Global Trade and Microbial Traffic

Ann Marie Kimball, MD., MPHSchool of Public Health and

Community MedicineUniversity of Washington

Global Trade and InfectionsGlobal Trade and Infections

• Conceptual framework, background• Summarize four illustrative infections:

HIV/AIDS, enteric infections from sprouts, cyclospora from rasberries, BSE from beef products

• Examine surveillance, prevention and control options extant through the WHO,WTO

• Conceptual framework, background• Summarize four illustrative infections:

HIV/AIDS, enteric infections from sprouts, cyclospora from rasberries, BSE from beef products

• Examine surveillance, prevention and control options extant through the WHO,WTO

“Trade-Related Infection” an infectious disease whose

“Trade-Related Infection” an infectious disease whose

• Emergence is hastened by ecological pressure of “scaling up” production to meet international trade markets

• Transmission is broadened through transportation or trade in goods

• Economic impact is large in terms of trade disruption

• Emergence is hastened by ecological pressure of “scaling up” production to meet international trade markets

• Transmission is broadened through transportation or trade in goods

• Economic impact is large in terms of trade disruption

Uneven Access to Water/SanitationUneven Access to Water/Sanitation

Uncontrolled UrbanizationUncontrolled Urbanization

International Agricultural Trade, 1961-2000

International Agricultural Trade, 1961-2000

0

20,000

40,000

60,000

80,000

100,000

120,000

140,000

160,000Fruit & Vegetable

Meat & MeatPreparations

Dairy Products &Eggs

Live Animals0

20,000

40,000

60,000

80,000

100,000

120,000

140,000

160,000Fruit & Vegetable

Meat & MeatPreparations

Dairy Products &Eggs

Live Animals

YearsYears

US

Dolla

rs (

mill

ion

s)U

S D

olla

rs (

mill

ion

s)

Source: UN Food and Agriculture Organization

***Value of food trade in US alone in 1994: $266 billion

Global Trade /GlobalizationGlobal Trade /Globalization

• Major increases in global trade, particularly in meats and fresh produce over the past thirty years

• Increased traffic of goods an humans overlayed on inadequate public health infrastructure, and increasing population, urbanization

• Major increases in global trade, particularly in meats and fresh produce over the past thirty years

• Increased traffic of goods an humans overlayed on inadequate public health infrastructure, and increasing population, urbanization

Human Disease as Travelers on the Global Express

Human Disease as Travelers on the Global Express

Examples of Global Epidemics

Examples of Global Epidemics

• HIV/AIDS- factors of urbanization, transportation, technology,trade,

• Enteric Disease• Bovine Spongiform

Encephalopathy (New variant Jacob Creutzfeldt Disease)

• HIV/AIDS- factors of urbanization, transportation, technology,trade,

• Enteric Disease• Bovine Spongiform

Encephalopathy (New variant Jacob Creutzfeldt Disease)

Adults and Children Estimated to be Living with HIV/AIDS as of end

2001

Adults and Children Estimated to be Living with HIV/AIDS as of end

2001Western Europe

560 000560 000North Africa & Middle East

440 000440 000Sub-Saharan

Africa

28.1 million28.1 million

Eastern Europe & Central Asia

1 million1 million

South & South-East Asia

6.1 million6.1 million

Australia & New Zealand

15 00015 000

North America

940 000940 000Caribbean

420 000420 000

Latin America

1.4 million1.4 million

Total: 40 millionTotal: 40 million

East Asia & Pacific

1 million1 million

Source: UNAIDS, 12/01Source: UNAIDS, 12/01

HIV in Factor VIII, IXHIV in Factor VIII, IX

• Factor VIII development, late 1970’s

• 1 unit derived from 20,000 units of plasma

• US hemophiliac HIV epidemic 1982-85, (followed hepatitis epidemic)

• Factor VIII development, late 1970’s

• 1 unit derived from 20,000 units of plasma

• US hemophiliac HIV epidemic 1982-85, (followed hepatitis epidemic)

• US main exporter of factor VIII in 1980’s

• Japan epidemic began with commercial product introduction

• 1993 64% of HIV/AIDS cases in Japan in hemophiliacs

• US main exporter of factor VIII in 1980’s

• Japan epidemic began with commercial product introduction

• 1993 64% of HIV/AIDS cases in Japan in hemophiliacs

Big Four Pharma Plasma to Blood Products

Fractionation

Big Four Pharma Plasma to Blood Products

Fractionation

• Alpha Therapeutic (owned by Green Cross, Japan)

• Armour Pharmaceutical

• Hyland of Travenol Labs (later Baxter)

• Cutter Division, Miles labs (later Bayer)

• Alpha Therapeutic (owned by Green Cross, Japan)

• Armour Pharmaceutical

• Hyland of Travenol Labs (later Baxter)

• Cutter Division, Miles labs (later Bayer)

• 1981 sales $10 million, 1988 $38m

• 1982 sales $51m,1988 $125m.

