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Brian S. Murphy, MD, MPHNovember 5, 200840th Annual Family Medicine Review 

ObjectivesObjectives

Discuss epidemiological trends in food‐borne illillnesses

Identify and discuss common infectious organisms for food‐borne illnesses and their disease presentation

Discuss basic management and outbreak control methods for food‐borne illnesses

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76 million illnesses

325,000 hospitalizations

5,000 deaths

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Case Case PresentationPresentation

83 y/o nursing home patient 1 week history of diarrhea with blood C/o Fever, shaking chills and abdominal pain Admitted with probable ischemic colitis Admission fever 1020F Initial labs show serum creatinine of 9, 

l l f 0 000 d i h lplatelet count of 50,000, and peripheral smear shows RBC fragments

What is the differential diagnosis?

Emergence of Emergence of FoodFood‐‐borne Pathogensborne Pathogens

Botulism Norwalk-like viruses Arcobacter

1975-19951900

Brucellosis

Cholera

Hepatitis

Scarlet fever (streptococcus)

Staphylococcal food poisoning

Campylobacter jenjuni

Salmonella Enteritidis

Shiga toxin-producing E. coli O157:H7, O111:NM, O104:H21

Listeria monocytogenes

Clostridium botulinum

butzleri

Hepatitis E

Cryptosporidium parvum

Giardia lamblia

Cyclospora cayetanensispoisoning

Tuberculosis

Typhoid fever

Clostridium botulinum(infant)

Vibrio cholerae 0139

Vibrio vulnificus

Yersinia enterocolitica

cayetanensis

Toxoplasma gondii

BSE prion

Nitzchia pungens (dinoflagellate)

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Most Most Common Causes Common Causes of of FoodFood‐‐borne borne Illness, 1999Illness, 1999

Norwalk-like virusNorwalk-like virus

CampylobacterCampylobacter

SalmonellaSalmonella

C. perfringensC. perfringens

0000 2,000,0002,000,0002,000,0002,000,000 4,000,0004,000,0004,000,0004,000,000 6,000,0006,000,0006,000,0006,000,000 8,000,0008,000,0008,000,0008,000,000 10,000,00010,000,00010,000,00010,000,000

GiardiaGiardia

S. aureusS. aureus

E.coli 0157:H7 Salmonella enteriditis Listeria monocytogenes Campylobacter jejuni Campylobacter jejuni

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DysenteryDysentery

Salmonella spp.pp Shigella Campylobacter Enteroinvasive and enterohemorrhagic E coli Aeromonas spp. Some noncholera vibrios Some noncholera vibrios Amebiasis 

Deaths Deaths Due Due to to FoodFood‐‐borne Illnessesborne Illnesses

Salmonella

Listeria

Other

31.0%28.0%

21.0% 5.0%

ToxoplasmosisNorwalk-like

CampylobacterE. coli 0157

7.0%

5.0%

3.0%

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Foodborne Disease by Incubation PeriodFoodborne Disease by Incubation Period

< 2hrs—Chemical agentg

MSG, neurotoxin

2‐7 hrs—Preformed toxin

S. aureus, B. cereus

8‐14 hrs—C. perfringens, high‐dose bacterial pathogenpathogen

> 14 hrs—Most bacterial or viral pathogens

Seafood Seafood Neurotoxin FoodNeurotoxin Food‐‐borne Diseaseborne Disease

Parlaytic shellfish

Toxin from dinoflagellates in mollusks

N. England & W. Coast

Ciguatera

Toxin from DF in large fish

Florida, Hawaii

h llf h Neurotoxic Shellfish

Toxin from DF inhaled during algal blooms (Red Tide)

Pufferfish

Toxin from DF in pufferfish (Japan)

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CaseCase——A A Fish AttackFish Attack

A patient develops numbness of lips, burning and tingling of his extremities and vomiting 30 minutes after a meal in Jamaica. Progresses to respiratory failure. What’s the dx?

