
Escherichia coli 488 22 481a 30a
Salmonella 42354 1098 3475 144
Shigella 9576 5 495 12
Staphylococcus aureus 3356 94 554 25
Hepatitis 4218 86 238 1
Listeria monocytogenes 04 02 22 2
Giardia 368 14 2 1
Norovirus 584 04 10854 338
Vibrio (all) 114 18 114 5
Unknown etiologies 40483 1422 4052 30
Source From Refs [9 10]a Include both Shiga toxigenic and enterotoxigenic
2 CHAPTER 1 MOTIVATION
2002ndash2006) There is a mix of causal agents including bacteria virus and protozoaIt is noteworthy that (as in the case of waterborne outbreaks) the frequency ofoutbreaks of unknown etiology has dramatically decreased but the frequency of out-breaks associated with norovirus has dramatically increased These changes are duein part to the ability to better identify causal agents (eg via molecular methods)
It is generally recognized that reported outbreaks either of water- or foodborneinfectious disease represent only a small fractionof the total populationdisease burdenHowever particularly in the United States voluntary reporting systems and theoccurrence of mild cases (for which no medical attention is sought but neverthelessare frank cases of disease) have made it difficult to estimate the total caseload
In the United Kingdom comparisons between the number of confirmed casesin infectious disease outbreaks and total confirmed laboratory illnesses (occurring inEngland and Wales) have been made (Table 12) This suggests that the ratio ofreported outbreak cases to total cases that may seek medical attention may be from10 to 5001 with some dependency on the particular agent
Colford et al [12] developed estimates for the total disease burden associatedwith acute gastroenteritis from drinking water This relies on combining the reportedoutbreak data with interventional epidemiologic studies Based on their analysis thetotal US disease burden is estimated to be 426ndash1169 million cases per year in theUnited States which is substantially in excess of the reported outbreaks In the case offoodborne illness there are an estimated 14 million cases per year [13]
Drinking water and food are by no means the only potential routes of exposureto infectious agents in the environment Recreation in water (either natural or artificialpools) containing pathogens can produce illness [14]
Indoor air transmission can be a vehicle of infection Legionella transmittedthrough indoor environments has been a concern since the 1970s [15] The multina-tional epidemic of severe acute respiratory syndrome (SARS) caused by a coronavi-rus was abetted at least in one location in Hong Kong by indoor aerosol transmissionbetween apartments of infected individuals and susceptible individuals [16] A broadspectrum of other respiratory pathogens including influenza rhinoviruses and myco-bacteria can be transmitted by this route [17]
TABLE 12 Comparison of Laboratory Isolations and Outbreak Cases in Englandand Wales 1992ndash1994
Agent
Cases 1992ndash1994
RatioAll Laboratory Reports Confirmed Outbreak Cases
Campylobacter 122250 240 5094
Rotavirus 47463 127 3737
S sonnei 29080 847 343
Salmonella 92416 5960 155
Cryptosporidium 14454 1066 136
E coli O157 1266 128 99
Source Modified from Ref [11]
PREVALENCE OF INFECTIOUS DISEASE 3
The deliberate release of Bacillus anthracis spores in 2001 (the ldquoAmerithraxrdquoincidents) brought widespread awareness to the potential for indoor releases (as wellas releases in other venues) of bioterrorist agents to cause risk [18] Therefore ofnecessity microbial risk assessors may need to consider the impact of maliciousactivity in certain applications
PRIOR APPROACHES
Concerns for microbial quality of food water and other environmental media havelong existed In the early twentieth century the use of indicator microorganismswas developed for the control and assessment of the hygienic quality of such mediaand the adequacy of disinfection and sterilization processes The coliform group oforganisms was perhaps first employed for this purpose [19ndash21] Indicator techniqueshave also found utility in the food industry such as the total count for milk and othermore recent proposals [22] Other indicator groups for food water or environmentalmedia have been examined such as enterococci [23ndash25] acid-fast bacteria [26]bacteriophage [27ndash29] and Clostridia spores [29ndash31]
The use of indicator organisms was historically justified in because of difficultyin enumerating pathogens However with the increasing availability of modernmicrobial methods for example PCR immunoassay etc for direct pathogen assess-ment this justification has become less persuasive In addition in order to develophealth-based standards from indicators extensive epidemiologic surveillance is oftennecessary The use of epidemiology has limitations with respect to detection limits(for an adverse effect) and is also quite expensive to conduct Indicator methodsare also limited in that many pathogens are more resistant to die off in receiving envir-onments or source waters than indicators or have greater resistance to removal bytreatment processes than indicators [26 28 29 32] Thus the absence of indicatorsmay not suffice to ensure the absence of pathogens Even after a century of use theindicator concept remains imperfect [33]
The use of quantitative microbial risk assessment (QMRA) will enable directmeasurements of pathogens to be used to develop acceptancerejection guidelinesfor food water and other vehicles that may be the source of microbial exposureto human populations The objective of this book is to present these methods in asystematic and unified manner
SCOPE OF COVERAGE
QMRA is the application of principles of risk assessment to the estimate ofconsequences from a planned or actual exposure to infectious microorganismsIn performing a QMRA the risk assessor aims to bring the best available informationto bear in understanding the nature of the potential effects from a microbial exposureSince the information (such as dosendashresponse relationships exposure magnitudes) isalmost invariably incomplete it is also necessary to ascertain the potential error
4 CHAPTER 1 MOTIVATION
involved in the risk assessment With such information necessary steps to mitigatecontrol or defend against such exposures may be developed
At the outset of performing a risk assessment a scoping task should be under-taken This task should set forth the objectives of the analysis and the principal issuesto be addressed Items such as consideration of secondary cases individual versuspopulation risk agent or agents to be examined exposure routes andor accident sce-narios must be stipulated However this scoping may be changed during the course ofa QMRA to reflect the input derived from the risk manager(s) and other stakeholders
POTENTIAL OBJECTIVES OF A QMRA
There may be diverse objectives for a QMRA These objectives relate to the rationalefor the performance of the assessment as well as the methods to be employedBroadly the different objectives reflect different scales at which a risk assessmentmay be performed The step of problem formulation is critical to any risk estimate[34] It is necessary that the problem be formulated to meet the needs of the riskmanagers and stakeholders indeed it is now recognized that the successful practiceof risk analysis requires frequent interchange with manager and stakeholders [3]In general the problems posed are of several types
Site-Specific Assessment
The simplest type of QMRA that may be performed involves one site or exposurescenario The following are typical of the questions that might be asked
1 If a water treatment plant is designed in a certain way (with given removals ofpathogens) then what is the risk that would be placed upon the populationserved
2 A swimming outbreak (in a recreational lake) has just occurred I believe that itresulted from a short-duration contamination event What pathogen levelswould be consistent with the observed attack rate
3 Microbial sampling of a finished food product has found certain pathogensWhat level of risk does this pose to consumers of the product
4 A certain amount of infectious agent has been released into a room What is theimmediate danger to occupants and how stringent should cleanup levels be
Note that there are certain other contrasts in the objectives of the risk assessments tobe posed In (1) and (3) a before-the-fact computation is desired while in (2) and (4)an after-the-fact computation is described Also in (1) (3) and (4) pathogen levelsare available (or somehow are estimated) while in (2) an inverse computation isneeded given an observed attack rate
In performing this risk assessment the relationship between an exposure ortechnological metric and a risk measurement must be ascertained and then theparticular point of correspondence determined (Fig 12) In cases (1) (3) and (4)for a known (or assumed) exposure (on the x-axis) the corresponding range of risks
POTENTIAL OBJECTIVES OF A QMRA 5
on the y-axis is sought In cases (2) for known or assumed risks (on the y-axis)the corresponding range of exposures (or level of technological protection) is to bedetermined (on the x-axis)
Ensemble of Sites
A somewhat more complex situation occurs if the risk for a set of events or sites mustbe estimated Basically this now includes the necessity to incorporate site-to-sitefactors into the assessment Some examples of this are as follows
1 If I desire keeping the risk to a population served by multiple water treatmentplants at a given level (or better) then what criteria should I use (microbiallevels)
2 For a food product subject to contamination by pathogens what would be anacceptable treatment specification (eg heating time holding period) to ensuremicrobial acceptability
3 I am designing a water quality standard for recreational bathing waters If auniform (eg national) standard is to be developed what standard would ensurethat average risk was acceptable with keeping the risk of a large ldquoclusterrdquo ofillnesses low
In addition to incorporating a measure of ensemble average risk in general it is alsodesired to ensure that no single member of the ensemble be unacceptably extreme Forexample consider the evaluation of three options of disease control among three com-munities as indicated in Table 13
This table indicates the number of cases and the rate among the three commu-nities The three policy options yield the same number of expected cases Howeverthere are differences in the allocation of risk among the communities of different sizesIn option A all communities have an identical level of estimated risk In option B therisk increases as community size decreases while in option C the risk increases ascommunity size increases This distribution of risk among affected subsets of the
Exposure
Ris
k
Level of technological protection
Figure 12 Relationship between exposurelevel of technological protection andmicrobial risk The middle curve indicatesthe best estimate The other two curvesindicate the upper and lower confidenceregions
6 CHAPTER 1 MOTIVATION
ensemble being considered adds an additional dimension for consideration by a riskmanagermdashwhich may be termed risk equity
SECONDARY TRANSMISSION
Infectious microbial diseases are different in terms of risk to a population than arechemical agents in that an individual who may become infected (with or withoutillness) can then proceed to infect additional individuals These secondary (tertiaryquaternary etc) cases may be persons who had no direct contact with the initialvehicle of exposure but nevertheless in fairly accounting for the public health impactthey should be considered
Secondary cases may arise by a variety of mechanisms Particularly amongclose family members household secondary cases can arise by direct or indirect(eg surface contamination) contact this is particularly so when the primary caseor one household secondary case is a child [35ndash37] Table 14 summarizes secondarycase statistics obtained from a variety of outbreaks As will be discussed inChapter 10 the secondary case rate is a complex factor involving (among other things)the nature of the venue and contact patterns when infected and susceptible individualsintermingle
Presumably secondary cases may also arise from close contact with anasymptomatic individual (in the ldquocarrierrdquo state) This is well known for highly acuteand (now) uncommon illnesses (such as typhoid) Excretion of Norwalk virusfollowing recovery (and resulting in additional cases) has been documented to occurfor as long as 48 h post recovery [44]
OUTBREAKS VERSUS ENDEMIC CASES
As noted previously there may be a substantial difference between reported outbreakcases and total disease burden in a community In order for a disease case to receiverecognition by the public health authorities the following specific and sequential stepsmust occur [47]
TABLE 13 Effect of Different Hypothetical Policy Options on Distribution of Risk AmongCommunities (for a Fixed Total Risk)
CommunityExposedPopulation
Policy Option A Policy Option B Policy Option C
CasesIncidence(10000) Cases
Incidence(10000) Cases
Incidence(10000)
A 100000 20 2 6 06 24 24
B 50000 10 2 18 36 7 14
C 10000 2 2 8 8 1 1
Total 160000 32 2 32 2 16 2
OUTBREAKS VERSUS ENDEMIC CASES 7
1 An ill person must seek medical care
2 Appropriate clinical tests (eg blood stool) must be ordered by the attendingphysician
3 The patient must comply with obtaining the sample
4 The laboratory must be capable of detecting the relevant pathogens
5 The clinical test must be positive
6 The test result must be reported to the health agency in a timely manner
If any of the links in this sequential chain are broken then a disease case will not enterthe records maintained by health authorities For example with increasing controls on
TABLE 14 Summary of Secondary Case Data in Outbreak Situations
Organism
SecondaryAttackRatioa
SecondaryPrevalence inHouseholdsb Remarks Reference
Cryptosporidiumparvum
033 033 Outbreak in contaminatedapple cider
[38]
C parvum NA 0042 Drinking water outbreak(Milwaukee)
[37]
Shigella 028 026 Day-care center outbreaksin children
[39]
Rotavirus 042 015 Day-care center outbreaksin children
[30]
Giardia lamblia 133 017 Day-care center outbreaksin children
[39]
Viral gastroenteritis 022 011c Drinking waterborneoutbreak
[40]
Viral gastroenteritis 056 NA Drinking water outbreak(Denmark)
[41]
Norovirus 05ndash10 019 Swimming outbreak [42]
Norovirus 11 029 Swimming outbreakin children
[43]
Norovirus NA 044 Foodborne outbreakin children and teachers
[36]
Norovirus 04 NA Foodborne outbreak [44]
E coli O157H7 NA 018c Day-care center outbreakin children
[45]
Unidentifiedday-care diarrhealdiseases
138 009c [46]
NA information not availableaRatio of secondary cases to primary casesb Proportion of households with one or more primary cases who have one or more secondary casesc Proportion of persons in contact with one or more primary cases who have a secondary case
8 CHAPTER 1 MOTIVATION
medical care stool samples may not be obtained from mild cases of illness Someorganisms may only be present sporadically or may be difficult to test in stool orblood sample Patients may not seek medical attention for mild cases of illness Fur-thermore in the United States in particular the surveillance of environmentallyinduced disease is done on a passive basis and hence the number of actual illnessclusters that are actually compiled into recorded statistics is only a small fractionof such clusters of illness that occur [47]
From a more fundamental point of view an outbreak of illness is generallydefined as occurrence of the illness at a level greater than normal or anticipated Thisdefinition recognizes that there is a level of illness (endemic) that may exist underusual circumstances The detection of such outbreaks poses a particular challengeThe problem is illustrated conceptually in Figure 13
Additional complications arise from the different patterns of illness in acommunity including definite periodicities as well as temporal trends and fromthe presence of reporting lags associated with laboratory analysis and time for patientsto seek medical attention Figure 14 illustrates the different patterns of illness inthe case of six pathogens for England and Wales [48]
In the case of waterborne and foodborne illnesses it is highly likely that thelevel of such endemic illnesses is substantially greater than those occurring duringoutbreaks (even accounting for unrecognized outbreaks)
As a result there are often many cases of environmentally caused (water airfood) infectious disease that are unrecognized One example of this isCampylobacterThere has been an average of about 200 cases per year of water- and foodborne illnessin outbreaks of this organism and yet estimates of the disease burden suggest about2100000 cases per year that is approximately 10000 cases per case of detectableoutbreak illness Therefore it will be important to assess the factors that may influenceoutbreak detection These issues will be discussed in subsequent chapters
Detectedoutbreak
Undetectedoutbreak
Threshold of detection
Hyper endemicSporadic
Endemic rate
Time
Num
ber
of c
ases
Figure 13 Schematic of disease occurrence in a hypothetical community (Modified fromRef [47])
OUTBREAKS VERSUS ENDEMIC CASES 9
REFERENCES
1 Levin B R 1996 The Evolution and Maintenance of Virulence in Microparasites Emerging InfectiousDisease 293ndash102
2 National Academy of Sciences 1983 Risk Assessment in the Federal Government Managing theProcess National Academy Press Washington DC
3 National Research Council 2009 Science and Decisions Advancing Risk Assessment NationalAcademies Press Washington DC
10090807060504030201001190 1191 1192 1193 1194 1195
(b)
140
120
100
80
60
40
20
01190 1191 1192 1193 1194 1195
(f)
700
600
500
400
300
200
100
01190 1191 1192 1193 1194 1195
(d)
1200
1000
800
600
400
200
1190 1191 1192 1193 1194 1195
(a)
240
200
160
120
80
40
01190 1191 1192 1193 1194 1195
(e)
7
6
5
4
3
2
1
01190 1191 1192 1193 1194 1195
(c)
Figure 14 Weekly count of reported organism isolations in England andWales (a) rotavirus(b) Clostridium difficile (c) Salmonella derby (d) Shigella sonnei (e) influenza B and (f)Salmonella typhimurium DT 104 (From Ref [48])
10 CHAPTER 1 MOTIVATION
4 Fogarty J L Thornton and R Corcoran 1995 Illness in a Community Associated with an Episode ofWater Contamination with Sewage Epidemiology and Infection 114289ndash295
5 Scallan E 2011 Foodborne Illness Acquired in the United StatesmdashUnspecified Agents EmergingInfectious Diseases 17 16ndash22
6 Craun G F J M Brunkard J S Yoder V A Roberts J Carpenter T Wade R L CalderonJ M Roberts M J Beach and S L Roy 2010 Causes of Outbreaks Associated with Drinking Waterin the United States from 1971 to 2006 Clinical Microbiology Reviews 23507ndash528
7 Edwards D D 1993 Troubled Waters in Milwaukee ASM News 59342ndash3458 MacKenzie W R N J Hoxie M E Proctor M S Gradus K A Blair D E Peterson
J J Kazmierczak K R Fox D G Addias J B Rose and J P Davis 1994 Massive WaterborneOutbreak of Cryptosporidium Infection Associated with a Filtered Public Water Supply MilwaukeeWisconsin March and April 1993 New England Journal of Medicine 331161ndash167
9 Anonymous 2010 Surveillance for Foodborne Disease OutbreaksmdashUnited States 2007 Morbidityand Mortality Weekly Reports 59973ndash979
10 Bean N H J S Goulding C Lau and F J Angulo 1996 Surveillance for Foodborne-DiseaseOutbreaksmdashUnited States 1988ndash1992 Morbidity and Mortality Weekly Reports 451ndash66
11 Wall P G J de Louvois R J Gilbert and B Rowe 1996 Food Poisoning NotificationsLaboratory Reports and OutbreaksmdashWhere do the Statistics Come From and What Do They MeanCommunicable Disease Report Review 6 R93ndashR100
12 Colford J M S Roy M J Beach A Hightower S E Shaw and T J Wade 2006 A Review ofHousehold Drinking Water Intervention Trials and an Approach to the Estimation of EndemicWaterborne Gastroenteritis in the United States Journal of Water and Health 471
13 Mead P S L Slutsker V Dietz L F McCaig J S Bresee C Shapiro P M Griffinand R V Tauxe 1999 Food Related Illness and Death in the United States Emerging InfectiousDisease 5607ndash625
14 Dziuban E J J L Liang G F Craun V Hill P A Yu J Painter M R Moore R L CalderonS L Roy and M J Beach 2006 Surveillance for Waterborne Disease and Outbreaks Associatedwith Recreational WatermdashUnited States 2003ndash2004 and Surveillance for Waterborne Disease andOutbreaks Associated with Drinking Water and Water not Intended for DrinkingmdashUnited States2003ndash2004 Morbidity and Mortality Weekly Reports 551ndash30
15 Fliermans C B 1996 Ecology of Legionella From Data to Knowledge with a Little WisdomMicrobial Ecology 32203ndash228
16 Li Y S Duan I T Yu and T W Wong 2005 Multi-Zone Modeling of Probable SARS VirusTransmission by Airflow Between Flats in Block E Amoy Gardens Indoor Air 1596ndash111
17 Peccia J D K Milton T Reponen and J Hill 2008 A Role for Environmental Engineering andScience in Preventing Bioaerosol-Related Disease Environmental Science amp Technology424631ndash4637
18 Jernigan D B P L Raghunathan B P Bell R Brechner E A Bresnitz J C Butler M CetronM Cohen T Doyle and M Fischer 2002 Investigation of Bioterrorism-Related AnthraxUnited States 2001 Epidemiologic Findings Emerging Infectious Diseases 81019ndash1028
19 Greenwood M and G U Yule 1917 On the Statistical Interpretation of Some BacteriologicalMethods Employed in Water Analysis Journal of Hygiene 1636ndash56
20 Phelps E 1909 The Disinfection of Sewage and Sewage Filter Effluents USGS Water Supply Paper229 GPO Washington DC
21 Rudolfs W and H W Gehm 1935 Multiplication of Total Bacteria and B coli after SewageChlorination Sewage Works Journal 7991ndash996
22 Subcommittee onMicrobiological Criteria 1985 An Evaluation of the Role ofMicrobiological Criteriafor Foods and Food Ingredients National Academy Press Washington DC
23 Cabelli V J A P Dufour L J McCabe and M A Levin 1982 Swimming-AssociatedGastroenteritis and Water Quality American Journal of Epidemiology 115606ndash616
24 Dufour A P 1984 Health Effects Criteria for Fresh Recreational Waters USEPA Research TrianglePark NC
25 Fleisher J M F Jones and D Kay 1993 Water and Non-Water-Related Risk Factors forGastroenteritis among Bathers Exposed to Sewage-Contaminated Marine Waters InternationalJournal of Epidemiology 22698ndash708
REFERENCES 11
26 Engelbrecht R S C N Haas J A Shular D L Dunn D Roy A Lalchandani B F Severin andS Farooq 1979 Acid-Fast Bacteria and Yeasts as Indicators of Disinfection Efficiency EPA-6002-79-091 US Environmental Protection Agency Cincinnati OH
27 Grabow W O K 1983 Inactivation of Hepatitis A Virus and Indicator Organisms in Water by FreeChlorine Residuals Applied and Environmental Microbiology 46619
28 Helmer R D and G R Finch 1993 Use of MS2 Coliphage as a Surrogate for Enteric Viruses inSurface Waters Disinfected with Ozone Ozone Science and Engineering 15279ndash293
29 Payment P and E Franco 1993Clostridium Perfringens and Somatic Coliphages as Indicators of theEfficiency of Drinking Water Treatment for Viruses and Protozoan Cysts Applied and EnvironmentalMicrobiology 592418ndash2424
30 Cabelli V J 1977Clostridium Perfringens as aWater Quality Indicator pp 65ndash79 InA Hoadley andB Dutka (eds) Bacterial IndicatorsHealth Hazards Associated with Water ASTM Philadelphia PA
31 Rice E W K R Fox R J Miltner D A Lytle and C H Johnson 1996 Evaluating PlantPerformance with Endospores Journal of the American Water Works Association 88122ndash130
32 Engelbrecht R S B F Severin M T Masarik S Farooq S H Lee C N Haas and A Lalchandani1977 New Microbial Indicators of Disinfection Efficiency EPA-6002-77-052 US EnvironmentalProtection Agency Cincinnati OH
33 Committee on Indicators for Waterborne Pathogens ndash National Research Council 2004 Indicators forWaterborne Pathogens National Academies Press Washington DC
34 PresidentialCongressional Commission on Risk Assessment and RiskManagement 1997 Frameworkfor Environmental Health Risk Management The Commission Washington DC
35 Griffin P M and R V Tauxe 1991 The Epidemiology of Infections Caused by Escherichiacoli O157H7 Other Enterohemorrhagic E coli and the Associated Hemolytic Uremic SyndromeEpidemiologic Reviews 1360ndash98
36 Heun E M R L Vogt P J Hudson S Parren and G W Gary 1987 Risk Factors for SecondaryTransmission in Households after a Common Source Outbreak of Norwalk Gastroenteritis AmericanJournal of Epidemiology 1261181ndash1186
37 MacKenzie W R W L Schell B A Blair D G Addiss D E Peterson N J HozieJ J Kazmierczak and J P Davis 1995 Massive Outbreak of Waterborne CryptosporidiumInfection in Milwaukee Wisconsin Recurrence of Illness and Risk of Secondary TransmissionClinical Infectious Diseases 2157ndash62
38 Millard P K Gensheimer D G Addiss D M Sosin G A Beckett A Houck-Jankoski andA Hudson 1994 An Outbreak of Cryptosporidiosis from Fresh-Pressed Apple Cider Journal ofthe American Medical Association 2721592ndash1596
39 Pickering L K D G Evans H L DuPont J J Vollet and D J Evans Jr 1981 Diarrhea Caused byShigella Rotavirus and Giardia in Day Care Centers Prospective Study Journal of Pediatrics9951ndash56
40 Morens D M R M Zweighaft T M Vernon G W Gary J J Eslien B T Wood R C Holmanand R Dolin 1979 A Waterborne Outbreak of Gastroenteritis with Secondary Person to PersonSpread Lancet 5964ndash966
41 Laursen E O Mygind B Rasmussen and T Ronne 1994 Gastroenteritis A Waterborne OutbreakAffecting 1600 People in a Small Danish Town Journal of Epidemiology amp Community Health48453ndash458
42 Baron R C F D Murphy H B Greenberg C E Davis D J Bregman G W Gary J M Hughesand L B Schonberger 1982 Norwalk Gastrointestinal Illness An Outbreak Associated withSwimming in a Recreational Lake and Secondary Person to Person Transmission American Journalof Epidemiology 115163ndash172
43 Kappus K D J S Marks R C Holman J K Bryant C Baker G W Gary and H B Greenberg1982 An Outbreak of Norwalk Gastroenteritis Associated with Swimming in a Pool and SecondaryPerson to Person Transmission American Journal of Epidemiology 116834ndash839
44 White K E M T Osterbolm J A Mariotti J A Korlath D H Lawrence T L Ristinen andH B Greenberg 1986 A Foodborne Outbreak of Norwalk Virus Gastroenteritis American Journalof Epidemiology 124120ndash126
45 Spika J S J E Parsons and D Nordenberg 1986 Hemolytic Uremic Syndrome and DiarrheaAssociated with Escherichia coli O157H7 in a Day Care Center Journal of Pediatrics 109287ndash291
12 CHAPTER 1 MOTIVATION
46 Ferguson J K L R Jorm C D Allen P KWhitehead and G L Gilbert 1995 Prospective Study ofDiarrhoeal Outbreaks in Child Long Daycare Centres in Western Sydney Medical Journal of Australia163137ndash140
47 Frost F J G F Craun and R L Calderon 1996 Waterborne Disease Surveillance Journal of theAmerican Water Works Association 8866ndash75
48 Farrington C P N J Andrews A D Beale and M A Catchpole 1996 A Statistical Algorithmfor the Early Detection of Outbreaks of Infectious Disease Journal of the Royal StatisticalSociety A 159547ndash563
REFERENCES 13
CHAPTER2MICROBIAL AGENTS ANDTRANSMISSION
MICROBIAL TAXONOMY
The development of techniques for examining the nucleic acids of microorganisms hasseen major changes in which we classify and group related microorganisms This isespecially true for the study of ribosomal ribonucleic acid (rRNA) which is a highlyconserved sequence involved in the synthesis of proteins in all living organisms Basedon this analysis the classification of living things has been placed into a three-domainsystem consisting of Archaea Eukarya and Bacteria Of these the Bacteria andArchaea are termed prokaryotes (no organized cell nucleus) and the Eukarya areknown as eukaryotes (an organized cell nucleus) Eukaryotic microbes other thanalgae and fungi are collectively calledprotistsWithin theEukarya are fungi protozoahelminth worms algae plants animals and humans Archaea are microbes that looksomewhat similar to bacteria in size and shape under the light microscope but they areactually genetically and biochemically quite different They appear to be a simpler formof life and may in fact be the oldest form of life on earth Viruses are obligate intercel-lular parasites and are not amember of any group They are usually composed only of anucleic acid surrounded by a protein coat Eukaryotes are much more complex thanprokaryotic cells in structure and nutritional requirements Prokaryotes divide by sim-ple binary fissionwhereas eukaryotes divide byamore complexprocess calledmitosis
Eukaryotes
Fungi protozoa and helminth worms are all eukaryotes All contain members that arepathogenic to man and animals While algae do not infect humans they can producetoxins that are harmful to animals and man Fungi obtain nutrients solely by adsorp-tion of organic matter from dead organisms Even when they invade living tissuesthey typically kill cells and then adsorb the nutrients from them Some fungi are capa-ble of developing environmentally resistant spores which can be transported throughthe air Fungal diseases in humans are referred to asmycoses Airborne fungal sporesare responsible for some allergies in humans Yeasts are classified with the fungi and
Quantitative Microbial Risk Assessment Second Edition Charles N Haas Joan B Roseand Charles P Gerbacopy 2014 John Wiley amp Sons Inc Published 2014 by John Wiley amp Sons Inc
15
some are pathogenic to humans (Candida albicans) Certain fungi produce toxins(ie aflatoxins) when growing in foods that are mutagenic and carcinogenic in ani-mals Inhalation is an important route of transmission for some fungal diseases suchas aspergillosis blastomycosis coccidioidomycosis and histoplasmosis These fungiare found growing in animal feces soil or decaying organic matter (compost manure)and may be transmitted through the air when this matter is disturbed Some fungi maybe transmitted by direct contact with the skin Fungi are often found in drinking waterdistribution systems and they have been linked to infections in immunocompromisedindividuals [1] Food is not believed to be a significant route of transmission ofpathogenic fungi
Protozoans are unicellular organisms that are surrounded by a cytoplasmicmembrane that is covered by a protective structure called a pellicle Most are freeliving feeding off of bacteria Some of these can cause disease while others are obli-gate parasites They are capable of forming structures called cysts oocysts or spores(depending on the life cycle of the organism) resistant to adverse environmentalconditions such as desiccation starvation high temperatures and disinfectantsSome pathogenic protozoa are found mainly in the soil (Naegleria) or water(Acanthamoeba) Others such a Giardia and Cryptosporidium whose natural habitatis the intestines of warm-blooded animals are capable of causing disease in bothhumans and animals Others such as Entamoeba histolytica are only capable ofcausing disease in humans
Pathogenic enteric (replicate in the intestines) protozoans are usually excretedin the feces or urine and can be transmitted by fecally contaminated food and waterSome protozoa may be transmitted through the air (Acanthamoeba) or throughfomites (inanimate objects) Some important environmentally transmitted protozoaare listed in Table 21 The clinically important protozoa are divided taxonomicallyinto the amoebas (Entamoeba spp) flagellates (Giardia) and coccidian meaningldquoglobose in shaperdquo (Cryptosporidium and Cyclospora) Microsporidia are alsocapable of causing intestinal infections but their classification is uncertain becausethey have many characteristics associated with fungi They are all obligate parasitesand are transmitted via infectious cysts oocysts or spores by the fecalndashoral routeThe life cycles of these protozoa are similar The initial stage occurs during ingestionof the cyst oocyst or spore After ingestion the body temperature and passagethrough the stomach cause these infective stages to open up in a process calledexcystation
The Giardia cysts house two trophozoites which is the stage that attaches tointestinal cells and grows in the intestinal tract through asexual reproduction As thetrophozoites grow and begin to cover the wall of the intestinal tract diarrhea canresult As the trophozoites are released some form cysts as they pass through thebowels Cryptosporidium and Cyclospora both produce oocysts The life cycle ofCyclospora is still not well known except that its oocysts require some period of timein the environment before they are infective Cryptosporidium oocysts contain foursporozoites which enter the intestinal cells and begin the infection process As morecells become infected the illness begins and oocysts are excreted in high numbers inthe feces (about 100000g)
Worms and helminths are small multicellular animals that are parasiticto humans and animals They include flukes tapeworms and roundworms
16 CHAPTER 2 MICROBIAL AGENTS AND TRANSMISSION
CHAPTER1MOTIVATION
THE PREVENTION of infectious disease transmission from human exposure tocontaminated food water soil and air remains a major task of environmental andpublic health professionals There are numerous microbial hazards including expo-sure via food water air and malicious release of pathogens that may arise Indeedsome have argued that the property of virulence of human pathogens is one which isfavored by evolutionary interactions between pathogens and host populations andtherefore will always be of important concern [1] To make rational decisions in pre-paring responding and recovering from exposures to such hazards a quantitativeframework is of high benefit
The objective of this book is to comprehensively set forth the methods forassessment of risk from infectious agents transmitted via these routes in a frameworkthat is compatible with the framework for other risk assessments (eg for chemicalagents) as set forth in standard protocols [2 3]
In this chapter information on the occurrence of infectious disease in broadcategories will be presented along with a historical background on prior methodsfor assessment of microbial safety of food water and air This will be followed byan overview of key issues covered in this book
PREVALENCE OF INFECTIOUS DISEASE
Outbreaks of infectious waterborne illness continue to occur although it remainsimpossible to identify the infectious agent in all cases For example in 1991 a water-borne outbreak in Ireland resulting from sewage contamination of water suppliesinfected about 5000 persons However the infectious agent responsible for thisoutbreak could not be determined [4] In the United States it has been estimated that38 million cases of foodborne infectious disease occur annually with unidentifiedagents [5]
In the United States there have typically been three to five reported outbreaksper year in community drinking water systems involving infectious microorganismswith perhaps up to 10000 annual cases [6] The 1994 Milwaukee Cryptosporidiumoutbreak with over 400000 cases [7 8] was a highly unusual event among thesestatistics As shown in Figure 11 there has been an increasing ability to identify
Quantitative Microbial Risk Assessment Second Edition Charles N Haas Joan B Roseand Charles P Gerbacopy 2014 John Wiley amp Sons Inc Published 2014 by John Wiley amp Sons Inc
1
microorganisms responsible for waterborne diseases and it is expected that withadvances in molecular biology this will increase
There are substantially more outbreaks and cases of foodborne infectiousdiseases than are reported Table 11 summarizes reports of US cases of principalmicrobial infectious foodborne illnesses for two 5-year periods (1988ndash1992 and
1971ndash1982
10
20
30
40
Perc
ent o
f out
brea
ks
50
60
1983ndash1994Period
1995ndash2006
Figure 11 Percentages of outbreaks associated with public water systems (n = 680) by timeperiod 1971ndash2006 that had unknown etiologies based on data from Ref [6]
TABLE 11 Comparison of Five-Year Averages for Common Foodborne Reported Outbreaks
Agent
Annual Average 1988ndash1992 Annual Average 2002ndash2006
Cases Outbreaks Cases Outbreaks
Campylobacter 996 44 624 22
Escherichia coli 488 22 481a 30a
Salmonella 42354 1098 3475 144
Shigella 9576 5 495 12
Staphylococcus aureus 3356 94 554 25
Hepatitis 4218 86 238 1
Listeria monocytogenes 04 02 22 2
Giardia 368 14 2 1
Norovirus 584 04 10854 338
Vibrio (all) 114 18 114 5
Unknown etiologies 40483 1422 4052 30
Source From Refs [9 10]a Include both Shiga toxigenic and enterotoxigenic
2 CHAPTER 1 MOTIVATION
2002ndash2006) There is a mix of causal agents including bacteria virus and protozoaIt is noteworthy that (as in the case of waterborne outbreaks) the frequency ofoutbreaks of unknown etiology has dramatically decreased but the frequency of out-breaks associated with norovirus has dramatically increased These changes are duein part to the ability to better identify causal agents (eg via molecular methods)
It is generally recognized that reported outbreaks either of water- or foodborneinfectious disease represent only a small fractionof the total populationdisease burdenHowever particularly in the United States voluntary reporting systems and theoccurrence of mild cases (for which no medical attention is sought but neverthelessare frank cases of disease) have made it difficult to estimate the total caseload
In the United Kingdom comparisons between the number of confirmed casesin infectious disease outbreaks and total confirmed laboratory illnesses (occurring inEngland and Wales) have been made (Table 12) This suggests that the ratio ofreported outbreak cases to total cases that may seek medical attention may be from10 to 5001 with some dependency on the particular agent
Colford et al [12] developed estimates for the total disease burden associatedwith acute gastroenteritis from drinking water This relies on combining the reportedoutbreak data with interventional epidemiologic studies Based on their analysis thetotal US disease burden is estimated to be 426ndash1169 million cases per year in theUnited States which is substantially in excess of the reported outbreaks In the case offoodborne illness there are an estimated 14 million cases per year [13]
Drinking water and food are by no means the only potential routes of exposureto infectious agents in the environment Recreation in water (either natural or artificialpools) containing pathogens can produce illness [14]
Indoor air transmission can be a vehicle of infection Legionella transmittedthrough indoor environments has been a concern since the 1970s [15] The multina-tional epidemic of severe acute respiratory syndrome (SARS) caused by a coronavi-rus was abetted at least in one location in Hong Kong by indoor aerosol transmissionbetween apartments of infected individuals and susceptible individuals [16] A broadspectrum of other respiratory pathogens including influenza rhinoviruses and myco-bacteria can be transmitted by this route [17]
TABLE 12 Comparison of Laboratory Isolations and Outbreak Cases in Englandand Wales 1992ndash1994
Agent
Cases 1992ndash1994
RatioAll Laboratory Reports Confirmed Outbreak Cases
Campylobacter 122250 240 5094
Rotavirus 47463 127 3737
S sonnei 29080 847 343
Salmonella 92416 5960 155
Cryptosporidium 14454 1066 136
E coli O157 1266 128 99
Source Modified from Ref [11]
PREVALENCE OF INFECTIOUS DISEASE 3
The deliberate release of Bacillus anthracis spores in 2001 (the ldquoAmerithraxrdquoincidents) brought widespread awareness to the potential for indoor releases (as wellas releases in other venues) of bioterrorist agents to cause risk [18] Therefore ofnecessity microbial risk assessors may need to consider the impact of maliciousactivity in certain applications
PRIOR APPROACHES
Concerns for microbial quality of food water and other environmental media havelong existed In the early twentieth century the use of indicator microorganismswas developed for the control and assessment of the hygienic quality of such mediaand the adequacy of disinfection and sterilization processes The coliform group oforganisms was perhaps first employed for this purpose [19ndash21] Indicator techniqueshave also found utility in the food industry such as the total count for milk and othermore recent proposals [22] Other indicator groups for food water or environmentalmedia have been examined such as enterococci [23ndash25] acid-fast bacteria [26]bacteriophage [27ndash29] and Clostridia spores [29ndash31]
The use of indicator organisms was historically justified in because of difficultyin enumerating pathogens However with the increasing availability of modernmicrobial methods for example PCR immunoassay etc for direct pathogen assess-ment this justification has become less persuasive In addition in order to develophealth-based standards from indicators extensive epidemiologic surveillance is oftennecessary The use of epidemiology has limitations with respect to detection limits(for an adverse effect) and is also quite expensive to conduct Indicator methodsare also limited in that many pathogens are more resistant to die off in receiving envir-onments or source waters than indicators or have greater resistance to removal bytreatment processes than indicators [26 28 29 32] Thus the absence of indicatorsmay not suffice to ensure the absence of pathogens Even after a century of use theindicator concept remains imperfect [33]