• 1982 sales $60 million, 1988 $98 m.

• 1982 sales $69 million, 1988 $123m.

• 1981 sales $10 million, 1988 $38m

• 1982 sales $51m,1988 $125m.

• 1982 sales $60 million, 1988 $98 m.

• 1982 sales $69 million, 1988 $123m.

US Export of Blood Fractions & Modified Immunological Products

1989 – 2000

US Export of Blood Fractions & Modified Immunological Products

1989 – 2000

Years

1,00

0 U

S D

olla

rs

United States International Trade Commission, Interactive Tariff and Trade DataWeb

0

200,000

400,000

600,000

800,000

1,000,000

1,200,000

1,400,000

1,600,000

1989

1991

1993

1995

1997

1999

Blood Fractions &ModifiedImmunologicalProducts

• Global trade provides access to fresh produce year-round

• Consumers seek fresh fruits and vegetables as part of a healthy diet

• Unlike bacteria traveling on meat, those on produce often escape cooking “kill-step”

• Seed contamination probable, bacteria multiply in sprouting

• Global trade provides access to fresh produce year-round

• Consumers seek fresh fruits and vegetables as part of a healthy diet

• Unlike bacteria traveling on meat, those on produce often escape cooking “kill-step”

• Seed contamination probable, bacteria multiply in sprouting

Sprouts and Enteric DiseaseSprouts and Enteric Disease

• Seeds purchased from a distributor and sprouted locally• Several opportunities for contamination• Provides ideal conditions for bacterial growth

Sprout Production ProcessSprout Production Process

Many unexpected casesMany unexpected cases

• Serotype specific CDC surveillance system begun

• Salmonella stanley isolates were the cause of numerous reports of gastroenteritis in 1995

Three S. stanley outbreaksThree S. stanley outbreaks

• Two states– Michigan– Arizona

• SALM-Net – Finland– from Mahon, BE et al, JID

1997;175:876

Identifying a common sourceIdentifying a common source• Case control studies conducted in each

location • Confirmed the role of alfalfa sprouts in

transmitting the variant Salmonella

1–5, outbreak isolates (1 and 2, Arizona; 3, Michigan; 4, Finland; 5, Ohio). Lanes 7–10,sporadic isolates not linked to outbreak (7, Arizona;8, Missouri; 9, Finland; 10, Virginia).Lane 6, l ladder molecular weight marker.

outbreak sporadic

Molecular Epidemiology

• PFGE & antibiogram– common

source for the three outbreaks

– Unique isolate found at all locations

TracebacksTracebacks• Case interviews

– Trace contaminated sprouts to their source– identify retail outlets and dates of purchase– determine shippers and growers who provided

sprouts– Invoices and delivery records identify seed

suppliers, lot numbers, and dates of sprouting• 50 successful tracebacks

– 9 growers used single U.S. supplier– seeds from Netherlands distributor– combination of lots from Hungary, Pakistan, &

Italy

• Case interviews – Trace contaminated sprouts to their source– identify retail outlets and dates of purchase– determine shippers and growers who provided

sprouts– Invoices and delivery records identify seed

suppliers, lot numbers, and dates of sprouting• 50 successful tracebacks

– 9 growers used single U.S. supplier– seeds from Netherlands distributor– combination of lots from Hungary, Pakistan, &

Italy

Sprouts: an international threatSprouts: an international threatYear Pathogen

No. of Cases

Location of Outbreak

Type of Sprout

Likely Source of Contamination Reference

1988 S. Saint-Paul 143 United Kingdom

Mung Bean

Seed O'Mahony et al., 1990

1989 S. Gold-Coast 31 United Kingdom

Cress Unkown Joce et al., 1990

1994 S. Bovismorbificans

492 Sweden, Finland

Alfalfa Seed Ponca et al., 1995 Puohiniemi et al., 1997

1995 S. Stanley 114 Finland Alfalfa Seed Kontiainen et al., 1996 Mahon et al., 1997

1995 S. Newpor t ???? Denmark, Canada

Alfalfa Seed Oregon Health Division, 1995 Aabo and Baggesen, 1997

1996 . E coli O157:H7 >6,000 Japan Radish Unknown Nat'l Inst. Infect. Dis. and Infect. Dis. Ctrl Div., Ministry of Health and Welfare of Japan,