Ciguatera

Paralytic shellfish poisoning

Scombroid

Neurotoxic shellfish poisoning

MSG toxicity

CaseCase——Another Another Fish AttackFish Attack

10 minutes after eating a fish buffet of tuna, bonito and mahi‐mahi, two adult brothers become ill

They become flushed with a HA, dizziness, nausea, abdominal pain, diarrhea and vomiting

One develops uritcaria and mouth burning

They are well in 12 hoursS b id▪ Scombroid

▪ Ciguatera

▪ MSG toxicity

▪ Mushroom poisoning

▪ Hysteria

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Food Food PoisoningPoisoning——IntoxicationIntoxication(Incubation 2(Incubation 2‐‐14 hours)14 hours)

S. aureus Incubation period 2‐7 hours

Cytokines and interferon induce vomiting

Detection of organism or toxin in food Clostridium perfringens Incubation period 8‐14 hours

Vomiting unusual; watery diarrhea mostlyg ; y y

Detection of toxin in stool specimens Bacillus cereus 2 forms (1 like S. aureus and 1 like C. perfringens)

Detection of organism or toxin in food

ShigatoxinShigatoxin‐‐producing producing E. coliE. coli (EHEC)(EHEC)

70K cases/yr in the US Low dose pathogen 85% of cases are from food

Bloody diarrhea Fever absent or minimal60% i US O157 H7 60% in US O157:H7

HUS risk <15 &>65 Fatal hemorrhagic colitis in elderly

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Screening for Screening for E. coli E. coli O157:H7O157:H7

Requires McConkeybit l disorbitol medium

Only done in 55% of hospitals

95% of E. coli O157 cases come from patients with bloody diarrhea

Slide agglutinatin with latex reagents

Serology may be helpful early

Reported Reported Cases Cases of of E. coli E. coli O157:H7, 1997O157:H7, 1997

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Antibiotics for HUS?Antibiotics for HUS?

Some antibiotics predispose to HUS TMP/SMX

Quinolones

Beta lactams Others do not Azithromycin

Rifaximin

Antiperistaltic agents increase the risk of systemic complications after EHEC infections

Enterotoxigenic Enterotoxigenic E. coliE. coli (ETEC)(ETEC)

Most common cause of traveler’s diarrhea Estimated causes over 650 million cases of

diarrhea worldwide and 380K deaths in children < 5 y/o

16%-70% of diarrheal cases in travelers Often acquired by ingesting fecally Often acquired by ingesting fecally

contaminated water (including ice cubes) Higher incidence in warmer months than

colder months

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Risk for Risk for Traveler’s DiarrheaTraveler’s Diarrhea

Low

Medium

Highg

ETECETEC

Symptoms usually begin 3‐14 days after ingestion of the organism

Watery (not bloody diarrhea)

Abdominal crampsO i ll d Occasionally nausea and vomiting

No leukocytes on stool exam

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ETEC treatmentETEC treatment

Usually self‐limited (1‐5 days)y ( y ) Can be reduced by antimicrobial therapy at the onset of sx

Increasing incidence of resistance to ampicillin, bactrim, and tetracycline

Fluoroquinolone x 3 days for adults Bactrim x 3 days for children

Other Other Causes Causes of of Traveler’s DiarrheaTraveler’s Diarrhea

In Latin America and Africa diarrheagenicgE. coli predominates ETEC 20-40%

EAEC 19-33% In S. Asia

Shi ll C l b t S l ll 15 25% Shigella, Campylobacter, Salmonella 15-25% Worldwide Noroviruses 17%

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EnteroaggregativeEnteroaggregative E. coli E. coli (EAEC)(EAEC)

Major cause of persistent diarrhea in children j pin tropics, travelers’ diarrhea and patients with AIDS‐associated chronic diarrhea

Recently appreciated as cause of acute pediatric diarrhea in US

Intestinal (HEP 2) cells attachment and Intestinal (HEP‐2) cells attachment and damage

ProtozoaProtozoa——Other Other Causes Causes of of Persistent Persistent DiarrheaDiarrhea

Giardia—first exposure symptomatic E. histolytica—reduced hygiene, liver abscess, highest in males

Cryptosporidium—animal reservoir, water vehicle of transmission

Cyclospora—Nepal, Haiti, Peru, Guatemalan b i l l i iraspberries, seasonal sporulation time 

influences epidemiology

Each will respond to antimicrobial therapy

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Effective Effective Antibacterial Drugs Antibacterial Drugs in in Traveler’s Traveler’s DiarrheaDiarrhea

Bismuth subsalicylate daily is used for y yprevention

2 tablets or 2 Tbsp QID

Overdose can cause ringing in ears Rare encephalopathy (reported in HIV patientspatients

80% effective

Rifaximin 1 QD; 70 % effective

Summer 2008Summer 2008

35 y/o traveler from the US develops diarrhea y/ pwhile snorkeling at a Red Sea Resort

She takes Kaopectate® for the diarrhea which she brought from the US

The next day her stools are pitch black in color

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What is What is Going OnGoing On??