The use of quantitative microbial risk assessment (QMRA) will enable directmeasurements of pathogens to be used to develop acceptancerejection guidelinesfor food water and other vehicles that may be the source of microbial exposureto human populations The objective of this book is to present these methods in asystematic and unified manner
SCOPE OF COVERAGE
QMRA is the application of principles of risk assessment to the estimate ofconsequences from a planned or actual exposure to infectious microorganismsIn performing a QMRA the risk assessor aims to bring the best available informationto bear in understanding the nature of the potential effects from a microbial exposureSince the information (such as dosendashresponse relationships exposure magnitudes) isalmost invariably incomplete it is also necessary to ascertain the potential error
4 CHAPTER 1 MOTIVATION
involved in the risk assessment With such information necessary steps to mitigatecontrol or defend against such exposures may be developed
At the outset of performing a risk assessment a scoping task should be under-taken This task should set forth the objectives of the analysis and the principal issuesto be addressed Items such as consideration of secondary cases individual versuspopulation risk agent or agents to be examined exposure routes andor accident sce-narios must be stipulated However this scoping may be changed during the course ofa QMRA to reflect the input derived from the risk manager(s) and other stakeholders
POTENTIAL OBJECTIVES OF A QMRA
There may be diverse objectives for a QMRA These objectives relate to the rationalefor the performance of the assessment as well as the methods to be employedBroadly the different objectives reflect different scales at which a risk assessmentmay be performed The step of problem formulation is critical to any risk estimate[34] It is necessary that the problem be formulated to meet the needs of the riskmanagers and stakeholders indeed it is now recognized that the successful practiceof risk analysis requires frequent interchange with manager and stakeholders [3]In general the problems posed are of several types
Site-Specific Assessment
The simplest type of QMRA that may be performed involves one site or exposurescenario The following are typical of the questions that might be asked
1 If a water treatment plant is designed in a certain way (with given removals ofpathogens) then what is the risk that would be placed upon the populationserved
2 A swimming outbreak (in a recreational lake) has just occurred I believe that itresulted from a short-duration contamination event What pathogen levelswould be consistent with the observed attack rate
3 Microbial sampling of a finished food product has found certain pathogensWhat level of risk does this pose to consumers of the product
4 A certain amount of infectious agent has been released into a room What is theimmediate danger to occupants and how stringent should cleanup levels be
Note that there are certain other contrasts in the objectives of the risk assessments tobe posed In (1) and (3) a before-the-fact computation is desired while in (2) and (4)an after-the-fact computation is described Also in (1) (3) and (4) pathogen levelsare available (or somehow are estimated) while in (2) an inverse computation isneeded given an observed attack rate
In performing this risk assessment the relationship between an exposure ortechnological metric and a risk measurement must be ascertained and then theparticular point of correspondence determined (Fig 12) In cases (1) (3) and (4)for a known (or assumed) exposure (on the x-axis) the corresponding range of risks
POTENTIAL OBJECTIVES OF A QMRA 5
on the y-axis is sought In cases (2) for known or assumed risks (on the y-axis)the corresponding range of exposures (or level of technological protection) is to bedetermined (on the x-axis)
Ensemble of Sites
A somewhat more complex situation occurs if the risk for a set of events or sites mustbe estimated Basically this now includes the necessity to incorporate site-to-sitefactors into the assessment Some examples of this are as follows
1 If I desire keeping the risk to a population served by multiple water treatmentplants at a given level (or better) then what criteria should I use (microbiallevels)
2 For a food product subject to contamination by pathogens what would be anacceptable treatment specification (eg heating time holding period) to ensuremicrobial acceptability
3 I am designing a water quality standard for recreational bathing waters If auniform (eg national) standard is to be developed what standard would ensurethat average risk was acceptable with keeping the risk of a large ldquoclusterrdquo ofillnesses low
In addition to incorporating a measure of ensemble average risk in general it is alsodesired to ensure that no single member of the ensemble be unacceptably extreme Forexample consider the evaluation of three options of disease control among three com-munities as indicated in Table 13
This table indicates the number of cases and the rate among the three commu-nities The three policy options yield the same number of expected cases Howeverthere are differences in the allocation of risk among the communities of different sizesIn option A all communities have an identical level of estimated risk In option B therisk increases as community size decreases while in option C the risk increases ascommunity size increases This distribution of risk among affected subsets of the
Exposure
Ris
k
Level of technological protection
Figure 12 Relationship between exposurelevel of technological protection andmicrobial risk The middle curve indicatesthe best estimate The other two curvesindicate the upper and lower confidenceregions
6 CHAPTER 1 MOTIVATION
ensemble being considered adds an additional dimension for consideration by a riskmanagermdashwhich may be termed risk equity
SECONDARY TRANSMISSION
Infectious microbial diseases are different in terms of risk to a population than arechemical agents in that an individual who may become infected (with or withoutillness) can then proceed to infect additional individuals These secondary (tertiaryquaternary etc) cases may be persons who had no direct contact with the initialvehicle of exposure but nevertheless in fairly accounting for the public health impactthey should be considered
Secondary cases may arise by a variety of mechanisms Particularly amongclose family members household secondary cases can arise by direct or indirect(eg surface contamination) contact this is particularly so when the primary caseor one household secondary case is a child [35ndash37] Table 14 summarizes secondarycase statistics obtained from a variety of outbreaks As will be discussed inChapter 10 the secondary case rate is a complex factor involving (among other things)the nature of the venue and contact patterns when infected and susceptible individualsintermingle
Presumably secondary cases may also arise from close contact with anasymptomatic individual (in the ldquocarrierrdquo state) This is well known for highly acuteand (now) uncommon illnesses (such as typhoid) Excretion of Norwalk virusfollowing recovery (and resulting in additional cases) has been documented to occurfor as long as 48 h post recovery [44]
OUTBREAKS VERSUS ENDEMIC CASES
As noted previously there may be a substantial difference between reported outbreakcases and total disease burden in a community In order for a disease case to receiverecognition by the public health authorities the following specific and sequential stepsmust occur [47]
TABLE 13 Effect of Different Hypothetical Policy Options on Distribution of Risk AmongCommunities (for a Fixed Total Risk)
CommunityExposedPopulation
Policy Option A Policy Option B Policy Option C
CasesIncidence(10000) Cases
Incidence(10000) Cases
Incidence(10000)
A 100000 20 2 6 06 24 24
B 50000 10 2 18 36 7 14
C 10000 2 2 8 8 1 1
Total 160000 32 2 32 2 16 2
OUTBREAKS VERSUS ENDEMIC CASES 7
1 An ill person must seek medical care
2 Appropriate clinical tests (eg blood stool) must be ordered by the attendingphysician
3 The patient must comply with obtaining the sample
4 The laboratory must be capable of detecting the relevant pathogens
5 The clinical test must be positive
6 The test result must be reported to the health agency in a timely manner
If any of the links in this sequential chain are broken then a disease case will not enterthe records maintained by health authorities For example with increasing controls on
TABLE 14 Summary of Secondary Case Data in Outbreak Situations
Organism
SecondaryAttackRatioa
SecondaryPrevalence inHouseholdsb Remarks Reference
Cryptosporidiumparvum
033 033 Outbreak in contaminatedapple cider
[38]
C parvum NA 0042 Drinking water outbreak(Milwaukee)
[37]
Shigella 028 026 Day-care center outbreaksin children
[39]
Rotavirus 042 015 Day-care center outbreaksin children
[30]
Giardia lamblia 133 017 Day-care center outbreaksin children
[39]
Viral gastroenteritis 022 011c Drinking waterborneoutbreak
[40]
Viral gastroenteritis 056 NA Drinking water outbreak(Denmark)
[41]
Norovirus 05ndash10 019 Swimming outbreak [42]
Norovirus 11 029 Swimming outbreakin children
[43]
Norovirus NA 044 Foodborne outbreakin children and teachers
[36]
Norovirus 04 NA Foodborne outbreak [44]
E coli O157H7 NA 018c Day-care center outbreakin children
[45]
Unidentifiedday-care diarrhealdiseases
138 009c [46]
NA information not availableaRatio of secondary cases to primary casesb Proportion of households with one or more primary cases who have one or more secondary casesc Proportion of persons in contact with one or more primary cases who have a secondary case
8 CHAPTER 1 MOTIVATION
medical care stool samples may not be obtained from mild cases of illness Someorganisms may only be present sporadically or may be difficult to test in stool orblood sample Patients may not seek medical attention for mild cases of illness Fur-thermore in the United States in particular the surveillance of environmentallyinduced disease is done on a passive basis and hence the number of actual illnessclusters that are actually compiled into recorded statistics is only a small fractionof such clusters of illness that occur [47]
From a more fundamental point of view an outbreak of illness is generallydefined as occurrence of the illness at a level greater than normal or anticipated Thisdefinition recognizes that there is a level of illness (endemic) that may exist underusual circumstances The detection of such outbreaks poses a particular challengeThe problem is illustrated conceptually in Figure 13
Additional complications arise from the different patterns of illness in acommunity including definite periodicities as well as temporal trends and fromthe presence of reporting lags associated with laboratory analysis and time for patientsto seek medical attention Figure 14 illustrates the different patterns of illness inthe case of six pathogens for England and Wales [48]
In the case of waterborne and foodborne illnesses it is highly likely that thelevel of such endemic illnesses is substantially greater than those occurring duringoutbreaks (even accounting for unrecognized outbreaks)
As a result there are often many cases of environmentally caused (water airfood) infectious disease that are unrecognized One example of this isCampylobacterThere has been an average of about 200 cases per year of water- and foodborne illnessin outbreaks of this organism and yet estimates of the disease burden suggest about2100000 cases per year that is approximately 10000 cases per case of detectableoutbreak illness Therefore it will be important to assess the factors that may influenceoutbreak detection These issues will be discussed in subsequent chapters
Detectedoutbreak
Undetectedoutbreak
Threshold of detection
Hyper endemicSporadic
Endemic rate
Time
Num
ber
of c
ases
Figure 13 Schematic of disease occurrence in a hypothetical community (Modified fromRef [47])
OUTBREAKS VERSUS ENDEMIC CASES 9
REFERENCES
1 Levin B R 1996 The Evolution and Maintenance of Virulence in Microparasites Emerging InfectiousDisease 293ndash102
2 National Academy of Sciences 1983 Risk Assessment in the Federal Government Managing theProcess National Academy Press Washington DC
3 National Research Council 2009 Science and Decisions Advancing Risk Assessment NationalAcademies Press Washington DC
10090807060504030201001190 1191 1192 1193 1194 1195
(b)
140
120
100
80
60
40
20
01190 1191 1192 1193 1194 1195
(f)
700
600
500
400
300
200
100
01190 1191 1192 1193 1194 1195
(d)
1200
1000
800
600
400
200
1190 1191 1192 1193 1194 1195
(a)
240
200
160
120
80
40
01190 1191 1192 1193 1194 1195
(e)
7
6
5
4
3
2
1
01190 1191 1192 1193 1194 1195
(c)
Figure 14 Weekly count of reported organism isolations in England andWales (a) rotavirus(b) Clostridium difficile (c) Salmonella derby (d) Shigella sonnei (e) influenza B and (f)Salmonella typhimurium DT 104 (From Ref [48])
10 CHAPTER 1 MOTIVATION
4 Fogarty J L Thornton and R Corcoran 1995 Illness in a Community Associated with an Episode ofWater Contamination with Sewage Epidemiology and Infection 114289ndash295
5 Scallan E 2011 Foodborne Illness Acquired in the United StatesmdashUnspecified Agents EmergingInfectious Diseases 17 16ndash22
6 Craun G F J M Brunkard J S Yoder V A Roberts J Carpenter T Wade R L CalderonJ M Roberts M J Beach and S L Roy 2010 Causes of Outbreaks Associated with Drinking Waterin the United States from 1971 to 2006 Clinical Microbiology Reviews 23507ndash528
7 Edwards D D 1993 Troubled Waters in Milwaukee ASM News 59342ndash3458 MacKenzie W R N J Hoxie M E Proctor M S Gradus K A Blair D E Peterson
J J Kazmierczak K R Fox D G Addias J B Rose and J P Davis 1994 Massive WaterborneOutbreak of Cryptosporidium Infection Associated with a Filtered Public Water Supply MilwaukeeWisconsin March and April 1993 New England Journal of Medicine 331161ndash167
9 Anonymous 2010 Surveillance for Foodborne Disease OutbreaksmdashUnited States 2007 Morbidityand Mortality Weekly Reports 59973ndash979
10 Bean N H J S Goulding C Lau and F J Angulo 1996 Surveillance for Foodborne-DiseaseOutbreaksmdashUnited States 1988ndash1992 Morbidity and Mortality Weekly Reports 451ndash66
11 Wall P G J de Louvois R J Gilbert and B Rowe 1996 Food Poisoning NotificationsLaboratory Reports and OutbreaksmdashWhere do the Statistics Come From and What Do They MeanCommunicable Disease Report Review 6 R93ndashR100
12 Colford J M S Roy M J Beach A Hightower S E Shaw and T J Wade 2006 A Review ofHousehold Drinking Water Intervention Trials and an Approach to the Estimation of EndemicWaterborne Gastroenteritis in the United States Journal of Water and Health 471
13 Mead P S L Slutsker V Dietz L F McCaig J S Bresee C Shapiro P M Griffinand R V Tauxe 1999 Food Related Illness and Death in the United States Emerging InfectiousDisease 5607ndash625
14 Dziuban E J J L Liang G F Craun V Hill P A Yu J Painter M R Moore R L CalderonS L Roy and M J Beach 2006 Surveillance for Waterborne Disease and Outbreaks Associatedwith Recreational WatermdashUnited States 2003ndash2004 and Surveillance for Waterborne Disease andOutbreaks Associated with Drinking Water and Water not Intended for DrinkingmdashUnited States2003ndash2004 Morbidity and Mortality Weekly Reports 551ndash30
15 Fliermans C B 1996 Ecology of Legionella From Data to Knowledge with a Little WisdomMicrobial Ecology 32203ndash228
16 Li Y S Duan I T Yu and T W Wong 2005 Multi-Zone Modeling of Probable SARS VirusTransmission by Airflow Between Flats in Block E Amoy Gardens Indoor Air 1596ndash111
17 Peccia J D K Milton T Reponen and J Hill 2008 A Role for Environmental Engineering andScience in Preventing Bioaerosol-Related Disease Environmental Science amp Technology424631ndash4637
18 Jernigan D B P L Raghunathan B P Bell R Brechner E A Bresnitz J C Butler M CetronM Cohen T Doyle and M Fischer 2002 Investigation of Bioterrorism-Related AnthraxUnited States 2001 Epidemiologic Findings Emerging Infectious Diseases 81019ndash1028
19 Greenwood M and G U Yule 1917 On the Statistical Interpretation of Some BacteriologicalMethods Employed in Water Analysis Journal of Hygiene 1636ndash56
20 Phelps E 1909 The Disinfection of Sewage and Sewage Filter Effluents USGS Water Supply Paper229 GPO Washington DC
21 Rudolfs W and H W Gehm 1935 Multiplication of Total Bacteria and B coli after SewageChlorination Sewage Works Journal 7991ndash996
22 Subcommittee onMicrobiological Criteria 1985 An Evaluation of the Role ofMicrobiological Criteriafor Foods and Food Ingredients National Academy Press Washington DC
23 Cabelli V J A P Dufour L J McCabe and M A Levin 1982 Swimming-AssociatedGastroenteritis and Water Quality American Journal of Epidemiology 115606ndash616
24 Dufour A P 1984 Health Effects Criteria for Fresh Recreational Waters USEPA Research TrianglePark NC
25 Fleisher J M F Jones and D Kay 1993 Water and Non-Water-Related Risk Factors forGastroenteritis among Bathers Exposed to Sewage-Contaminated Marine Waters InternationalJournal of Epidemiology 22698ndash708
REFERENCES 11
26 Engelbrecht R S C N Haas J A Shular D L Dunn D Roy A Lalchandani B F Severin andS Farooq 1979 Acid-Fast Bacteria and Yeasts as Indicators of Disinfection Efficiency EPA-6002-79-091 US Environmental Protection Agency Cincinnati OH
27 Grabow W O K 1983 Inactivation of Hepatitis A Virus and Indicator Organisms in Water by FreeChlorine Residuals Applied and Environmental Microbiology 46619
28 Helmer R D and G R Finch 1993 Use of MS2 Coliphage as a Surrogate for Enteric Viruses inSurface Waters Disinfected with Ozone Ozone Science and Engineering 15279ndash293
29 Payment P and E Franco 1993Clostridium Perfringens and Somatic Coliphages as Indicators of theEfficiency of Drinking Water Treatment for Viruses and Protozoan Cysts Applied and EnvironmentalMicrobiology 592418ndash2424
30 Cabelli V J 1977Clostridium Perfringens as aWater Quality Indicator pp 65ndash79 InA Hoadley andB Dutka (eds) Bacterial IndicatorsHealth Hazards Associated with Water ASTM Philadelphia PA
31 Rice E W K R Fox R J Miltner D A Lytle and C H Johnson 1996 Evaluating PlantPerformance with Endospores Journal of the American Water Works Association 88122ndash130
32 Engelbrecht R S B F Severin M T Masarik S Farooq S H Lee C N Haas and A Lalchandani1977 New Microbial Indicators of Disinfection Efficiency EPA-6002-77-052 US EnvironmentalProtection Agency Cincinnati OH
33 Committee on Indicators for Waterborne Pathogens ndash National Research Council 2004 Indicators forWaterborne Pathogens National Academies Press Washington DC
34 PresidentialCongressional Commission on Risk Assessment and RiskManagement 1997 Frameworkfor Environmental Health Risk Management The Commission Washington DC
35 Griffin P M and R V Tauxe 1991 The Epidemiology of Infections Caused by Escherichiacoli O157H7 Other Enterohemorrhagic E coli and the Associated Hemolytic Uremic SyndromeEpidemiologic Reviews 1360ndash98
36 Heun E M R L Vogt P J Hudson S Parren and G W Gary 1987 Risk Factors for SecondaryTransmission in Households after a Common Source Outbreak of Norwalk Gastroenteritis AmericanJournal of Epidemiology 1261181ndash1186
37 MacKenzie W R W L Schell B A Blair D G Addiss D E Peterson N J HozieJ J Kazmierczak and J P Davis 1995 Massive Outbreak of Waterborne CryptosporidiumInfection in Milwaukee Wisconsin Recurrence of Illness and Risk of Secondary TransmissionClinical Infectious Diseases 2157ndash62
38 Millard P K Gensheimer D G Addiss D M Sosin G A Beckett A Houck-Jankoski andA Hudson 1994 An Outbreak of Cryptosporidiosis from Fresh-Pressed Apple Cider Journal ofthe American Medical Association 2721592ndash1596
39 Pickering L K D G Evans H L DuPont J J Vollet and D J Evans Jr 1981 Diarrhea Caused byShigella Rotavirus and Giardia in Day Care Centers Prospective Study Journal of Pediatrics9951ndash56
40 Morens D M R M Zweighaft T M Vernon G W Gary J J Eslien B T Wood R C Holmanand R Dolin 1979 A Waterborne Outbreak of Gastroenteritis with Secondary Person to PersonSpread Lancet 5964ndash966
41 Laursen E O Mygind B Rasmussen and T Ronne 1994 Gastroenteritis A Waterborne OutbreakAffecting 1600 People in a Small Danish Town Journal of Epidemiology amp Community Health48453ndash458
42 Baron R C F D Murphy H B Greenberg C E Davis D J Bregman G W Gary J M Hughesand L B Schonberger 1982 Norwalk Gastrointestinal Illness An Outbreak Associated withSwimming in a Recreational Lake and Secondary Person to Person Transmission American Journalof Epidemiology 115163ndash172
43 Kappus K D J S Marks R C Holman J K Bryant C Baker G W Gary and H B Greenberg1982 An Outbreak of Norwalk Gastroenteritis Associated with Swimming in a Pool and SecondaryPerson to Person Transmission American Journal of Epidemiology 116834ndash839
44 White K E M T Osterbolm J A Mariotti J A Korlath D H Lawrence T L Ristinen andH B Greenberg 1986 A Foodborne Outbreak of Norwalk Virus Gastroenteritis American Journalof Epidemiology 124120ndash126
45 Spika J S J E Parsons and D Nordenberg 1986 Hemolytic Uremic Syndrome and DiarrheaAssociated with Escherichia coli O157H7 in a Day Care Center Journal of Pediatrics 109287ndash291
12 CHAPTER 1 MOTIVATION
46 Ferguson J K L R Jorm C D Allen P KWhitehead and G L Gilbert 1995 Prospective Study ofDiarrhoeal Outbreaks in Child Long Daycare Centres in Western Sydney Medical Journal of Australia163137ndash140
47 Frost F J G F Craun and R L Calderon 1996 Waterborne Disease Surveillance Journal of theAmerican Water Works Association 8866ndash75
48 Farrington C P N J Andrews A D Beale and M A Catchpole 1996 A Statistical Algorithmfor the Early Detection of Outbreaks of Infectious Disease Journal of the Royal StatisticalSociety A 159547ndash563
REFERENCES 13
CHAPTER2MICROBIAL AGENTS ANDTRANSMISSION
MICROBIAL TAXONOMY
The development of techniques for examining the nucleic acids of microorganisms hasseen major changes in which we classify and group related microorganisms This isespecially true for the study of ribosomal ribonucleic acid (rRNA) which is a highlyconserved sequence involved in the synthesis of proteins in all living organisms Basedon this analysis the classification of living things has been placed into a three-domainsystem consisting of Archaea Eukarya and Bacteria Of these the Bacteria andArchaea are termed prokaryotes (no organized cell nucleus) and the Eukarya areknown as eukaryotes (an organized cell nucleus) Eukaryotic microbes other thanalgae and fungi are collectively calledprotistsWithin theEukarya are fungi protozoahelminth worms algae plants animals and humans Archaea are microbes that looksomewhat similar to bacteria in size and shape under the light microscope but they areactually genetically and biochemically quite different They appear to be a simpler formof life and may in fact be the oldest form of life on earth Viruses are obligate intercel-lular parasites and are not amember of any group They are usually composed only of anucleic acid surrounded by a protein coat Eukaryotes are much more complex thanprokaryotic cells in structure and nutritional requirements Prokaryotes divide by sim-ple binary fissionwhereas eukaryotes divide byamore complexprocess calledmitosis
Eukaryotes
Fungi protozoa and helminth worms are all eukaryotes All contain members that arepathogenic to man and animals While algae do not infect humans they can producetoxins that are harmful to animals and man Fungi obtain nutrients solely by adsorp-tion of organic matter from dead organisms Even when they invade living tissuesthey typically kill cells and then adsorb the nutrients from them Some fungi are capa-ble of developing environmentally resistant spores which can be transported throughthe air Fungal diseases in humans are referred to asmycoses Airborne fungal sporesare responsible for some allergies in humans Yeasts are classified with the fungi and
Quantitative Microbial Risk Assessment Second Edition Charles N Haas Joan B Roseand Charles P Gerbacopy 2014 John Wiley amp Sons Inc Published 2014 by John Wiley amp Sons Inc
15
some are pathogenic to humans (Candida albicans) Certain fungi produce toxins(ie aflatoxins) when growing in foods that are mutagenic and carcinogenic in ani-mals Inhalation is an important route of transmission for some fungal diseases suchas aspergillosis blastomycosis coccidioidomycosis and histoplasmosis These fungiare found growing in animal feces soil or decaying organic matter (compost manure)and may be transmitted through the air when this matter is disturbed Some fungi maybe transmitted by direct contact with the skin Fungi are often found in drinking waterdistribution systems and they have been linked to infections in immunocompromisedindividuals [1] Food is not believed to be a significant route of transmission ofpathogenic fungi
Protozoans are unicellular organisms that are surrounded by a cytoplasmicmembrane that is covered by a protective structure called a pellicle Most are freeliving feeding off of bacteria Some of these can cause disease while others are obli-gate parasites They are capable of forming structures called cysts oocysts or spores(depending on the life cycle of the organism) resistant to adverse environmentalconditions such as desiccation starvation high temperatures and disinfectantsSome pathogenic protozoa are found mainly in the soil (Naegleria) or water(Acanthamoeba) Others such a Giardia and Cryptosporidium whose natural habitatis the intestines of warm-blooded animals are capable of causing disease in bothhumans and animals Others such as Entamoeba histolytica are only capable ofcausing disease in humans
Pathogenic enteric (replicate in the intestines) protozoans are usually excretedin the feces or urine and can be transmitted by fecally contaminated food and waterSome protozoa may be transmitted through the air (Acanthamoeba) or throughfomites (inanimate objects) Some important environmentally transmitted protozoaare listed in Table 21 The clinically important protozoa are divided taxonomicallyinto the amoebas (Entamoeba spp) flagellates (Giardia) and coccidian meaningldquoglobose in shaperdquo (Cryptosporidium and Cyclospora) Microsporidia are alsocapable of causing intestinal infections but their classification is uncertain becausethey have many characteristics associated with fungi They are all obligate parasitesand are transmitted via infectious cysts oocysts or spores by the fecalndashoral routeThe life cycles of these protozoa are similar The initial stage occurs during ingestionof the cyst oocyst or spore After ingestion the body temperature and passagethrough the stomach cause these infective stages to open up in a process calledexcystation
The Giardia cysts house two trophozoites which is the stage that attaches tointestinal cells and grows in the intestinal tract through asexual reproduction As thetrophozoites grow and begin to cover the wall of the intestinal tract diarrhea canresult As the trophozoites are released some form cysts as they pass through thebowels Cryptosporidium and Cyclospora both produce oocysts The life cycle ofCyclospora is still not well known except that its oocysts require some period of timein the environment before they are infective Cryptosporidium oocysts contain foursporozoites which enter the intestinal cells and begin the infection process As morecells become infected the illness begins and oocysts are excreted in high numbers inthe feces (about 100000g)
Worms and helminths are small multicellular animals that are parasiticto humans and animals They include flukes tapeworms and roundworms
16 CHAPTER 2 MICROBIAL AGENTS AND TRANSMISSION
microorganisms responsible for waterborne diseases and it is expected that withadvances in molecular biology this will increase
There are substantially more outbreaks and cases of foodborne infectiousdiseases than are reported Table 11 summarizes reports of US cases of principalmicrobial infectious foodborne illnesses for two 5-year periods (1988ndash1992 and
1971ndash1982
10
20
30
40
Perc
ent o
f out
brea
ks
50
60
1983ndash1994Period
1995ndash2006
Figure 11 Percentages of outbreaks associated with public water systems (n = 680) by timeperiod 1971ndash2006 that had unknown etiologies based on data from Ref [6]
TABLE 11 Comparison of Five-Year Averages for Common Foodborne Reported Outbreaks
Agent
Annual Average 1988ndash1992 Annual Average 2002ndash2006
Cases Outbreaks Cases Outbreaks
Campylobacter 996 44 624 22
Escherichia coli 488 22 481a 30a
Salmonella 42354 1098 3475 144
Shigella 9576 5 495 12
Staphylococcus aureus 3356 94 554 25
Hepatitis 4218 86 238 1
Listeria monocytogenes 04 02 22 2
Giardia 368 14 2 1
Norovirus 584 04 10854 338
Vibrio (all) 114 18 114 5
Unknown etiologies 40483 1422 4052 30
Source From Refs [9 10]a Include both Shiga toxigenic and enterotoxigenic
2 CHAPTER 1 MOTIVATION
2002ndash2006) There is a mix of causal agents including bacteria virus and protozoaIt is noteworthy that (as in the case of waterborne outbreaks) the frequency ofoutbreaks of unknown etiology has dramatically decreased but the frequency of out-breaks associated with norovirus has dramatically increased These changes are duein part to the ability to better identify causal agents (eg via molecular methods)
It is generally recognized that reported outbreaks either of water- or foodborneinfectious disease represent only a small fractionof the total populationdisease burdenHowever particularly in the United States voluntary reporting systems and theoccurrence of mild cases (for which no medical attention is sought but neverthelessare frank cases of disease) have made it difficult to estimate the total caseload
In the United Kingdom comparisons between the number of confirmed casesin infectious disease outbreaks and total confirmed laboratory illnesses (occurring inEngland and Wales) have been made (Table 12) This suggests that the ratio ofreported outbreak cases to total cases that may seek medical attention may be from10 to 5001 with some dependency on the particular agent
Colford et al [12] developed estimates for the total disease burden associatedwith acute gastroenteritis from drinking water This relies on combining the reportedoutbreak data with interventional epidemiologic studies Based on their analysis thetotal US disease burden is estimated to be 426ndash1169 million cases per year in theUnited States which is substantially in excess of the reported outbreaks In the case offoodborne illness there are an estimated 14 million cases per year [13]
Drinking water and food are by no means the only potential routes of exposureto infectious agents in the environment Recreation in water (either natural or artificialpools) containing pathogens can produce illness [14]
Indoor air transmission can be a vehicle of infection Legionella transmittedthrough indoor environments has been a concern since the 1970s [15] The multina-tional epidemic of severe acute respiratory syndrome (SARS) caused by a coronavi-rus was abetted at least in one location in Hong Kong by indoor aerosol transmissionbetween apartments of infected individuals and susceptible individuals [16] A broadspectrum of other respiratory pathogens including influenza rhinoviruses and myco-bacteria can be transmitted by this route [17]
TABLE 12 Comparison of Laboratory Isolations and Outbreak Cases in Englandand Wales 1992ndash1994
Agent
Cases 1992ndash1994
RatioAll Laboratory Reports Confirmed Outbreak Cases
Campylobacter 122250 240 5094
Rotavirus 47463 127 3737
S sonnei 29080 847 343
Salmonella 92416 5960 155
Cryptosporidium 14454 1066 136
E coli O157 1266 128 99
Source Modified from Ref [11]
PREVALENCE OF INFECTIOUS DISEASE 3
The deliberate release of Bacillus anthracis spores in 2001 (the ldquoAmerithraxrdquoincidents) brought widespread awareness to the potential for indoor releases (as wellas releases in other venues) of bioterrorist agents to cause risk [18] Therefore ofnecessity microbial risk assessors may need to consider the impact of maliciousactivity in certain applications
PRIOR APPROACHES
Concerns for microbial quality of food water and other environmental media havelong existed In the early twentieth century the use of indicator microorganismswas developed for the control and assessment of the hygienic quality of such mediaand the adequacy of disinfection and sterilization processes The coliform group oforganisms was perhaps first employed for this purpose [19ndash21] Indicator techniqueshave also found utility in the food industry such as the total count for milk and othermore recent proposals [22] Other indicator groups for food water or environmentalmedia have been examined such as enterococci [23ndash25] acid-fast bacteria [26]bacteriophage [27ndash29] and Clostridia spores [29ndash31]
The use of indicator organisms was historically justified in because of difficultyin enumerating pathogens However with the increasing availability of modernmicrobial methods for example PCR immunoassay etc for direct pathogen assess-ment this justification has become less persuasive In addition in order to develophealth-based standards from indicators extensive epidemiologic surveillance is oftennecessary The use of epidemiology has limitations with respect to detection limits(for an adverse effect) and is also quite expensive to conduct Indicator methodsare also limited in that many pathogens are more resistant to die off in receiving envir-onments or source waters than indicators or have greater resistance to removal bytreatment processes than indicators [26 28 29 32] Thus the absence of indicatorsmay not suffice to ensure the absence of pathogens Even after a century of use theindicator concept remains imperfect [33]
The use of quantitative microbial risk assessment (QMRA) will enable directmeasurements of pathogens to be used to develop acceptancerejection guidelinesfor food water and other vehicles that may be the source of microbial exposureto human populations The objective of this book is to present these methods in asystematic and unified manner
SCOPE OF COVERAGE
QMRA is the application of principles of risk assessment to the estimate ofconsequences from a planned or actual exposure to infectious microorganismsIn performing a QMRA the risk assessor aims to bring the best available informationto bear in understanding the nature of the potential effects from a microbial exposureSince the information (such as dosendashresponse relationships exposure magnitudes) isalmost invariably incomplete it is also necessary to ascertain the potential error
4 CHAPTER 1 MOTIVATION
involved in the risk assessment With such information necessary steps to mitigatecontrol or defend against such exposures may be developed
At the outset of performing a risk assessment a scoping task should be under-taken This task should set forth the objectives of the analysis and the principal issuesto be addressed Items such as consideration of secondary cases individual versuspopulation risk agent or agents to be examined exposure routes andor accident sce-narios must be stipulated However this scoping may be changed during the course ofa QMRA to reflect the input derived from the risk manager(s) and other stakeholders
POTENTIAL OBJECTIVES OF A QMRA
There may be diverse objectives for a QMRA These objectives relate to the rationalefor the performance of the assessment as well as the methods to be employedBroadly the different objectives reflect different scales at which a risk assessmentmay be performed The step of problem formulation is critical to any risk estimate[34] It is necessary that the problem be formulated to meet the needs of the riskmanagers and stakeholders indeed it is now recognized that the successful practiceof risk analysis requires frequent interchange with manager and stakeholders [3]In general the problems posed are of several types
Site-Specific Assessment
The simplest type of QMRA that may be performed involves one site or exposurescenario The following are typical of the questions that might be asked
1 If a water treatment plant is designed in a certain way (with given removals ofpathogens) then what is the risk that would be placed upon the populationserved
2 A swimming outbreak (in a recreational lake) has just occurred I believe that itresulted from a short-duration contamination event What pathogen levelswould be consistent with the observed attack rate
3 Microbial sampling of a finished food product has found certain pathogensWhat level of risk does this pose to consumers of the product
4 A certain amount of infectious agent has been released into a room What is theimmediate danger to occupants and how stringent should cleanup levels be
Note that there are certain other contrasts in the objectives of the risk assessments tobe posed In (1) and (3) a before-the-fact computation is desired while in (2) and (4)an after-the-fact computation is described Also in (1) (3) and (4) pathogen levelsare available (or somehow are estimated) while in (2) an inverse computation isneeded given an observed attack rate
In performing this risk assessment the relationship between an exposure ortechnological metric and a risk measurement must be ascertained and then theparticular point of correspondence determined (Fig 12) In cases (1) (3) and (4)for a known (or assumed) exposure (on the x-axis) the corresponding range of risks
POTENTIAL OBJECTIVES OF A QMRA 5
on the y-axis is sought In cases (2) for known or assumed risks (on the y-axis)the corresponding range of exposures (or level of technological protection) is to bedetermined (on the x-axis)
Ensemble of Sites
A somewhat more complex situation occurs if the risk for a set of events or sites mustbe estimated Basically this now includes the necessity to incorporate site-to-sitefactors into the assessment Some examples of this are as follows
1 If I desire keeping the risk to a population served by multiple water treatmentplants at a given level (or better) then what criteria should I use (microbiallevels)
2 For a food product subject to contamination by pathogens what would be anacceptable treatment specification (eg heating time holding period) to ensuremicrobial acceptability
3 I am designing a water quality standard for recreational bathing waters If auniform (eg national) standard is to be developed what standard would ensurethat average risk was acceptable with keeping the risk of a large ldquoclusterrdquo ofillnesses low
In addition to incorporating a measure of ensemble average risk in general it is alsodesired to ensure that no single member of the ensemble be unacceptably extreme Forexample consider the evaluation of three options of disease control among three com-munities as indicated in Table 13
This table indicates the number of cases and the rate among the three commu-nities The three policy options yield the same number of expected cases Howeverthere are differences in the allocation of risk among the communities of different sizesIn option A all communities have an identical level of estimated risk In option B therisk increases as community size decreases while in option C the risk increases ascommunity size increases This distribution of risk among affected subsets of the
Exposure
Ris
k
Level of technological protection
Figure 12 Relationship between exposurelevel of technological protection andmicrobial risk The middle curve indicatesthe best estimate The other two curvesindicate the upper and lower confidenceregions
6 CHAPTER 1 MOTIVATION
ensemble being considered adds an additional dimension for consideration by a riskmanagermdashwhich may be termed risk equity
SECONDARY TRANSMISSION
Infectious microbial diseases are different in terms of risk to a population than arechemical agents in that an individual who may become infected (with or withoutillness) can then proceed to infect additional individuals These secondary (tertiaryquaternary etc) cases may be persons who had no direct contact with the initialvehicle of exposure but nevertheless in fairly accounting for the public health impactthey should be considered
Secondary cases may arise by a variety of mechanisms Particularly amongclose family members household secondary cases can arise by direct or indirect(eg surface contamination) contact this is particularly so when the primary caseor one household secondary case is a child [35ndash37] Table 14 summarizes secondarycase statistics obtained from a variety of outbreaks As will be discussed inChapter 10 the secondary case rate is a complex factor involving (among other things)the nature of the venue and contact patterns when infected and susceptible individualsintermingle
Presumably secondary cases may also arise from close contact with anasymptomatic individual (in the ldquocarrierrdquo state) This is well known for highly acuteand (now) uncommon illnesses (such as typhoid) Excretion of Norwalk virusfollowing recovery (and resulting in additional cases) has been documented to occurfor as long as 48 h post recovery [44]
OUTBREAKS VERSUS ENDEMIC CASES
As noted previously there may be a substantial difference between reported outbreakcases and total disease burden in a community In order for a disease case to receiverecognition by the public health authorities the following specific and sequential stepsmust occur [47]
TABLE 13 Effect of Different Hypothetical Policy Options on Distribution of Risk AmongCommunities (for a Fixed Total Risk)
CommunityExposedPopulation
Policy Option A Policy Option B Policy Option C
CasesIncidence(10000) Cases
Incidence(10000) Cases
Incidence(10000)
A 100000 20 2 6 06 24 24
B 50000 10 2 18 36 7 14
C 10000 2 2 8 8 1 1