1997

1997 S. Meleagrid is 78 Canada Alfalfa Seed Buck et al., 1998

1997 E. coli O157:H7 126 Japan Radish Unkown Gutierrez, 1997

Cylcospora cayetanesisCylcospora cayetanesis

• Emerging infection• First documented case in 1977• Confirmed coccidian parasite in 1993• Received its name in 1994• Outbreaks starting in 1995

• Emerging infection• First documented case in 1977• Confirmed coccidian parasite in 1993• Received its name in 1994• Outbreaks starting in 1995

LifecycleLifecycle

• Not completely understood• Humans are only known host• Infectious spores are ingested• Prolonged GI illness• Oocysts excreted in feces

• Not completely understood• Humans are only known host• Infectious spores are ingested• Prolonged GI illness• Oocysts excreted in feces

“Sentinel” Outbreaks in 1995“Sentinel” Outbreaks in 1995

• First North American outbreaks • New York and Florida• Three small clusters • Inconclusive investigation• Suggested raspberries and

strawberries

• First North American outbreaks • New York and Florida• Three small clusters • Inconclusive investigation• Suggested raspberries and

strawberries

Difficult Detective WorkDifficult Detective Work• Trace-back and case-control studies• Delayed GI illness

– Delayed diagnosis– Difficult to remember food intake– Fresh fruit no longer available

• No brand name recognition

• Trace-back and case-control studies• Delayed GI illness

– Delayed diagnosis– Difficult to remember food intake– Fresh fruit no longer available

• No brand name recognition

Outbreak in 1996Outbreak in 1996

• 1465 cases in US and Canada• 55 event clusters• Guatemalan Raspberries were implicated• Widespread contamination prior to export

– Multiple farms– Varied ports of entry– Many distribution patterns within North

America– Herwaldt B et al NEJM 1997

• 1465 cases in US and Canada• 55 event clusters• Guatemalan Raspberries were implicated• Widespread contamination prior to export

– Multiple farms– Varied ports of entry– Many distribution patterns within North

America– Herwaldt B et al NEJM 1997

• Canada and US both experienced clusters of disease

• 737 lab confirmed cases clustered seasonally

• Canada and US both experienced clusters of disease

• 737 lab confirmed cases clustered seasonally

Cultivation Related Contamination

Cultivation Related Contamination

• Infected humans contaminate water sources

• Water used in crop treatments– Insecticides– Fertilizers

• Contaminated raspberries exported

• Infected humans contaminate water sources

• Water used in crop treatments– Insecticides– Fertilizers

• Contaminated raspberries exported

Virulence FactorsVirulence Factors• Single raspberry can cause infection• Simple water wash ineffective• Resistant to Chlorine treatment of

water• Oocyst is very strong and can survive

difficult environments• Food-borne and water-borne

transmission

• Single raspberry can cause infection• Simple water wash ineffective• Resistant to Chlorine treatment of

water• Oocyst is very strong and can survive

difficult environments• Food-borne and water-borne

transmission

Outbreak in 1997Outbreak in 1997

• Guatemalan Berry Commission implemented voluntary control measures– Hygiene– Sanitation– Water sources

• Another multi-state, multi-cluster outbreak in the U.S, Canada

• Suspension of export by Guatemala to N. American markets ended the outbreak

• Guatemalan Berry Commission implemented voluntary control measures– Hygiene– Sanitation– Water sources

• Another multi-state, multi-cluster outbreak in the U.S, Canada

• Suspension of export by Guatemala to N. American markets ended the outbreak

Despite measures,41 new clusters occurredShipments were stoppedfrom Guatemala end ofMay, 1997 (voluntary)

Outbreak in 1998Outbreak in 1998• FDA prohibited importation of

Guatemalan raspberries• “Interventional study” where Canada

was exposed and the US was the control

• No outbreak in the US• Multi-cluster outbreak in Canada

• FDA prohibited importation of Guatemalan raspberries

• “Interventional study” where Canada was exposed and the US was the control

• No outbreak in the US• Multi-cluster outbreak in Canada

Guatemalan RaspberriesGuatemalan Raspberries

• The epidemiologic evidence was strong

• Tighter controls within Guatemala decreased number of outbreaks in following years

• Definitive control with trade import restriction by U.S.