1. She makes a mistake and is taking gPeptoBismol®

2. Think of something other than Kaopectate® which is kaolin and pectin

3. This represents a GI bleed secondary to the underlying infectionunderlying infection

4. KPC is bismuth subsalicylate and the stool contains harmless bismuth sulfide

Noroviruses “Winter vomiting”Noroviruses “Winter vomiting”

50% of all food‐borne id i i th USepidemics in the US

Outbreaks occur in camps, cruise ships, hotels, nursing homes

High attack rate All groups except infants 

affectedF l l l ft Fecal‐oral or aerosol after projectile vomiting

Raw shellfish and contaminated drinking water

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NorwalkNorwalk‐‐like like Virus Virus Outbreaks, Outbreaks, 1997 1997 –– 20002000

Mode of transmissionSettings

38%16%

10%

5%5%

Restaurants/ catered events

Nursing

Schools/ daycares

Vacation/ cruise ships

Other

Not given

58%3%

23% Food borne

Water

Person-to-person

Not determined

Total: 229

%

26%

Nursing homes

Total: 172

16%person

NorovirusesNoroviruses

Average incubation 12‐48 hoursg Vomiting often the predominant feature Clinical symptoms last a median of 5 days Shedding continues for 3 weeks Most patients are resistant to re‐infection for 4 6 months4‐6 months

Detected through hemagglutination assays, ELISA and RT‐PCR

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RotavirusRotavirus

#1 killer of infants globallyg y 3.5 million cases in US Detected by commercial ELISA

Clinical caseClinical case

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SalmonellaSalmonella

NonNon‐‐Tyhpoid SalmonellosisTyhpoid Salmonellosis

95% of cases from food Poultry or other meat,

eggs, fruits and vegetables, exotic pets

1.4 million cases/year Highest < 1 yearHighest 1 year Bacteremia rate, in

healthy 8%, high risk ~50%

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Emergence of Emergence of NonNon‐‐typhoid typhoid Salmonella: Salmonella: Reported Reported Infections  Infections  USA, 1920USA, 1920‐‐19971997

CDC, National surveillance data

20

25

30

35

40

45

50

00

,00

0 p

opu

lati

on

Typhoid

Non-Typhoid

0

5

10

15

20

1920 1930 1940 1950 1960 1970 1980 1990

Inci

den

ce p

er 1

0

Campylobacter Campylobacter jejunijejuni DiarrheaDiarrhea

1.4 to 2.4 million cases/yr in US/y 80% from food poultry, receipt of antibiotics, international travel

Ciprofloxacin resistance common worldwide

Use macrolide for therapy

Complications: Guillain Barre syndrome IBS Complications: Guillain‐Barre syndrome, IBS, reactive arthritis

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All All But One But One is a is a LowLow‐‐dose Pathogendose Pathogen

Commonly spread person‐to‐person causing y p p p goutbreaks in day care centers and nursing homes

Shigella

Cryptosporidium

C l b t j j i Campylobacter jejuni

Giardia

All or low dose organisms

Usual Usual Dose Dose of of Viable Microbes Responsible Viable Microbes Responsible for for Disease Produce Disease Produce (ID25)(ID25)

Shigella 10‐100g Giardia & C. parvum 30‐100 EHEC 10‐100 Norwalk 10‐100 Salmonella 10E3‐10E5 Campylobacter 10E3‐10E6 Campylobacter 10E3‐10E6 Vibrio cholerae 10E6 ETEC 10E6

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Clinical Clinical CaseCase

30% of the residents at our patient’s NH now phave diarrhea

Some with fever and systemic toxicity and the others with moderately severe illness

A non‐typhoid Salmonella is also grown from 3 of 4 patients cultured3 of 4 patients cultured

Which of our Which of our Patient’s Fellow Nursing Patient’s Fellow Nursing Home Residents Would You TreatHome Residents Would You Treat??