Total 160000 32 2 32 2 16 2
OUTBREAKS VERSUS ENDEMIC CASES 7
1 An ill person must seek medical care
2 Appropriate clinical tests (eg blood stool) must be ordered by the attendingphysician
3 The patient must comply with obtaining the sample
4 The laboratory must be capable of detecting the relevant pathogens
5 The clinical test must be positive
6 The test result must be reported to the health agency in a timely manner
If any of the links in this sequential chain are broken then a disease case will not enterthe records maintained by health authorities For example with increasing controls on
TABLE 14 Summary of Secondary Case Data in Outbreak Situations
Organism
SecondaryAttackRatioa
SecondaryPrevalence inHouseholdsb Remarks Reference
Cryptosporidiumparvum
033 033 Outbreak in contaminatedapple cider
[38]
C parvum NA 0042 Drinking water outbreak(Milwaukee)
[37]
Shigella 028 026 Day-care center outbreaksin children
[39]
Rotavirus 042 015 Day-care center outbreaksin children
[30]
Giardia lamblia 133 017 Day-care center outbreaksin children
[39]
Viral gastroenteritis 022 011c Drinking waterborneoutbreak
[40]
Viral gastroenteritis 056 NA Drinking water outbreak(Denmark)
[41]
Norovirus 05ndash10 019 Swimming outbreak [42]
Norovirus 11 029 Swimming outbreakin children
[43]
Norovirus NA 044 Foodborne outbreakin children and teachers
[36]
Norovirus 04 NA Foodborne outbreak [44]
E coli O157H7 NA 018c Day-care center outbreakin children
[45]
Unidentifiedday-care diarrhealdiseases
138 009c [46]
NA information not availableaRatio of secondary cases to primary casesb Proportion of households with one or more primary cases who have one or more secondary casesc Proportion of persons in contact with one or more primary cases who have a secondary case
8 CHAPTER 1 MOTIVATION
medical care stool samples may not be obtained from mild cases of illness Someorganisms may only be present sporadically or may be difficult to test in stool orblood sample Patients may not seek medical attention for mild cases of illness Fur-thermore in the United States in particular the surveillance of environmentallyinduced disease is done on a passive basis and hence the number of actual illnessclusters that are actually compiled into recorded statistics is only a small fractionof such clusters of illness that occur [47]
From a more fundamental point of view an outbreak of illness is generallydefined as occurrence of the illness at a level greater than normal or anticipated Thisdefinition recognizes that there is a level of illness (endemic) that may exist underusual circumstances The detection of such outbreaks poses a particular challengeThe problem is illustrated conceptually in Figure 13
Additional complications arise from the different patterns of illness in acommunity including definite periodicities as well as temporal trends and fromthe presence of reporting lags associated with laboratory analysis and time for patientsto seek medical attention Figure 14 illustrates the different patterns of illness inthe case of six pathogens for England and Wales [48]
In the case of waterborne and foodborne illnesses it is highly likely that thelevel of such endemic illnesses is substantially greater than those occurring duringoutbreaks (even accounting for unrecognized outbreaks)
As a result there are often many cases of environmentally caused (water airfood) infectious disease that are unrecognized One example of this isCampylobacterThere has been an average of about 200 cases per year of water- and foodborne illnessin outbreaks of this organism and yet estimates of the disease burden suggest about2100000 cases per year that is approximately 10000 cases per case of detectableoutbreak illness Therefore it will be important to assess the factors that may influenceoutbreak detection These issues will be discussed in subsequent chapters
Detectedoutbreak
Undetectedoutbreak
Threshold of detection
Hyper endemicSporadic
Endemic rate
Time
Num
ber
of c
ases
Figure 13 Schematic of disease occurrence in a hypothetical community (Modified fromRef [47])
OUTBREAKS VERSUS ENDEMIC CASES 9
REFERENCES
1 Levin B R 1996 The Evolution and Maintenance of Virulence in Microparasites Emerging InfectiousDisease 293ndash102
2 National Academy of Sciences 1983 Risk Assessment in the Federal Government Managing theProcess National Academy Press Washington DC
3 National Research Council 2009 Science and Decisions Advancing Risk Assessment NationalAcademies Press Washington DC
10090807060504030201001190 1191 1192 1193 1194 1195
(b)
140
120
100
80
60
40
20
01190 1191 1192 1193 1194 1195
(f)
700
600
500
400
300
200
100
01190 1191 1192 1193 1194 1195
(d)
1200
1000
800
600
400
200
1190 1191 1192 1193 1194 1195
(a)
240
200
160
120
80
40
01190 1191 1192 1193 1194 1195
(e)
7
6
5
4
3
2
1
01190 1191 1192 1193 1194 1195
(c)
Figure 14 Weekly count of reported organism isolations in England andWales (a) rotavirus(b) Clostridium difficile (c) Salmonella derby (d) Shigella sonnei (e) influenza B and (f)Salmonella typhimurium DT 104 (From Ref [48])
10 CHAPTER 1 MOTIVATION
4 Fogarty J L Thornton and R Corcoran 1995 Illness in a Community Associated with an Episode ofWater Contamination with Sewage Epidemiology and Infection 114289ndash295
5 Scallan E 2011 Foodborne Illness Acquired in the United StatesmdashUnspecified Agents EmergingInfectious Diseases 17 16ndash22
6 Craun G F J M Brunkard J S Yoder V A Roberts J Carpenter T Wade R L CalderonJ M Roberts M J Beach and S L Roy 2010 Causes of Outbreaks Associated with Drinking Waterin the United States from 1971 to 2006 Clinical Microbiology Reviews 23507ndash528
7 Edwards D D 1993 Troubled Waters in Milwaukee ASM News 59342ndash3458 MacKenzie W R N J Hoxie M E Proctor M S Gradus K A Blair D E Peterson
J J Kazmierczak K R Fox D G Addias J B Rose and J P Davis 1994 Massive WaterborneOutbreak of Cryptosporidium Infection Associated with a Filtered Public Water Supply MilwaukeeWisconsin March and April 1993 New England Journal of Medicine 331161ndash167
9 Anonymous 2010 Surveillance for Foodborne Disease OutbreaksmdashUnited States 2007 Morbidityand Mortality Weekly Reports 59973ndash979
10 Bean N H J S Goulding C Lau and F J Angulo 1996 Surveillance for Foodborne-DiseaseOutbreaksmdashUnited States 1988ndash1992 Morbidity and Mortality Weekly Reports 451ndash66
11 Wall P G J de Louvois R J Gilbert and B Rowe 1996 Food Poisoning NotificationsLaboratory Reports and OutbreaksmdashWhere do the Statistics Come From and What Do They MeanCommunicable Disease Report Review 6 R93ndashR100
12 Colford J M S Roy M J Beach A Hightower S E Shaw and T J Wade 2006 A Review ofHousehold Drinking Water Intervention Trials and an Approach to the Estimation of EndemicWaterborne Gastroenteritis in the United States Journal of Water and Health 471
13 Mead P S L Slutsker V Dietz L F McCaig J S Bresee C Shapiro P M Griffinand R V Tauxe 1999 Food Related Illness and Death in the United States Emerging InfectiousDisease 5607ndash625
14 Dziuban E J J L Liang G F Craun V Hill P A Yu J Painter M R Moore R L CalderonS L Roy and M J Beach 2006 Surveillance for Waterborne Disease and Outbreaks Associatedwith Recreational WatermdashUnited States 2003ndash2004 and Surveillance for Waterborne Disease andOutbreaks Associated with Drinking Water and Water not Intended for DrinkingmdashUnited States2003ndash2004 Morbidity and Mortality Weekly Reports 551ndash30
15 Fliermans C B 1996 Ecology of Legionella From Data to Knowledge with a Little WisdomMicrobial Ecology 32203ndash228
16 Li Y S Duan I T Yu and T W Wong 2005 Multi-Zone Modeling of Probable SARS VirusTransmission by Airflow Between Flats in Block E Amoy Gardens Indoor Air 1596ndash111
17 Peccia J D K Milton T Reponen and J Hill 2008 A Role for Environmental Engineering andScience in Preventing Bioaerosol-Related Disease Environmental Science amp Technology424631ndash4637
18 Jernigan D B P L Raghunathan B P Bell R Brechner E A Bresnitz J C Butler M CetronM Cohen T Doyle and M Fischer 2002 Investigation of Bioterrorism-Related AnthraxUnited States 2001 Epidemiologic Findings Emerging Infectious Diseases 81019ndash1028
19 Greenwood M and G U Yule 1917 On the Statistical Interpretation of Some BacteriologicalMethods Employed in Water Analysis Journal of Hygiene 1636ndash56
20 Phelps E 1909 The Disinfection of Sewage and Sewage Filter Effluents USGS Water Supply Paper229 GPO Washington DC
21 Rudolfs W and H W Gehm 1935 Multiplication of Total Bacteria and B coli after SewageChlorination Sewage Works Journal 7991ndash996
22 Subcommittee onMicrobiological Criteria 1985 An Evaluation of the Role ofMicrobiological Criteriafor Foods and Food Ingredients National Academy Press Washington DC
23 Cabelli V J A P Dufour L J McCabe and M A Levin 1982 Swimming-AssociatedGastroenteritis and Water Quality American Journal of Epidemiology 115606ndash616
24 Dufour A P 1984 Health Effects Criteria for Fresh Recreational Waters USEPA Research TrianglePark NC
25 Fleisher J M F Jones and D Kay 1993 Water and Non-Water-Related Risk Factors forGastroenteritis among Bathers Exposed to Sewage-Contaminated Marine Waters InternationalJournal of Epidemiology 22698ndash708
REFERENCES 11
26 Engelbrecht R S C N Haas J A Shular D L Dunn D Roy A Lalchandani B F Severin andS Farooq 1979 Acid-Fast Bacteria and Yeasts as Indicators of Disinfection Efficiency EPA-6002-79-091 US Environmental Protection Agency Cincinnati OH
27 Grabow W O K 1983 Inactivation of Hepatitis A Virus and Indicator Organisms in Water by FreeChlorine Residuals Applied and Environmental Microbiology 46619
28 Helmer R D and G R Finch 1993 Use of MS2 Coliphage as a Surrogate for Enteric Viruses inSurface Waters Disinfected with Ozone Ozone Science and Engineering 15279ndash293
29 Payment P and E Franco 1993Clostridium Perfringens and Somatic Coliphages as Indicators of theEfficiency of Drinking Water Treatment for Viruses and Protozoan Cysts Applied and EnvironmentalMicrobiology 592418ndash2424
30 Cabelli V J 1977Clostridium Perfringens as aWater Quality Indicator pp 65ndash79 InA Hoadley andB Dutka (eds) Bacterial IndicatorsHealth Hazards Associated with Water ASTM Philadelphia PA
31 Rice E W K R Fox R J Miltner D A Lytle and C H Johnson 1996 Evaluating PlantPerformance with Endospores Journal of the American Water Works Association 88122ndash130
32 Engelbrecht R S B F Severin M T Masarik S Farooq S H Lee C N Haas and A Lalchandani1977 New Microbial Indicators of Disinfection Efficiency EPA-6002-77-052 US EnvironmentalProtection Agency Cincinnati OH
33 Committee on Indicators for Waterborne Pathogens ndash National Research Council 2004 Indicators forWaterborne Pathogens National Academies Press Washington DC
34 PresidentialCongressional Commission on Risk Assessment and RiskManagement 1997 Frameworkfor Environmental Health Risk Management The Commission Washington DC
35 Griffin P M and R V Tauxe 1991 The Epidemiology of Infections Caused by Escherichiacoli O157H7 Other Enterohemorrhagic E coli and the Associated Hemolytic Uremic SyndromeEpidemiologic Reviews 1360ndash98
36 Heun E M R L Vogt P J Hudson S Parren and G W Gary 1987 Risk Factors for SecondaryTransmission in Households after a Common Source Outbreak of Norwalk Gastroenteritis AmericanJournal of Epidemiology 1261181ndash1186
37 MacKenzie W R W L Schell B A Blair D G Addiss D E Peterson N J HozieJ J Kazmierczak and J P Davis 1995 Massive Outbreak of Waterborne CryptosporidiumInfection in Milwaukee Wisconsin Recurrence of Illness and Risk of Secondary TransmissionClinical Infectious Diseases 2157ndash62
38 Millard P K Gensheimer D G Addiss D M Sosin G A Beckett A Houck-Jankoski andA Hudson 1994 An Outbreak of Cryptosporidiosis from Fresh-Pressed Apple Cider Journal ofthe American Medical Association 2721592ndash1596
39 Pickering L K D G Evans H L DuPont J J Vollet and D J Evans Jr 1981 Diarrhea Caused byShigella Rotavirus and Giardia in Day Care Centers Prospective Study Journal of Pediatrics9951ndash56
40 Morens D M R M Zweighaft T M Vernon G W Gary J J Eslien B T Wood R C Holmanand R Dolin 1979 A Waterborne Outbreak of Gastroenteritis with Secondary Person to PersonSpread Lancet 5964ndash966
41 Laursen E O Mygind B Rasmussen and T Ronne 1994 Gastroenteritis A Waterborne OutbreakAffecting 1600 People in a Small Danish Town Journal of Epidemiology amp Community Health48453ndash458
42 Baron R C F D Murphy H B Greenberg C E Davis D J Bregman G W Gary J M Hughesand L B Schonberger 1982 Norwalk Gastrointestinal Illness An Outbreak Associated withSwimming in a Recreational Lake and Secondary Person to Person Transmission American Journalof Epidemiology 115163ndash172
43 Kappus K D J S Marks R C Holman J K Bryant C Baker G W Gary and H B Greenberg1982 An Outbreak of Norwalk Gastroenteritis Associated with Swimming in a Pool and SecondaryPerson to Person Transmission American Journal of Epidemiology 116834ndash839
44 White K E M T Osterbolm J A Mariotti J A Korlath D H Lawrence T L Ristinen andH B Greenberg 1986 A Foodborne Outbreak of Norwalk Virus Gastroenteritis American Journalof Epidemiology 124120ndash126
45 Spika J S J E Parsons and D Nordenberg 1986 Hemolytic Uremic Syndrome and DiarrheaAssociated with Escherichia coli O157H7 in a Day Care Center Journal of Pediatrics 109287ndash291
12 CHAPTER 1 MOTIVATION
46 Ferguson J K L R Jorm C D Allen P KWhitehead and G L Gilbert 1995 Prospective Study ofDiarrhoeal Outbreaks in Child Long Daycare Centres in Western Sydney Medical Journal of Australia163137ndash140
47 Frost F J G F Craun and R L Calderon 1996 Waterborne Disease Surveillance Journal of theAmerican Water Works Association 8866ndash75
48 Farrington C P N J Andrews A D Beale and M A Catchpole 1996 A Statistical Algorithmfor the Early Detection of Outbreaks of Infectious Disease Journal of the Royal StatisticalSociety A 159547ndash563
REFERENCES 13
CHAPTER2MICROBIAL AGENTS ANDTRANSMISSION
MICROBIAL TAXONOMY
The development of techniques for examining the nucleic acids of microorganisms hasseen major changes in which we classify and group related microorganisms This isespecially true for the study of ribosomal ribonucleic acid (rRNA) which is a highlyconserved sequence involved in the synthesis of proteins in all living organisms Basedon this analysis the classification of living things has been placed into a three-domainsystem consisting of Archaea Eukarya and Bacteria Of these the Bacteria andArchaea are termed prokaryotes (no organized cell nucleus) and the Eukarya areknown as eukaryotes (an organized cell nucleus) Eukaryotic microbes other thanalgae and fungi are collectively calledprotistsWithin theEukarya are fungi protozoahelminth worms algae plants animals and humans Archaea are microbes that looksomewhat similar to bacteria in size and shape under the light microscope but they areactually genetically and biochemically quite different They appear to be a simpler formof life and may in fact be the oldest form of life on earth Viruses are obligate intercel-lular parasites and are not amember of any group They are usually composed only of anucleic acid surrounded by a protein coat Eukaryotes are much more complex thanprokaryotic cells in structure and nutritional requirements Prokaryotes divide by sim-ple binary fissionwhereas eukaryotes divide byamore complexprocess calledmitosis
Eukaryotes
Fungi protozoa and helminth worms are all eukaryotes All contain members that arepathogenic to man and animals While algae do not infect humans they can producetoxins that are harmful to animals and man Fungi obtain nutrients solely by adsorp-tion of organic matter from dead organisms Even when they invade living tissuesthey typically kill cells and then adsorb the nutrients from them Some fungi are capa-ble of developing environmentally resistant spores which can be transported throughthe air Fungal diseases in humans are referred to asmycoses Airborne fungal sporesare responsible for some allergies in humans Yeasts are classified with the fungi and
Quantitative Microbial Risk Assessment Second Edition Charles N Haas Joan B Roseand Charles P Gerbacopy 2014 John Wiley amp Sons Inc Published 2014 by John Wiley amp Sons Inc
15
some are pathogenic to humans (Candida albicans) Certain fungi produce toxins(ie aflatoxins) when growing in foods that are mutagenic and carcinogenic in ani-mals Inhalation is an important route of transmission for some fungal diseases suchas aspergillosis blastomycosis coccidioidomycosis and histoplasmosis These fungiare found growing in animal feces soil or decaying organic matter (compost manure)and may be transmitted through the air when this matter is disturbed Some fungi maybe transmitted by direct contact with the skin Fungi are often found in drinking waterdistribution systems and they have been linked to infections in immunocompromisedindividuals [1] Food is not believed to be a significant route of transmission ofpathogenic fungi
Protozoans are unicellular organisms that are surrounded by a cytoplasmicmembrane that is covered by a protective structure called a pellicle Most are freeliving feeding off of bacteria Some of these can cause disease while others are obli-gate parasites They are capable of forming structures called cysts oocysts or spores(depending on the life cycle of the organism) resistant to adverse environmentalconditions such as desiccation starvation high temperatures and disinfectantsSome pathogenic protozoa are found mainly in the soil (Naegleria) or water(Acanthamoeba) Others such a Giardia and Cryptosporidium whose natural habitatis the intestines of warm-blooded animals are capable of causing disease in bothhumans and animals Others such as Entamoeba histolytica are only capable ofcausing disease in humans
Pathogenic enteric (replicate in the intestines) protozoans are usually excretedin the feces or urine and can be transmitted by fecally contaminated food and waterSome protozoa may be transmitted through the air (Acanthamoeba) or throughfomites (inanimate objects) Some important environmentally transmitted protozoaare listed in Table 21 The clinically important protozoa are divided taxonomicallyinto the amoebas (Entamoeba spp) flagellates (Giardia) and coccidian meaningldquoglobose in shaperdquo (Cryptosporidium and Cyclospora) Microsporidia are alsocapable of causing intestinal infections but their classification is uncertain becausethey have many characteristics associated with fungi They are all obligate parasitesand are transmitted via infectious cysts oocysts or spores by the fecalndashoral routeThe life cycles of these protozoa are similar The initial stage occurs during ingestionof the cyst oocyst or spore After ingestion the body temperature and passagethrough the stomach cause these infective stages to open up in a process calledexcystation
The Giardia cysts house two trophozoites which is the stage that attaches tointestinal cells and grows in the intestinal tract through asexual reproduction As thetrophozoites grow and begin to cover the wall of the intestinal tract diarrhea canresult As the trophozoites are released some form cysts as they pass through thebowels Cryptosporidium and Cyclospora both produce oocysts The life cycle ofCyclospora is still not well known except that its oocysts require some period of timein the environment before they are infective Cryptosporidium oocysts contain foursporozoites which enter the intestinal cells and begin the infection process As morecells become infected the illness begins and oocysts are excreted in high numbers inthe feces (about 100000g)
Worms and helminths are small multicellular animals that are parasiticto humans and animals They include flukes tapeworms and roundworms
16 CHAPTER 2 MICROBIAL AGENTS AND TRANSMISSION
2002ndash2006) There is a mix of causal agents including bacteria virus and protozoaIt is noteworthy that (as in the case of waterborne outbreaks) the frequency ofoutbreaks of unknown etiology has dramatically decreased but the frequency of out-breaks associated with norovirus has dramatically increased These changes are duein part to the ability to better identify causal agents (eg via molecular methods)
It is generally recognized that reported outbreaks either of water- or foodborneinfectious disease represent only a small fractionof the total populationdisease burdenHowever particularly in the United States voluntary reporting systems and theoccurrence of mild cases (for which no medical attention is sought but neverthelessare frank cases of disease) have made it difficult to estimate the total caseload
In the United Kingdom comparisons between the number of confirmed casesin infectious disease outbreaks and total confirmed laboratory illnesses (occurring inEngland and Wales) have been made (Table 12) This suggests that the ratio ofreported outbreak cases to total cases that may seek medical attention may be from10 to 5001 with some dependency on the particular agent
Colford et al [12] developed estimates for the total disease burden associatedwith acute gastroenteritis from drinking water This relies on combining the reportedoutbreak data with interventional epidemiologic studies Based on their analysis thetotal US disease burden is estimated to be 426ndash1169 million cases per year in theUnited States which is substantially in excess of the reported outbreaks In the case offoodborne illness there are an estimated 14 million cases per year [13]
Drinking water and food are by no means the only potential routes of exposureto infectious agents in the environment Recreation in water (either natural or artificialpools) containing pathogens can produce illness [14]
Indoor air transmission can be a vehicle of infection Legionella transmittedthrough indoor environments has been a concern since the 1970s [15] The multina-tional epidemic of severe acute respiratory syndrome (SARS) caused by a coronavi-rus was abetted at least in one location in Hong Kong by indoor aerosol transmissionbetween apartments of infected individuals and susceptible individuals [16] A broadspectrum of other respiratory pathogens including influenza rhinoviruses and myco-bacteria can be transmitted by this route [17]
TABLE 12 Comparison of Laboratory Isolations and Outbreak Cases in Englandand Wales 1992ndash1994
Agent
Cases 1992ndash1994
RatioAll Laboratory Reports Confirmed Outbreak Cases
Campylobacter 122250 240 5094
Rotavirus 47463 127 3737
S sonnei 29080 847 343
Salmonella 92416 5960 155
Cryptosporidium 14454 1066 136
E coli O157 1266 128 99
Source Modified from Ref [11]
PREVALENCE OF INFECTIOUS DISEASE 3
The deliberate release of Bacillus anthracis spores in 2001 (the ldquoAmerithraxrdquoincidents) brought widespread awareness to the potential for indoor releases (as wellas releases in other venues) of bioterrorist agents to cause risk [18] Therefore ofnecessity microbial risk assessors may need to consider the impact of maliciousactivity in certain applications
PRIOR APPROACHES
Concerns for microbial quality of food water and other environmental media havelong existed In the early twentieth century the use of indicator microorganismswas developed for the control and assessment of the hygienic quality of such mediaand the adequacy of disinfection and sterilization processes The coliform group oforganisms was perhaps first employed for this purpose [19ndash21] Indicator techniqueshave also found utility in the food industry such as the total count for milk and othermore recent proposals [22] Other indicator groups for food water or environmentalmedia have been examined such as enterococci [23ndash25] acid-fast bacteria [26]bacteriophage [27ndash29] and Clostridia spores [29ndash31]
The use of indicator organisms was historically justified in because of difficultyin enumerating pathogens However with the increasing availability of modernmicrobial methods for example PCR immunoassay etc for direct pathogen assess-ment this justification has become less persuasive In addition in order to develophealth-based standards from indicators extensive epidemiologic surveillance is oftennecessary The use of epidemiology has limitations with respect to detection limits(for an adverse effect) and is also quite expensive to conduct Indicator methodsare also limited in that many pathogens are more resistant to die off in receiving envir-onments or source waters than indicators or have greater resistance to removal bytreatment processes than indicators [26 28 29 32] Thus the absence of indicatorsmay not suffice to ensure the absence of pathogens Even after a century of use theindicator concept remains imperfect [33]
The use of quantitative microbial risk assessment (QMRA) will enable directmeasurements of pathogens to be used to develop acceptancerejection guidelinesfor food water and other vehicles that may be the source of microbial exposureto human populations The objective of this book is to present these methods in asystematic and unified manner
SCOPE OF COVERAGE
QMRA is the application of principles of risk assessment to the estimate ofconsequences from a planned or actual exposure to infectious microorganismsIn performing a QMRA the risk assessor aims to bring the best available informationto bear in understanding the nature of the potential effects from a microbial exposureSince the information (such as dosendashresponse relationships exposure magnitudes) isalmost invariably incomplete it is also necessary to ascertain the potential error
4 CHAPTER 1 MOTIVATION
involved in the risk assessment With such information necessary steps to mitigatecontrol or defend against such exposures may be developed
At the outset of performing a risk assessment a scoping task should be under-taken This task should set forth the objectives of the analysis and the principal issuesto be addressed Items such as consideration of secondary cases individual versuspopulation risk agent or agents to be examined exposure routes andor accident sce-narios must be stipulated However this scoping may be changed during the course ofa QMRA to reflect the input derived from the risk manager(s) and other stakeholders
POTENTIAL OBJECTIVES OF A QMRA
There may be diverse objectives for a QMRA These objectives relate to the rationalefor the performance of the assessment as well as the methods to be employedBroadly the different objectives reflect different scales at which a risk assessmentmay be performed The step of problem formulation is critical to any risk estimate[34] It is necessary that the problem be formulated to meet the needs of the riskmanagers and stakeholders indeed it is now recognized that the successful practiceof risk analysis requires frequent interchange with manager and stakeholders [3]In general the problems posed are of several types
Site-Specific Assessment
The simplest type of QMRA that may be performed involves one site or exposurescenario The following are typical of the questions that might be asked
1 If a water treatment plant is designed in a certain way (with given removals ofpathogens) then what is the risk that would be placed upon the populationserved
2 A swimming outbreak (in a recreational lake) has just occurred I believe that itresulted from a short-duration contamination event What pathogen levelswould be consistent with the observed attack rate
3 Microbial sampling of a finished food product has found certain pathogensWhat level of risk does this pose to consumers of the product
4 A certain amount of infectious agent has been released into a room What is theimmediate danger to occupants and how stringent should cleanup levels be
Note that there are certain other contrasts in the objectives of the risk assessments tobe posed In (1) and (3) a before-the-fact computation is desired while in (2) and (4)an after-the-fact computation is described Also in (1) (3) and (4) pathogen levelsare available (or somehow are estimated) while in (2) an inverse computation isneeded given an observed attack rate
In performing this risk assessment the relationship between an exposure ortechnological metric and a risk measurement must be ascertained and then theparticular point of correspondence determined (Fig 12) In cases (1) (3) and (4)for a known (or assumed) exposure (on the x-axis) the corresponding range of risks
POTENTIAL OBJECTIVES OF A QMRA 5
on the y-axis is sought In cases (2) for known or assumed risks (on the y-axis)the corresponding range of exposures (or level of technological protection) is to bedetermined (on the x-axis)
Ensemble of Sites
A somewhat more complex situation occurs if the risk for a set of events or sites mustbe estimated Basically this now includes the necessity to incorporate site-to-sitefactors into the assessment Some examples of this are as follows
1 If I desire keeping the risk to a population served by multiple water treatmentplants at a given level (or better) then what criteria should I use (microbiallevels)
2 For a food product subject to contamination by pathogens what would be anacceptable treatment specification (eg heating time holding period) to ensuremicrobial acceptability
3 I am designing a water quality standard for recreational bathing waters If auniform (eg national) standard is to be developed what standard would ensurethat average risk was acceptable with keeping the risk of a large ldquoclusterrdquo ofillnesses low
In addition to incorporating a measure of ensemble average risk in general it is alsodesired to ensure that no single member of the ensemble be unacceptably extreme Forexample consider the evaluation of three options of disease control among three com-munities as indicated in Table 13
This table indicates the number of cases and the rate among the three commu-nities The three policy options yield the same number of expected cases Howeverthere are differences in the allocation of risk among the communities of different sizesIn option A all communities have an identical level of estimated risk In option B therisk increases as community size decreases while in option C the risk increases ascommunity size increases This distribution of risk among affected subsets of the
Exposure
Ris
k
Level of technological protection
Figure 12 Relationship between exposurelevel of technological protection andmicrobial risk The middle curve indicatesthe best estimate The other two curvesindicate the upper and lower confidenceregions
6 CHAPTER 1 MOTIVATION
ensemble being considered adds an additional dimension for consideration by a riskmanagermdashwhich may be termed risk equity
SECONDARY TRANSMISSION
Infectious microbial diseases are different in terms of risk to a population than arechemical agents in that an individual who may become infected (with or withoutillness) can then proceed to infect additional individuals These secondary (tertiaryquaternary etc) cases may be persons who had no direct contact with the initialvehicle of exposure but nevertheless in fairly accounting for the public health impactthey should be considered
Secondary cases may arise by a variety of mechanisms Particularly amongclose family members household secondary cases can arise by direct or indirect(eg surface contamination) contact this is particularly so when the primary caseor one household secondary case is a child [35ndash37] Table 14 summarizes secondarycase statistics obtained from a variety of outbreaks As will be discussed inChapter 10 the secondary case rate is a complex factor involving (among other things)the nature of the venue and contact patterns when infected and susceptible individualsintermingle
Presumably secondary cases may also arise from close contact with anasymptomatic individual (in the ldquocarrierrdquo state) This is well known for highly acuteand (now) uncommon illnesses (such as typhoid) Excretion of Norwalk virusfollowing recovery (and resulting in additional cases) has been documented to occurfor as long as 48 h post recovery [44]
OUTBREAKS VERSUS ENDEMIC CASES
As noted previously there may be a substantial difference between reported outbreakcases and total disease burden in a community In order for a disease case to receiverecognition by the public health authorities the following specific and sequential stepsmust occur [47]
TABLE 13 Effect of Different Hypothetical Policy Options on Distribution of Risk AmongCommunities (for a Fixed Total Risk)
CommunityExposedPopulation
Policy Option A Policy Option B Policy Option C
CasesIncidence(10000) Cases
Incidence(10000) Cases
Incidence(10000)
A 100000 20 2 6 06 24 24
B 50000 10 2 18 36 7 14
C 10000 2 2 8 8 1 1
Total 160000 32 2 32 2 16 2
OUTBREAKS VERSUS ENDEMIC CASES 7
1 An ill person must seek medical care
2 Appropriate clinical tests (eg blood stool) must be ordered by the attendingphysician
3 The patient must comply with obtaining the sample
4 The laboratory must be capable of detecting the relevant pathogens
5 The clinical test must be positive
6 The test result must be reported to the health agency in a timely manner
If any of the links in this sequential chain are broken then a disease case will not enterthe records maintained by health authorities For example with increasing controls on
TABLE 14 Summary of Secondary Case Data in Outbreak Situations
Organism
SecondaryAttackRatioa
SecondaryPrevalence inHouseholdsb Remarks Reference
Cryptosporidiumparvum
033 033 Outbreak in contaminatedapple cider
[38]
C parvum NA 0042 Drinking water outbreak(Milwaukee)
[37]
Shigella 028 026 Day-care center outbreaksin children
[39]
Rotavirus 042 015 Day-care center outbreaksin children
[30]
Giardia lamblia 133 017 Day-care center outbreaksin children
[39]
Viral gastroenteritis 022 011c Drinking waterborneoutbreak
[40]
Viral gastroenteritis 056 NA Drinking water outbreak(Denmark)
[41]
Norovirus 05ndash10 019 Swimming outbreak [42]
Norovirus 11 029 Swimming outbreakin children
[43]
Norovirus NA 044 Foodborne outbreakin children and teachers
[36]
Norovirus 04 NA Foodborne outbreak [44]
E coli O157H7 NA 018c Day-care center outbreakin children
[45]
Unidentifiedday-care diarrhealdiseases
138 009c [46]
NA information not availableaRatio of secondary cases to primary casesb Proportion of households with one or more primary cases who have one or more secondary casesc Proportion of persons in contact with one or more primary cases who have a secondary case
8 CHAPTER 1 MOTIVATION
medical care stool samples may not be obtained from mild cases of illness Someorganisms may only be present sporadically or may be difficult to test in stool orblood sample Patients may not seek medical attention for mild cases of illness Fur-thermore in the United States in particular the surveillance of environmentallyinduced disease is done on a passive basis and hence the number of actual illnessclusters that are actually compiled into recorded statistics is only a small fractionof such clusters of illness that occur [47]
From a more fundamental point of view an outbreak of illness is generallydefined as occurrence of the illness at a level greater than normal or anticipated Thisdefinition recognizes that there is a level of illness (endemic) that may exist underusual circumstances The detection of such outbreaks poses a particular challengeThe problem is illustrated conceptually in Figure 13
Additional complications arise from the different patterns of illness in acommunity including definite periodicities as well as temporal trends and fromthe presence of reporting lags associated with laboratory analysis and time for patientsto seek medical attention Figure 14 illustrates the different patterns of illness inthe case of six pathogens for England and Wales [48]
In the case of waterborne and foodborne illnesses it is highly likely that thelevel of such endemic illnesses is substantially greater than those occurring duringoutbreaks (even accounting for unrecognized outbreaks)
As a result there are often many cases of environmentally caused (water airfood) infectious disease that are unrecognized One example of this isCampylobacterThere has been an average of about 200 cases per year of water- and foodborne illnessin outbreaks of this organism and yet estimates of the disease burden suggest about2100000 cases per year that is approximately 10000 cases per case of detectableoutbreak illness Therefore it will be important to assess the factors that may influenceoutbreak detection These issues will be discussed in subsequent chapters
Detectedoutbreak
Undetectedoutbreak
Threshold of detection
Hyper endemicSporadic
Endemic rate
Time
Num
ber
of c
ases
Figure 13 Schematic of disease occurrence in a hypothetical community (Modified fromRef [47])
OUTBREAKS VERSUS ENDEMIC CASES 9
REFERENCES
1 Levin B R 1996 The Evolution and Maintenance of Virulence in Microparasites Emerging InfectiousDisease 293ndash102
2 National Academy of Sciences 1983 Risk Assessment in the Federal Government Managing theProcess National Academy Press Washington DC
3 National Research Council 2009 Science and Decisions Advancing Risk Assessment NationalAcademies Press Washington DC
10090807060504030201001190 1191 1192 1193 1194 1195
(b)
140
120
100
80
60
40
20
01190 1191 1192 1193 1194 1195
(f)
700
600
500
400
300
200
100
01190 1191 1192 1193 1194 1195
(d)
1200
1000
800
600
400
200
1190 1191 1192 1193 1194 1195
(a)
240
200
160
120
80
40
01190 1191 1192 1193 1194 1195
(e)
7
6
5
4
3
2
1
01190 1191 1192 1193 1194 1195
(c)
Figure 14 Weekly count of reported organism isolations in England andWales (a) rotavirus(b) Clostridium difficile (c) Salmonella derby (d) Shigella sonnei (e) influenza B and (f)Salmonella typhimurium DT 104 (From Ref [48])
10 CHAPTER 1 MOTIVATION
4 Fogarty J L Thornton and R Corcoran 1995 Illness in a Community Associated with an Episode ofWater Contamination with Sewage Epidemiology and Infection 114289ndash295
5 Scallan E 2011 Foodborne Illness Acquired in the United StatesmdashUnspecified Agents EmergingInfectious Diseases 17 16ndash22
6 Craun G F J M Brunkard J S Yoder V A Roberts J Carpenter T Wade R L CalderonJ M Roberts M J Beach and S L Roy 2010 Causes of Outbreaks Associated with Drinking Waterin the United States from 1971 to 2006 Clinical Microbiology Reviews 23507ndash528
7 Edwards D D 1993 Troubled Waters in Milwaukee ASM News 59342ndash3458 MacKenzie W R N J Hoxie M E Proctor M S Gradus K A Blair D E Peterson
J J Kazmierczak K R Fox D G Addias J B Rose and J P Davis 1994 Massive WaterborneOutbreak of Cryptosporidium Infection Associated with a Filtered Public Water Supply MilwaukeeWisconsin March and April 1993 New England Journal of Medicine 331161ndash167
9 Anonymous 2010 Surveillance for Foodborne Disease OutbreaksmdashUnited States 2007 Morbidityand Mortality Weekly Reports 59973ndash979
10 Bean N H J S Goulding C Lau and F J Angulo 1996 Surveillance for Foodborne-DiseaseOutbreaksmdashUnited States 1988ndash1992 Morbidity and Mortality Weekly Reports 451ndash66
11 Wall P G J de Louvois R J Gilbert and B Rowe 1996 Food Poisoning NotificationsLaboratory Reports and OutbreaksmdashWhere do the Statistics Come From and What Do They MeanCommunicable Disease Report Review 6 R93ndashR100
12 Colford J M S Roy M J Beach A Hightower S E Shaw and T J Wade 2006 A Review ofHousehold Drinking Water Intervention Trials and an Approach to the Estimation of EndemicWaterborne Gastroenteritis in the United States Journal of Water and Health 471
13 Mead P S L Slutsker V Dietz L F McCaig J S Bresee C Shapiro P M Griffinand R V Tauxe 1999 Food Related Illness and Death in the United States Emerging InfectiousDisease 5607ndash625
14 Dziuban E J J L Liang G F Craun V Hill P A Yu J Painter M R Moore R L CalderonS L Roy and M J Beach 2006 Surveillance for Waterborne Disease and Outbreaks Associatedwith Recreational WatermdashUnited States 2003ndash2004 and Surveillance for Waterborne Disease andOutbreaks Associated with Drinking Water and Water not Intended for DrinkingmdashUnited States2003ndash2004 Morbidity and Mortality Weekly Reports 551ndash30
15 Fliermans C B 1996 Ecology of Legionella From Data to Knowledge with a Little WisdomMicrobial Ecology 32203ndash228
16 Li Y S Duan I T Yu and T W Wong 2005 Multi-Zone Modeling of Probable SARS VirusTransmission by Airflow Between Flats in Block E Amoy Gardens Indoor Air 1596ndash111
17 Peccia J D K Milton T Reponen and J Hill 2008 A Role for Environmental Engineering andScience in Preventing Bioaerosol-Related Disease Environmental Science amp Technology424631ndash4637
18 Jernigan D B P L Raghunathan B P Bell R Brechner E A Bresnitz J C Butler M CetronM Cohen T Doyle and M Fischer 2002 Investigation of Bioterrorism-Related AnthraxUnited States 2001 Epidemiologic Findings Emerging Infectious Diseases 81019ndash1028
19 Greenwood M and G U Yule 1917 On the Statistical Interpretation of Some BacteriologicalMethods Employed in Water Analysis Journal of Hygiene 1636ndash56
20 Phelps E 1909 The Disinfection of Sewage and Sewage Filter Effluents USGS Water Supply Paper229 GPO Washington DC
21 Rudolfs W and H W Gehm 1935 Multiplication of Total Bacteria and B coli after SewageChlorination Sewage Works Journal 7991ndash996
22 Subcommittee onMicrobiological Criteria 1985 An Evaluation of the Role ofMicrobiological Criteriafor Foods and Food Ingredients National Academy Press Washington DC
23 Cabelli V J A P Dufour L J McCabe and M A Levin 1982 Swimming-AssociatedGastroenteritis and Water Quality American Journal of Epidemiology 115606ndash616
24 Dufour A P 1984 Health Effects Criteria for Fresh Recreational Waters USEPA Research TrianglePark NC