• The epidemiologic evidence was strong

• Tighter controls within Guatemala decreased number of outbreaks in following years

• Definitive control with trade import restriction by U.S.

The Guatemalan IncidentThe Guatemalan Incident

• Unsafe cultivation in resource poor setting of a newly introduced cash crop

• Role of surveillance• Is trade restriction the only remedy?

• Unsafe cultivation in resource poor setting of a newly introduced cash crop

• Role of surveillance• Is trade restriction the only remedy?

BSE/nCJD DiseaseBSE/nCJD Disease

• Change in rendering, husbandry practice implicated in emergence

• silent global circulation in product

• Novel agent (prion), long latency,

• Change in rendering, husbandry practice implicated in emergence

• silent global circulation in product

• Novel agent (prion), long latency,

Cases of vCJD, worldwide, as of end of August 2001

Cases of vCJD, worldwide, as of end of August 2001

number of cases

1995

30

25

20

15

10

5

01996 1997 1998 1999 2000 2001

Source: UK, France

Bovine Spongiform Encephalopathy, United Kingdom

BSE and vCJD: potential exposure through international trade, early 1990s

Live cattleLive cattle

Food containing beefFood containing beef

PharmaceuticalsPharmaceuticalsBlood Blood and bloodand bloodproductsproducts

Meat and Meat and bone mealbone meal

Human and Human and bovinebovinetissue used tissue used in biologicalsin biologicals

UK Beef Exports1970 - 1999

UK Beef Exports1970 - 1999

Food and Agriculture Organization of the United Nations, FAOSTAT

Years

1,00

0 U

S

Dol

lars

0

100,000

200,000

300,000

400,000

500,000

600,000

700,000

800,000

900,000

1970

1973

1976

1979

1982

1985

1988

1991

1994

1997

UK Bovine MeatUK Beef and Veal

Contaminated MeatContaminated Meat

• Numerous examples of enteritis outbreaks from contaminated meat worldwide and in U.S. (Ecoli O157, Salmonella typhimurium DT104)

Coincides with marked increase in meat and meat product trading worldwide

• Numerous examples of enteritis outbreaks from contaminated meat worldwide and in U.S. (Ecoli O157, Salmonella typhimurium DT104)

Coincides with marked increase in meat and meat product trading worldwide

US Meat Exports1989 – 2000

US Meat Exports1989 – 2000

Years

1,00

0 U

S D

olla

rs

United States Department of Agriculture, Foreign Agriculture Service

0

1,000,000

2,000,000

3,000,000

4,000,000

5,000,000

6,000,000

7,000,0001989

1991

1993

1995

1997

1999

US Bovine Meat

Total US Meat andEdible Offal

E. Coli in Meat, BSE analogiesE. Coli in Meat, BSE analogies

Changes in productionto dramatically increase yield, and economize inexpense predated outbreakemergent infections linkedto meat products for humanconsumption. Was Global Trade a driver?

Addressing Direct Trade Related Infections

Addressing Direct Trade Related Infections

• “Primary prevention” prevention of emergence of new infections

• “Secondary Prevention” through prevention of dissemination through trade

• “Primary prevention” prevention of emergence of new infections

• “Secondary Prevention” through prevention of dissemination through trade

• “Surveillance and timely control” through enhanced surveillance systems

• What is new in Trade - related surveillance for trade related infections?

• “Surveillance and timely control” through enhanced surveillance systems

• What is new in Trade - related surveillance for trade related infections?