1. Only those with fever or dysenteryy y y2. Those with any diarrhea3. Only those with severe diarrhea of any sort4. None to prevent prolonged excretion of 

Salmonella5 No answer is correct5. No answer is correct

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Indications for Indications for Antibiotics Antibiotics in in NonNon‐‐typhoid typhoid SalmonellosisSalmonellosis

< 3mos, > 65 yrs. Ceftriaxone for infants  Fever or toxicity Immunosuppressed Renal failure, HD Steroid use Sickle Cell DiseaseIBD

(7‐10 days)

Fluoroquinolones for adults (7‐10 days)

I d IBD Aortic aneurysm, prosthesis

Immunosuppressed (14 days)

Imported Food Consumption on the Rise Imported Food Consumption on the Rise SourceSource:: USDA Agricultural Research ServiceUSDA Agricultural Research Service

62%70%

45%

62%

24%

34%

20%

30%

40%

50%

60%

rcen

t of

Com

mod

ity 1980

1997

5.40%10%

0.40%

10.40%

0%

10%Per

Fish, fishproducts, &

shellfish

Fresh fruits Freshvegetables

Foreign-grownwheat

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Examples of Examples of US Outbreaks Traced US Outbreaks Traced to to Foods Foods from from Other CountriesOther Countries

Norwalk‐like virus & Raspberries (Europe and p ( pCanada) 

Seafood salad on an airplane from Peru caused cholera 

Cyclospora & Raspberries from Guatemala Salmonella & OJ from Mexico Salmonella & OJ from Mexico Alfalfa seeds shipped from Netherlands caused Salmonella diarrhea in persons who ate alfalfa sprouts

1999 FDA Imported Produce Sampling, 1999 FDA Imported Produce Sampling, n=1003n=1003

4.4% positivep No E. coli 0157:H7 Salmonella - 80% of violations

•Domestic Produce Sampling ProgramDomestic Produce Sampling Program Contamination Rate: 1.6% (as of July 2001)

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Large, Large, MultiMulti‐‐state Outbreaksstate Outbreaks

1990 Salmonella & Cantaloup 295 infections in 28 states

1991 Salmonella & Salads 400 infections in 23 states & Canada

1993 E. coli 0157 in hamburger >700 cases - 4 died in four states

1994 Salmonella in ice cream ~ 224,000 ill in 41 states

1995 S. Stanley in Alfalfa sprouts 242 ill in 17 states

1996 Cyclospora & raspberries >1,000 ill - 22 hospitalizations

1997 E coli 0157 & alfalfa sprouts 108 ill in 2 states1997 E. coli 0157 & alfalfa sprouts 108 ill in 2 states

1998 Listeria in hotdogs >100 ill - 21 deaths in 21 states

1999 Salmonella & OJ 360 ill in 16 states and Canada

2000 Norwalk-like virus & pasta salad 333 ill in 13 states

2006 E. coli 0157 & spinach 95 infections in 26 states

Number of Number of MultiMulti‐‐state Outbreaksstate Outbreaks

3

4

5

6

7

8

9

0

1

2

1991 1992 1993 1994 1995 1996 1997 1998 1999

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Why an Why an IncreaseIncrease??

Increased numbers of susceptible persons

Aging , HIV infection, immunosuppressive drugs

Changing eating habits Changes in types of foods consumed

Popularity of "fast food" & salad bars

Increased availability of ready-to-eat

Dietary, "fast food“, eating out,…

Improved surveillance & detection

Bioterrrorism

It’s It’s Getting WorseGetting Worse. Isn’t it?. Isn’t it?

23% overall drop in seven bacterial pfoodborne illnesses since 1996

27% Campylobacter15% Salmonella35% Listeria49% Yersinia49% Yersinia

MMWR

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Addressing Addressing Food Hazards Food Hazards in the in the 2121stst CenturyCentury

Inspection & regulation (GAPs, GMPs, HACCP)

Hygienic processing, Water chlorination

Refrigeration, safe canning, additives & preservatives

Pasteurization, monitoringg

Medical advances: antibiotics, vaccines

Foodhandler education & behavior change

“I “I Always Get Sick When Always Get Sick When I I Travel Travel and and My My Wife Never Does Wife Never Does . . . “. . . “

Genes associated with inflammation, immunity, and pathogenesis IL‐8 polymorphisms and EAEC diarrhea

Lactoferrin and all traveler’s diarrhea

SNPs in the FUT2 predicts resistance to Noroviruses

Diarrhea is hereditary It runs in your genes