25 Fleisher J M F Jones and D Kay 1993 Water and Non-Water-Related Risk Factors forGastroenteritis among Bathers Exposed to Sewage-Contaminated Marine Waters InternationalJournal of Epidemiology 22698ndash708
REFERENCES 11
26 Engelbrecht R S C N Haas J A Shular D L Dunn D Roy A Lalchandani B F Severin andS Farooq 1979 Acid-Fast Bacteria and Yeasts as Indicators of Disinfection Efficiency EPA-6002-79-091 US Environmental Protection Agency Cincinnati OH
27 Grabow W O K 1983 Inactivation of Hepatitis A Virus and Indicator Organisms in Water by FreeChlorine Residuals Applied and Environmental Microbiology 46619
28 Helmer R D and G R Finch 1993 Use of MS2 Coliphage as a Surrogate for Enteric Viruses inSurface Waters Disinfected with Ozone Ozone Science and Engineering 15279ndash293
29 Payment P and E Franco 1993Clostridium Perfringens and Somatic Coliphages as Indicators of theEfficiency of Drinking Water Treatment for Viruses and Protozoan Cysts Applied and EnvironmentalMicrobiology 592418ndash2424
30 Cabelli V J 1977Clostridium Perfringens as aWater Quality Indicator pp 65ndash79 InA Hoadley andB Dutka (eds) Bacterial IndicatorsHealth Hazards Associated with Water ASTM Philadelphia PA
31 Rice E W K R Fox R J Miltner D A Lytle and C H Johnson 1996 Evaluating PlantPerformance with Endospores Journal of the American Water Works Association 88122ndash130
32 Engelbrecht R S B F Severin M T Masarik S Farooq S H Lee C N Haas and A Lalchandani1977 New Microbial Indicators of Disinfection Efficiency EPA-6002-77-052 US EnvironmentalProtection Agency Cincinnati OH
33 Committee on Indicators for Waterborne Pathogens ndash National Research Council 2004 Indicators forWaterborne Pathogens National Academies Press Washington DC
34 PresidentialCongressional Commission on Risk Assessment and RiskManagement 1997 Frameworkfor Environmental Health Risk Management The Commission Washington DC
35 Griffin P M and R V Tauxe 1991 The Epidemiology of Infections Caused by Escherichiacoli O157H7 Other Enterohemorrhagic E coli and the Associated Hemolytic Uremic SyndromeEpidemiologic Reviews 1360ndash98
36 Heun E M R L Vogt P J Hudson S Parren and G W Gary 1987 Risk Factors for SecondaryTransmission in Households after a Common Source Outbreak of Norwalk Gastroenteritis AmericanJournal of Epidemiology 1261181ndash1186
37 MacKenzie W R W L Schell B A Blair D G Addiss D E Peterson N J HozieJ J Kazmierczak and J P Davis 1995 Massive Outbreak of Waterborne CryptosporidiumInfection in Milwaukee Wisconsin Recurrence of Illness and Risk of Secondary TransmissionClinical Infectious Diseases 2157ndash62
38 Millard P K Gensheimer D G Addiss D M Sosin G A Beckett A Houck-Jankoski andA Hudson 1994 An Outbreak of Cryptosporidiosis from Fresh-Pressed Apple Cider Journal ofthe American Medical Association 2721592ndash1596
39 Pickering L K D G Evans H L DuPont J J Vollet and D J Evans Jr 1981 Diarrhea Caused byShigella Rotavirus and Giardia in Day Care Centers Prospective Study Journal of Pediatrics9951ndash56
40 Morens D M R M Zweighaft T M Vernon G W Gary J J Eslien B T Wood R C Holmanand R Dolin 1979 A Waterborne Outbreak of Gastroenteritis with Secondary Person to PersonSpread Lancet 5964ndash966
41 Laursen E O Mygind B Rasmussen and T Ronne 1994 Gastroenteritis A Waterborne OutbreakAffecting 1600 People in a Small Danish Town Journal of Epidemiology amp Community Health48453ndash458
42 Baron R C F D Murphy H B Greenberg C E Davis D J Bregman G W Gary J M Hughesand L B Schonberger 1982 Norwalk Gastrointestinal Illness An Outbreak Associated withSwimming in a Recreational Lake and Secondary Person to Person Transmission American Journalof Epidemiology 115163ndash172
43 Kappus K D J S Marks R C Holman J K Bryant C Baker G W Gary and H B Greenberg1982 An Outbreak of Norwalk Gastroenteritis Associated with Swimming in a Pool and SecondaryPerson to Person Transmission American Journal of Epidemiology 116834ndash839
44 White K E M T Osterbolm J A Mariotti J A Korlath D H Lawrence T L Ristinen andH B Greenberg 1986 A Foodborne Outbreak of Norwalk Virus Gastroenteritis American Journalof Epidemiology 124120ndash126
45 Spika J S J E Parsons and D Nordenberg 1986 Hemolytic Uremic Syndrome and DiarrheaAssociated with Escherichia coli O157H7 in a Day Care Center Journal of Pediatrics 109287ndash291
12 CHAPTER 1 MOTIVATION
46 Ferguson J K L R Jorm C D Allen P KWhitehead and G L Gilbert 1995 Prospective Study ofDiarrhoeal Outbreaks in Child Long Daycare Centres in Western Sydney Medical Journal of Australia163137ndash140
47 Frost F J G F Craun and R L Calderon 1996 Waterborne Disease Surveillance Journal of theAmerican Water Works Association 8866ndash75
48 Farrington C P N J Andrews A D Beale and M A Catchpole 1996 A Statistical Algorithmfor the Early Detection of Outbreaks of Infectious Disease Journal of the Royal StatisticalSociety A 159547ndash563
REFERENCES 13
CHAPTER2MICROBIAL AGENTS ANDTRANSMISSION
MICROBIAL TAXONOMY
The development of techniques for examining the nucleic acids of microorganisms hasseen major changes in which we classify and group related microorganisms This isespecially true for the study of ribosomal ribonucleic acid (rRNA) which is a highlyconserved sequence involved in the synthesis of proteins in all living organisms Basedon this analysis the classification of living things has been placed into a three-domainsystem consisting of Archaea Eukarya and Bacteria Of these the Bacteria andArchaea are termed prokaryotes (no organized cell nucleus) and the Eukarya areknown as eukaryotes (an organized cell nucleus) Eukaryotic microbes other thanalgae and fungi are collectively calledprotistsWithin theEukarya are fungi protozoahelminth worms algae plants animals and humans Archaea are microbes that looksomewhat similar to bacteria in size and shape under the light microscope but they areactually genetically and biochemically quite different They appear to be a simpler formof life and may in fact be the oldest form of life on earth Viruses are obligate intercel-lular parasites and are not amember of any group They are usually composed only of anucleic acid surrounded by a protein coat Eukaryotes are much more complex thanprokaryotic cells in structure and nutritional requirements Prokaryotes divide by sim-ple binary fissionwhereas eukaryotes divide byamore complexprocess calledmitosis
Eukaryotes
Fungi protozoa and helminth worms are all eukaryotes All contain members that arepathogenic to man and animals While algae do not infect humans they can producetoxins that are harmful to animals and man Fungi obtain nutrients solely by adsorp-tion of organic matter from dead organisms Even when they invade living tissuesthey typically kill cells and then adsorb the nutrients from them Some fungi are capa-ble of developing environmentally resistant spores which can be transported throughthe air Fungal diseases in humans are referred to asmycoses Airborne fungal sporesare responsible for some allergies in humans Yeasts are classified with the fungi and
Quantitative Microbial Risk Assessment Second Edition Charles N Haas Joan B Roseand Charles P Gerbacopy 2014 John Wiley amp Sons Inc Published 2014 by John Wiley amp Sons Inc
15
some are pathogenic to humans (Candida albicans) Certain fungi produce toxins(ie aflatoxins) when growing in foods that are mutagenic and carcinogenic in ani-mals Inhalation is an important route of transmission for some fungal diseases suchas aspergillosis blastomycosis coccidioidomycosis and histoplasmosis These fungiare found growing in animal feces soil or decaying organic matter (compost manure)and may be transmitted through the air when this matter is disturbed Some fungi maybe transmitted by direct contact with the skin Fungi are often found in drinking waterdistribution systems and they have been linked to infections in immunocompromisedindividuals [1] Food is not believed to be a significant route of transmission ofpathogenic fungi
Protozoans are unicellular organisms that are surrounded by a cytoplasmicmembrane that is covered by a protective structure called a pellicle Most are freeliving feeding off of bacteria Some of these can cause disease while others are obli-gate parasites They are capable of forming structures called cysts oocysts or spores(depending on the life cycle of the organism) resistant to adverse environmentalconditions such as desiccation starvation high temperatures and disinfectantsSome pathogenic protozoa are found mainly in the soil (Naegleria) or water(Acanthamoeba) Others such a Giardia and Cryptosporidium whose natural habitatis the intestines of warm-blooded animals are capable of causing disease in bothhumans and animals Others such as Entamoeba histolytica are only capable ofcausing disease in humans
Pathogenic enteric (replicate in the intestines) protozoans are usually excretedin the feces or urine and can be transmitted by fecally contaminated food and waterSome protozoa may be transmitted through the air (Acanthamoeba) or throughfomites (inanimate objects) Some important environmentally transmitted protozoaare listed in Table 21 The clinically important protozoa are divided taxonomicallyinto the amoebas (Entamoeba spp) flagellates (Giardia) and coccidian meaningldquoglobose in shaperdquo (Cryptosporidium and Cyclospora) Microsporidia are alsocapable of causing intestinal infections but their classification is uncertain becausethey have many characteristics associated with fungi They are all obligate parasitesand are transmitted via infectious cysts oocysts or spores by the fecalndashoral routeThe life cycles of these protozoa are similar The initial stage occurs during ingestionof the cyst oocyst or spore After ingestion the body temperature and passagethrough the stomach cause these infective stages to open up in a process calledexcystation
The Giardia cysts house two trophozoites which is the stage that attaches tointestinal cells and grows in the intestinal tract through asexual reproduction As thetrophozoites grow and begin to cover the wall of the intestinal tract diarrhea canresult As the trophozoites are released some form cysts as they pass through thebowels Cryptosporidium and Cyclospora both produce oocysts The life cycle ofCyclospora is still not well known except that its oocysts require some period of timein the environment before they are infective Cryptosporidium oocysts contain foursporozoites which enter the intestinal cells and begin the infection process As morecells become infected the illness begins and oocysts are excreted in high numbers inthe feces (about 100000g)
Worms and helminths are small multicellular animals that are parasiticto humans and animals They include flukes tapeworms and roundworms
16 CHAPTER 2 MICROBIAL AGENTS AND TRANSMISSION
The deliberate release of Bacillus anthracis spores in 2001 (the ldquoAmerithraxrdquoincidents) brought widespread awareness to the potential for indoor releases (as wellas releases in other venues) of bioterrorist agents to cause risk [18] Therefore ofnecessity microbial risk assessors may need to consider the impact of maliciousactivity in certain applications
PRIOR APPROACHES
Concerns for microbial quality of food water and other environmental media havelong existed In the early twentieth century the use of indicator microorganismswas developed for the control and assessment of the hygienic quality of such mediaand the adequacy of disinfection and sterilization processes The coliform group oforganisms was perhaps first employed for this purpose [19ndash21] Indicator techniqueshave also found utility in the food industry such as the total count for milk and othermore recent proposals [22] Other indicator groups for food water or environmentalmedia have been examined such as enterococci [23ndash25] acid-fast bacteria [26]bacteriophage [27ndash29] and Clostridia spores [29ndash31]
The use of indicator organisms was historically justified in because of difficultyin enumerating pathogens However with the increasing availability of modernmicrobial methods for example PCR immunoassay etc for direct pathogen assess-ment this justification has become less persuasive In addition in order to develophealth-based standards from indicators extensive epidemiologic surveillance is oftennecessary The use of epidemiology has limitations with respect to detection limits(for an adverse effect) and is also quite expensive to conduct Indicator methodsare also limited in that many pathogens are more resistant to die off in receiving envir-onments or source waters than indicators or have greater resistance to removal bytreatment processes than indicators [26 28 29 32] Thus the absence of indicatorsmay not suffice to ensure the absence of pathogens Even after a century of use theindicator concept remains imperfect [33]
The use of quantitative microbial risk assessment (QMRA) will enable directmeasurements of pathogens to be used to develop acceptancerejection guidelinesfor food water and other vehicles that may be the source of microbial exposureto human populations The objective of this book is to present these methods in asystematic and unified manner
SCOPE OF COVERAGE
QMRA is the application of principles of risk assessment to the estimate ofconsequences from a planned or actual exposure to infectious microorganismsIn performing a QMRA the risk assessor aims to bring the best available informationto bear in understanding the nature of the potential effects from a microbial exposureSince the information (such as dosendashresponse relationships exposure magnitudes) isalmost invariably incomplete it is also necessary to ascertain the potential error
4 CHAPTER 1 MOTIVATION
involved in the risk assessment With such information necessary steps to mitigatecontrol or defend against such exposures may be developed
At the outset of performing a risk assessment a scoping task should be under-taken This task should set forth the objectives of the analysis and the principal issuesto be addressed Items such as consideration of secondary cases individual versuspopulation risk agent or agents to be examined exposure routes andor accident sce-narios must be stipulated However this scoping may be changed during the course ofa QMRA to reflect the input derived from the risk manager(s) and other stakeholders
POTENTIAL OBJECTIVES OF A QMRA
There may be diverse objectives for a QMRA These objectives relate to the rationalefor the performance of the assessment as well as the methods to be employedBroadly the different objectives reflect different scales at which a risk assessmentmay be performed The step of problem formulation is critical to any risk estimate[34] It is necessary that the problem be formulated to meet the needs of the riskmanagers and stakeholders indeed it is now recognized that the successful practiceof risk analysis requires frequent interchange with manager and stakeholders [3]In general the problems posed are of several types
Site-Specific Assessment
The simplest type of QMRA that may be performed involves one site or exposurescenario The following are typical of the questions that might be asked
1 If a water treatment plant is designed in a certain way (with given removals ofpathogens) then what is the risk that would be placed upon the populationserved
2 A swimming outbreak (in a recreational lake) has just occurred I believe that itresulted from a short-duration contamination event What pathogen levelswould be consistent with the observed attack rate
3 Microbial sampling of a finished food product has found certain pathogensWhat level of risk does this pose to consumers of the product
4 A certain amount of infectious agent has been released into a room What is theimmediate danger to occupants and how stringent should cleanup levels be
Note that there are certain other contrasts in the objectives of the risk assessments tobe posed In (1) and (3) a before-the-fact computation is desired while in (2) and (4)an after-the-fact computation is described Also in (1) (3) and (4) pathogen levelsare available (or somehow are estimated) while in (2) an inverse computation isneeded given an observed attack rate
In performing this risk assessment the relationship between an exposure ortechnological metric and a risk measurement must be ascertained and then theparticular point of correspondence determined (Fig 12) In cases (1) (3) and (4)for a known (or assumed) exposure (on the x-axis) the corresponding range of risks
POTENTIAL OBJECTIVES OF A QMRA 5
on the y-axis is sought In cases (2) for known or assumed risks (on the y-axis)the corresponding range of exposures (or level of technological protection) is to bedetermined (on the x-axis)
Ensemble of Sites
A somewhat more complex situation occurs if the risk for a set of events or sites mustbe estimated Basically this now includes the necessity to incorporate site-to-sitefactors into the assessment Some examples of this are as follows
1 If I desire keeping the risk to a population served by multiple water treatmentplants at a given level (or better) then what criteria should I use (microbiallevels)
2 For a food product subject to contamination by pathogens what would be anacceptable treatment specification (eg heating time holding period) to ensuremicrobial acceptability
3 I am designing a water quality standard for recreational bathing waters If auniform (eg national) standard is to be developed what standard would ensurethat average risk was acceptable with keeping the risk of a large ldquoclusterrdquo ofillnesses low
In addition to incorporating a measure of ensemble average risk in general it is alsodesired to ensure that no single member of the ensemble be unacceptably extreme Forexample consider the evaluation of three options of disease control among three com-munities as indicated in Table 13
This table indicates the number of cases and the rate among the three commu-nities The three policy options yield the same number of expected cases Howeverthere are differences in the allocation of risk among the communities of different sizesIn option A all communities have an identical level of estimated risk In option B therisk increases as community size decreases while in option C the risk increases ascommunity size increases This distribution of risk among affected subsets of the
Exposure
Ris
k
Level of technological protection
Figure 12 Relationship between exposurelevel of technological protection andmicrobial risk The middle curve indicatesthe best estimate The other two curvesindicate the upper and lower confidenceregions
6 CHAPTER 1 MOTIVATION
ensemble being considered adds an additional dimension for consideration by a riskmanagermdashwhich may be termed risk equity
SECONDARY TRANSMISSION
Infectious microbial diseases are different in terms of risk to a population than arechemical agents in that an individual who may become infected (with or withoutillness) can then proceed to infect additional individuals These secondary (tertiaryquaternary etc) cases may be persons who had no direct contact with the initialvehicle of exposure but nevertheless in fairly accounting for the public health impactthey should be considered
Secondary cases may arise by a variety of mechanisms Particularly amongclose family members household secondary cases can arise by direct or indirect(eg surface contamination) contact this is particularly so when the primary caseor one household secondary case is a child [35ndash37] Table 14 summarizes secondarycase statistics obtained from a variety of outbreaks As will be discussed inChapter 10 the secondary case rate is a complex factor involving (among other things)the nature of the venue and contact patterns when infected and susceptible individualsintermingle
Presumably secondary cases may also arise from close contact with anasymptomatic individual (in the ldquocarrierrdquo state) This is well known for highly acuteand (now) uncommon illnesses (such as typhoid) Excretion of Norwalk virusfollowing recovery (and resulting in additional cases) has been documented to occurfor as long as 48 h post recovery [44]
OUTBREAKS VERSUS ENDEMIC CASES
As noted previously there may be a substantial difference between reported outbreakcases and total disease burden in a community In order for a disease case to receiverecognition by the public health authorities the following specific and sequential stepsmust occur [47]
TABLE 13 Effect of Different Hypothetical Policy Options on Distribution of Risk AmongCommunities (for a Fixed Total Risk)
CommunityExposedPopulation
Policy Option A Policy Option B Policy Option C
CasesIncidence(10000) Cases
Incidence(10000) Cases
Incidence(10000)
A 100000 20 2 6 06 24 24
B 50000 10 2 18 36 7 14
C 10000 2 2 8 8 1 1
Total 160000 32 2 32 2 16 2
OUTBREAKS VERSUS ENDEMIC CASES 7
1 An ill person must seek medical care
2 Appropriate clinical tests (eg blood stool) must be ordered by the attendingphysician
3 The patient must comply with obtaining the sample
4 The laboratory must be capable of detecting the relevant pathogens
5 The clinical test must be positive
6 The test result must be reported to the health agency in a timely manner
If any of the links in this sequential chain are broken then a disease case will not enterthe records maintained by health authorities For example with increasing controls on
TABLE 14 Summary of Secondary Case Data in Outbreak Situations
Organism
SecondaryAttackRatioa
SecondaryPrevalence inHouseholdsb Remarks Reference
Cryptosporidiumparvum
033 033 Outbreak in contaminatedapple cider
[38]
C parvum NA 0042 Drinking water outbreak(Milwaukee)
[37]
Shigella 028 026 Day-care center outbreaksin children
[39]
Rotavirus 042 015 Day-care center outbreaksin children
[30]
Giardia lamblia 133 017 Day-care center outbreaksin children
[39]
Viral gastroenteritis 022 011c Drinking waterborneoutbreak
[40]
Viral gastroenteritis 056 NA Drinking water outbreak(Denmark)
[41]
Norovirus 05ndash10 019 Swimming outbreak [42]
Norovirus 11 029 Swimming outbreakin children
[43]
Norovirus NA 044 Foodborne outbreakin children and teachers
[36]
Norovirus 04 NA Foodborne outbreak [44]
E coli O157H7 NA 018c Day-care center outbreakin children
[45]
Unidentifiedday-care diarrhealdiseases
138 009c [46]
NA information not availableaRatio of secondary cases to primary casesb Proportion of households with one or more primary cases who have one or more secondary casesc Proportion of persons in contact with one or more primary cases who have a secondary case
8 CHAPTER 1 MOTIVATION
medical care stool samples may not be obtained from mild cases of illness Someorganisms may only be present sporadically or may be difficult to test in stool orblood sample Patients may not seek medical attention for mild cases of illness Fur-thermore in the United States in particular the surveillance of environmentallyinduced disease is done on a passive basis and hence the number of actual illnessclusters that are actually compiled into recorded statistics is only a small fractionof such clusters of illness that occur [47]
From a more fundamental point of view an outbreak of illness is generallydefined as occurrence of the illness at a level greater than normal or anticipated Thisdefinition recognizes that there is a level of illness (endemic) that may exist underusual circumstances The detection of such outbreaks poses a particular challengeThe problem is illustrated conceptually in Figure 13
Additional complications arise from the different patterns of illness in acommunity including definite periodicities as well as temporal trends and fromthe presence of reporting lags associated with laboratory analysis and time for patientsto seek medical attention Figure 14 illustrates the different patterns of illness inthe case of six pathogens for England and Wales [48]
In the case of waterborne and foodborne illnesses it is highly likely that thelevel of such endemic illnesses is substantially greater than those occurring duringoutbreaks (even accounting for unrecognized outbreaks)
As a result there are often many cases of environmentally caused (water airfood) infectious disease that are unrecognized One example of this isCampylobacterThere has been an average of about 200 cases per year of water- and foodborne illnessin outbreaks of this organism and yet estimates of the disease burden suggest about2100000 cases per year that is approximately 10000 cases per case of detectableoutbreak illness Therefore it will be important to assess the factors that may influenceoutbreak detection These issues will be discussed in subsequent chapters
Detectedoutbreak
Undetectedoutbreak
Threshold of detection
Hyper endemicSporadic
Endemic rate
Time
Num
ber
of c
ases
Figure 13 Schematic of disease occurrence in a hypothetical community (Modified fromRef [47])
OUTBREAKS VERSUS ENDEMIC CASES 9
REFERENCES
1 Levin B R 1996 The Evolution and Maintenance of Virulence in Microparasites Emerging InfectiousDisease 293ndash102
2 National Academy of Sciences 1983 Risk Assessment in the Federal Government Managing theProcess National Academy Press Washington DC
3 National Research Council 2009 Science and Decisions Advancing Risk Assessment NationalAcademies Press Washington DC
10090807060504030201001190 1191 1192 1193 1194 1195
(b)
140
120
100
80
60
40
20
01190 1191 1192 1193 1194 1195
(f)
700
600
500
400
300
200
100
01190 1191 1192 1193 1194 1195
(d)
1200
1000
800
600
400
200
1190 1191 1192 1193 1194 1195
(a)
240
200
160
120
80
40
01190 1191 1192 1193 1194 1195
(e)
7
6
5
4
3
2
1
01190 1191 1192 1193 1194 1195
(c)
Figure 14 Weekly count of reported organism isolations in England andWales (a) rotavirus(b) Clostridium difficile (c) Salmonella derby (d) Shigella sonnei (e) influenza B and (f)Salmonella typhimurium DT 104 (From Ref [48])
10 CHAPTER 1 MOTIVATION
4 Fogarty J L Thornton and R Corcoran 1995 Illness in a Community Associated with an Episode ofWater Contamination with Sewage Epidemiology and Infection 114289ndash295
5 Scallan E 2011 Foodborne Illness Acquired in the United StatesmdashUnspecified Agents EmergingInfectious Diseases 17 16ndash22
6 Craun G F J M Brunkard J S Yoder V A Roberts J Carpenter T Wade R L CalderonJ M Roberts M J Beach and S L Roy 2010 Causes of Outbreaks Associated with Drinking Waterin the United States from 1971 to 2006 Clinical Microbiology Reviews 23507ndash528
7 Edwards D D 1993 Troubled Waters in Milwaukee ASM News 59342ndash3458 MacKenzie W R N J Hoxie M E Proctor M S Gradus K A Blair D E Peterson
J J Kazmierczak K R Fox D G Addias J B Rose and J P Davis 1994 Massive WaterborneOutbreak of Cryptosporidium Infection Associated with a Filtered Public Water Supply MilwaukeeWisconsin March and April 1993 New England Journal of Medicine 331161ndash167
9 Anonymous 2010 Surveillance for Foodborne Disease OutbreaksmdashUnited States 2007 Morbidityand Mortality Weekly Reports 59973ndash979
10 Bean N H J S Goulding C Lau and F J Angulo 1996 Surveillance for Foodborne-DiseaseOutbreaksmdashUnited States 1988ndash1992 Morbidity and Mortality Weekly Reports 451ndash66
11 Wall P G J de Louvois R J Gilbert and B Rowe 1996 Food Poisoning NotificationsLaboratory Reports and OutbreaksmdashWhere do the Statistics Come From and What Do They MeanCommunicable Disease Report Review 6 R93ndashR100
12 Colford J M S Roy M J Beach A Hightower S E Shaw and T J Wade 2006 A Review ofHousehold Drinking Water Intervention Trials and an Approach to the Estimation of EndemicWaterborne Gastroenteritis in the United States Journal of Water and Health 471
13 Mead P S L Slutsker V Dietz L F McCaig J S Bresee C Shapiro P M Griffinand R V Tauxe 1999 Food Related Illness and Death in the United States Emerging InfectiousDisease 5607ndash625
14 Dziuban E J J L Liang G F Craun V Hill P A Yu J Painter M R Moore R L CalderonS L Roy and M J Beach 2006 Surveillance for Waterborne Disease and Outbreaks Associatedwith Recreational WatermdashUnited States 2003ndash2004 and Surveillance for Waterborne Disease andOutbreaks Associated with Drinking Water and Water not Intended for DrinkingmdashUnited States2003ndash2004 Morbidity and Mortality Weekly Reports 551ndash30
15 Fliermans C B 1996 Ecology of Legionella From Data to Knowledge with a Little WisdomMicrobial Ecology 32203ndash228
16 Li Y S Duan I T Yu and T W Wong 2005 Multi-Zone Modeling of Probable SARS VirusTransmission by Airflow Between Flats in Block E Amoy Gardens Indoor Air 1596ndash111
17 Peccia J D K Milton T Reponen and J Hill 2008 A Role for Environmental Engineering andScience in Preventing Bioaerosol-Related Disease Environmental Science amp Technology424631ndash4637
18 Jernigan D B P L Raghunathan B P Bell R Brechner E A Bresnitz J C Butler M CetronM Cohen T Doyle and M Fischer 2002 Investigation of Bioterrorism-Related AnthraxUnited States 2001 Epidemiologic Findings Emerging Infectious Diseases 81019ndash1028
19 Greenwood M and G U Yule 1917 On the Statistical Interpretation of Some BacteriologicalMethods Employed in Water Analysis Journal of Hygiene 1636ndash56
20 Phelps E 1909 The Disinfection of Sewage and Sewage Filter Effluents USGS Water Supply Paper229 GPO Washington DC
21 Rudolfs W and H W Gehm 1935 Multiplication of Total Bacteria and B coli after SewageChlorination Sewage Works Journal 7991ndash996
22 Subcommittee onMicrobiological Criteria 1985 An Evaluation of the Role ofMicrobiological Criteriafor Foods and Food Ingredients National Academy Press Washington DC
23 Cabelli V J A P Dufour L J McCabe and M A Levin 1982 Swimming-AssociatedGastroenteritis and Water Quality American Journal of Epidemiology 115606ndash616
24 Dufour A P 1984 Health Effects Criteria for Fresh Recreational Waters USEPA Research TrianglePark NC
25 Fleisher J M F Jones and D Kay 1993 Water and Non-Water-Related Risk Factors forGastroenteritis among Bathers Exposed to Sewage-Contaminated Marine Waters InternationalJournal of Epidemiology 22698ndash708
REFERENCES 11
26 Engelbrecht R S C N Haas J A Shular D L Dunn D Roy A Lalchandani B F Severin andS Farooq 1979 Acid-Fast Bacteria and Yeasts as Indicators of Disinfection Efficiency EPA-6002-79-091 US Environmental Protection Agency Cincinnati OH
27 Grabow W O K 1983 Inactivation of Hepatitis A Virus and Indicator Organisms in Water by FreeChlorine Residuals Applied and Environmental Microbiology 46619
28 Helmer R D and G R Finch 1993 Use of MS2 Coliphage as a Surrogate for Enteric Viruses inSurface Waters Disinfected with Ozone Ozone Science and Engineering 15279ndash293
29 Payment P and E Franco 1993Clostridium Perfringens and Somatic Coliphages as Indicators of theEfficiency of Drinking Water Treatment for Viruses and Protozoan Cysts Applied and EnvironmentalMicrobiology 592418ndash2424
30 Cabelli V J 1977Clostridium Perfringens as aWater Quality Indicator pp 65ndash79 InA Hoadley andB Dutka (eds) Bacterial IndicatorsHealth Hazards Associated with Water ASTM Philadelphia PA
31 Rice E W K R Fox R J Miltner D A Lytle and C H Johnson 1996 Evaluating PlantPerformance with Endospores Journal of the American Water Works Association 88122ndash130
32 Engelbrecht R S B F Severin M T Masarik S Farooq S H Lee C N Haas and A Lalchandani1977 New Microbial Indicators of Disinfection Efficiency EPA-6002-77-052 US EnvironmentalProtection Agency Cincinnati OH
33 Committee on Indicators for Waterborne Pathogens ndash National Research Council 2004 Indicators forWaterborne Pathogens National Academies Press Washington DC
34 PresidentialCongressional Commission on Risk Assessment and RiskManagement 1997 Frameworkfor Environmental Health Risk Management The Commission Washington DC
35 Griffin P M and R V Tauxe 1991 The Epidemiology of Infections Caused by Escherichiacoli O157H7 Other Enterohemorrhagic E coli and the Associated Hemolytic Uremic SyndromeEpidemiologic Reviews 1360ndash98
36 Heun E M R L Vogt P J Hudson S Parren and G W Gary 1987 Risk Factors for SecondaryTransmission in Households after a Common Source Outbreak of Norwalk Gastroenteritis AmericanJournal of Epidemiology 1261181ndash1186
37 MacKenzie W R W L Schell B A Blair D G Addiss D E Peterson N J HozieJ J Kazmierczak and J P Davis 1995 Massive Outbreak of Waterborne CryptosporidiumInfection in Milwaukee Wisconsin Recurrence of Illness and Risk of Secondary TransmissionClinical Infectious Diseases 2157ndash62
38 Millard P K Gensheimer D G Addiss D M Sosin G A Beckett A Houck-Jankoski andA Hudson 1994 An Outbreak of Cryptosporidiosis from Fresh-Pressed Apple Cider Journal ofthe American Medical Association 2721592ndash1596
39 Pickering L K D G Evans H L DuPont J J Vollet and D J Evans Jr 1981 Diarrhea Caused byShigella Rotavirus and Giardia in Day Care Centers Prospective Study Journal of Pediatrics9951ndash56
40 Morens D M R M Zweighaft T M Vernon G W Gary J J Eslien B T Wood R C Holmanand R Dolin 1979 A Waterborne Outbreak of Gastroenteritis with Secondary Person to PersonSpread Lancet 5964ndash966
41 Laursen E O Mygind B Rasmussen and T Ronne 1994 Gastroenteritis A Waterborne OutbreakAffecting 1600 People in a Small Danish Town Journal of Epidemiology amp Community Health48453ndash458
42 Baron R C F D Murphy H B Greenberg C E Davis D J Bregman G W Gary J M Hughesand L B Schonberger 1982 Norwalk Gastrointestinal Illness An Outbreak Associated withSwimming in a Recreational Lake and Secondary Person to Person Transmission American Journalof Epidemiology 115163ndash172
43 Kappus K D J S Marks R C Holman J K Bryant C Baker G W Gary and H B Greenberg1982 An Outbreak of Norwalk Gastroenteritis Associated with Swimming in a Pool and SecondaryPerson to Person Transmission American Journal of Epidemiology 116834ndash839
44 White K E M T Osterbolm J A Mariotti J A Korlath D H Lawrence T L Ristinen andH B Greenberg 1986 A Foodborne Outbreak of Norwalk Virus Gastroenteritis American Journalof Epidemiology 124120ndash126
45 Spika J S J E Parsons and D Nordenberg 1986 Hemolytic Uremic Syndrome and DiarrheaAssociated with Escherichia coli O157H7 in a Day Care Center Journal of Pediatrics 109287ndash291
12 CHAPTER 1 MOTIVATION
46 Ferguson J K L R Jorm C D Allen P KWhitehead and G L Gilbert 1995 Prospective Study ofDiarrhoeal Outbreaks in Child Long Daycare Centres in Western Sydney Medical Journal of Australia163137ndash140
47 Frost F J G F Craun and R L Calderon 1996 Waterborne Disease Surveillance Journal of theAmerican Water Works Association 8866ndash75
48 Farrington C P N J Andrews A D Beale and M A Catchpole 1996 A Statistical Algorithmfor the Early Detection of Outbreaks of Infectious Disease Journal of the Royal StatisticalSociety A 159547ndash563
REFERENCES 13
CHAPTER2MICROBIAL AGENTS ANDTRANSMISSION
MICROBIAL TAXONOMY
The development of techniques for examining the nucleic acids of microorganisms hasseen major changes in which we classify and group related microorganisms This isespecially true for the study of ribosomal ribonucleic acid (rRNA) which is a highlyconserved sequence involved in the synthesis of proteins in all living organisms Basedon this analysis the classification of living things has been placed into a three-domainsystem consisting of Archaea Eukarya and Bacteria Of these the Bacteria andArchaea are termed prokaryotes (no organized cell nucleus) and the Eukarya areknown as eukaryotes (an organized cell nucleus) Eukaryotic microbes other thanalgae and fungi are collectively calledprotistsWithin theEukarya are fungi protozoahelminth worms algae plants animals and humans Archaea are microbes that looksomewhat similar to bacteria in size and shape under the light microscope but they areactually genetically and biochemically quite different They appear to be a simpler formof life and may in fact be the oldest form of life on earth Viruses are obligate intercel-lular parasites and are not amember of any group They are usually composed only of anucleic acid surrounded by a protein coat Eukaryotes are much more complex thanprokaryotic cells in structure and nutritional requirements Prokaryotes divide by sim-ple binary fissionwhereas eukaryotes divide byamore complexprocess calledmitosis
Eukaryotes
Fungi protozoa and helminth worms are all eukaryotes All contain members that arepathogenic to man and animals While algae do not infect humans they can producetoxins that are harmful to animals and man Fungi obtain nutrients solely by adsorp-tion of organic matter from dead organisms Even when they invade living tissuesthey typically kill cells and then adsorb the nutrients from them Some fungi are capa-ble of developing environmentally resistant spores which can be transported throughthe air Fungal diseases in humans are referred to asmycoses Airborne fungal sporesare responsible for some allergies in humans Yeasts are classified with the fungi and
Quantitative Microbial Risk Assessment Second Edition Charles N Haas Joan B Roseand Charles P Gerbacopy 2014 John Wiley amp Sons Inc Published 2014 by John Wiley amp Sons Inc
15
some are pathogenic to humans (Candida albicans) Certain fungi produce toxins(ie aflatoxins) when growing in foods that are mutagenic and carcinogenic in ani-mals Inhalation is an important route of transmission for some fungal diseases suchas aspergillosis blastomycosis coccidioidomycosis and histoplasmosis These fungiare found growing in animal feces soil or decaying organic matter (compost manure)and may be transmitted through the air when this matter is disturbed Some fungi maybe transmitted by direct contact with the skin Fungi are often found in drinking waterdistribution systems and they have been linked to infections in immunocompromisedindividuals [1] Food is not believed to be a significant route of transmission ofpathogenic fungi
Protozoans are unicellular organisms that are surrounded by a cytoplasmicmembrane that is covered by a protective structure called a pellicle Most are freeliving feeding off of bacteria Some of these can cause disease while others are obli-gate parasites They are capable of forming structures called cysts oocysts or spores(depending on the life cycle of the organism) resistant to adverse environmentalconditions such as desiccation starvation high temperatures and disinfectantsSome pathogenic protozoa are found mainly in the soil (Naegleria) or water(Acanthamoeba) Others such a Giardia and Cryptosporidium whose natural habitatis the intestines of warm-blooded animals are capable of causing disease in bothhumans and animals Others such as Entamoeba histolytica are only capable ofcausing disease in humans
Pathogenic enteric (replicate in the intestines) protozoans are usually excretedin the feces or urine and can be transmitted by fecally contaminated food and waterSome protozoa may be transmitted through the air (Acanthamoeba) or throughfomites (inanimate objects) Some important environmentally transmitted protozoaare listed in Table 21 The clinically important protozoa are divided taxonomicallyinto the amoebas (Entamoeba spp) flagellates (Giardia) and coccidian meaningldquoglobose in shaperdquo (Cryptosporidium and Cyclospora) Microsporidia are alsocapable of causing intestinal infections but their classification is uncertain becausethey have many characteristics associated with fungi They are all obligate parasitesand are transmitted via infectious cysts oocysts or spores by the fecalndashoral routeThe life cycles of these protozoa are similar The initial stage occurs during ingestionof the cyst oocyst or spore After ingestion the body temperature and passagethrough the stomach cause these infective stages to open up in a process calledexcystation
The Giardia cysts house two trophozoites which is the stage that attaches tointestinal cells and grows in the intestinal tract through asexual reproduction As thetrophozoites grow and begin to cover the wall of the intestinal tract diarrhea canresult As the trophozoites are released some form cysts as they pass through thebowels Cryptosporidium and Cyclospora both produce oocysts The life cycle ofCyclospora is still not well known except that its oocysts require some period of timein the environment before they are infective Cryptosporidium oocysts contain foursporozoites which enter the intestinal cells and begin the infection process As morecells become infected the illness begins and oocysts are excreted in high numbers inthe feces (about 100000g)
Worms and helminths are small multicellular animals that are parasiticto humans and animals They include flukes tapeworms and roundworms
16 CHAPTER 2 MICROBIAL AGENTS AND TRANSMISSION
involved in the risk assessment With such information necessary steps to mitigatecontrol or defend against such exposures may be developed
At the outset of performing a risk assessment a scoping task should be under-taken This task should set forth the objectives of the analysis and the principal issuesto be addressed Items such as consideration of secondary cases individual versuspopulation risk agent or agents to be examined exposure routes andor accident sce-narios must be stipulated However this scoping may be changed during the course ofa QMRA to reflect the input derived from the risk manager(s) and other stakeholders
POTENTIAL OBJECTIVES OF A QMRA
There may be diverse objectives for a QMRA These objectives relate to the rationalefor the performance of the assessment as well as the methods to be employedBroadly the different objectives reflect different scales at which a risk assessmentmay be performed The step of problem formulation is critical to any risk estimate[34] It is necessary that the problem be formulated to meet the needs of the riskmanagers and stakeholders indeed it is now recognized that the successful practiceof risk analysis requires frequent interchange with manager and stakeholders [3]In general the problems posed are of several types
Site-Specific Assessment
The simplest type of QMRA that may be performed involves one site or exposurescenario The following are typical of the questions that might be asked
1 If a water treatment plant is designed in a certain way (with given removals ofpathogens) then what is the risk that would be placed upon the populationserved
2 A swimming outbreak (in a recreational lake) has just occurred I believe that itresulted from a short-duration contamination event What pathogen levelswould be consistent with the observed attack rate
3 Microbial sampling of a finished food product has found certain pathogensWhat level of risk does this pose to consumers of the product
4 A certain amount of infectious agent has been released into a room What is theimmediate danger to occupants and how stringent should cleanup levels be
Note that there are certain other contrasts in the objectives of the risk assessments tobe posed In (1) and (3) a before-the-fact computation is desired while in (2) and (4)an after-the-fact computation is described Also in (1) (3) and (4) pathogen levelsare available (or somehow are estimated) while in (2) an inverse computation isneeded given an observed attack rate
In performing this risk assessment the relationship between an exposure ortechnological metric and a risk measurement must be ascertained and then theparticular point of correspondence determined (Fig 12) In cases (1) (3) and (4)for a known (or assumed) exposure (on the x-axis) the corresponding range of risks
POTENTIAL OBJECTIVES OF A QMRA 5
on the y-axis is sought In cases (2) for known or assumed risks (on the y-axis)the corresponding range of exposures (or level of technological protection) is to bedetermined (on the x-axis)
Ensemble of Sites
A somewhat more complex situation occurs if the risk for a set of events or sites mustbe estimated Basically this now includes the necessity to incorporate site-to-sitefactors into the assessment Some examples of this are as follows
1 If I desire keeping the risk to a population served by multiple water treatmentplants at a given level (or better) then what criteria should I use (microbiallevels)
2 For a food product subject to contamination by pathogens what would be anacceptable treatment specification (eg heating time holding period) to ensuremicrobial acceptability
3 I am designing a water quality standard for recreational bathing waters If auniform (eg national) standard is to be developed what standard would ensurethat average risk was acceptable with keeping the risk of a large ldquoclusterrdquo ofillnesses low
In addition to incorporating a measure of ensemble average risk in general it is alsodesired to ensure that no single member of the ensemble be unacceptably extreme Forexample consider the evaluation of three options of disease control among three com-munities as indicated in Table 13
This table indicates the number of cases and the rate among the three commu-nities The three policy options yield the same number of expected cases Howeverthere are differences in the allocation of risk among the communities of different sizesIn option A all communities have an identical level of estimated risk In option B therisk increases as community size decreases while in option C the risk increases ascommunity size increases This distribution of risk among affected subsets of the
Exposure
Ris
k
Level of technological protection
Figure 12 Relationship between exposurelevel of technological protection andmicrobial risk The middle curve indicatesthe best estimate The other two curvesindicate the upper and lower confidenceregions
6 CHAPTER 1 MOTIVATION
ensemble being considered adds an additional dimension for consideration by a riskmanagermdashwhich may be termed risk equity
SECONDARY TRANSMISSION
Infectious microbial diseases are different in terms of risk to a population than arechemical agents in that an individual who may become infected (with or withoutillness) can then proceed to infect additional individuals These secondary (tertiaryquaternary etc) cases may be persons who had no direct contact with the initialvehicle of exposure but nevertheless in fairly accounting for the public health impactthey should be considered
Secondary cases may arise by a variety of mechanisms Particularly amongclose family members household secondary cases can arise by direct or indirect(eg surface contamination) contact this is particularly so when the primary caseor one household secondary case is a child [35ndash37] Table 14 summarizes secondarycase statistics obtained from a variety of outbreaks As will be discussed inChapter 10 the secondary case rate is a complex factor involving (among other things)the nature of the venue and contact patterns when infected and susceptible individualsintermingle
Presumably secondary cases may also arise from close contact with anasymptomatic individual (in the ldquocarrierrdquo state) This is well known for highly acuteand (now) uncommon illnesses (such as typhoid) Excretion of Norwalk virusfollowing recovery (and resulting in additional cases) has been documented to occurfor as long as 48 h post recovery [44]
OUTBREAKS VERSUS ENDEMIC CASES
As noted previously there may be a substantial difference between reported outbreakcases and total disease burden in a community In order for a disease case to receiverecognition by the public health authorities the following specific and sequential stepsmust occur [47]
TABLE 13 Effect of Different Hypothetical Policy Options on Distribution of Risk AmongCommunities (for a Fixed Total Risk)
CommunityExposedPopulation
Policy Option A Policy Option B Policy Option C
CasesIncidence(10000) Cases
Incidence(10000) Cases
Incidence(10000)
A 100000 20 2 6 06 24 24
B 50000 10 2 18 36 7 14
C 10000 2 2 8 8 1 1
Total 160000 32 2 32 2 16 2
OUTBREAKS VERSUS ENDEMIC CASES 7
1 An ill person must seek medical care
2 Appropriate clinical tests (eg blood stool) must be ordered by the attendingphysician
3 The patient must comply with obtaining the sample
4 The laboratory must be capable of detecting the relevant pathogens
5 The clinical test must be positive
6 The test result must be reported to the health agency in a timely manner
If any of the links in this sequential chain are broken then a disease case will not enterthe records maintained by health authorities For example with increasing controls on
TABLE 14 Summary of Secondary Case Data in Outbreak Situations
Organism
SecondaryAttackRatioa
SecondaryPrevalence inHouseholdsb Remarks Reference
Cryptosporidiumparvum
033 033 Outbreak in contaminatedapple cider
[38]
C parvum NA 0042 Drinking water outbreak(Milwaukee)
[37]
Shigella 028 026 Day-care center outbreaksin children
[39]
Rotavirus 042 015 Day-care center outbreaksin children
[30]
Giardia lamblia 133 017 Day-care center outbreaksin children
[39]
Viral gastroenteritis 022 011c Drinking waterborneoutbreak
[40]
Viral gastroenteritis 056 NA Drinking water outbreak(Denmark)
[41]
Norovirus 05ndash10 019 Swimming outbreak [42]
Norovirus 11 029 Swimming outbreakin children
[43]
Norovirus NA 044 Foodborne outbreakin children and teachers
[36]
Norovirus 04 NA Foodborne outbreak [44]
E coli O157H7 NA 018c Day-care center outbreakin children
[45]
Unidentifiedday-care diarrhealdiseases
138 009c [46]
NA information not availableaRatio of secondary cases to primary casesb Proportion of households with one or more primary cases who have one or more secondary casesc Proportion of persons in contact with one or more primary cases who have a secondary case
8 CHAPTER 1 MOTIVATION
medical care stool samples may not be obtained from mild cases of illness Someorganisms may only be present sporadically or may be difficult to test in stool orblood sample Patients may not seek medical attention for mild cases of illness Fur-thermore in the United States in particular the surveillance of environmentallyinduced disease is done on a passive basis and hence the number of actual illnessclusters that are actually compiled into recorded statistics is only a small fractionof such clusters of illness that occur [47]
From a more fundamental point of view an outbreak of illness is generallydefined as occurrence of the illness at a level greater than normal or anticipated Thisdefinition recognizes that there is a level of illness (endemic) that may exist underusual circumstances The detection of such outbreaks poses a particular challengeThe problem is illustrated conceptually in Figure 13
Additional complications arise from the different patterns of illness in acommunity including definite periodicities as well as temporal trends and fromthe presence of reporting lags associated with laboratory analysis and time for patientsto seek medical attention Figure 14 illustrates the different patterns of illness inthe case of six pathogens for England and Wales [48]
In the case of waterborne and foodborne illnesses it is highly likely that thelevel of such endemic illnesses is substantially greater than those occurring duringoutbreaks (even accounting for unrecognized outbreaks)
As a result there are often many cases of environmentally caused (water airfood) infectious disease that are unrecognized One example of this isCampylobacterThere has been an average of about 200 cases per year of water- and foodborne illnessin outbreaks of this organism and yet estimates of the disease burden suggest about2100000 cases per year that is approximately 10000 cases per case of detectableoutbreak illness Therefore it will be important to assess the factors that may influenceoutbreak detection These issues will be discussed in subsequent chapters
Detectedoutbreak
Undetectedoutbreak
Threshold of detection
Hyper endemicSporadic
Endemic rate
Time
Num
ber
of c
ases
Figure 13 Schematic of disease occurrence in a hypothetical community (Modified fromRef [47])
OUTBREAKS VERSUS ENDEMIC CASES 9
REFERENCES
1 Levin B R 1996 The Evolution and Maintenance of Virulence in Microparasites Emerging InfectiousDisease 293ndash102
2 National Academy of Sciences 1983 Risk Assessment in the Federal Government Managing theProcess National Academy Press Washington DC
3 National Research Council 2009 Science and Decisions Advancing Risk Assessment NationalAcademies Press Washington DC
10090807060504030201001190 1191 1192 1193 1194 1195
(b)
140
120
100
80
60
40
20
01190 1191 1192 1193 1194 1195
(f)
700
600
500
400
300
200
100
01190 1191 1192 1193 1194 1195
(d)
1200
1000
800
600
400
200
1190 1191 1192 1193 1194 1195
(a)
240
200
160
120
80
40
01190 1191 1192 1193 1194 1195
(e)
7
6
5
4
3
2
1
01190 1191 1192 1193 1194 1195
(c)
Figure 14 Weekly count of reported organism isolations in England andWales (a) rotavirus(b) Clostridium difficile (c) Salmonella derby (d) Shigella sonnei (e) influenza B and (f)Salmonella typhimurium DT 104 (From Ref [48])
10 CHAPTER 1 MOTIVATION
4 Fogarty J L Thornton and R Corcoran 1995 Illness in a Community Associated with an Episode ofWater Contamination with Sewage Epidemiology and Infection 114289ndash295
5 Scallan E 2011 Foodborne Illness Acquired in the United StatesmdashUnspecified Agents EmergingInfectious Diseases 17 16ndash22
6 Craun G F J M Brunkard J S Yoder V A Roberts J Carpenter T Wade R L CalderonJ M Roberts M J Beach and S L Roy 2010 Causes of Outbreaks Associated with Drinking Waterin the United States from 1971 to 2006 Clinical Microbiology Reviews 23507ndash528
7 Edwards D D 1993 Troubled Waters in Milwaukee ASM News 59342ndash3458 MacKenzie W R N J Hoxie M E Proctor M S Gradus K A Blair D E Peterson
J J Kazmierczak K R Fox D G Addias J B Rose and J P Davis 1994 Massive WaterborneOutbreak of Cryptosporidium Infection Associated with a Filtered Public Water Supply MilwaukeeWisconsin March and April 1993 New England Journal of Medicine 331161ndash167
9 Anonymous 2010 Surveillance for Foodborne Disease OutbreaksmdashUnited States 2007 Morbidityand Mortality Weekly Reports 59973ndash979
10 Bean N H J S Goulding C Lau and F J Angulo 1996 Surveillance for Foodborne-DiseaseOutbreaksmdashUnited States 1988ndash1992 Morbidity and Mortality Weekly Reports 451ndash66
11 Wall P G J de Louvois R J Gilbert and B Rowe 1996 Food Poisoning NotificationsLaboratory Reports and OutbreaksmdashWhere do the Statistics Come From and What Do They MeanCommunicable Disease Report Review 6 R93ndashR100
12 Colford J M S Roy M J Beach A Hightower S E Shaw and T J Wade 2006 A Review ofHousehold Drinking Water Intervention Trials and an Approach to the Estimation of EndemicWaterborne Gastroenteritis in the United States Journal of Water and Health 471
13 Mead P S L Slutsker V Dietz L F McCaig J S Bresee C Shapiro P M Griffinand R V Tauxe 1999 Food Related Illness and Death in the United States Emerging InfectiousDisease 5607ndash625
14 Dziuban E J J L Liang G F Craun V Hill P A Yu J Painter M R Moore R L CalderonS L Roy and M J Beach 2006 Surveillance for Waterborne Disease and Outbreaks Associatedwith Recreational WatermdashUnited States 2003ndash2004 and Surveillance for Waterborne Disease andOutbreaks Associated with Drinking Water and Water not Intended for DrinkingmdashUnited States2003ndash2004 Morbidity and Mortality Weekly Reports 551ndash30
15 Fliermans C B 1996 Ecology of Legionella From Data to Knowledge with a Little WisdomMicrobial Ecology 32203ndash228
16 Li Y S Duan I T Yu and T W Wong 2005 Multi-Zone Modeling of Probable SARS VirusTransmission by Airflow Between Flats in Block E Amoy Gardens Indoor Air 1596ndash111
17 Peccia J D K Milton T Reponen and J Hill 2008 A Role for Environmental Engineering andScience in Preventing Bioaerosol-Related Disease Environmental Science amp Technology424631ndash4637
18 Jernigan D B P L Raghunathan B P Bell R Brechner E A Bresnitz J C Butler M CetronM Cohen T Doyle and M Fischer 2002 Investigation of Bioterrorism-Related AnthraxUnited States 2001 Epidemiologic Findings Emerging Infectious Diseases 81019ndash1028
19 Greenwood M and G U Yule 1917 On the Statistical Interpretation of Some BacteriologicalMethods Employed in Water Analysis Journal of Hygiene 1636ndash56
20 Phelps E 1909 The Disinfection of Sewage and Sewage Filter Effluents USGS Water Supply Paper229 GPO Washington DC
21 Rudolfs W and H W Gehm 1935 Multiplication of Total Bacteria and B coli after SewageChlorination Sewage Works Journal 7991ndash996
22 Subcommittee onMicrobiological Criteria 1985 An Evaluation of the Role ofMicrobiological Criteriafor Foods and Food Ingredients National Academy Press Washington DC
23 Cabelli V J A P Dufour L J McCabe and M A Levin 1982 Swimming-AssociatedGastroenteritis and Water Quality American Journal of Epidemiology 115606ndash616
24 Dufour A P 1984 Health Effects Criteria for Fresh Recreational Waters USEPA Research TrianglePark NC
25 Fleisher J M F Jones and D Kay 1993 Water and Non-Water-Related Risk Factors forGastroenteritis among Bathers Exposed to Sewage-Contaminated Marine Waters InternationalJournal of Epidemiology 22698ndash708
REFERENCES 11
26 Engelbrecht R S C N Haas J A Shular D L Dunn D Roy A Lalchandani B F Severin andS Farooq 1979 Acid-Fast Bacteria and Yeasts as Indicators of Disinfection Efficiency EPA-6002-79-091 US Environmental Protection Agency Cincinnati OH
27 Grabow W O K 1983 Inactivation of Hepatitis A Virus and Indicator Organisms in Water by FreeChlorine Residuals Applied and Environmental Microbiology 46619
28 Helmer R D and G R Finch 1993 Use of MS2 Coliphage as a Surrogate for Enteric Viruses inSurface Waters Disinfected with Ozone Ozone Science and Engineering 15279ndash293
29 Payment P and E Franco 1993Clostridium Perfringens and Somatic Coliphages as Indicators of theEfficiency of Drinking Water Treatment for Viruses and Protozoan Cysts Applied and EnvironmentalMicrobiology 592418ndash2424
30 Cabelli V J 1977Clostridium Perfringens as aWater Quality Indicator pp 65ndash79 InA Hoadley andB Dutka (eds) Bacterial IndicatorsHealth Hazards Associated with Water ASTM Philadelphia PA
31 Rice E W K R Fox R J Miltner D A Lytle and C H Johnson 1996 Evaluating PlantPerformance with Endospores Journal of the American Water Works Association 88122ndash130
32 Engelbrecht R S B F Severin M T Masarik S Farooq S H Lee C N Haas and A Lalchandani1977 New Microbial Indicators of Disinfection Efficiency EPA-6002-77-052 US EnvironmentalProtection Agency Cincinnati OH
33 Committee on Indicators for Waterborne Pathogens ndash National Research Council 2004 Indicators forWaterborne Pathogens National Academies Press Washington DC
34 PresidentialCongressional Commission on Risk Assessment and RiskManagement 1997 Frameworkfor Environmental Health Risk Management The Commission Washington DC
35 Griffin P M and R V Tauxe 1991 The Epidemiology of Infections Caused by Escherichiacoli O157H7 Other Enterohemorrhagic E coli and the Associated Hemolytic Uremic SyndromeEpidemiologic Reviews 1360ndash98
36 Heun E M R L Vogt P J Hudson S Parren and G W Gary 1987 Risk Factors for SecondaryTransmission in Households after a Common Source Outbreak of Norwalk Gastroenteritis AmericanJournal of Epidemiology 1261181ndash1186
37 MacKenzie W R W L Schell B A Blair D G Addiss D E Peterson N J HozieJ J Kazmierczak and J P Davis 1995 Massive Outbreak of Waterborne CryptosporidiumInfection in Milwaukee Wisconsin Recurrence of Illness and Risk of Secondary TransmissionClinical Infectious Diseases 2157ndash62
38 Millard P K Gensheimer D G Addiss D M Sosin G A Beckett A Houck-Jankoski andA Hudson 1994 An Outbreak of Cryptosporidiosis from Fresh-Pressed Apple Cider Journal ofthe American Medical Association 2721592ndash1596
39 Pickering L K D G Evans H L DuPont J J Vollet and D J Evans Jr 1981 Diarrhea Caused byShigella Rotavirus and Giardia in Day Care Centers Prospective Study Journal of Pediatrics9951ndash56
40 Morens D M R M Zweighaft T M Vernon G W Gary J J Eslien B T Wood R C Holmanand R Dolin 1979 A Waterborne Outbreak of Gastroenteritis with Secondary Person to PersonSpread Lancet 5964ndash966
41 Laursen E O Mygind B Rasmussen and T Ronne 1994 Gastroenteritis A Waterborne OutbreakAffecting 1600 People in a Small Danish Town Journal of Epidemiology amp Community Health48453ndash458
42 Baron R C F D Murphy H B Greenberg C E Davis D J Bregman G W Gary J M Hughesand L B Schonberger 1982 Norwalk Gastrointestinal Illness An Outbreak Associated withSwimming in a Recreational Lake and Secondary Person to Person Transmission American Journalof Epidemiology 115163ndash172
43 Kappus K D J S Marks R C Holman J K Bryant C Baker G W Gary and H B Greenberg1982 An Outbreak of Norwalk Gastroenteritis Associated with Swimming in a Pool and SecondaryPerson to Person Transmission American Journal of Epidemiology 116834ndash839
44 White K E M T Osterbolm J A Mariotti J A Korlath D H Lawrence T L Ristinen andH B Greenberg 1986 A Foodborne Outbreak of Norwalk Virus Gastroenteritis American Journalof Epidemiology 124120ndash126
45 Spika J S J E Parsons and D Nordenberg 1986 Hemolytic Uremic Syndrome and DiarrheaAssociated with Escherichia coli O157H7 in a Day Care Center Journal of Pediatrics 109287ndash291
12 CHAPTER 1 MOTIVATION
46 Ferguson J K L R Jorm C D Allen P KWhitehead and G L Gilbert 1995 Prospective Study ofDiarrhoeal Outbreaks in Child Long Daycare Centres in Western Sydney Medical Journal of Australia163137ndash140
47 Frost F J G F Craun and R L Calderon 1996 Waterborne Disease Surveillance Journal of theAmerican Water Works Association 8866ndash75
48 Farrington C P N J Andrews A D Beale and M A Catchpole 1996 A Statistical Algorithmfor the Early Detection of Outbreaks of Infectious Disease Journal of the Royal StatisticalSociety A 159547ndash563
REFERENCES 13
CHAPTER2MICROBIAL AGENTS ANDTRANSMISSION
MICROBIAL TAXONOMY
The development of techniques for examining the nucleic acids of microorganisms hasseen major changes in which we classify and group related microorganisms This isespecially true for the study of ribosomal ribonucleic acid (rRNA) which is a highlyconserved sequence involved in the synthesis of proteins in all living organisms Basedon this analysis the classification of living things has been placed into a three-domainsystem consisting of Archaea Eukarya and Bacteria Of these the Bacteria andArchaea are termed prokaryotes (no organized cell nucleus) and the Eukarya areknown as eukaryotes (an organized cell nucleus) Eukaryotic microbes other thanalgae and fungi are collectively calledprotistsWithin theEukarya are fungi protozoahelminth worms algae plants animals and humans Archaea are microbes that looksomewhat similar to bacteria in size and shape under the light microscope but they areactually genetically and biochemically quite different They appear to be a simpler formof life and may in fact be the oldest form of life on earth Viruses are obligate intercel-lular parasites and are not amember of any group They are usually composed only of anucleic acid surrounded by a protein coat Eukaryotes are much more complex thanprokaryotic cells in structure and nutritional requirements Prokaryotes divide by sim-ple binary fissionwhereas eukaryotes divide byamore complexprocess calledmitosis
Eukaryotes
Fungi protozoa and helminth worms are all eukaryotes All contain members that arepathogenic to man and animals While algae do not infect humans they can producetoxins that are harmful to animals and man Fungi obtain nutrients solely by adsorp-tion of organic matter from dead organisms Even when they invade living tissuesthey typically kill cells and then adsorb the nutrients from them Some fungi are capa-ble of developing environmentally resistant spores which can be transported throughthe air Fungal diseases in humans are referred to asmycoses Airborne fungal sporesare responsible for some allergies in humans Yeasts are classified with the fungi and
Quantitative Microbial Risk Assessment Second Edition Charles N Haas Joan B Roseand Charles P Gerbacopy 2014 John Wiley amp Sons Inc Published 2014 by John Wiley amp Sons Inc
15
some are pathogenic to humans (Candida albicans) Certain fungi produce toxins(ie aflatoxins) when growing in foods that are mutagenic and carcinogenic in ani-mals Inhalation is an important route of transmission for some fungal diseases suchas aspergillosis blastomycosis coccidioidomycosis and histoplasmosis These fungiare found growing in animal feces soil or decaying organic matter (compost manure)and may be transmitted through the air when this matter is disturbed Some fungi maybe transmitted by direct contact with the skin Fungi are often found in drinking waterdistribution systems and they have been linked to infections in immunocompromisedindividuals [1] Food is not believed to be a significant route of transmission ofpathogenic fungi
Protozoans are unicellular organisms that are surrounded by a cytoplasmicmembrane that is covered by a protective structure called a pellicle Most are freeliving feeding off of bacteria Some of these can cause disease while others are obli-gate parasites They are capable of forming structures called cysts oocysts or spores(depending on the life cycle of the organism) resistant to adverse environmentalconditions such as desiccation starvation high temperatures and disinfectantsSome pathogenic protozoa are found mainly in the soil (Naegleria) or water(Acanthamoeba) Others such a Giardia and Cryptosporidium whose natural habitatis the intestines of warm-blooded animals are capable of causing disease in bothhumans and animals Others such as Entamoeba histolytica are only capable ofcausing disease in humans
Pathogenic enteric (replicate in the intestines) protozoans are usually excretedin the feces or urine and can be transmitted by fecally contaminated food and waterSome protozoa may be transmitted through the air (Acanthamoeba) or throughfomites (inanimate objects) Some important environmentally transmitted protozoaare listed in Table 21 The clinically important protozoa are divided taxonomicallyinto the amoebas (Entamoeba spp) flagellates (Giardia) and coccidian meaningldquoglobose in shaperdquo (Cryptosporidium and Cyclospora) Microsporidia are alsocapable of causing intestinal infections but their classification is uncertain becausethey have many characteristics associated with fungi They are all obligate parasitesand are transmitted via infectious cysts oocysts or spores by the fecalndashoral routeThe life cycles of these protozoa are similar The initial stage occurs during ingestionof the cyst oocyst or spore After ingestion the body temperature and passagethrough the stomach cause these infective stages to open up in a process calledexcystation
The Giardia cysts house two trophozoites which is the stage that attaches tointestinal cells and grows in the intestinal tract through asexual reproduction As thetrophozoites grow and begin to cover the wall of the intestinal tract diarrhea canresult As the trophozoites are released some form cysts as they pass through thebowels Cryptosporidium and Cyclospora both produce oocysts The life cycle ofCyclospora is still not well known except that its oocysts require some period of timein the environment before they are infective Cryptosporidium oocysts contain foursporozoites which enter the intestinal cells and begin the infection process As morecells become infected the illness begins and oocysts are excreted in high numbers inthe feces (about 100000g)
Worms and helminths are small multicellular animals that are parasiticto humans and animals They include flukes tapeworms and roundworms
16 CHAPTER 2 MICROBIAL AGENTS AND TRANSMISSION
on the y-axis is sought In cases (2) for known or assumed risks (on the y-axis)the corresponding range of exposures (or level of technological protection) is to bedetermined (on the x-axis)
Ensemble of Sites
A somewhat more complex situation occurs if the risk for a set of events or sites mustbe estimated Basically this now includes the necessity to incorporate site-to-sitefactors into the assessment Some examples of this are as follows
1 If I desire keeping the risk to a population served by multiple water treatmentplants at a given level (or better) then what criteria should I use (microbiallevels)
2 For a food product subject to contamination by pathogens what would be anacceptable treatment specification (eg heating time holding period) to ensuremicrobial acceptability
3 I am designing a water quality standard for recreational bathing waters If auniform (eg national) standard is to be developed what standard would ensurethat average risk was acceptable with keeping the risk of a large ldquoclusterrdquo ofillnesses low
In addition to incorporating a measure of ensemble average risk in general it is alsodesired to ensure that no single member of the ensemble be unacceptably extreme Forexample consider the evaluation of three options of disease control among three com-munities as indicated in Table 13
This table indicates the number of cases and the rate among the three commu-nities The three policy options yield the same number of expected cases Howeverthere are differences in the allocation of risk among the communities of different sizesIn option A all communities have an identical level of estimated risk In option B therisk increases as community size decreases while in option C the risk increases ascommunity size increases This distribution of risk among affected subsets of the
Exposure
Ris
k
Level of technological protection
Figure 12 Relationship between exposurelevel of technological protection andmicrobial risk The middle curve indicatesthe best estimate The other two curvesindicate the upper and lower confidenceregions
6 CHAPTER 1 MOTIVATION
ensemble being considered adds an additional dimension for consideration by a riskmanagermdashwhich may be termed risk equity
SECONDARY TRANSMISSION
Infectious microbial diseases are different in terms of risk to a population than arechemical agents in that an individual who may become infected (with or withoutillness) can then proceed to infect additional individuals These secondary (tertiaryquaternary etc) cases may be persons who had no direct contact with the initialvehicle of exposure but nevertheless in fairly accounting for the public health impactthey should be considered
Secondary cases may arise by a variety of mechanisms Particularly amongclose family members household secondary cases can arise by direct or indirect(eg surface contamination) contact this is particularly so when the primary caseor one household secondary case is a child [35ndash37] Table 14 summarizes secondarycase statistics obtained from a variety of outbreaks As will be discussed inChapter 10 the secondary case rate is a complex factor involving (among other things)the nature of the venue and contact patterns when infected and susceptible individualsintermingle
Presumably secondary cases may also arise from close contact with anasymptomatic individual (in the ldquocarrierrdquo state) This is well known for highly acuteand (now) uncommon illnesses (such as typhoid) Excretion of Norwalk virusfollowing recovery (and resulting in additional cases) has been documented to occurfor as long as 48 h post recovery [44]
OUTBREAKS VERSUS ENDEMIC CASES
As noted previously there may be a substantial difference between reported outbreakcases and total disease burden in a community In order for a disease case to receiverecognition by the public health authorities the following specific and sequential stepsmust occur [47]
TABLE 13 Effect of Different Hypothetical Policy Options on Distribution of Risk AmongCommunities (for a Fixed Total Risk)
CommunityExposedPopulation
Policy Option A Policy Option B Policy Option C
CasesIncidence(10000) Cases
Incidence(10000) Cases
Incidence(10000)
A 100000 20 2 6 06 24 24
B 50000 10 2 18 36 7 14
C 10000 2 2 8 8 1 1
Total 160000 32 2 32 2 16 2
OUTBREAKS VERSUS ENDEMIC CASES 7
1 An ill person must seek medical care
2 Appropriate clinical tests (eg blood stool) must be ordered by the attendingphysician
3 The patient must comply with obtaining the sample
4 The laboratory must be capable of detecting the relevant pathogens
5 The clinical test must be positive
6 The test result must be reported to the health agency in a timely manner
If any of the links in this sequential chain are broken then a disease case will not enterthe records maintained by health authorities For example with increasing controls on
TABLE 14 Summary of Secondary Case Data in Outbreak Situations
Organism
SecondaryAttackRatioa
SecondaryPrevalence inHouseholdsb Remarks Reference
Cryptosporidiumparvum
033 033 Outbreak in contaminatedapple cider
[38]
C parvum NA 0042 Drinking water outbreak(Milwaukee)
[37]
Shigella 028 026 Day-care center outbreaksin children
[39]
Rotavirus 042 015 Day-care center outbreaksin children
[30]
Giardia lamblia 133 017 Day-care center outbreaksin children
[39]
Viral gastroenteritis 022 011c Drinking waterborneoutbreak
[40]
Viral gastroenteritis 056 NA Drinking water outbreak(Denmark)
[41]
Norovirus 05ndash10 019 Swimming outbreak [42]
Norovirus 11 029 Swimming outbreakin children
[43]
Norovirus NA 044 Foodborne outbreakin children and teachers
[36]
Norovirus 04 NA Foodborne outbreak [44]
E coli O157H7 NA 018c Day-care center outbreakin children
[45]
Unidentifiedday-care diarrhealdiseases
138 009c [46]
NA information not availableaRatio of secondary cases to primary casesb Proportion of households with one or more primary cases who have one or more secondary casesc Proportion of persons in contact with one or more primary cases who have a secondary case
8 CHAPTER 1 MOTIVATION
medical care stool samples may not be obtained from mild cases of illness Someorganisms may only be present sporadically or may be difficult to test in stool orblood sample Patients may not seek medical attention for mild cases of illness Fur-thermore in the United States in particular the surveillance of environmentallyinduced disease is done on a passive basis and hence the number of actual illnessclusters that are actually compiled into recorded statistics is only a small fractionof such clusters of illness that occur [47]
From a more fundamental point of view an outbreak of illness is generallydefined as occurrence of the illness at a level greater than normal or anticipated Thisdefinition recognizes that there is a level of illness (endemic) that may exist underusual circumstances The detection of such outbreaks poses a particular challengeThe problem is illustrated conceptually in Figure 13
Additional complications arise from the different patterns of illness in acommunity including definite periodicities as well as temporal trends and fromthe presence of reporting lags associated with laboratory analysis and time for patientsto seek medical attention Figure 14 illustrates the different patterns of illness inthe case of six pathogens for England and Wales [48]
In the case of waterborne and foodborne illnesses it is highly likely that thelevel of such endemic illnesses is substantially greater than those occurring duringoutbreaks (even accounting for unrecognized outbreaks)
As a result there are often many cases of environmentally caused (water airfood) infectious disease that are unrecognized One example of this isCampylobacterThere has been an average of about 200 cases per year of water- and foodborne illnessin outbreaks of this organism and yet estimates of the disease burden suggest about2100000 cases per year that is approximately 10000 cases per case of detectableoutbreak illness Therefore it will be important to assess the factors that may influenceoutbreak detection These issues will be discussed in subsequent chapters
Detectedoutbreak
Undetectedoutbreak
Threshold of detection
Hyper endemicSporadic
Endemic rate
Time
Num
ber
of c
ases
Figure 13 Schematic of disease occurrence in a hypothetical community (Modified fromRef [47])
OUTBREAKS VERSUS ENDEMIC CASES 9
REFERENCES
1 Levin B R 1996 The Evolution and Maintenance of Virulence in Microparasites Emerging InfectiousDisease 293ndash102
2 National Academy of Sciences 1983 Risk Assessment in the Federal Government Managing theProcess National Academy Press Washington DC
3 National Research Council 2009 Science and Decisions Advancing Risk Assessment NationalAcademies Press Washington DC
10090807060504030201001190 1191 1192 1193 1194 1195
(b)
140
120
100
80
60
40
20
01190 1191 1192 1193 1194 1195
(f)
700
600
500
400
300
200
100
01190 1191 1192 1193 1194 1195
(d)
1200
1000
800
600
400
200
1190 1191 1192 1193 1194 1195
(a)
240
200
160
120
80
40
01190 1191 1192 1193 1194 1195
(e)
7
6
5
4
3
2
1
01190 1191 1192 1193 1194 1195
(c)
Figure 14 Weekly count of reported organism isolations in England andWales (a) rotavirus(b) Clostridium difficile (c) Salmonella derby (d) Shigella sonnei (e) influenza B and (f)Salmonella typhimurium DT 104 (From Ref [48])
10 CHAPTER 1 MOTIVATION
4 Fogarty J L Thornton and R Corcoran 1995 Illness in a Community Associated with an Episode ofWater Contamination with Sewage Epidemiology and Infection 114289ndash295
5 Scallan E 2011 Foodborne Illness Acquired in the United StatesmdashUnspecified Agents EmergingInfectious Diseases 17 16ndash22
6 Craun G F J M Brunkard J S Yoder V A Roberts J Carpenter T Wade R L CalderonJ M Roberts M J Beach and S L Roy 2010 Causes of Outbreaks Associated with Drinking Waterin the United States from 1971 to 2006 Clinical Microbiology Reviews 23507ndash528
7 Edwards D D 1993 Troubled Waters in Milwaukee ASM News 59342ndash3458 MacKenzie W R N J Hoxie M E Proctor M S Gradus K A Blair D E Peterson
J J Kazmierczak K R Fox D G Addias J B Rose and J P Davis 1994 Massive WaterborneOutbreak of Cryptosporidium Infection Associated with a Filtered Public Water Supply MilwaukeeWisconsin March and April 1993 New England Journal of Medicine 331161ndash167
9 Anonymous 2010 Surveillance for Foodborne Disease OutbreaksmdashUnited States 2007 Morbidityand Mortality Weekly Reports 59973ndash979
10 Bean N H J S Goulding C Lau and F J Angulo 1996 Surveillance for Foodborne-DiseaseOutbreaksmdashUnited States 1988ndash1992 Morbidity and Mortality Weekly Reports 451ndash66
11 Wall P G J de Louvois R J Gilbert and B Rowe 1996 Food Poisoning NotificationsLaboratory Reports and OutbreaksmdashWhere do the Statistics Come From and What Do They MeanCommunicable Disease Report Review 6 R93ndashR100
12 Colford J M S Roy M J Beach A Hightower S E Shaw and T J Wade 2006 A Review ofHousehold Drinking Water Intervention Trials and an Approach to the Estimation of EndemicWaterborne Gastroenteritis in the United States Journal of Water and Health 471
13 Mead P S L Slutsker V Dietz L F McCaig J S Bresee C Shapiro P M Griffinand R V Tauxe 1999 Food Related Illness and Death in the United States Emerging InfectiousDisease 5607ndash625
14 Dziuban E J J L Liang G F Craun V Hill P A Yu J Painter M R Moore R L CalderonS L Roy and M J Beach 2006 Surveillance for Waterborne Disease and Outbreaks Associatedwith Recreational WatermdashUnited States 2003ndash2004 and Surveillance for Waterborne Disease andOutbreaks Associated with Drinking Water and Water not Intended for DrinkingmdashUnited States2003ndash2004 Morbidity and Mortality Weekly Reports 551ndash30
15 Fliermans C B 1996 Ecology of Legionella From Data to Knowledge with a Little WisdomMicrobial Ecology 32203ndash228
16 Li Y S Duan I T Yu and T W Wong 2005 Multi-Zone Modeling of Probable SARS VirusTransmission by Airflow Between Flats in Block E Amoy Gardens Indoor Air 1596ndash111
17 Peccia J D K Milton T Reponen and J Hill 2008 A Role for Environmental Engineering andScience in Preventing Bioaerosol-Related Disease Environmental Science amp Technology424631ndash4637
18 Jernigan D B P L Raghunathan B P Bell R Brechner E A Bresnitz J C Butler M CetronM Cohen T Doyle and M Fischer 2002 Investigation of Bioterrorism-Related AnthraxUnited States 2001 Epidemiologic Findings Emerging Infectious Diseases 81019ndash1028
19 Greenwood M and G U Yule 1917 On the Statistical Interpretation of Some BacteriologicalMethods Employed in Water Analysis Journal of Hygiene 1636ndash56
20 Phelps E 1909 The Disinfection of Sewage and Sewage Filter Effluents USGS Water Supply Paper229 GPO Washington DC
21 Rudolfs W and H W Gehm 1935 Multiplication of Total Bacteria and B coli after SewageChlorination Sewage Works Journal 7991ndash996
22 Subcommittee onMicrobiological Criteria 1985 An Evaluation of the Role ofMicrobiological Criteriafor Foods and Food Ingredients National Academy Press Washington DC
23 Cabelli V J A P Dufour L J McCabe and M A Levin 1982 Swimming-AssociatedGastroenteritis and Water Quality American Journal of Epidemiology 115606ndash616
24 Dufour A P 1984 Health Effects Criteria for Fresh Recreational Waters USEPA Research TrianglePark NC
25 Fleisher J M F Jones and D Kay 1993 Water and Non-Water-Related Risk Factors forGastroenteritis among Bathers Exposed to Sewage-Contaminated Marine Waters InternationalJournal of Epidemiology 22698ndash708
REFERENCES 11
26 Engelbrecht R S C N Haas J A Shular D L Dunn D Roy A Lalchandani B F Severin andS Farooq 1979 Acid-Fast Bacteria and Yeasts as Indicators of Disinfection Efficiency EPA-6002-79-091 US Environmental Protection Agency Cincinnati OH
27 Grabow W O K 1983 Inactivation of Hepatitis A Virus and Indicator Organisms in Water by FreeChlorine Residuals Applied and Environmental Microbiology 46619
28 Helmer R D and G R Finch 1993 Use of MS2 Coliphage as a Surrogate for Enteric Viruses inSurface Waters Disinfected with Ozone Ozone Science and Engineering 15279ndash293
29 Payment P and E Franco 1993Clostridium Perfringens and Somatic Coliphages as Indicators of theEfficiency of Drinking Water Treatment for Viruses and Protozoan Cysts Applied and EnvironmentalMicrobiology 592418ndash2424
30 Cabelli V J 1977Clostridium Perfringens as aWater Quality Indicator pp 65ndash79 InA Hoadley andB Dutka (eds) Bacterial IndicatorsHealth Hazards Associated with Water ASTM Philadelphia PA
31 Rice E W K R Fox R J Miltner D A Lytle and C H Johnson 1996 Evaluating PlantPerformance with Endospores Journal of the American Water Works Association 88122ndash130
32 Engelbrecht R S B F Severin M T Masarik S Farooq S H Lee C N Haas and A Lalchandani1977 New Microbial Indicators of Disinfection Efficiency EPA-6002-77-052 US EnvironmentalProtection Agency Cincinnati OH
33 Committee on Indicators for Waterborne Pathogens ndash National Research Council 2004 Indicators forWaterborne Pathogens National Academies Press Washington DC
34 PresidentialCongressional Commission on Risk Assessment and RiskManagement 1997 Frameworkfor Environmental Health Risk Management The Commission Washington DC
35 Griffin P M and R V Tauxe 1991 The Epidemiology of Infections Caused by Escherichiacoli O157H7 Other Enterohemorrhagic E coli and the Associated Hemolytic Uremic SyndromeEpidemiologic Reviews 1360ndash98
36 Heun E M R L Vogt P J Hudson S Parren and G W Gary 1987 Risk Factors for SecondaryTransmission in Households after a Common Source Outbreak of Norwalk Gastroenteritis AmericanJournal of Epidemiology 1261181ndash1186
37 MacKenzie W R W L Schell B A Blair D G Addiss D E Peterson N J HozieJ J Kazmierczak and J P Davis 1995 Massive Outbreak of Waterborne CryptosporidiumInfection in Milwaukee Wisconsin Recurrence of Illness and Risk of Secondary TransmissionClinical Infectious Diseases 2157ndash62
38 Millard P K Gensheimer D G Addiss D M Sosin G A Beckett A Houck-Jankoski andA Hudson 1994 An Outbreak of Cryptosporidiosis from Fresh-Pressed Apple Cider Journal ofthe American Medical Association 2721592ndash1596
39 Pickering L K D G Evans H L DuPont J J Vollet and D J Evans Jr 1981 Diarrhea Caused byShigella Rotavirus and Giardia in Day Care Centers Prospective Study Journal of Pediatrics9951ndash56
40 Morens D M R M Zweighaft T M Vernon G W Gary J J Eslien B T Wood R C Holmanand R Dolin 1979 A Waterborne Outbreak of Gastroenteritis with Secondary Person to PersonSpread Lancet 5964ndash966
41 Laursen E O Mygind B Rasmussen and T Ronne 1994 Gastroenteritis A Waterborne OutbreakAffecting 1600 People in a Small Danish Town Journal of Epidemiology amp Community Health48453ndash458
42 Baron R C F D Murphy H B Greenberg C E Davis D J Bregman G W Gary J M Hughesand L B Schonberger 1982 Norwalk Gastrointestinal Illness An Outbreak Associated withSwimming in a Recreational Lake and Secondary Person to Person Transmission American Journalof Epidemiology 115163ndash172
43 Kappus K D J S Marks R C Holman J K Bryant C Baker G W Gary and H B Greenberg1982 An Outbreak of Norwalk Gastroenteritis Associated with Swimming in a Pool and SecondaryPerson to Person Transmission American Journal of Epidemiology 116834ndash839
44 White K E M T Osterbolm J A Mariotti J A Korlath D H Lawrence T L Ristinen andH B Greenberg 1986 A Foodborne Outbreak of Norwalk Virus Gastroenteritis American Journalof Epidemiology 124120ndash126
45 Spika J S J E Parsons and D Nordenberg 1986 Hemolytic Uremic Syndrome and DiarrheaAssociated with Escherichia coli O157H7 in a Day Care Center Journal of Pediatrics 109287ndash291
12 CHAPTER 1 MOTIVATION
46 Ferguson J K L R Jorm C D Allen P KWhitehead and G L Gilbert 1995 Prospective Study ofDiarrhoeal Outbreaks in Child Long Daycare Centres in Western Sydney Medical Journal of Australia163137ndash140
47 Frost F J G F Craun and R L Calderon 1996 Waterborne Disease Surveillance Journal of theAmerican Water Works Association 8866ndash75
48 Farrington C P N J Andrews A D Beale and M A Catchpole 1996 A Statistical Algorithmfor the Early Detection of Outbreaks of Infectious Disease Journal of the Royal StatisticalSociety A 159547ndash563
REFERENCES 13
CHAPTER2MICROBIAL AGENTS ANDTRANSMISSION
MICROBIAL TAXONOMY
The development of techniques for examining the nucleic acids of microorganisms hasseen major changes in which we classify and group related microorganisms This isespecially true for the study of ribosomal ribonucleic acid (rRNA) which is a highlyconserved sequence involved in the synthesis of proteins in all living organisms Basedon this analysis the classification of living things has been placed into a three-domainsystem consisting of Archaea Eukarya and Bacteria Of these the Bacteria andArchaea are termed prokaryotes (no organized cell nucleus) and the Eukarya areknown as eukaryotes (an organized cell nucleus) Eukaryotic microbes other thanalgae and fungi are collectively calledprotistsWithin theEukarya are fungi protozoahelminth worms algae plants animals and humans Archaea are microbes that looksomewhat similar to bacteria in size and shape under the light microscope but they areactually genetically and biochemically quite different They appear to be a simpler formof life and may in fact be the oldest form of life on earth Viruses are obligate intercel-lular parasites and are not amember of any group They are usually composed only of anucleic acid surrounded by a protein coat Eukaryotes are much more complex thanprokaryotic cells in structure and nutritional requirements Prokaryotes divide by sim-ple binary fissionwhereas eukaryotes divide byamore complexprocess calledmitosis
Eukaryotes
Fungi protozoa and helminth worms are all eukaryotes All contain members that arepathogenic to man and animals While algae do not infect humans they can producetoxins that are harmful to animals and man Fungi obtain nutrients solely by adsorp-tion of organic matter from dead organisms Even when they invade living tissuesthey typically kill cells and then adsorb the nutrients from them Some fungi are capa-ble of developing environmentally resistant spores which can be transported throughthe air Fungal diseases in humans are referred to asmycoses Airborne fungal sporesare responsible for some allergies in humans Yeasts are classified with the fungi and
Quantitative Microbial Risk Assessment Second Edition Charles N Haas Joan B Roseand Charles P Gerbacopy 2014 John Wiley amp Sons Inc Published 2014 by John Wiley amp Sons Inc
15
some are pathogenic to humans (Candida albicans) Certain fungi produce toxins(ie aflatoxins) when growing in foods that are mutagenic and carcinogenic in ani-mals Inhalation is an important route of transmission for some fungal diseases suchas aspergillosis blastomycosis coccidioidomycosis and histoplasmosis These fungiare found growing in animal feces soil or decaying organic matter (compost manure)and may be transmitted through the air when this matter is disturbed Some fungi maybe transmitted by direct contact with the skin Fungi are often found in drinking waterdistribution systems and they have been linked to infections in immunocompromisedindividuals [1] Food is not believed to be a significant route of transmission ofpathogenic fungi
Protozoans are unicellular organisms that are surrounded by a cytoplasmicmembrane that is covered by a protective structure called a pellicle Most are freeliving feeding off of bacteria Some of these can cause disease while others are obli-gate parasites They are capable of forming structures called cysts oocysts or spores(depending on the life cycle of the organism) resistant to adverse environmentalconditions such as desiccation starvation high temperatures and disinfectantsSome pathogenic protozoa are found mainly in the soil (Naegleria) or water(Acanthamoeba) Others such a Giardia and Cryptosporidium whose natural habitatis the intestines of warm-blooded animals are capable of causing disease in bothhumans and animals Others such as Entamoeba histolytica are only capable ofcausing disease in humans
Pathogenic enteric (replicate in the intestines) protozoans are usually excretedin the feces or urine and can be transmitted by fecally contaminated food and waterSome protozoa may be transmitted through the air (Acanthamoeba) or throughfomites (inanimate objects) Some important environmentally transmitted protozoaare listed in Table 21 The clinically important protozoa are divided taxonomicallyinto the amoebas (Entamoeba spp) flagellates (Giardia) and coccidian meaningldquoglobose in shaperdquo (Cryptosporidium and Cyclospora) Microsporidia are alsocapable of causing intestinal infections but their classification is uncertain becausethey have many characteristics associated with fungi They are all obligate parasitesand are transmitted via infectious cysts oocysts or spores by the fecalndashoral routeThe life cycles of these protozoa are similar The initial stage occurs during ingestionof the cyst oocyst or spore After ingestion the body temperature and passagethrough the stomach cause these infective stages to open up in a process calledexcystation
The Giardia cysts house two trophozoites which is the stage that attaches tointestinal cells and grows in the intestinal tract through asexual reproduction As thetrophozoites grow and begin to cover the wall of the intestinal tract diarrhea canresult As the trophozoites are released some form cysts as they pass through thebowels Cryptosporidium and Cyclospora both produce oocysts The life cycle ofCyclospora is still not well known except that its oocysts require some period of timein the environment before they are infective Cryptosporidium oocysts contain foursporozoites which enter the intestinal cells and begin the infection process As morecells become infected the illness begins and oocysts are excreted in high numbers inthe feces (about 100000g)
Worms and helminths are small multicellular animals that are parasiticto humans and animals They include flukes tapeworms and roundworms
16 CHAPTER 2 MICROBIAL AGENTS AND TRANSMISSION
ensemble being considered adds an additional dimension for consideration by a riskmanagermdashwhich may be termed risk equity
SECONDARY TRANSMISSION
Infectious microbial diseases are different in terms of risk to a population than arechemical agents in that an individual who may become infected (with or withoutillness) can then proceed to infect additional individuals These secondary (tertiaryquaternary etc) cases may be persons who had no direct contact with the initialvehicle of exposure but nevertheless in fairly accounting for the public health impactthey should be considered
Secondary cases may arise by a variety of mechanisms Particularly amongclose family members household secondary cases can arise by direct or indirect(eg surface contamination) contact this is particularly so when the primary caseor one household secondary case is a child [35ndash37] Table 14 summarizes secondarycase statistics obtained from a variety of outbreaks As will be discussed inChapter 10 the secondary case rate is a complex factor involving (among other things)the nature of the venue and contact patterns when infected and susceptible individualsintermingle
Presumably secondary cases may also arise from close contact with anasymptomatic individual (in the ldquocarrierrdquo state) This is well known for highly acuteand (now) uncommon illnesses (such as typhoid) Excretion of Norwalk virusfollowing recovery (and resulting in additional cases) has been documented to occurfor as long as 48 h post recovery [44]
OUTBREAKS VERSUS ENDEMIC CASES
As noted previously there may be a substantial difference between reported outbreakcases and total disease burden in a community In order for a disease case to receiverecognition by the public health authorities the following specific and sequential stepsmust occur [47]
TABLE 13 Effect of Different Hypothetical Policy Options on Distribution of Risk AmongCommunities (for a Fixed Total Risk)
CommunityExposedPopulation
Policy Option A Policy Option B Policy Option C
CasesIncidence(10000) Cases
Incidence(10000) Cases
Incidence(10000)
A 100000 20 2 6 06 24 24
B 50000 10 2 18 36 7 14
C 10000 2 2 8 8 1 1
Total 160000 32 2 32 2 16 2
OUTBREAKS VERSUS ENDEMIC CASES 7
1 An ill person must seek medical care
2 Appropriate clinical tests (eg blood stool) must be ordered by the attendingphysician
3 The patient must comply with obtaining the sample
4 The laboratory must be capable of detecting the relevant pathogens
5 The clinical test must be positive
6 The test result must be reported to the health agency in a timely manner
If any of the links in this sequential chain are broken then a disease case will not enterthe records maintained by health authorities For example with increasing controls on
TABLE 14 Summary of Secondary Case Data in Outbreak Situations
Organism
SecondaryAttackRatioa
SecondaryPrevalence inHouseholdsb Remarks Reference
Cryptosporidiumparvum
033 033 Outbreak in contaminatedapple cider
[38]
C parvum NA 0042 Drinking water outbreak(Milwaukee)
[37]
Shigella 028 026 Day-care center outbreaksin children
[39]
Rotavirus 042 015 Day-care center outbreaksin children
[30]
Giardia lamblia 133 017 Day-care center outbreaksin children
[39]
Viral gastroenteritis 022 011c Drinking waterborneoutbreak
[40]
Viral gastroenteritis 056 NA Drinking water outbreak(Denmark)
[41]
Norovirus 05ndash10 019 Swimming outbreak [42]
Norovirus 11 029 Swimming outbreakin children
[43]
Norovirus NA 044 Foodborne outbreakin children and teachers
[36]
Norovirus 04 NA Foodborne outbreak [44]
E coli O157H7 NA 018c Day-care center outbreakin children
[45]
Unidentifiedday-care diarrhealdiseases
138 009c [46]
NA information not availableaRatio of secondary cases to primary casesb Proportion of households with one or more primary cases who have one or more secondary casesc Proportion of persons in contact with one or more primary cases who have a secondary case
8 CHAPTER 1 MOTIVATION
medical care stool samples may not be obtained from mild cases of illness Someorganisms may only be present sporadically or may be difficult to test in stool orblood sample Patients may not seek medical attention for mild cases of illness Fur-thermore in the United States in particular the surveillance of environmentallyinduced disease is done on a passive basis and hence the number of actual illnessclusters that are actually compiled into recorded statistics is only a small fractionof such clusters of illness that occur [47]
From a more fundamental point of view an outbreak of illness is generallydefined as occurrence of the illness at a level greater than normal or anticipated Thisdefinition recognizes that there is a level of illness (endemic) that may exist underusual circumstances The detection of such outbreaks poses a particular challengeThe problem is illustrated conceptually in Figure 13
Additional complications arise from the different patterns of illness in acommunity including definite periodicities as well as temporal trends and fromthe presence of reporting lags associated with laboratory analysis and time for patientsto seek medical attention Figure 14 illustrates the different patterns of illness inthe case of six pathogens for England and Wales [48]
In the case of waterborne and foodborne illnesses it is highly likely that thelevel of such endemic illnesses is substantially greater than those occurring duringoutbreaks (even accounting for unrecognized outbreaks)
As a result there are often many cases of environmentally caused (water airfood) infectious disease that are unrecognized One example of this isCampylobacterThere has been an average of about 200 cases per year of water- and foodborne illnessin outbreaks of this organism and yet estimates of the disease burden suggest about2100000 cases per year that is approximately 10000 cases per case of detectableoutbreak illness Therefore it will be important to assess the factors that may influenceoutbreak detection These issues will be discussed in subsequent chapters
Detectedoutbreak
Undetectedoutbreak
Threshold of detection
Hyper endemicSporadic
Endemic rate
Time
Num
ber
of c
ases
Figure 13 Schematic of disease occurrence in a hypothetical community (Modified fromRef [47])
OUTBREAKS VERSUS ENDEMIC CASES 9
REFERENCES
1 Levin B R 1996 The Evolution and Maintenance of Virulence in Microparasites Emerging InfectiousDisease 293ndash102
2 National Academy of Sciences 1983 Risk Assessment in the Federal Government Managing theProcess National Academy Press Washington DC
3 National Research Council 2009 Science and Decisions Advancing Risk Assessment NationalAcademies Press Washington DC
10090807060504030201001190 1191 1192 1193 1194 1195
(b)
140
120
100
80
60
40
20
01190 1191 1192 1193 1194 1195
(f)
700
600
500
400
300
200
100
01190 1191 1192 1193 1194 1195
(d)
1200
1000
800
600
400
200
1190 1191 1192 1193 1194 1195
(a)
240
200
160
120
80
40
01190 1191 1192 1193 1194 1195
(e)
7
6
5
4
3
2
1
01190 1191 1192 1193 1194 1195
(c)
Figure 14 Weekly count of reported organism isolations in England andWales (a) rotavirus(b) Clostridium difficile (c) Salmonella derby (d) Shigella sonnei (e) influenza B and (f)Salmonella typhimurium DT 104 (From Ref [48])
10 CHAPTER 1 MOTIVATION
4 Fogarty J L Thornton and R Corcoran 1995 Illness in a Community Associated with an Episode ofWater Contamination with Sewage Epidemiology and Infection 114289ndash295
5 Scallan E 2011 Foodborne Illness Acquired in the United StatesmdashUnspecified Agents EmergingInfectious Diseases 17 16ndash22
6 Craun G F J M Brunkard J S Yoder V A Roberts J Carpenter T Wade R L CalderonJ M Roberts M J Beach and S L Roy 2010 Causes of Outbreaks Associated with Drinking Waterin the United States from 1971 to 2006 Clinical Microbiology Reviews 23507ndash528
7 Edwards D D 1993 Troubled Waters in Milwaukee ASM News 59342ndash3458 MacKenzie W R N J Hoxie M E Proctor M S Gradus K A Blair D E Peterson
J J Kazmierczak K R Fox D G Addias J B Rose and J P Davis 1994 Massive WaterborneOutbreak of Cryptosporidium Infection Associated with a Filtered Public Water Supply MilwaukeeWisconsin March and April 1993 New England Journal of Medicine 331161ndash167
9 Anonymous 2010 Surveillance for Foodborne Disease OutbreaksmdashUnited States 2007 Morbidityand Mortality Weekly Reports 59973ndash979
10 Bean N H J S Goulding C Lau and F J Angulo 1996 Surveillance for Foodborne-DiseaseOutbreaksmdashUnited States 1988ndash1992 Morbidity and Mortality Weekly Reports 451ndash66
11 Wall P G J de Louvois R J Gilbert and B Rowe 1996 Food Poisoning NotificationsLaboratory Reports and OutbreaksmdashWhere do the Statistics Come From and What Do They MeanCommunicable Disease Report Review 6 R93ndashR100
12 Colford J M S Roy M J Beach A Hightower S E Shaw and T J Wade 2006 A Review ofHousehold Drinking Water Intervention Trials and an Approach to the Estimation of EndemicWaterborne Gastroenteritis in the United States Journal of Water and Health 471
13 Mead P S L Slutsker V Dietz L F McCaig J S Bresee C Shapiro P M Griffinand R V Tauxe 1999 Food Related Illness and Death in the United States Emerging InfectiousDisease 5607ndash625
14 Dziuban E J J L Liang G F Craun V Hill P A Yu J Painter M R Moore R L CalderonS L Roy and M J Beach 2006 Surveillance for Waterborne Disease and Outbreaks Associatedwith Recreational WatermdashUnited States 2003ndash2004 and Surveillance for Waterborne Disease andOutbreaks Associated with Drinking Water and Water not Intended for DrinkingmdashUnited States2003ndash2004 Morbidity and Mortality Weekly Reports 551ndash30
15 Fliermans C B 1996 Ecology of Legionella From Data to Knowledge with a Little WisdomMicrobial Ecology 32203ndash228
16 Li Y S Duan I T Yu and T W Wong 2005 Multi-Zone Modeling of Probable SARS VirusTransmission by Airflow Between Flats in Block E Amoy Gardens Indoor Air 1596ndash111
17 Peccia J D K Milton T Reponen and J Hill 2008 A Role for Environmental Engineering andScience in Preventing Bioaerosol-Related Disease Environmental Science amp Technology424631ndash4637
18 Jernigan D B P L Raghunathan B P Bell R Brechner E A Bresnitz J C Butler M CetronM Cohen T Doyle and M Fischer 2002 Investigation of Bioterrorism-Related AnthraxUnited States 2001 Epidemiologic Findings Emerging Infectious Diseases 81019ndash1028
19 Greenwood M and G U Yule 1917 On the Statistical Interpretation of Some BacteriologicalMethods Employed in Water Analysis Journal of Hygiene 1636ndash56
20 Phelps E 1909 The Disinfection of Sewage and Sewage Filter Effluents USGS Water Supply Paper229 GPO Washington DC
21 Rudolfs W and H W Gehm 1935 Multiplication of Total Bacteria and B coli after SewageChlorination Sewage Works Journal 7991ndash996
22 Subcommittee onMicrobiological Criteria 1985 An Evaluation of the Role ofMicrobiological Criteriafor Foods and Food Ingredients National Academy Press Washington DC
23 Cabelli V J A P Dufour L J McCabe and M A Levin 1982 Swimming-AssociatedGastroenteritis and Water Quality American Journal of Epidemiology 115606ndash616
24 Dufour A P 1984 Health Effects Criteria for Fresh Recreational Waters USEPA Research TrianglePark NC
25 Fleisher J M F Jones and D Kay 1993 Water and Non-Water-Related Risk Factors forGastroenteritis among Bathers Exposed to Sewage-Contaminated Marine Waters InternationalJournal of Epidemiology 22698ndash708
REFERENCES 11
26 Engelbrecht R S C N Haas J A Shular D L Dunn D Roy A Lalchandani B F Severin andS Farooq 1979 Acid-Fast Bacteria and Yeasts as Indicators of Disinfection Efficiency EPA-6002-79-091 US Environmental Protection Agency Cincinnati OH
27 Grabow W O K 1983 Inactivation of Hepatitis A Virus and Indicator Organisms in Water by FreeChlorine Residuals Applied and Environmental Microbiology 46619
28 Helmer R D and G R Finch 1993 Use of MS2 Coliphage as a Surrogate for Enteric Viruses inSurface Waters Disinfected with Ozone Ozone Science and Engineering 15279ndash293
29 Payment P and E Franco 1993Clostridium Perfringens and Somatic Coliphages as Indicators of theEfficiency of Drinking Water Treatment for Viruses and Protozoan Cysts Applied and EnvironmentalMicrobiology 592418ndash2424
30 Cabelli V J 1977Clostridium Perfringens as aWater Quality Indicator pp 65ndash79 InA Hoadley andB Dutka (eds) Bacterial IndicatorsHealth Hazards Associated with Water ASTM Philadelphia PA
31 Rice E W K R Fox R J Miltner D A Lytle and C H Johnson 1996 Evaluating PlantPerformance with Endospores Journal of the American Water Works Association 88122ndash130
32 Engelbrecht R S B F Severin M T Masarik S Farooq S H Lee C N Haas and A Lalchandani1977 New Microbial Indicators of Disinfection Efficiency EPA-6002-77-052 US EnvironmentalProtection Agency Cincinnati OH
33 Committee on Indicators for Waterborne Pathogens ndash National Research Council 2004 Indicators forWaterborne Pathogens National Academies Press Washington DC
34 PresidentialCongressional Commission on Risk Assessment and RiskManagement 1997 Frameworkfor Environmental Health Risk Management The Commission Washington DC
35 Griffin P M and R V Tauxe 1991 The Epidemiology of Infections Caused by Escherichiacoli O157H7 Other Enterohemorrhagic E coli and the Associated Hemolytic Uremic SyndromeEpidemiologic Reviews 1360ndash98
36 Heun E M R L Vogt P J Hudson S Parren and G W Gary 1987 Risk Factors for SecondaryTransmission in Households after a Common Source Outbreak of Norwalk Gastroenteritis AmericanJournal of Epidemiology 1261181ndash1186
37 MacKenzie W R W L Schell B A Blair D G Addiss D E Peterson N J HozieJ J Kazmierczak and J P Davis 1995 Massive Outbreak of Waterborne CryptosporidiumInfection in Milwaukee Wisconsin Recurrence of Illness and Risk of Secondary TransmissionClinical Infectious Diseases 2157ndash62
38 Millard P K Gensheimer D G Addiss D M Sosin G A Beckett A Houck-Jankoski andA Hudson 1994 An Outbreak of Cryptosporidiosis from Fresh-Pressed Apple Cider Journal ofthe American Medical Association 2721592ndash1596
39 Pickering L K D G Evans H L DuPont J J Vollet and D J Evans Jr 1981 Diarrhea Caused byShigella Rotavirus and Giardia in Day Care Centers Prospective Study Journal of Pediatrics9951ndash56
40 Morens D M R M Zweighaft T M Vernon G W Gary J J Eslien B T Wood R C Holmanand R Dolin 1979 A Waterborne Outbreak of Gastroenteritis with Secondary Person to PersonSpread Lancet 5964ndash966
41 Laursen E O Mygind B Rasmussen and T Ronne 1994 Gastroenteritis A Waterborne OutbreakAffecting 1600 People in a Small Danish Town Journal of Epidemiology amp Community Health48453ndash458
42 Baron R C F D Murphy H B Greenberg C E Davis D J Bregman G W Gary J M Hughesand L B Schonberger 1982 Norwalk Gastrointestinal Illness An Outbreak Associated withSwimming in a Recreational Lake and Secondary Person to Person Transmission American Journalof Epidemiology 115163ndash172
43 Kappus K D J S Marks R C Holman J K Bryant C Baker G W Gary and H B Greenberg1982 An Outbreak of Norwalk Gastroenteritis Associated with Swimming in a Pool and SecondaryPerson to Person Transmission American Journal of Epidemiology 116834ndash839
44 White K E M T Osterbolm J A Mariotti J A Korlath D H Lawrence T L Ristinen andH B Greenberg 1986 A Foodborne Outbreak of Norwalk Virus Gastroenteritis American Journalof Epidemiology 124120ndash126
45 Spika J S J E Parsons and D Nordenberg 1986 Hemolytic Uremic Syndrome and DiarrheaAssociated with Escherichia coli O157H7 in a Day Care Center Journal of Pediatrics 109287ndash291
12 CHAPTER 1 MOTIVATION
46 Ferguson J K L R Jorm C D Allen P KWhitehead and G L Gilbert 1995 Prospective Study ofDiarrhoeal Outbreaks in Child Long Daycare Centres in Western Sydney Medical Journal of Australia163137ndash140
47 Frost F J G F Craun and R L Calderon 1996 Waterborne Disease Surveillance Journal of theAmerican Water Works Association 8866ndash75
48 Farrington C P N J Andrews A D Beale and M A Catchpole 1996 A Statistical Algorithmfor the Early Detection of Outbreaks of Infectious Disease Journal of the Royal StatisticalSociety A 159547ndash563
REFERENCES 13
CHAPTER2MICROBIAL AGENTS ANDTRANSMISSION
MICROBIAL TAXONOMY
The development of techniques for examining the nucleic acids of microorganisms hasseen major changes in which we classify and group related microorganisms This isespecially true for the study of ribosomal ribonucleic acid (rRNA) which is a highlyconserved sequence involved in the synthesis of proteins in all living organisms Basedon this analysis the classification of living things has been placed into a three-domainsystem consisting of Archaea Eukarya and Bacteria Of these the Bacteria andArchaea are termed prokaryotes (no organized cell nucleus) and the Eukarya areknown as eukaryotes (an organized cell nucleus) Eukaryotic microbes other thanalgae and fungi are collectively calledprotistsWithin theEukarya are fungi protozoahelminth worms algae plants animals and humans Archaea are microbes that looksomewhat similar to bacteria in size and shape under the light microscope but they areactually genetically and biochemically quite different They appear to be a simpler formof life and may in fact be the oldest form of life on earth Viruses are obligate intercel-lular parasites and are not amember of any group They are usually composed only of anucleic acid surrounded by a protein coat Eukaryotes are much more complex thanprokaryotic cells in structure and nutritional requirements Prokaryotes divide by sim-ple binary fissionwhereas eukaryotes divide byamore complexprocess calledmitosis
Eukaryotes
Fungi protozoa and helminth worms are all eukaryotes All contain members that arepathogenic to man and animals While algae do not infect humans they can producetoxins that are harmful to animals and man Fungi obtain nutrients solely by adsorp-tion of organic matter from dead organisms Even when they invade living tissuesthey typically kill cells and then adsorb the nutrients from them Some fungi are capa-ble of developing environmentally resistant spores which can be transported throughthe air Fungal diseases in humans are referred to asmycoses Airborne fungal sporesare responsible for some allergies in humans Yeasts are classified with the fungi and
Quantitative Microbial Risk Assessment Second Edition Charles N Haas Joan B Roseand Charles P Gerbacopy 2014 John Wiley amp Sons Inc Published 2014 by John Wiley amp Sons Inc
15
some are pathogenic to humans (Candida albicans) Certain fungi produce toxins(ie aflatoxins) when growing in foods that are mutagenic and carcinogenic in ani-mals Inhalation is an important route of transmission for some fungal diseases suchas aspergillosis blastomycosis coccidioidomycosis and histoplasmosis These fungiare found growing in animal feces soil or decaying organic matter (compost manure)and may be transmitted through the air when this matter is disturbed Some fungi maybe transmitted by direct contact with the skin Fungi are often found in drinking waterdistribution systems and they have been linked to infections in immunocompromisedindividuals [1] Food is not believed to be a significant route of transmission ofpathogenic fungi
Protozoans are unicellular organisms that are surrounded by a cytoplasmicmembrane that is covered by a protective structure called a pellicle Most are freeliving feeding off of bacteria Some of these can cause disease while others are obli-gate parasites They are capable of forming structures called cysts oocysts or spores(depending on the life cycle of the organism) resistant to adverse environmentalconditions such as desiccation starvation high temperatures and disinfectantsSome pathogenic protozoa are found mainly in the soil (Naegleria) or water(Acanthamoeba) Others such a Giardia and Cryptosporidium whose natural habitatis the intestines of warm-blooded animals are capable of causing disease in bothhumans and animals Others such as Entamoeba histolytica are only capable ofcausing disease in humans
Pathogenic enteric (replicate in the intestines) protozoans are usually excretedin the feces or urine and can be transmitted by fecally contaminated food and waterSome protozoa may be transmitted through the air (Acanthamoeba) or throughfomites (inanimate objects) Some important environmentally transmitted protozoaare listed in Table 21 The clinically important protozoa are divided taxonomicallyinto the amoebas (Entamoeba spp) flagellates (Giardia) and coccidian meaningldquoglobose in shaperdquo (Cryptosporidium and Cyclospora) Microsporidia are alsocapable of causing intestinal infections but their classification is uncertain becausethey have many characteristics associated with fungi They are all obligate parasitesand are transmitted via infectious cysts oocysts or spores by the fecalndashoral routeThe life cycles of these protozoa are similar The initial stage occurs during ingestionof the cyst oocyst or spore After ingestion the body temperature and passagethrough the stomach cause these infective stages to open up in a process calledexcystation
The Giardia cysts house two trophozoites which is the stage that attaches tointestinal cells and grows in the intestinal tract through asexual reproduction As thetrophozoites grow and begin to cover the wall of the intestinal tract diarrhea canresult As the trophozoites are released some form cysts as they pass through thebowels Cryptosporidium and Cyclospora both produce oocysts The life cycle ofCyclospora is still not well known except that its oocysts require some period of timein the environment before they are infective Cryptosporidium oocysts contain foursporozoites which enter the intestinal cells and begin the infection process As morecells become infected the illness begins and oocysts are excreted in high numbers inthe feces (about 100000g)
Worms and helminths are small multicellular animals that are parasiticto humans and animals They include flukes tapeworms and roundworms
16 CHAPTER 2 MICROBIAL AGENTS AND TRANSMISSION
1 An ill person must seek medical care
2 Appropriate clinical tests (eg blood stool) must be ordered by the attendingphysician
3 The patient must comply with obtaining the sample
4 The laboratory must be capable of detecting the relevant pathogens
5 The clinical test must be positive
6 The test result must be reported to the health agency in a timely manner
If any of the links in this sequential chain are broken then a disease case will not enterthe records maintained by health authorities For example with increasing controls on
TABLE 14 Summary of Secondary Case Data in Outbreak Situations
Organism
SecondaryAttackRatioa
SecondaryPrevalence inHouseholdsb Remarks Reference
Cryptosporidiumparvum
033 033 Outbreak in contaminatedapple cider
[38]
C parvum NA 0042 Drinking water outbreak(Milwaukee)
[37]
Shigella 028 026 Day-care center outbreaksin children
[39]
Rotavirus 042 015 Day-care center outbreaksin children
[30]
Giardia lamblia 133 017 Day-care center outbreaksin children
[39]
Viral gastroenteritis 022 011c Drinking waterborneoutbreak
[40]
Viral gastroenteritis 056 NA Drinking water outbreak(Denmark)
[41]
Norovirus 05ndash10 019 Swimming outbreak [42]
Norovirus 11 029 Swimming outbreakin children
[43]
Norovirus NA 044 Foodborne outbreakin children and teachers
[36]
Norovirus 04 NA Foodborne outbreak [44]
E coli O157H7 NA 018c Day-care center outbreakin children
[45]
Unidentifiedday-care diarrhealdiseases
138 009c [46]
NA information not availableaRatio of secondary cases to primary casesb Proportion of households with one or more primary cases who have one or more secondary casesc Proportion of persons in contact with one or more primary cases who have a secondary case
8 CHAPTER 1 MOTIVATION
medical care stool samples may not be obtained from mild cases of illness Someorganisms may only be present sporadically or may be difficult to test in stool orblood sample Patients may not seek medical attention for mild cases of illness Fur-thermore in the United States in particular the surveillance of environmentallyinduced disease is done on a passive basis and hence the number of actual illnessclusters that are actually compiled into recorded statistics is only a small fractionof such clusters of illness that occur [47]
From a more fundamental point of view an outbreak of illness is generallydefined as occurrence of the illness at a level greater than normal or anticipated Thisdefinition recognizes that there is a level of illness (endemic) that may exist underusual circumstances The detection of such outbreaks poses a particular challengeThe problem is illustrated conceptually in Figure 13
Additional complications arise from the different patterns of illness in acommunity including definite periodicities as well as temporal trends and fromthe presence of reporting lags associated with laboratory analysis and time for patientsto seek medical attention Figure 14 illustrates the different patterns of illness inthe case of six pathogens for England and Wales [48]
In the case of waterborne and foodborne illnesses it is highly likely that thelevel of such endemic illnesses is substantially greater than those occurring duringoutbreaks (even accounting for unrecognized outbreaks)
As a result there are often many cases of environmentally caused (water airfood) infectious disease that are unrecognized One example of this isCampylobacterThere has been an average of about 200 cases per year of water- and foodborne illnessin outbreaks of this organism and yet estimates of the disease burden suggest about2100000 cases per year that is approximately 10000 cases per case of detectableoutbreak illness Therefore it will be important to assess the factors that may influenceoutbreak detection These issues will be discussed in subsequent chapters
Detectedoutbreak
Undetectedoutbreak
Threshold of detection
Hyper endemicSporadic
Endemic rate
Time
Num
ber
of c
ases
Figure 13 Schematic of disease occurrence in a hypothetical community (Modified fromRef [47])
OUTBREAKS VERSUS ENDEMIC CASES 9
REFERENCES
1 Levin B R 1996 The Evolution and Maintenance of Virulence in Microparasites Emerging InfectiousDisease 293ndash102
2 National Academy of Sciences 1983 Risk Assessment in the Federal Government Managing theProcess National Academy Press Washington DC
3 National Research Council 2009 Science and Decisions Advancing Risk Assessment NationalAcademies Press Washington DC
10090807060504030201001190 1191 1192 1193 1194 1195
(b)
140
120
100
80
60
40
20
01190 1191 1192 1193 1194 1195
(f)
700
600
500
400
300
200
100
01190 1191 1192 1193 1194 1195
(d)
1200
1000
800
600
400
200
1190 1191 1192 1193 1194 1195
(a)
240
200
160
120
80
40
01190 1191 1192 1193 1194 1195
(e)
7
6
5
4
3
2
1
01190 1191 1192 1193 1194 1195
(c)
Figure 14 Weekly count of reported organism isolations in England andWales (a) rotavirus(b) Clostridium difficile (c) Salmonella derby (d) Shigella sonnei (e) influenza B and (f)Salmonella typhimurium DT 104 (From Ref [48])
10 CHAPTER 1 MOTIVATION
4 Fogarty J L Thornton and R Corcoran 1995 Illness in a Community Associated with an Episode ofWater Contamination with Sewage Epidemiology and Infection 114289ndash295
5 Scallan E 2011 Foodborne Illness Acquired in the United StatesmdashUnspecified Agents EmergingInfectious Diseases 17 16ndash22
6 Craun G F J M Brunkard J S Yoder V A Roberts J Carpenter T Wade R L CalderonJ M Roberts M J Beach and S L Roy 2010 Causes of Outbreaks Associated with Drinking Waterin the United States from 1971 to 2006 Clinical Microbiology Reviews 23507ndash528
7 Edwards D D 1993 Troubled Waters in Milwaukee ASM News 59342ndash3458 MacKenzie W R N J Hoxie M E Proctor M S Gradus K A Blair D E Peterson
J J Kazmierczak K R Fox D G Addias J B Rose and J P Davis 1994 Massive WaterborneOutbreak of Cryptosporidium Infection Associated with a Filtered Public Water Supply MilwaukeeWisconsin March and April 1993 New England Journal of Medicine 331161ndash167
9 Anonymous 2010 Surveillance for Foodborne Disease OutbreaksmdashUnited States 2007 Morbidityand Mortality Weekly Reports 59973ndash979
10 Bean N H J S Goulding C Lau and F J Angulo 1996 Surveillance for Foodborne-DiseaseOutbreaksmdashUnited States 1988ndash1992 Morbidity and Mortality Weekly Reports 451ndash66
11 Wall P G J de Louvois R J Gilbert and B Rowe 1996 Food Poisoning NotificationsLaboratory Reports and OutbreaksmdashWhere do the Statistics Come From and What Do They MeanCommunicable Disease Report Review 6 R93ndashR100
12 Colford J M S Roy M J Beach A Hightower S E Shaw and T J Wade 2006 A Review ofHousehold Drinking Water Intervention Trials and an Approach to the Estimation of EndemicWaterborne Gastroenteritis in the United States Journal of Water and Health 471
13 Mead P S L Slutsker V Dietz L F McCaig J S Bresee C Shapiro P M Griffinand R V Tauxe 1999 Food Related Illness and Death in the United States Emerging InfectiousDisease 5607ndash625
14 Dziuban E J J L Liang G F Craun V Hill P A Yu J Painter M R Moore R L CalderonS L Roy and M J Beach 2006 Surveillance for Waterborne Disease and Outbreaks Associatedwith Recreational WatermdashUnited States 2003ndash2004 and Surveillance for Waterborne Disease andOutbreaks Associated with Drinking Water and Water not Intended for DrinkingmdashUnited States2003ndash2004 Morbidity and Mortality Weekly Reports 551ndash30
15 Fliermans C B 1996 Ecology of Legionella From Data to Knowledge with a Little WisdomMicrobial Ecology 32203ndash228
16 Li Y S Duan I T Yu and T W Wong 2005 Multi-Zone Modeling of Probable SARS VirusTransmission by Airflow Between Flats in Block E Amoy Gardens Indoor Air 1596ndash111
17 Peccia J D K Milton T Reponen and J Hill 2008 A Role for Environmental Engineering andScience in Preventing Bioaerosol-Related Disease Environmental Science amp Technology424631ndash4637
18 Jernigan D B P L Raghunathan B P Bell R Brechner E A Bresnitz J C Butler M CetronM Cohen T Doyle and M Fischer 2002 Investigation of Bioterrorism-Related AnthraxUnited States 2001 Epidemiologic Findings Emerging Infectious Diseases 81019ndash1028
19 Greenwood M and G U Yule 1917 On the Statistical Interpretation of Some BacteriologicalMethods Employed in Water Analysis Journal of Hygiene 1636ndash56
20 Phelps E 1909 The Disinfection of Sewage and Sewage Filter Effluents USGS Water Supply Paper229 GPO Washington DC
21 Rudolfs W and H W Gehm 1935 Multiplication of Total Bacteria and B coli after SewageChlorination Sewage Works Journal 7991ndash996
22 Subcommittee onMicrobiological Criteria 1985 An Evaluation of the Role ofMicrobiological Criteriafor Foods and Food Ingredients National Academy Press Washington DC
23 Cabelli V J A P Dufour L J McCabe and M A Levin 1982 Swimming-AssociatedGastroenteritis and Water Quality American Journal of Epidemiology 115606ndash616
24 Dufour A P 1984 Health Effects Criteria for Fresh Recreational Waters USEPA Research TrianglePark NC
25 Fleisher J M F Jones and D Kay 1993 Water and Non-Water-Related Risk Factors forGastroenteritis among Bathers Exposed to Sewage-Contaminated Marine Waters InternationalJournal of Epidemiology 22698ndash708
REFERENCES 11
26 Engelbrecht R S C N Haas J A Shular D L Dunn D Roy A Lalchandani B F Severin andS Farooq 1979 Acid-Fast Bacteria and Yeasts as Indicators of Disinfection Efficiency EPA-6002-79-091 US Environmental Protection Agency Cincinnati OH
27 Grabow W O K 1983 Inactivation of Hepatitis A Virus and Indicator Organisms in Water by FreeChlorine Residuals Applied and Environmental Microbiology 46619
28 Helmer R D and G R Finch 1993 Use of MS2 Coliphage as a Surrogate for Enteric Viruses inSurface Waters Disinfected with Ozone Ozone Science and Engineering 15279ndash293
29 Payment P and E Franco 1993Clostridium Perfringens and Somatic Coliphages as Indicators of theEfficiency of Drinking Water Treatment for Viruses and Protozoan Cysts Applied and EnvironmentalMicrobiology 592418ndash2424
30 Cabelli V J 1977Clostridium Perfringens as aWater Quality Indicator pp 65ndash79 InA Hoadley andB Dutka (eds) Bacterial IndicatorsHealth Hazards Associated with Water ASTM Philadelphia PA
31 Rice E W K R Fox R J Miltner D A Lytle and C H Johnson 1996 Evaluating PlantPerformance with Endospores Journal of the American Water Works Association 88122ndash130
32 Engelbrecht R S B F Severin M T Masarik S Farooq S H Lee C N Haas and A Lalchandani1977 New Microbial Indicators of Disinfection Efficiency EPA-6002-77-052 US EnvironmentalProtection Agency Cincinnati OH
33 Committee on Indicators for Waterborne Pathogens ndash National Research Council 2004 Indicators forWaterborne Pathogens National Academies Press Washington DC
34 PresidentialCongressional Commission on Risk Assessment and RiskManagement 1997 Frameworkfor Environmental Health Risk Management The Commission Washington DC
35 Griffin P M and R V Tauxe 1991 The Epidemiology of Infections Caused by Escherichiacoli O157H7 Other Enterohemorrhagic E coli and the Associated Hemolytic Uremic SyndromeEpidemiologic Reviews 1360ndash98
36 Heun E M R L Vogt P J Hudson S Parren and G W Gary 1987 Risk Factors for SecondaryTransmission in Households after a Common Source Outbreak of Norwalk Gastroenteritis AmericanJournal of Epidemiology 1261181ndash1186
37 MacKenzie W R W L Schell B A Blair D G Addiss D E Peterson N J HozieJ J Kazmierczak and J P Davis 1995 Massive Outbreak of Waterborne CryptosporidiumInfection in Milwaukee Wisconsin Recurrence of Illness and Risk of Secondary TransmissionClinical Infectious Diseases 2157ndash62
38 Millard P K Gensheimer D G Addiss D M Sosin G A Beckett A Houck-Jankoski andA Hudson 1994 An Outbreak of Cryptosporidiosis from Fresh-Pressed Apple Cider Journal ofthe American Medical Association 2721592ndash1596
39 Pickering L K D G Evans H L DuPont J J Vollet and D J Evans Jr 1981 Diarrhea Caused byShigella Rotavirus and Giardia in Day Care Centers Prospective Study Journal of Pediatrics9951ndash56
40 Morens D M R M Zweighaft T M Vernon G W Gary J J Eslien B T Wood R C Holmanand R Dolin 1979 A Waterborne Outbreak of Gastroenteritis with Secondary Person to PersonSpread Lancet 5964ndash966
41 Laursen E O Mygind B Rasmussen and T Ronne 1994 Gastroenteritis A Waterborne OutbreakAffecting 1600 People in a Small Danish Town Journal of Epidemiology amp Community Health48453ndash458
42 Baron R C F D Murphy H B Greenberg C E Davis D J Bregman G W Gary J M Hughesand L B Schonberger 1982 Norwalk Gastrointestinal Illness An Outbreak Associated withSwimming in a Recreational Lake and Secondary Person to Person Transmission American Journalof Epidemiology 115163ndash172
43 Kappus K D J S Marks R C Holman J K Bryant C Baker G W Gary and H B Greenberg1982 An Outbreak of Norwalk Gastroenteritis Associated with Swimming in a Pool and SecondaryPerson to Person Transmission American Journal of Epidemiology 116834ndash839
44 White K E M T Osterbolm J A Mariotti J A Korlath D H Lawrence T L Ristinen andH B Greenberg 1986 A Foodborne Outbreak of Norwalk Virus Gastroenteritis American Journalof Epidemiology 124120ndash126
45 Spika J S J E Parsons and D Nordenberg 1986 Hemolytic Uremic Syndrome and DiarrheaAssociated with Escherichia coli O157H7 in a Day Care Center Journal of Pediatrics 109287ndash291
12 CHAPTER 1 MOTIVATION
46 Ferguson J K L R Jorm C D Allen P KWhitehead and G L Gilbert 1995 Prospective Study ofDiarrhoeal Outbreaks in Child Long Daycare Centres in Western Sydney Medical Journal of Australia163137ndash140
47 Frost F J G F Craun and R L Calderon 1996 Waterborne Disease Surveillance Journal of theAmerican Water Works Association 8866ndash75
48 Farrington C P N J Andrews A D Beale and M A Catchpole 1996 A Statistical Algorithmfor the Early Detection of Outbreaks of Infectious Disease Journal of the Royal StatisticalSociety A 159547ndash563
REFERENCES 13
CHAPTER2MICROBIAL AGENTS ANDTRANSMISSION
MICROBIAL TAXONOMY
The development of techniques for examining the nucleic acids of microorganisms hasseen major changes in which we classify and group related microorganisms This isespecially true for the study of ribosomal ribonucleic acid (rRNA) which is a highlyconserved sequence involved in the synthesis of proteins in all living organisms Basedon this analysis the classification of living things has been placed into a three-domainsystem consisting of Archaea Eukarya and Bacteria Of these the Bacteria andArchaea are termed prokaryotes (no organized cell nucleus) and the Eukarya areknown as eukaryotes (an organized cell nucleus) Eukaryotic microbes other thanalgae and fungi are collectively calledprotistsWithin theEukarya are fungi protozoahelminth worms algae plants animals and humans Archaea are microbes that looksomewhat similar to bacteria in size and shape under the light microscope but they areactually genetically and biochemically quite different They appear to be a simpler formof life and may in fact be the oldest form of life on earth Viruses are obligate intercel-lular parasites and are not amember of any group They are usually composed only of anucleic acid surrounded by a protein coat Eukaryotes are much more complex thanprokaryotic cells in structure and nutritional requirements Prokaryotes divide by sim-ple binary fissionwhereas eukaryotes divide byamore complexprocess calledmitosis
Eukaryotes
Fungi protozoa and helminth worms are all eukaryotes All contain members that arepathogenic to man and animals While algae do not infect humans they can producetoxins that are harmful to animals and man Fungi obtain nutrients solely by adsorp-tion of organic matter from dead organisms Even when they invade living tissuesthey typically kill cells and then adsorb the nutrients from them Some fungi are capa-ble of developing environmentally resistant spores which can be transported throughthe air Fungal diseases in humans are referred to asmycoses Airborne fungal sporesare responsible for some allergies in humans Yeasts are classified with the fungi and
Quantitative Microbial Risk Assessment Second Edition Charles N Haas Joan B Roseand Charles P Gerbacopy 2014 John Wiley amp Sons Inc Published 2014 by John Wiley amp Sons Inc
15
some are pathogenic to humans (Candida albicans) Certain fungi produce toxins(ie aflatoxins) when growing in foods that are mutagenic and carcinogenic in ani-mals Inhalation is an important route of transmission for some fungal diseases suchas aspergillosis blastomycosis coccidioidomycosis and histoplasmosis These fungiare found growing in animal feces soil or decaying organic matter (compost manure)and may be transmitted through the air when this matter is disturbed Some fungi maybe transmitted by direct contact with the skin Fungi are often found in drinking waterdistribution systems and they have been linked to infections in immunocompromisedindividuals [1] Food is not believed to be a significant route of transmission ofpathogenic fungi
Protozoans are unicellular organisms that are surrounded by a cytoplasmicmembrane that is covered by a protective structure called a pellicle Most are freeliving feeding off of bacteria Some of these can cause disease while others are obli-gate parasites They are capable of forming structures called cysts oocysts or spores(depending on the life cycle of the organism) resistant to adverse environmentalconditions such as desiccation starvation high temperatures and disinfectantsSome pathogenic protozoa are found mainly in the soil (Naegleria) or water(Acanthamoeba) Others such a Giardia and Cryptosporidium whose natural habitatis the intestines of warm-blooded animals are capable of causing disease in bothhumans and animals Others such as Entamoeba histolytica are only capable ofcausing disease in humans
Pathogenic enteric (replicate in the intestines) protozoans are usually excretedin the feces or urine and can be transmitted by fecally contaminated food and waterSome protozoa may be transmitted through the air (Acanthamoeba) or throughfomites (inanimate objects) Some important environmentally transmitted protozoaare listed in Table 21 The clinically important protozoa are divided taxonomicallyinto the amoebas (Entamoeba spp) flagellates (Giardia) and coccidian meaningldquoglobose in shaperdquo (Cryptosporidium and Cyclospora) Microsporidia are alsocapable of causing intestinal infections but their classification is uncertain becausethey have many characteristics associated with fungi They are all obligate parasitesand are transmitted via infectious cysts oocysts or spores by the fecalndashoral routeThe life cycles of these protozoa are similar The initial stage occurs during ingestionof the cyst oocyst or spore After ingestion the body temperature and passagethrough the stomach cause these infective stages to open up in a process calledexcystation
The Giardia cysts house two trophozoites which is the stage that attaches tointestinal cells and grows in the intestinal tract through asexual reproduction As thetrophozoites grow and begin to cover the wall of the intestinal tract diarrhea canresult As the trophozoites are released some form cysts as they pass through thebowels Cryptosporidium and Cyclospora both produce oocysts The life cycle ofCyclospora is still not well known except that its oocysts require some period of timein the environment before they are infective Cryptosporidium oocysts contain foursporozoites which enter the intestinal cells and begin the infection process As morecells become infected the illness begins and oocysts are excreted in high numbers inthe feces (about 100000g)
Worms and helminths are small multicellular animals that are parasiticto humans and animals They include flukes tapeworms and roundworms
16 CHAPTER 2 MICROBIAL AGENTS AND TRANSMISSION
medical care stool samples may not be obtained from mild cases of illness Someorganisms may only be present sporadically or may be difficult to test in stool orblood sample Patients may not seek medical attention for mild cases of illness Fur-thermore in the United States in particular the surveillance of environmentallyinduced disease is done on a passive basis and hence the number of actual illnessclusters that are actually compiled into recorded statistics is only a small fractionof such clusters of illness that occur [47]
From a more fundamental point of view an outbreak of illness is generallydefined as occurrence of the illness at a level greater than normal or anticipated Thisdefinition recognizes that there is a level of illness (endemic) that may exist underusual circumstances The detection of such outbreaks poses a particular challengeThe problem is illustrated conceptually in Figure 13
Additional complications arise from the different patterns of illness in acommunity including definite periodicities as well as temporal trends and fromthe presence of reporting lags associated with laboratory analysis and time for patientsto seek medical attention Figure 14 illustrates the different patterns of illness inthe case of six pathogens for England and Wales [48]
In the case of waterborne and foodborne illnesses it is highly likely that thelevel of such endemic illnesses is substantially greater than those occurring duringoutbreaks (even accounting for unrecognized outbreaks)
As a result there are often many cases of environmentally caused (water airfood) infectious disease that are unrecognized One example of this isCampylobacterThere has been an average of about 200 cases per year of water- and foodborne illnessin outbreaks of this organism and yet estimates of the disease burden suggest about2100000 cases per year that is approximately 10000 cases per case of detectableoutbreak illness Therefore it will be important to assess the factors that may influenceoutbreak detection These issues will be discussed in subsequent chapters
Detectedoutbreak
Undetectedoutbreak
Threshold of detection
Hyper endemicSporadic
Endemic rate
Time
Num
ber
of c
ases
Figure 13 Schematic of disease occurrence in a hypothetical community (Modified fromRef [47])
OUTBREAKS VERSUS ENDEMIC CASES 9
REFERENCES
1 Levin B R 1996 The Evolution and Maintenance of Virulence in Microparasites Emerging InfectiousDisease 293ndash102
2 National Academy of Sciences 1983 Risk Assessment in the Federal Government Managing theProcess National Academy Press Washington DC
3 National Research Council 2009 Science and Decisions Advancing Risk Assessment NationalAcademies Press Washington DC
10090807060504030201001190 1191 1192 1193 1194 1195
(b)
140
120
100
80
60
40
20
01190 1191 1192 1193 1194 1195
(f)
700
600
500
400
300
200
100
01190 1191 1192 1193 1194 1195
(d)
1200
1000
800
600
400
200
1190 1191 1192 1193 1194 1195
(a)
240
200
160
120
80
40
01190 1191 1192 1193 1194 1195
(e)
7
6
5
4
3
2
1
01190 1191 1192 1193 1194 1195
(c)
Figure 14 Weekly count of reported organism isolations in England andWales (a) rotavirus(b) Clostridium difficile (c) Salmonella derby (d) Shigella sonnei (e) influenza B and (f)Salmonella typhimurium DT 104 (From Ref [48])
10 CHAPTER 1 MOTIVATION
4 Fogarty J L Thornton and R Corcoran 1995 Illness in a Community Associated with an Episode ofWater Contamination with Sewage Epidemiology and Infection 114289ndash295
5 Scallan E 2011 Foodborne Illness Acquired in the United StatesmdashUnspecified Agents EmergingInfectious Diseases 17 16ndash22
6 Craun G F J M Brunkard J S Yoder V A Roberts J Carpenter T Wade R L CalderonJ M Roberts M J Beach and S L Roy 2010 Causes of Outbreaks Associated with Drinking Waterin the United States from 1971 to 2006 Clinical Microbiology Reviews 23507ndash528
7 Edwards D D 1993 Troubled Waters in Milwaukee ASM News 59342ndash3458 MacKenzie W R N J Hoxie M E Proctor M S Gradus K A Blair D E Peterson
J J Kazmierczak K R Fox D G Addias J B Rose and J P Davis 1994 Massive WaterborneOutbreak of Cryptosporidium Infection Associated with a Filtered Public Water Supply MilwaukeeWisconsin March and April 1993 New England Journal of Medicine 331161ndash167
9 Anonymous 2010 Surveillance for Foodborne Disease OutbreaksmdashUnited States 2007 Morbidityand Mortality Weekly Reports 59973ndash979
10 Bean N H J S Goulding C Lau and F J Angulo 1996 Surveillance for Foodborne-DiseaseOutbreaksmdashUnited States 1988ndash1992 Morbidity and Mortality Weekly Reports 451ndash66
11 Wall P G J de Louvois R J Gilbert and B Rowe 1996 Food Poisoning NotificationsLaboratory Reports and OutbreaksmdashWhere do the Statistics Come From and What Do They MeanCommunicable Disease Report Review 6 R93ndashR100
12 Colford J M S Roy M J Beach A Hightower S E Shaw and T J Wade 2006 A Review ofHousehold Drinking Water Intervention Trials and an Approach to the Estimation of EndemicWaterborne Gastroenteritis in the United States Journal of Water and Health 471
13 Mead P S L Slutsker V Dietz L F McCaig J S Bresee C Shapiro P M Griffinand R V Tauxe 1999 Food Related Illness and Death in the United States Emerging InfectiousDisease 5607ndash625
14 Dziuban E J J L Liang G F Craun V Hill P A Yu J Painter M R Moore R L CalderonS L Roy and M J Beach 2006 Surveillance for Waterborne Disease and Outbreaks Associatedwith Recreational WatermdashUnited States 2003ndash2004 and Surveillance for Waterborne Disease andOutbreaks Associated with Drinking Water and Water not Intended for DrinkingmdashUnited States2003ndash2004 Morbidity and Mortality Weekly Reports 551ndash30
15 Fliermans C B 1996 Ecology of Legionella From Data to Knowledge with a Little WisdomMicrobial Ecology 32203ndash228
16 Li Y S Duan I T Yu and T W Wong 2005 Multi-Zone Modeling of Probable SARS VirusTransmission by Airflow Between Flats in Block E Amoy Gardens Indoor Air 1596ndash111
17 Peccia J D K Milton T Reponen and J Hill 2008 A Role for Environmental Engineering andScience in Preventing Bioaerosol-Related Disease Environmental Science amp Technology424631ndash4637
18 Jernigan D B P L Raghunathan B P Bell R Brechner E A Bresnitz J C Butler M CetronM Cohen T Doyle and M Fischer 2002 Investigation of Bioterrorism-Related AnthraxUnited States 2001 Epidemiologic Findings Emerging Infectious Diseases 81019ndash1028
19 Greenwood M and G U Yule 1917 On the Statistical Interpretation of Some BacteriologicalMethods Employed in Water Analysis Journal of Hygiene 1636ndash56
20 Phelps E 1909 The Disinfection of Sewage and Sewage Filter Effluents USGS Water Supply Paper229 GPO Washington DC
21 Rudolfs W and H W Gehm 1935 Multiplication of Total Bacteria and B coli after SewageChlorination Sewage Works Journal 7991ndash996
22 Subcommittee onMicrobiological Criteria 1985 An Evaluation of the Role ofMicrobiological Criteriafor Foods and Food Ingredients National Academy Press Washington DC
23 Cabelli V J A P Dufour L J McCabe and M A Levin 1982 Swimming-AssociatedGastroenteritis and Water Quality American Journal of Epidemiology 115606ndash616
24 Dufour A P 1984 Health Effects Criteria for Fresh Recreational Waters USEPA Research TrianglePark NC
25 Fleisher J M F Jones and D Kay 1993 Water and Non-Water-Related Risk Factors forGastroenteritis among Bathers Exposed to Sewage-Contaminated Marine Waters InternationalJournal of Epidemiology 22698ndash708
REFERENCES 11
26 Engelbrecht R S C N Haas J A Shular D L Dunn D Roy A Lalchandani B F Severin andS Farooq 1979 Acid-Fast Bacteria and Yeasts as Indicators of Disinfection Efficiency EPA-6002-79-091 US Environmental Protection Agency Cincinnati OH
27 Grabow W O K 1983 Inactivation of Hepatitis A Virus and Indicator Organisms in Water by FreeChlorine Residuals Applied and Environmental Microbiology 46619
28 Helmer R D and G R Finch 1993 Use of MS2 Coliphage as a Surrogate for Enteric Viruses inSurface Waters Disinfected with Ozone Ozone Science and Engineering 15279ndash293
29 Payment P and E Franco 1993Clostridium Perfringens and Somatic Coliphages as Indicators of theEfficiency of Drinking Water Treatment for Viruses and Protozoan Cysts Applied and EnvironmentalMicrobiology 592418ndash2424
30 Cabelli V J 1977Clostridium Perfringens as aWater Quality Indicator pp 65ndash79 InA Hoadley andB Dutka (eds) Bacterial IndicatorsHealth Hazards Associated with Water ASTM Philadelphia PA
31 Rice E W K R Fox R J Miltner D A Lytle and C H Johnson 1996 Evaluating PlantPerformance with Endospores Journal of the American Water Works Association 88122ndash130
32 Engelbrecht R S B F Severin M T Masarik S Farooq S H Lee C N Haas and A Lalchandani1977 New Microbial Indicators of Disinfection Efficiency EPA-6002-77-052 US EnvironmentalProtection Agency Cincinnati OH
33 Committee on Indicators for Waterborne Pathogens ndash National Research Council 2004 Indicators forWaterborne Pathogens National Academies Press Washington DC
34 PresidentialCongressional Commission on Risk Assessment and RiskManagement 1997 Frameworkfor Environmental Health Risk Management The Commission Washington DC
35 Griffin P M and R V Tauxe 1991 The Epidemiology of Infections Caused by Escherichiacoli O157H7 Other Enterohemorrhagic E coli and the Associated Hemolytic Uremic SyndromeEpidemiologic Reviews 1360ndash98
36 Heun E M R L Vogt P J Hudson S Parren and G W Gary 1987 Risk Factors for SecondaryTransmission in Households after a Common Source Outbreak of Norwalk Gastroenteritis AmericanJournal of Epidemiology 1261181ndash1186
37 MacKenzie W R W L Schell B A Blair D G Addiss D E Peterson N J HozieJ J Kazmierczak and J P Davis 1995 Massive Outbreak of Waterborne CryptosporidiumInfection in Milwaukee Wisconsin Recurrence of Illness and Risk of Secondary TransmissionClinical Infectious Diseases 2157ndash62
38 Millard P K Gensheimer D G Addiss D M Sosin G A Beckett A Houck-Jankoski andA Hudson 1994 An Outbreak of Cryptosporidiosis from Fresh-Pressed Apple Cider Journal ofthe American Medical Association 2721592ndash1596
39 Pickering L K D G Evans H L DuPont J J Vollet and D J Evans Jr 1981 Diarrhea Caused byShigella Rotavirus and Giardia in Day Care Centers Prospective Study Journal of Pediatrics9951ndash56
40 Morens D M R M Zweighaft T M Vernon G W Gary J J Eslien B T Wood R C Holmanand R Dolin 1979 A Waterborne Outbreak of Gastroenteritis with Secondary Person to PersonSpread Lancet 5964ndash966
41 Laursen E O Mygind B Rasmussen and T Ronne 1994 Gastroenteritis A Waterborne OutbreakAffecting 1600 People in a Small Danish Town Journal of Epidemiology amp Community Health48453ndash458
42 Baron R C F D Murphy H B Greenberg C E Davis D J Bregman G W Gary J M Hughesand L B Schonberger 1982 Norwalk Gastrointestinal Illness An Outbreak Associated withSwimming in a Recreational Lake and Secondary Person to Person Transmission American Journalof Epidemiology 115163ndash172
43 Kappus K D J S Marks R C Holman J K Bryant C Baker G W Gary and H B Greenberg1982 An Outbreak of Norwalk Gastroenteritis Associated with Swimming in a Pool and SecondaryPerson to Person Transmission American Journal of Epidemiology 116834ndash839
44 White K E M T Osterbolm J A Mariotti J A Korlath D H Lawrence T L Ristinen andH B Greenberg 1986 A Foodborne Outbreak of Norwalk Virus Gastroenteritis American Journalof Epidemiology 124120ndash126
45 Spika J S J E Parsons and D Nordenberg 1986 Hemolytic Uremic Syndrome and DiarrheaAssociated with Escherichia coli O157H7 in a Day Care Center Journal of Pediatrics 109287ndash291
12 CHAPTER 1 MOTIVATION
46 Ferguson J K L R Jorm C D Allen P KWhitehead and G L Gilbert 1995 Prospective Study ofDiarrhoeal Outbreaks in Child Long Daycare Centres in Western Sydney Medical Journal of Australia163137ndash140
47 Frost F J G F Craun and R L Calderon 1996 Waterborne Disease Surveillance Journal of theAmerican Water Works Association 8866ndash75
48 Farrington C P N J Andrews A D Beale and M A Catchpole 1996 A Statistical Algorithmfor the Early Detection of Outbreaks of Infectious Disease Journal of the Royal StatisticalSociety A 159547ndash563
REFERENCES 13
CHAPTER2MICROBIAL AGENTS ANDTRANSMISSION
MICROBIAL TAXONOMY
The development of techniques for examining the nucleic acids of microorganisms hasseen major changes in which we classify and group related microorganisms This isespecially true for the study of ribosomal ribonucleic acid (rRNA) which is a highlyconserved sequence involved in the synthesis of proteins in all living organisms Basedon this analysis the classification of living things has been placed into a three-domainsystem consisting of Archaea Eukarya and Bacteria Of these the Bacteria andArchaea are termed prokaryotes (no organized cell nucleus) and the Eukarya areknown as eukaryotes (an organized cell nucleus) Eukaryotic microbes other thanalgae and fungi are collectively calledprotistsWithin theEukarya are fungi protozoahelminth worms algae plants animals and humans Archaea are microbes that looksomewhat similar to bacteria in size and shape under the light microscope but they areactually genetically and biochemically quite different They appear to be a simpler formof life and may in fact be the oldest form of life on earth Viruses are obligate intercel-lular parasites and are not amember of any group They are usually composed only of anucleic acid surrounded by a protein coat Eukaryotes are much more complex thanprokaryotic cells in structure and nutritional requirements Prokaryotes divide by sim-ple binary fissionwhereas eukaryotes divide byamore complexprocess calledmitosis
Eukaryotes
Fungi protozoa and helminth worms are all eukaryotes All contain members that arepathogenic to man and animals While algae do not infect humans they can producetoxins that are harmful to animals and man Fungi obtain nutrients solely by adsorp-tion of organic matter from dead organisms Even when they invade living tissuesthey typically kill cells and then adsorb the nutrients from them Some fungi are capa-ble of developing environmentally resistant spores which can be transported throughthe air Fungal diseases in humans are referred to asmycoses Airborne fungal sporesare responsible for some allergies in humans Yeasts are classified with the fungi and
Quantitative Microbial Risk Assessment Second Edition Charles N Haas Joan B Roseand Charles P Gerbacopy 2014 John Wiley amp Sons Inc Published 2014 by John Wiley amp Sons Inc
15
some are pathogenic to humans (Candida albicans) Certain fungi produce toxins(ie aflatoxins) when growing in foods that are mutagenic and carcinogenic in ani-mals Inhalation is an important route of transmission for some fungal diseases suchas aspergillosis blastomycosis coccidioidomycosis and histoplasmosis These fungiare found growing in animal feces soil or decaying organic matter (compost manure)and may be transmitted through the air when this matter is disturbed Some fungi maybe transmitted by direct contact with the skin Fungi are often found in drinking waterdistribution systems and they have been linked to infections in immunocompromisedindividuals [1] Food is not believed to be a significant route of transmission ofpathogenic fungi
Protozoans are unicellular organisms that are surrounded by a cytoplasmicmembrane that is covered by a protective structure called a pellicle Most are freeliving feeding off of bacteria Some of these can cause disease while others are obli-gate parasites They are capable of forming structures called cysts oocysts or spores(depending on the life cycle of the organism) resistant to adverse environmentalconditions such as desiccation starvation high temperatures and disinfectantsSome pathogenic protozoa are found mainly in the soil (Naegleria) or water(Acanthamoeba) Others such a Giardia and Cryptosporidium whose natural habitatis the intestines of warm-blooded animals are capable of causing disease in bothhumans and animals Others such as Entamoeba histolytica are only capable ofcausing disease in humans
Pathogenic enteric (replicate in the intestines) protozoans are usually excretedin the feces or urine and can be transmitted by fecally contaminated food and waterSome protozoa may be transmitted through the air (Acanthamoeba) or throughfomites (inanimate objects) Some important environmentally transmitted protozoaare listed in Table 21 The clinically important protozoa are divided taxonomicallyinto the amoebas (Entamoeba spp) flagellates (Giardia) and coccidian meaningldquoglobose in shaperdquo (Cryptosporidium and Cyclospora) Microsporidia are alsocapable of causing intestinal infections but their classification is uncertain becausethey have many characteristics associated with fungi They are all obligate parasitesand are transmitted via infectious cysts oocysts or spores by the fecalndashoral routeThe life cycles of these protozoa are similar The initial stage occurs during ingestionof the cyst oocyst or spore After ingestion the body temperature and passagethrough the stomach cause these infective stages to open up in a process calledexcystation
The Giardia cysts house two trophozoites which is the stage that attaches tointestinal cells and grows in the intestinal tract through asexual reproduction As thetrophozoites grow and begin to cover the wall of the intestinal tract diarrhea canresult As the trophozoites are released some form cysts as they pass through thebowels Cryptosporidium and Cyclospora both produce oocysts The life cycle ofCyclospora is still not well known except that its oocysts require some period of timein the environment before they are infective Cryptosporidium oocysts contain foursporozoites which enter the intestinal cells and begin the infection process As morecells become infected the illness begins and oocysts are excreted in high numbers inthe feces (about 100000g)
Worms and helminths are small multicellular animals that are parasiticto humans and animals They include flukes tapeworms and roundworms
16 CHAPTER 2 MICROBIAL AGENTS AND TRANSMISSION
REFERENCES
1 Levin B R 1996 The Evolution and Maintenance of Virulence in Microparasites Emerging InfectiousDisease 293ndash102
2 National Academy of Sciences 1983 Risk Assessment in the Federal Government Managing theProcess National Academy Press Washington DC
3 National Research Council 2009 Science and Decisions Advancing Risk Assessment NationalAcademies Press Washington DC
10090807060504030201001190 1191 1192 1193 1194 1195
(b)
140
120
100
80
60
40
20
01190 1191 1192 1193 1194 1195
(f)
700
600
500
400
300
200
100
01190 1191 1192 1193 1194 1195
(d)
1200
1000
800
600
400
200
1190 1191 1192 1193 1194 1195
(a)
240
200
160
120
80
40
01190 1191 1192 1193 1194 1195
(e)
7
6
5
4
3
2
1
01190 1191 1192 1193 1194 1195
(c)
Figure 14 Weekly count of reported organism isolations in England andWales (a) rotavirus(b) Clostridium difficile (c) Salmonella derby (d) Shigella sonnei (e) influenza B and (f)Salmonella typhimurium DT 104 (From Ref [48])
10 CHAPTER 1 MOTIVATION
4 Fogarty J L Thornton and R Corcoran 1995 Illness in a Community Associated with an Episode ofWater Contamination with Sewage Epidemiology and Infection 114289ndash295
5 Scallan E 2011 Foodborne Illness Acquired in the United StatesmdashUnspecified Agents EmergingInfectious Diseases 17 16ndash22
6 Craun G F J M Brunkard J S Yoder V A Roberts J Carpenter T Wade R L CalderonJ M Roberts M J Beach and S L Roy 2010 Causes of Outbreaks Associated with Drinking Waterin the United States from 1971 to 2006 Clinical Microbiology Reviews 23507ndash528
7 Edwards D D 1993 Troubled Waters in Milwaukee ASM News 59342ndash3458 MacKenzie W R N J Hoxie M E Proctor M S Gradus K A Blair D E Peterson
J J Kazmierczak K R Fox D G Addias J B Rose and J P Davis 1994 Massive WaterborneOutbreak of Cryptosporidium Infection Associated with a Filtered Public Water Supply MilwaukeeWisconsin March and April 1993 New England Journal of Medicine 331161ndash167
9 Anonymous 2010 Surveillance for Foodborne Disease OutbreaksmdashUnited States 2007 Morbidityand Mortality Weekly Reports 59973ndash979
10 Bean N H J S Goulding C Lau and F J Angulo 1996 Surveillance for Foodborne-DiseaseOutbreaksmdashUnited States 1988ndash1992 Morbidity and Mortality Weekly Reports 451ndash66
11 Wall P G J de Louvois R J Gilbert and B Rowe 1996 Food Poisoning NotificationsLaboratory Reports and OutbreaksmdashWhere do the Statistics Come From and What Do They MeanCommunicable Disease Report Review 6 R93ndashR100
12 Colford J M S Roy M J Beach A Hightower S E Shaw and T J Wade 2006 A Review ofHousehold Drinking Water Intervention Trials and an Approach to the Estimation of EndemicWaterborne Gastroenteritis in the United States Journal of Water and Health 471
13 Mead P S L Slutsker V Dietz L F McCaig J S Bresee C Shapiro P M Griffinand R V Tauxe 1999 Food Related Illness and Death in the United States Emerging InfectiousDisease 5607ndash625
14 Dziuban E J J L Liang G F Craun V Hill P A Yu J Painter M R Moore R L CalderonS L Roy and M J Beach 2006 Surveillance for Waterborne Disease and Outbreaks Associatedwith Recreational WatermdashUnited States 2003ndash2004 and Surveillance for Waterborne Disease andOutbreaks Associated with Drinking Water and Water not Intended for DrinkingmdashUnited States2003ndash2004 Morbidity and Mortality Weekly Reports 551ndash30
15 Fliermans C B 1996 Ecology of Legionella From Data to Knowledge with a Little WisdomMicrobial Ecology 32203ndash228
16 Li Y S Duan I T Yu and T W Wong 2005 Multi-Zone Modeling of Probable SARS VirusTransmission by Airflow Between Flats in Block E Amoy Gardens Indoor Air 1596ndash111
17 Peccia J D K Milton T Reponen and J Hill 2008 A Role for Environmental Engineering andScience in Preventing Bioaerosol-Related Disease Environmental Science amp Technology424631ndash4637
18 Jernigan D B P L Raghunathan B P Bell R Brechner E A Bresnitz J C Butler M CetronM Cohen T Doyle and M Fischer 2002 Investigation of Bioterrorism-Related AnthraxUnited States 2001 Epidemiologic Findings Emerging Infectious Diseases 81019ndash1028
19 Greenwood M and G U Yule 1917 On the Statistical Interpretation of Some BacteriologicalMethods Employed in Water Analysis Journal of Hygiene 1636ndash56
20 Phelps E 1909 The Disinfection of Sewage and Sewage Filter Effluents USGS Water Supply Paper229 GPO Washington DC
21 Rudolfs W and H W Gehm 1935 Multiplication of Total Bacteria and B coli after SewageChlorination Sewage Works Journal 7991ndash996
22 Subcommittee onMicrobiological Criteria 1985 An Evaluation of the Role ofMicrobiological Criteriafor Foods and Food Ingredients National Academy Press Washington DC
23 Cabelli V J A P Dufour L J McCabe and M A Levin 1982 Swimming-AssociatedGastroenteritis and Water Quality American Journal of Epidemiology 115606ndash616
24 Dufour A P 1984 Health Effects Criteria for Fresh Recreational Waters USEPA Research TrianglePark NC
25 Fleisher J M F Jones and D Kay 1993 Water and Non-Water-Related Risk Factors forGastroenteritis among Bathers Exposed to Sewage-Contaminated Marine Waters InternationalJournal of Epidemiology 22698ndash708
REFERENCES 11
26 Engelbrecht R S C N Haas J A Shular D L Dunn D Roy A Lalchandani B F Severin andS Farooq 1979 Acid-Fast Bacteria and Yeasts as Indicators of Disinfection Efficiency EPA-6002-79-091 US Environmental Protection Agency Cincinnati OH
27 Grabow W O K 1983 Inactivation of Hepatitis A Virus and Indicator Organisms in Water by FreeChlorine Residuals Applied and Environmental Microbiology 46619
28 Helmer R D and G R Finch 1993 Use of MS2 Coliphage as a Surrogate for Enteric Viruses inSurface Waters Disinfected with Ozone Ozone Science and Engineering 15279ndash293
29 Payment P and E Franco 1993Clostridium Perfringens and Somatic Coliphages as Indicators of theEfficiency of Drinking Water Treatment for Viruses and Protozoan Cysts Applied and EnvironmentalMicrobiology 592418ndash2424
30 Cabelli V J 1977Clostridium Perfringens as aWater Quality Indicator pp 65ndash79 InA Hoadley andB Dutka (eds) Bacterial IndicatorsHealth Hazards Associated with Water ASTM Philadelphia PA
31 Rice E W K R Fox R J Miltner D A Lytle and C H Johnson 1996 Evaluating PlantPerformance with Endospores Journal of the American Water Works Association 88122ndash130
32 Engelbrecht R S B F Severin M T Masarik S Farooq S H Lee C N Haas and A Lalchandani1977 New Microbial Indicators of Disinfection Efficiency EPA-6002-77-052 US EnvironmentalProtection Agency Cincinnati OH
33 Committee on Indicators for Waterborne Pathogens ndash National Research Council 2004 Indicators forWaterborne Pathogens National Academies Press Washington DC
34 PresidentialCongressional Commission on Risk Assessment and RiskManagement 1997 Frameworkfor Environmental Health Risk Management The Commission Washington DC
35 Griffin P M and R V Tauxe 1991 The Epidemiology of Infections Caused by Escherichiacoli O157H7 Other Enterohemorrhagic E coli and the Associated Hemolytic Uremic SyndromeEpidemiologic Reviews 1360ndash98
36 Heun E M R L Vogt P J Hudson S Parren and G W Gary 1987 Risk Factors for SecondaryTransmission in Households after a Common Source Outbreak of Norwalk Gastroenteritis AmericanJournal of Epidemiology 1261181ndash1186
37 MacKenzie W R W L Schell B A Blair D G Addiss D E Peterson N J HozieJ J Kazmierczak and J P Davis 1995 Massive Outbreak of Waterborne CryptosporidiumInfection in Milwaukee Wisconsin Recurrence of Illness and Risk of Secondary TransmissionClinical Infectious Diseases 2157ndash62
38 Millard P K Gensheimer D G Addiss D M Sosin G A Beckett A Houck-Jankoski andA Hudson 1994 An Outbreak of Cryptosporidiosis from Fresh-Pressed Apple Cider Journal ofthe American Medical Association 2721592ndash1596
39 Pickering L K D G Evans H L DuPont J J Vollet and D J Evans Jr 1981 Diarrhea Caused byShigella Rotavirus and Giardia in Day Care Centers Prospective Study Journal of Pediatrics9951ndash56
40 Morens D M R M Zweighaft T M Vernon G W Gary J J Eslien B T Wood R C Holmanand R Dolin 1979 A Waterborne Outbreak of Gastroenteritis with Secondary Person to PersonSpread Lancet 5964ndash966
41 Laursen E O Mygind B Rasmussen and T Ronne 1994 Gastroenteritis A Waterborne OutbreakAffecting 1600 People in a Small Danish Town Journal of Epidemiology amp Community Health48453ndash458
42 Baron R C F D Murphy H B Greenberg C E Davis D J Bregman G W Gary J M Hughesand L B Schonberger 1982 Norwalk Gastrointestinal Illness An Outbreak Associated withSwimming in a Recreational Lake and Secondary Person to Person Transmission American Journalof Epidemiology 115163ndash172
43 Kappus K D J S Marks R C Holman J K Bryant C Baker G W Gary and H B Greenberg1982 An Outbreak of Norwalk Gastroenteritis Associated with Swimming in a Pool and SecondaryPerson to Person Transmission American Journal of Epidemiology 116834ndash839
44 White K E M T Osterbolm J A Mariotti J A Korlath D H Lawrence T L Ristinen andH B Greenberg 1986 A Foodborne Outbreak of Norwalk Virus Gastroenteritis American Journalof Epidemiology 124120ndash126
45 Spika J S J E Parsons and D Nordenberg 1986 Hemolytic Uremic Syndrome and DiarrheaAssociated with Escherichia coli O157H7 in a Day Care Center Journal of Pediatrics 109287ndash291
12 CHAPTER 1 MOTIVATION
46 Ferguson J K L R Jorm C D Allen P KWhitehead and G L Gilbert 1995 Prospective Study ofDiarrhoeal Outbreaks in Child Long Daycare Centres in Western Sydney Medical Journal of Australia163137ndash140
47 Frost F J G F Craun and R L Calderon 1996 Waterborne Disease Surveillance Journal of theAmerican Water Works Association 8866ndash75
48 Farrington C P N J Andrews A D Beale and M A Catchpole 1996 A Statistical Algorithmfor the Early Detection of Outbreaks of Infectious Disease Journal of the Royal StatisticalSociety A 159547ndash563
REFERENCES 13
CHAPTER2MICROBIAL AGENTS ANDTRANSMISSION
MICROBIAL TAXONOMY
The development of techniques for examining the nucleic acids of microorganisms hasseen major changes in which we classify and group related microorganisms This isespecially true for the study of ribosomal ribonucleic acid (rRNA) which is a highlyconserved sequence involved in the synthesis of proteins in all living organisms Basedon this analysis the classification of living things has been placed into a three-domainsystem consisting of Archaea Eukarya and Bacteria Of these the Bacteria andArchaea are termed prokaryotes (no organized cell nucleus) and the Eukarya areknown as eukaryotes (an organized cell nucleus) Eukaryotic microbes other thanalgae and fungi are collectively calledprotistsWithin theEukarya are fungi protozoahelminth worms algae plants animals and humans Archaea are microbes that looksomewhat similar to bacteria in size and shape under the light microscope but they areactually genetically and biochemically quite different They appear to be a simpler formof life and may in fact be the oldest form of life on earth Viruses are obligate intercel-lular parasites and are not amember of any group They are usually composed only of anucleic acid surrounded by a protein coat Eukaryotes are much more complex thanprokaryotic cells in structure and nutritional requirements Prokaryotes divide by sim-ple binary fissionwhereas eukaryotes divide byamore complexprocess calledmitosis
Eukaryotes
Fungi protozoa and helminth worms are all eukaryotes All contain members that arepathogenic to man and animals While algae do not infect humans they can producetoxins that are harmful to animals and man Fungi obtain nutrients solely by adsorp-tion of organic matter from dead organisms Even when they invade living tissuesthey typically kill cells and then adsorb the nutrients from them Some fungi are capa-ble of developing environmentally resistant spores which can be transported throughthe air Fungal diseases in humans are referred to asmycoses Airborne fungal sporesare responsible for some allergies in humans Yeasts are classified with the fungi and
Quantitative Microbial Risk Assessment Second Edition Charles N Haas Joan B Roseand Charles P Gerbacopy 2014 John Wiley amp Sons Inc Published 2014 by John Wiley amp Sons Inc
15
some are pathogenic to humans (Candida albicans) Certain fungi produce toxins(ie aflatoxins) when growing in foods that are mutagenic and carcinogenic in ani-mals Inhalation is an important route of transmission for some fungal diseases suchas aspergillosis blastomycosis coccidioidomycosis and histoplasmosis These fungiare found growing in animal feces soil or decaying organic matter (compost manure)and may be transmitted through the air when this matter is disturbed Some fungi maybe transmitted by direct contact with the skin Fungi are often found in drinking waterdistribution systems and they have been linked to infections in immunocompromisedindividuals [1] Food is not believed to be a significant route of transmission ofpathogenic fungi
Protozoans are unicellular organisms that are surrounded by a cytoplasmicmembrane that is covered by a protective structure called a pellicle Most are freeliving feeding off of bacteria Some of these can cause disease while others are obli-gate parasites They are capable of forming structures called cysts oocysts or spores(depending on the life cycle of the organism) resistant to adverse environmentalconditions such as desiccation starvation high temperatures and disinfectantsSome pathogenic protozoa are found mainly in the soil (Naegleria) or water(Acanthamoeba) Others such a Giardia and Cryptosporidium whose natural habitatis the intestines of warm-blooded animals are capable of causing disease in bothhumans and animals Others such as Entamoeba histolytica are only capable ofcausing disease in humans
Pathogenic enteric (replicate in the intestines) protozoans are usually excretedin the feces or urine and can be transmitted by fecally contaminated food and waterSome protozoa may be transmitted through the air (Acanthamoeba) or throughfomites (inanimate objects) Some important environmentally transmitted protozoaare listed in Table 21 The clinically important protozoa are divided taxonomicallyinto the amoebas (Entamoeba spp) flagellates (Giardia) and coccidian meaningldquoglobose in shaperdquo (Cryptosporidium and Cyclospora) Microsporidia are alsocapable of causing intestinal infections but their classification is uncertain becausethey have many characteristics associated with fungi They are all obligate parasitesand are transmitted via infectious cysts oocysts or spores by the fecalndashoral routeThe life cycles of these protozoa are similar The initial stage occurs during ingestionof the cyst oocyst or spore After ingestion the body temperature and passagethrough the stomach cause these infective stages to open up in a process calledexcystation
The Giardia cysts house two trophozoites which is the stage that attaches tointestinal cells and grows in the intestinal tract through asexual reproduction As thetrophozoites grow and begin to cover the wall of the intestinal tract diarrhea canresult As the trophozoites are released some form cysts as they pass through thebowels Cryptosporidium and Cyclospora both produce oocysts The life cycle ofCyclospora is still not well known except that its oocysts require some period of timein the environment before they are infective Cryptosporidium oocysts contain foursporozoites which enter the intestinal cells and begin the infection process As morecells become infected the illness begins and oocysts are excreted in high numbers inthe feces (about 100000g)
Worms and helminths are small multicellular animals that are parasiticto humans and animals They include flukes tapeworms and roundworms
16 CHAPTER 2 MICROBIAL AGENTS AND TRANSMISSION
4 Fogarty J L Thornton and R Corcoran 1995 Illness in a Community Associated with an Episode ofWater Contamination with Sewage Epidemiology and Infection 114289ndash295
5 Scallan E 2011 Foodborne Illness Acquired in the United StatesmdashUnspecified Agents EmergingInfectious Diseases 17 16ndash22
6 Craun G F J M Brunkard J S Yoder V A Roberts J Carpenter T Wade R L CalderonJ M Roberts M J Beach and S L Roy 2010 Causes of Outbreaks Associated with Drinking Waterin the United States from 1971 to 2006 Clinical Microbiology Reviews 23507ndash528
7 Edwards D D 1993 Troubled Waters in Milwaukee ASM News 59342ndash3458 MacKenzie W R N J Hoxie M E Proctor M S Gradus K A Blair D E Peterson
J J Kazmierczak K R Fox D G Addias J B Rose and J P Davis 1994 Massive WaterborneOutbreak of Cryptosporidium Infection Associated with a Filtered Public Water Supply MilwaukeeWisconsin March and April 1993 New England Journal of Medicine 331161ndash167
9 Anonymous 2010 Surveillance for Foodborne Disease OutbreaksmdashUnited States 2007 Morbidityand Mortality Weekly Reports 59973ndash979
10 Bean N H J S Goulding C Lau and F J Angulo 1996 Surveillance for Foodborne-DiseaseOutbreaksmdashUnited States 1988ndash1992 Morbidity and Mortality Weekly Reports 451ndash66
11 Wall P G J de Louvois R J Gilbert and B Rowe 1996 Food Poisoning NotificationsLaboratory Reports and OutbreaksmdashWhere do the Statistics Come From and What Do They MeanCommunicable Disease Report Review 6 R93ndashR100
12 Colford J M S Roy M J Beach A Hightower S E Shaw and T J Wade 2006 A Review ofHousehold Drinking Water Intervention Trials and an Approach to the Estimation of EndemicWaterborne Gastroenteritis in the United States Journal of Water and Health 471
13 Mead P S L Slutsker V Dietz L F McCaig J S Bresee C Shapiro P M Griffinand R V Tauxe 1999 Food Related Illness and Death in the United States Emerging InfectiousDisease 5607ndash625
14 Dziuban E J J L Liang G F Craun V Hill P A Yu J Painter M R Moore R L CalderonS L Roy and M J Beach 2006 Surveillance for Waterborne Disease and Outbreaks Associatedwith Recreational WatermdashUnited States 2003ndash2004 and Surveillance for Waterborne Disease andOutbreaks Associated with Drinking Water and Water not Intended for DrinkingmdashUnited States2003ndash2004 Morbidity and Mortality Weekly Reports 551ndash30
15 Fliermans C B 1996 Ecology of Legionella From Data to Knowledge with a Little WisdomMicrobial Ecology 32203ndash228
16 Li Y S Duan I T Yu and T W Wong 2005 Multi-Zone Modeling of Probable SARS VirusTransmission by Airflow Between Flats in Block E Amoy Gardens Indoor Air 1596ndash111
17 Peccia J D K Milton T Reponen and J Hill 2008 A Role for Environmental Engineering andScience in Preventing Bioaerosol-Related Disease Environmental Science amp Technology424631ndash4637
18 Jernigan D B P L Raghunathan B P Bell R Brechner E A Bresnitz J C Butler M CetronM Cohen T Doyle and M Fischer 2002 Investigation of Bioterrorism-Related AnthraxUnited States 2001 Epidemiologic Findings Emerging Infectious Diseases 81019ndash1028
19 Greenwood M and G U Yule 1917 On the Statistical Interpretation of Some BacteriologicalMethods Employed in Water Analysis Journal of Hygiene 1636ndash56
20 Phelps E 1909 The Disinfection of Sewage and Sewage Filter Effluents USGS Water Supply Paper229 GPO Washington DC
21 Rudolfs W and H W Gehm 1935 Multiplication of Total Bacteria and B coli after SewageChlorination Sewage Works Journal 7991ndash996
22 Subcommittee onMicrobiological Criteria 1985 An Evaluation of the Role ofMicrobiological Criteriafor Foods and Food Ingredients National Academy Press Washington DC
23 Cabelli V J A P Dufour L J McCabe and M A Levin 1982 Swimming-AssociatedGastroenteritis and Water Quality American Journal of Epidemiology 115606ndash616
24 Dufour A P 1984 Health Effects Criteria for Fresh Recreational Waters USEPA Research TrianglePark NC
25 Fleisher J M F Jones and D Kay 1993 Water and Non-Water-Related Risk Factors forGastroenteritis among Bathers Exposed to Sewage-Contaminated Marine Waters InternationalJournal of Epidemiology 22698ndash708
REFERENCES 11
26 Engelbrecht R S C N Haas J A Shular D L Dunn D Roy A Lalchandani B F Severin andS Farooq 1979 Acid-Fast Bacteria and Yeasts as Indicators of Disinfection Efficiency EPA-6002-79-091 US Environmental Protection Agency Cincinnati OH
27 Grabow W O K 1983 Inactivation of Hepatitis A Virus and Indicator Organisms in Water by FreeChlorine Residuals Applied and Environmental Microbiology 46619
28 Helmer R D and G R Finch 1993 Use of MS2 Coliphage as a Surrogate for Enteric Viruses inSurface Waters Disinfected with Ozone Ozone Science and Engineering 15279ndash293
29 Payment P and E Franco 1993Clostridium Perfringens and Somatic Coliphages as Indicators of theEfficiency of Drinking Water Treatment for Viruses and Protozoan Cysts Applied and EnvironmentalMicrobiology 592418ndash2424
30 Cabelli V J 1977Clostridium Perfringens as aWater Quality Indicator pp 65ndash79 InA Hoadley andB Dutka (eds) Bacterial IndicatorsHealth Hazards Associated with Water ASTM Philadelphia PA
31 Rice E W K R Fox R J Miltner D A Lytle and C H Johnson 1996 Evaluating PlantPerformance with Endospores Journal of the American Water Works Association 88122ndash130
32 Engelbrecht R S B F Severin M T Masarik S Farooq S H Lee C N Haas and A Lalchandani1977 New Microbial Indicators of Disinfection Efficiency EPA-6002-77-052 US EnvironmentalProtection Agency Cincinnati OH
33 Committee on Indicators for Waterborne Pathogens ndash National Research Council 2004 Indicators forWaterborne Pathogens National Academies Press Washington DC
34 PresidentialCongressional Commission on Risk Assessment and RiskManagement 1997 Frameworkfor Environmental Health Risk Management The Commission Washington DC
35 Griffin P M and R V Tauxe 1991 The Epidemiology of Infections Caused by Escherichiacoli O157H7 Other Enterohemorrhagic E coli and the Associated Hemolytic Uremic SyndromeEpidemiologic Reviews 1360ndash98
36 Heun E M R L Vogt P J Hudson S Parren and G W Gary 1987 Risk Factors for SecondaryTransmission in Households after a Common Source Outbreak of Norwalk Gastroenteritis AmericanJournal of Epidemiology 1261181ndash1186
37 MacKenzie W R W L Schell B A Blair D G Addiss D E Peterson N J HozieJ J Kazmierczak and J P Davis 1995 Massive Outbreak of Waterborne CryptosporidiumInfection in Milwaukee Wisconsin Recurrence of Illness and Risk of Secondary TransmissionClinical Infectious Diseases 2157ndash62
38 Millard P K Gensheimer D G Addiss D M Sosin G A Beckett A Houck-Jankoski andA Hudson 1994 An Outbreak of Cryptosporidiosis from Fresh-Pressed Apple Cider Journal ofthe American Medical Association 2721592ndash1596
39 Pickering L K D G Evans H L DuPont J J Vollet and D J Evans Jr 1981 Diarrhea Caused byShigella Rotavirus and Giardia in Day Care Centers Prospective Study Journal of Pediatrics9951ndash56
40 Morens D M R M Zweighaft T M Vernon G W Gary J J Eslien B T Wood R C Holmanand R Dolin 1979 A Waterborne Outbreak of Gastroenteritis with Secondary Person to PersonSpread Lancet 5964ndash966
41 Laursen E O Mygind B Rasmussen and T Ronne 1994 Gastroenteritis A Waterborne OutbreakAffecting 1600 People in a Small Danish Town Journal of Epidemiology amp Community Health48453ndash458
42 Baron R C F D Murphy H B Greenberg C E Davis D J Bregman G W Gary J M Hughesand L B Schonberger 1982 Norwalk Gastrointestinal Illness An Outbreak Associated withSwimming in a Recreational Lake and Secondary Person to Person Transmission American Journalof Epidemiology 115163ndash172
43 Kappus K D J S Marks R C Holman J K Bryant C Baker G W Gary and H B Greenberg1982 An Outbreak of Norwalk Gastroenteritis Associated with Swimming in a Pool and SecondaryPerson to Person Transmission American Journal of Epidemiology 116834ndash839
44 White K E M T Osterbolm J A Mariotti J A Korlath D H Lawrence T L Ristinen andH B Greenberg 1986 A Foodborne Outbreak of Norwalk Virus Gastroenteritis American Journalof Epidemiology 124120ndash126
45 Spika J S J E Parsons and D Nordenberg 1986 Hemolytic Uremic Syndrome and DiarrheaAssociated with Escherichia coli O157H7 in a Day Care Center Journal of Pediatrics 109287ndash291
12 CHAPTER 1 MOTIVATION
46 Ferguson J K L R Jorm C D Allen P KWhitehead and G L Gilbert 1995 Prospective Study ofDiarrhoeal Outbreaks in Child Long Daycare Centres in Western Sydney Medical Journal of Australia163137ndash140
47 Frost F J G F Craun and R L Calderon 1996 Waterborne Disease Surveillance Journal of theAmerican Water Works Association 8866ndash75
48 Farrington C P N J Andrews A D Beale and M A Catchpole 1996 A Statistical Algorithmfor the Early Detection of Outbreaks of Infectious Disease Journal of the Royal StatisticalSociety A 159547ndash563
REFERENCES 13
CHAPTER2MICROBIAL AGENTS ANDTRANSMISSION
MICROBIAL TAXONOMY
The development of techniques for examining the nucleic acids of microorganisms hasseen major changes in which we classify and group related microorganisms This isespecially true for the study of ribosomal ribonucleic acid (rRNA) which is a highlyconserved sequence involved in the synthesis of proteins in all living organisms Basedon this analysis the classification of living things has been placed into a three-domainsystem consisting of Archaea Eukarya and Bacteria Of these the Bacteria andArchaea are termed prokaryotes (no organized cell nucleus) and the Eukarya areknown as eukaryotes (an organized cell nucleus) Eukaryotic microbes other thanalgae and fungi are collectively calledprotistsWithin theEukarya are fungi protozoahelminth worms algae plants animals and humans Archaea are microbes that looksomewhat similar to bacteria in size and shape under the light microscope but they areactually genetically and biochemically quite different They appear to be a simpler formof life and may in fact be the oldest form of life on earth Viruses are obligate intercel-lular parasites and are not amember of any group They are usually composed only of anucleic acid surrounded by a protein coat Eukaryotes are much more complex thanprokaryotic cells in structure and nutritional requirements Prokaryotes divide by sim-ple binary fissionwhereas eukaryotes divide byamore complexprocess calledmitosis
Eukaryotes
Fungi protozoa and helminth worms are all eukaryotes All contain members that arepathogenic to man and animals While algae do not infect humans they can producetoxins that are harmful to animals and man Fungi obtain nutrients solely by adsorp-tion of organic matter from dead organisms Even when they invade living tissuesthey typically kill cells and then adsorb the nutrients from them Some fungi are capa-ble of developing environmentally resistant spores which can be transported throughthe air Fungal diseases in humans are referred to asmycoses Airborne fungal sporesare responsible for some allergies in humans Yeasts are classified with the fungi and
Quantitative Microbial Risk Assessment Second Edition Charles N Haas Joan B Roseand Charles P Gerbacopy 2014 John Wiley amp Sons Inc Published 2014 by John Wiley amp Sons Inc
15
some are pathogenic to humans (Candida albicans) Certain fungi produce toxins(ie aflatoxins) when growing in foods that are mutagenic and carcinogenic in ani-mals Inhalation is an important route of transmission for some fungal diseases suchas aspergillosis blastomycosis coccidioidomycosis and histoplasmosis These fungiare found growing in animal feces soil or decaying organic matter (compost manure)and may be transmitted through the air when this matter is disturbed Some fungi maybe transmitted by direct contact with the skin Fungi are often found in drinking waterdistribution systems and they have been linked to infections in immunocompromisedindividuals [1] Food is not believed to be a significant route of transmission ofpathogenic fungi
Protozoans are unicellular organisms that are surrounded by a cytoplasmicmembrane that is covered by a protective structure called a pellicle Most are freeliving feeding off of bacteria Some of these can cause disease while others are obli-gate parasites They are capable of forming structures called cysts oocysts or spores(depending on the life cycle of the organism) resistant to adverse environmentalconditions such as desiccation starvation high temperatures and disinfectantsSome pathogenic protozoa are found mainly in the soil (Naegleria) or water(Acanthamoeba) Others such a Giardia and Cryptosporidium whose natural habitatis the intestines of warm-blooded animals are capable of causing disease in bothhumans and animals Others such as Entamoeba histolytica are only capable ofcausing disease in humans
Pathogenic enteric (replicate in the intestines) protozoans are usually excretedin the feces or urine and can be transmitted by fecally contaminated food and waterSome protozoa may be transmitted through the air (Acanthamoeba) or throughfomites (inanimate objects) Some important environmentally transmitted protozoaare listed in Table 21 The clinically important protozoa are divided taxonomicallyinto the amoebas (Entamoeba spp) flagellates (Giardia) and coccidian meaningldquoglobose in shaperdquo (Cryptosporidium and Cyclospora) Microsporidia are alsocapable of causing intestinal infections but their classification is uncertain becausethey have many characteristics associated with fungi They are all obligate parasitesand are transmitted via infectious cysts oocysts or spores by the fecalndashoral routeThe life cycles of these protozoa are similar The initial stage occurs during ingestionof the cyst oocyst or spore After ingestion the body temperature and passagethrough the stomach cause these infective stages to open up in a process calledexcystation
The Giardia cysts house two trophozoites which is the stage that attaches tointestinal cells and grows in the intestinal tract through asexual reproduction As thetrophozoites grow and begin to cover the wall of the intestinal tract diarrhea canresult As the trophozoites are released some form cysts as they pass through thebowels Cryptosporidium and Cyclospora both produce oocysts The life cycle ofCyclospora is still not well known except that its oocysts require some period of timein the environment before they are infective Cryptosporidium oocysts contain foursporozoites which enter the intestinal cells and begin the infection process As morecells become infected the illness begins and oocysts are excreted in high numbers inthe feces (about 100000g)
Worms and helminths are small multicellular animals that are parasiticto humans and animals They include flukes tapeworms and roundworms
16 CHAPTER 2 MICROBIAL AGENTS AND TRANSMISSION
26 Engelbrecht R S C N Haas J A Shular D L Dunn D Roy A Lalchandani B F Severin andS Farooq 1979 Acid-Fast Bacteria and Yeasts as Indicators of Disinfection Efficiency EPA-6002-79-091 US Environmental Protection Agency Cincinnati OH
27 Grabow W O K 1983 Inactivation of Hepatitis A Virus and Indicator Organisms in Water by FreeChlorine Residuals Applied and Environmental Microbiology 46619
28 Helmer R D and G R Finch 1993 Use of MS2 Coliphage as a Surrogate for Enteric Viruses inSurface Waters Disinfected with Ozone Ozone Science and Engineering 15279ndash293
29 Payment P and E Franco 1993Clostridium Perfringens and Somatic Coliphages as Indicators of theEfficiency of Drinking Water Treatment for Viruses and Protozoan Cysts Applied and EnvironmentalMicrobiology 592418ndash2424
30 Cabelli V J 1977Clostridium Perfringens as aWater Quality Indicator pp 65ndash79 InA Hoadley andB Dutka (eds) Bacterial IndicatorsHealth Hazards Associated with Water ASTM Philadelphia PA
31 Rice E W K R Fox R J Miltner D A Lytle and C H Johnson 1996 Evaluating PlantPerformance with Endospores Journal of the American Water Works Association 88122ndash130
32 Engelbrecht R S B F Severin M T Masarik S Farooq S H Lee C N Haas and A Lalchandani1977 New Microbial Indicators of Disinfection Efficiency EPA-6002-77-052 US EnvironmentalProtection Agency Cincinnati OH
33 Committee on Indicators for Waterborne Pathogens ndash National Research Council 2004 Indicators forWaterborne Pathogens National Academies Press Washington DC
34 PresidentialCongressional Commission on Risk Assessment and RiskManagement 1997 Frameworkfor Environmental Health Risk Management The Commission Washington DC
35 Griffin P M and R V Tauxe 1991 The Epidemiology of Infections Caused by Escherichiacoli O157H7 Other Enterohemorrhagic E coli and the Associated Hemolytic Uremic SyndromeEpidemiologic Reviews 1360ndash98
36 Heun E M R L Vogt P J Hudson S Parren and G W Gary 1987 Risk Factors for SecondaryTransmission in Households after a Common Source Outbreak of Norwalk Gastroenteritis AmericanJournal of Epidemiology 1261181ndash1186
37 MacKenzie W R W L Schell B A Blair D G Addiss D E Peterson N J HozieJ J Kazmierczak and J P Davis 1995 Massive Outbreak of Waterborne CryptosporidiumInfection in Milwaukee Wisconsin Recurrence of Illness and Risk of Secondary TransmissionClinical Infectious Diseases 2157ndash62
38 Millard P K Gensheimer D G Addiss D M Sosin G A Beckett A Houck-Jankoski andA Hudson 1994 An Outbreak of Cryptosporidiosis from Fresh-Pressed Apple Cider Journal ofthe American Medical Association 2721592ndash1596
39 Pickering L K D G Evans H L DuPont J J Vollet and D J Evans Jr 1981 Diarrhea Caused byShigella Rotavirus and Giardia in Day Care Centers Prospective Study Journal of Pediatrics9951ndash56
40 Morens D M R M Zweighaft T M Vernon G W Gary J J Eslien B T Wood R C Holmanand R Dolin 1979 A Waterborne Outbreak of Gastroenteritis with Secondary Person to PersonSpread Lancet 5964ndash966
41 Laursen E O Mygind B Rasmussen and T Ronne 1994 Gastroenteritis A Waterborne OutbreakAffecting 1600 People in a Small Danish Town Journal of Epidemiology amp Community Health48453ndash458
42 Baron R C F D Murphy H B Greenberg C E Davis D J Bregman G W Gary J M Hughesand L B Schonberger 1982 Norwalk Gastrointestinal Illness An Outbreak Associated withSwimming in a Recreational Lake and Secondary Person to Person Transmission American Journalof Epidemiology 115163ndash172
43 Kappus K D J S Marks R C Holman J K Bryant C Baker G W Gary and H B Greenberg1982 An Outbreak of Norwalk Gastroenteritis Associated with Swimming in a Pool and SecondaryPerson to Person Transmission American Journal of Epidemiology 116834ndash839
44 White K E M T Osterbolm J A Mariotti J A Korlath D H Lawrence T L Ristinen andH B Greenberg 1986 A Foodborne Outbreak of Norwalk Virus Gastroenteritis American Journalof Epidemiology 124120ndash126
45 Spika J S J E Parsons and D Nordenberg 1986 Hemolytic Uremic Syndrome and DiarrheaAssociated with Escherichia coli O157H7 in a Day Care Center Journal of Pediatrics 109287ndash291
12 CHAPTER 1 MOTIVATION
46 Ferguson J K L R Jorm C D Allen P KWhitehead and G L Gilbert 1995 Prospective Study ofDiarrhoeal Outbreaks in Child Long Daycare Centres in Western Sydney Medical Journal of Australia163137ndash140
47 Frost F J G F Craun and R L Calderon 1996 Waterborne Disease Surveillance Journal of theAmerican Water Works Association 8866ndash75
48 Farrington C P N J Andrews A D Beale and M A Catchpole 1996 A Statistical Algorithmfor the Early Detection of Outbreaks of Infectious Disease Journal of the Royal StatisticalSociety A 159547ndash563
REFERENCES 13
CHAPTER2MICROBIAL AGENTS ANDTRANSMISSION
MICROBIAL TAXONOMY
The development of techniques for examining the nucleic acids of microorganisms hasseen major changes in which we classify and group related microorganisms This isespecially true for the study of ribosomal ribonucleic acid (rRNA) which is a highlyconserved sequence involved in the synthesis of proteins in all living organisms Basedon this analysis the classification of living things has been placed into a three-domainsystem consisting of Archaea Eukarya and Bacteria Of these the Bacteria andArchaea are termed prokaryotes (no organized cell nucleus) and the Eukarya areknown as eukaryotes (an organized cell nucleus) Eukaryotic microbes other thanalgae and fungi are collectively calledprotistsWithin theEukarya are fungi protozoahelminth worms algae plants animals and humans Archaea are microbes that looksomewhat similar to bacteria in size and shape under the light microscope but they areactually genetically and biochemically quite different They appear to be a simpler formof life and may in fact be the oldest form of life on earth Viruses are obligate intercel-lular parasites and are not amember of any group They are usually composed only of anucleic acid surrounded by a protein coat Eukaryotes are much more complex thanprokaryotic cells in structure and nutritional requirements Prokaryotes divide by sim-ple binary fissionwhereas eukaryotes divide byamore complexprocess calledmitosis
Eukaryotes
Fungi protozoa and helminth worms are all eukaryotes All contain members that arepathogenic to man and animals While algae do not infect humans they can producetoxins that are harmful to animals and man Fungi obtain nutrients solely by adsorp-tion of organic matter from dead organisms Even when they invade living tissuesthey typically kill cells and then adsorb the nutrients from them Some fungi are capa-ble of developing environmentally resistant spores which can be transported throughthe air Fungal diseases in humans are referred to asmycoses Airborne fungal sporesare responsible for some allergies in humans Yeasts are classified with the fungi and
Quantitative Microbial Risk Assessment Second Edition Charles N Haas Joan B Roseand Charles P Gerbacopy 2014 John Wiley amp Sons Inc Published 2014 by John Wiley amp Sons Inc
15
some are pathogenic to humans (Candida albicans) Certain fungi produce toxins(ie aflatoxins) when growing in foods that are mutagenic and carcinogenic in ani-mals Inhalation is an important route of transmission for some fungal diseases suchas aspergillosis blastomycosis coccidioidomycosis and histoplasmosis These fungiare found growing in animal feces soil or decaying organic matter (compost manure)and may be transmitted through the air when this matter is disturbed Some fungi maybe transmitted by direct contact with the skin Fungi are often found in drinking waterdistribution systems and they have been linked to infections in immunocompromisedindividuals [1] Food is not believed to be a significant route of transmission ofpathogenic fungi
Protozoans are unicellular organisms that are surrounded by a cytoplasmicmembrane that is covered by a protective structure called a pellicle Most are freeliving feeding off of bacteria Some of these can cause disease while others are obli-gate parasites They are capable of forming structures called cysts oocysts or spores(depending on the life cycle of the organism) resistant to adverse environmentalconditions such as desiccation starvation high temperatures and disinfectantsSome pathogenic protozoa are found mainly in the soil (Naegleria) or water(Acanthamoeba) Others such a Giardia and Cryptosporidium whose natural habitatis the intestines of warm-blooded animals are capable of causing disease in bothhumans and animals Others such as Entamoeba histolytica are only capable ofcausing disease in humans
Pathogenic enteric (replicate in the intestines) protozoans are usually excretedin the feces or urine and can be transmitted by fecally contaminated food and waterSome protozoa may be transmitted through the air (Acanthamoeba) or throughfomites (inanimate objects) Some important environmentally transmitted protozoaare listed in Table 21 The clinically important protozoa are divided taxonomicallyinto the amoebas (Entamoeba spp) flagellates (Giardia) and coccidian meaningldquoglobose in shaperdquo (Cryptosporidium and Cyclospora) Microsporidia are alsocapable of causing intestinal infections but their classification is uncertain becausethey have many characteristics associated with fungi They are all obligate parasitesand are transmitted via infectious cysts oocysts or spores by the fecalndashoral routeThe life cycles of these protozoa are similar The initial stage occurs during ingestionof the cyst oocyst or spore After ingestion the body temperature and passagethrough the stomach cause these infective stages to open up in a process calledexcystation
The Giardia cysts house two trophozoites which is the stage that attaches tointestinal cells and grows in the intestinal tract through asexual reproduction As thetrophozoites grow and begin to cover the wall of the intestinal tract diarrhea canresult As the trophozoites are released some form cysts as they pass through thebowels Cryptosporidium and Cyclospora both produce oocysts The life cycle ofCyclospora is still not well known except that its oocysts require some period of timein the environment before they are infective Cryptosporidium oocysts contain foursporozoites which enter the intestinal cells and begin the infection process As morecells become infected the illness begins and oocysts are excreted in high numbers inthe feces (about 100000g)
Worms and helminths are small multicellular animals that are parasiticto humans and animals They include flukes tapeworms and roundworms
16 CHAPTER 2 MICROBIAL AGENTS AND TRANSMISSION
46 Ferguson J K L R Jorm C D Allen P KWhitehead and G L Gilbert 1995 Prospective Study ofDiarrhoeal Outbreaks in Child Long Daycare Centres in Western Sydney Medical Journal of Australia163137ndash140
47 Frost F J G F Craun and R L Calderon 1996 Waterborne Disease Surveillance Journal of theAmerican Water Works Association 8866ndash75
48 Farrington C P N J Andrews A D Beale and M A Catchpole 1996 A Statistical Algorithmfor the Early Detection of Outbreaks of Infectious Disease Journal of the Royal StatisticalSociety A 159547ndash563
REFERENCES 13
CHAPTER2MICROBIAL AGENTS ANDTRANSMISSION
MICROBIAL TAXONOMY
The development of techniques for examining the nucleic acids of microorganisms hasseen major changes in which we classify and group related microorganisms This isespecially true for the study of ribosomal ribonucleic acid (rRNA) which is a highlyconserved sequence involved in the synthesis of proteins in all living organisms Basedon this analysis the classification of living things has been placed into a three-domainsystem consisting of Archaea Eukarya and Bacteria Of these the Bacteria andArchaea are termed prokaryotes (no organized cell nucleus) and the Eukarya areknown as eukaryotes (an organized cell nucleus) Eukaryotic microbes other thanalgae and fungi are collectively calledprotistsWithin theEukarya are fungi protozoahelminth worms algae plants animals and humans Archaea are microbes that looksomewhat similar to bacteria in size and shape under the light microscope but they areactually genetically and biochemically quite different They appear to be a simpler formof life and may in fact be the oldest form of life on earth Viruses are obligate intercel-lular parasites and are not amember of any group They are usually composed only of anucleic acid surrounded by a protein coat Eukaryotes are much more complex thanprokaryotic cells in structure and nutritional requirements Prokaryotes divide by sim-ple binary fissionwhereas eukaryotes divide byamore complexprocess calledmitosis
Eukaryotes
Fungi protozoa and helminth worms are all eukaryotes All contain members that arepathogenic to man and animals While algae do not infect humans they can producetoxins that are harmful to animals and man Fungi obtain nutrients solely by adsorp-tion of organic matter from dead organisms Even when they invade living tissuesthey typically kill cells and then adsorb the nutrients from them Some fungi are capa-ble of developing environmentally resistant spores which can be transported throughthe air Fungal diseases in humans are referred to asmycoses Airborne fungal sporesare responsible for some allergies in humans Yeasts are classified with the fungi and
Quantitative Microbial Risk Assessment Second Edition Charles N Haas Joan B Roseand Charles P Gerbacopy 2014 John Wiley amp Sons Inc Published 2014 by John Wiley amp Sons Inc
15
some are pathogenic to humans (Candida albicans) Certain fungi produce toxins(ie aflatoxins) when growing in foods that are mutagenic and carcinogenic in ani-mals Inhalation is an important route of transmission for some fungal diseases suchas aspergillosis blastomycosis coccidioidomycosis and histoplasmosis These fungiare found growing in animal feces soil or decaying organic matter (compost manure)and may be transmitted through the air when this matter is disturbed Some fungi maybe transmitted by direct contact with the skin Fungi are often found in drinking waterdistribution systems and they have been linked to infections in immunocompromisedindividuals [1] Food is not believed to be a significant route of transmission ofpathogenic fungi
Protozoans are unicellular organisms that are surrounded by a cytoplasmicmembrane that is covered by a protective structure called a pellicle Most are freeliving feeding off of bacteria Some of these can cause disease while others are obli-gate parasites They are capable of forming structures called cysts oocysts or spores(depending on the life cycle of the organism) resistant to adverse environmentalconditions such as desiccation starvation high temperatures and disinfectantsSome pathogenic protozoa are found mainly in the soil (Naegleria) or water(Acanthamoeba) Others such a Giardia and Cryptosporidium whose natural habitatis the intestines of warm-blooded animals are capable of causing disease in bothhumans and animals Others such as Entamoeba histolytica are only capable ofcausing disease in humans
Pathogenic enteric (replicate in the intestines) protozoans are usually excretedin the feces or urine and can be transmitted by fecally contaminated food and waterSome protozoa may be transmitted through the air (Acanthamoeba) or throughfomites (inanimate objects) Some important environmentally transmitted protozoaare listed in Table 21 The clinically important protozoa are divided taxonomicallyinto the amoebas (Entamoeba spp) flagellates (Giardia) and coccidian meaningldquoglobose in shaperdquo (Cryptosporidium and Cyclospora) Microsporidia are alsocapable of causing intestinal infections but their classification is uncertain becausethey have many characteristics associated with fungi They are all obligate parasitesand are transmitted via infectious cysts oocysts or spores by the fecalndashoral routeThe life cycles of these protozoa are similar The initial stage occurs during ingestionof the cyst oocyst or spore After ingestion the body temperature and passagethrough the stomach cause these infective stages to open up in a process calledexcystation
The Giardia cysts house two trophozoites which is the stage that attaches tointestinal cells and grows in the intestinal tract through asexual reproduction As thetrophozoites grow and begin to cover the wall of the intestinal tract diarrhea canresult As the trophozoites are released some form cysts as they pass through thebowels Cryptosporidium and Cyclospora both produce oocysts The life cycle ofCyclospora is still not well known except that its oocysts require some period of timein the environment before they are infective Cryptosporidium oocysts contain foursporozoites which enter the intestinal cells and begin the infection process As morecells become infected the illness begins and oocysts are excreted in high numbers inthe feces (about 100000g)
Worms and helminths are small multicellular animals that are parasiticto humans and animals They include flukes tapeworms and roundworms
16 CHAPTER 2 MICROBIAL AGENTS AND TRANSMISSION
CHAPTER2MICROBIAL AGENTS ANDTRANSMISSION
MICROBIAL TAXONOMY
The development of techniques for examining the nucleic acids of microorganisms hasseen major changes in which we classify and group related microorganisms This isespecially true for the study of ribosomal ribonucleic acid (rRNA) which is a highlyconserved sequence involved in the synthesis of proteins in all living organisms Basedon this analysis the classification of living things has been placed into a three-domainsystem consisting of Archaea Eukarya and Bacteria Of these the Bacteria andArchaea are termed prokaryotes (no organized cell nucleus) and the Eukarya areknown as eukaryotes (an organized cell nucleus) Eukaryotic microbes other thanalgae and fungi are collectively calledprotistsWithin theEukarya are fungi protozoahelminth worms algae plants animals and humans Archaea are microbes that looksomewhat similar to bacteria in size and shape under the light microscope but they areactually genetically and biochemically quite different They appear to be a simpler formof life and may in fact be the oldest form of life on earth Viruses are obligate intercel-lular parasites and are not amember of any group They are usually composed only of anucleic acid surrounded by a protein coat Eukaryotes are much more complex thanprokaryotic cells in structure and nutritional requirements Prokaryotes divide by sim-ple binary fissionwhereas eukaryotes divide byamore complexprocess calledmitosis
Eukaryotes
Fungi protozoa and helminth worms are all eukaryotes All contain members that arepathogenic to man and animals While algae do not infect humans they can producetoxins that are harmful to animals and man Fungi obtain nutrients solely by adsorp-tion of organic matter from dead organisms Even when they invade living tissuesthey typically kill cells and then adsorb the nutrients from them Some fungi are capa-ble of developing environmentally resistant spores which can be transported throughthe air Fungal diseases in humans are referred to asmycoses Airborne fungal sporesare responsible for some allergies in humans Yeasts are classified with the fungi and
Quantitative Microbial Risk Assessment Second Edition Charles N Haas Joan B Roseand Charles P Gerbacopy 2014 John Wiley amp Sons Inc Published 2014 by John Wiley amp Sons Inc
15
some are pathogenic to humans (Candida albicans) Certain fungi produce toxins(ie aflatoxins) when growing in foods that are mutagenic and carcinogenic in ani-mals Inhalation is an important route of transmission for some fungal diseases suchas aspergillosis blastomycosis coccidioidomycosis and histoplasmosis These fungiare found growing in animal feces soil or decaying organic matter (compost manure)and may be transmitted through the air when this matter is disturbed Some fungi maybe transmitted by direct contact with the skin Fungi are often found in drinking waterdistribution systems and they have been linked to infections in immunocompromisedindividuals [1] Food is not believed to be a significant route of transmission ofpathogenic fungi
Protozoans are unicellular organisms that are surrounded by a cytoplasmicmembrane that is covered by a protective structure called a pellicle Most are freeliving feeding off of bacteria Some of these can cause disease while others are obli-gate parasites They are capable of forming structures called cysts oocysts or spores(depending on the life cycle of the organism) resistant to adverse environmentalconditions such as desiccation starvation high temperatures and disinfectantsSome pathogenic protozoa are found mainly in the soil (Naegleria) or water(Acanthamoeba) Others such a Giardia and Cryptosporidium whose natural habitatis the intestines of warm-blooded animals are capable of causing disease in bothhumans and animals Others such as Entamoeba histolytica are only capable ofcausing disease in humans
Pathogenic enteric (replicate in the intestines) protozoans are usually excretedin the feces or urine and can be transmitted by fecally contaminated food and waterSome protozoa may be transmitted through the air (Acanthamoeba) or throughfomites (inanimate objects) Some important environmentally transmitted protozoaare listed in Table 21 The clinically important protozoa are divided taxonomicallyinto the amoebas (Entamoeba spp) flagellates (Giardia) and coccidian meaningldquoglobose in shaperdquo (Cryptosporidium and Cyclospora) Microsporidia are alsocapable of causing intestinal infections but their classification is uncertain becausethey have many characteristics associated with fungi They are all obligate parasitesand are transmitted via infectious cysts oocysts or spores by the fecalndashoral routeThe life cycles of these protozoa are similar The initial stage occurs during ingestionof the cyst oocyst or spore After ingestion the body temperature and passagethrough the stomach cause these infective stages to open up in a process calledexcystation
The Giardia cysts house two trophozoites which is the stage that attaches tointestinal cells and grows in the intestinal tract through asexual reproduction As thetrophozoites grow and begin to cover the wall of the intestinal tract diarrhea canresult As the trophozoites are released some form cysts as they pass through thebowels Cryptosporidium and Cyclospora both produce oocysts The life cycle ofCyclospora is still not well known except that its oocysts require some period of timein the environment before they are infective Cryptosporidium oocysts contain foursporozoites which enter the intestinal cells and begin the infection process As morecells become infected the illness begins and oocysts are excreted in high numbers inthe feces (about 100000g)
Worms and helminths are small multicellular animals that are parasiticto humans and animals They include flukes tapeworms and roundworms
16 CHAPTER 2 MICROBIAL AGENTS AND TRANSMISSION
some are pathogenic to humans (Candida albicans) Certain fungi produce toxins(ie aflatoxins) when growing in foods that are mutagenic and carcinogenic in ani-mals Inhalation is an important route of transmission for some fungal diseases suchas aspergillosis blastomycosis coccidioidomycosis and histoplasmosis These fungiare found growing in animal feces soil or decaying organic matter (compost manure)and may be transmitted through the air when this matter is disturbed Some fungi maybe transmitted by direct contact with the skin Fungi are often found in drinking waterdistribution systems and they have been linked to infections in immunocompromisedindividuals [1] Food is not believed to be a significant route of transmission ofpathogenic fungi
Protozoans are unicellular organisms that are surrounded by a cytoplasmicmembrane that is covered by a protective structure called a pellicle Most are freeliving feeding off of bacteria Some of these can cause disease while others are obli-gate parasites They are capable of forming structures called cysts oocysts or spores(depending on the life cycle of the organism) resistant to adverse environmentalconditions such as desiccation starvation high temperatures and disinfectantsSome pathogenic protozoa are found mainly in the soil (Naegleria) or water(Acanthamoeba) Others such a Giardia and Cryptosporidium whose natural habitatis the intestines of warm-blooded animals are capable of causing disease in bothhumans and animals Others such as Entamoeba histolytica are only capable ofcausing disease in humans
Pathogenic enteric (replicate in the intestines) protozoans are usually excretedin the feces or urine and can be transmitted by fecally contaminated food and waterSome protozoa may be transmitted through the air (Acanthamoeba) or throughfomites (inanimate objects) Some important environmentally transmitted protozoaare listed in Table 21 The clinically important protozoa are divided taxonomicallyinto the amoebas (Entamoeba spp) flagellates (Giardia) and coccidian meaningldquoglobose in shaperdquo (Cryptosporidium and Cyclospora) Microsporidia are alsocapable of causing intestinal infections but their classification is uncertain becausethey have many characteristics associated with fungi They are all obligate parasitesand are transmitted via infectious cysts oocysts or spores by the fecalndashoral routeThe life cycles of these protozoa are similar The initial stage occurs during ingestionof the cyst oocyst or spore After ingestion the body temperature and passagethrough the stomach cause these infective stages to open up in a process calledexcystation
The Giardia cysts house two trophozoites which is the stage that attaches tointestinal cells and grows in the intestinal tract through asexual reproduction As thetrophozoites grow and begin to cover the wall of the intestinal tract diarrhea canresult As the trophozoites are released some form cysts as they pass through thebowels Cryptosporidium and Cyclospora both produce oocysts The life cycle ofCyclospora is still not well known except that its oocysts require some period of timein the environment before they are infective Cryptosporidium oocysts contain foursporozoites which enter the intestinal cells and begin the infection process As morecells become infected the illness begins and oocysts are excreted in high numbers inthe feces (about 100000g)
Worms and helminths are small multicellular animals that are parasiticto humans and animals They include flukes tapeworms and roundworms
16 CHAPTER 2 MICROBIAL AGENTS AND TRANSMISSION