Public Health and TradePublic Health and TradeWHO

•Improve health

•Prevent/control disease

•Provides health input to Codex Alimentarius

standards

•Develops and manageshealth regulations (IHR)

IHR•WHO establishes IHR

under Constitution

WTO•Establish trade rules•Solve trade problems

SPS Agreement•Recognizes Codex

Alimentarius standards as thereference for food safety

requirements when they affect health and international trade

CodexAlimentarius•Sets food standards

Evolution of the WTOEvolution of the WTO

• Bretton Woods 1944

• General Agreement on Tariffs and Trade 1947

• Codex Alimentarius Commission 1963 (FAO/WHO)

• Bretton Woods 1944

• General Agreement on Tariffs and Trade 1947

• Codex Alimentarius Commission 1963 (FAO/WHO)

• Technical Barriers to Trade (TBT)1979

• WTO created from 1994 GATT, SPS supersedes TBT

• Technical Barriers to Trade (TBT)1979

• WTO created from 1994 GATT, SPS supersedes TBT

Application of the InternationalHealth Regulations, 1969

Formal Country Disease notification

(cholera, plague or yellow fever)

National containment of

disease

National containment of

disease

Notification of cases in Weekly Epidemiologial Record &

recommendation by WHO of pre-set public health measures

Notification of cases in Weekly Epidemiologial Record &

recommendation by WHO of pre-set public health measures

Strengthen the global framework Strengthen the global framework

Application of International Health Regulations, proposed revision

National National containment of containment of

public health riskpublic health risk

Public health risk reporting by countries

National containment of public health risk

NOYES

Public health risk reporting from WHO alert and response network

Collaborative risk-based public health measures

identified and recommended by WHO

Decision-tree analysis to determine if of urgent international public health importance

Strengthen the global framework Strengthen the global framework

Electronic Discussion

sitesMedia

NGOs

MilitaryLaboratoryNetworks

WHO Collaborating Centres/Laboratories Epidemiology and

Surveillance Networks

WHO Regional & Country Offices

MOH/National Disease Control

Centres

UNSister Agencies

FORMALFORMAL

GPHIN

Global surveillance of infectious diseases: Network

of networks

INFORMALINFORMAL

Detect and respond to the unexpectedDetect and respond to the unexpected

Detect and respond to the unexpectedDetect and respond to the unexpected

Global Public Health Intelligence Network,

Canada

WTO Committee on Sanitary and Phytosanitary Measures,

“Notifications of Emergency Measures”

WTO Committee on Sanitary and Phytosanitary Measures,

“Notifications of Emergency Measures”

• Format for emergency notifications adopted in 1995 with revisions in 1996, 1999, and 2002.

• Collection time period for dataset: 04/96 to 08/01.

• Creation of 24 variables, including: date of report, country reporting, countries affected, nature of urgency, objective of reporting, and products covered.

• Frequency analysis conducted using Stata

• Format for emergency notifications adopted in 1995 with revisions in 1996, 1999, and 2002.

• Collection time period for dataset: 04/96 to 08/01.

• Creation of 24 variables, including: date of report, country reporting, countries affected, nature of urgency, objective of reporting, and products covered.

• Frequency analysis conducted using Stata

Notification Format - exampleNotification Format - example

11. Texts available from/and agency or authority designated to handle comments: [ ] National notification authority, [ ] National enquiry point, or address, fax number and E-mail address (if available) of other body:

10. Date of entry into force/period of application (as applicable):

9. Relevant documents and language(s) in which these are available:

8. An international standard, guideline or recommendation does not exist [ ].If an international standard, guideline or recommendation exists, give its appropriate reference and briefly identify deviations:

7. Nature of the urgent problem(s):

6. Objective and rationale: [  ] food safety, [  ] animal health, [  ] plant protection, [  ] protect humans from animal/plant pest or disease, [  ] protect territory from other damage from pests

5. Description of content:

4. Title and number of pages of the notified document:

3. Products covered (provide tariff item number(s) as specified in national schedules deposited with the WTO; ICS numbers may be provided in addition, where applicable). Regions or countries likely to be affected, to the extent relevant or practicable:

2. Agency responsible:

1. Member to Agreement notifying: If applicable, name of local government involved:

Number of Reports by YearNumber of Reports by Year

6 8 10 25 28

319

0

50

100

150

200

250

300

350

Year

Nu

mb

er

of

Rep

ort

s

Nature of Urgency by Year

18%

4%

78%

Human &PlantDiseasesPlantDiseases

Contaminants

2%

1%

3%

7%

22%

65%

Human &AnimalDiseases

PlantDiseases

Contaminants

GMOs

Regulation ofPesticideResidues

Other

2000 2001

Objective for Notifying by Year

Objective for Notifying by Year

0

20

40

60

80

100

120

140

160

180

200

1996 1997 1998 1999 2000 2001

Food Safety

Animal Health

PlantProtection

ProtectHumans fromPest/ DiseaseProtectTerritory fromPestsOther

Results for 2000 & 2001Results for 2000 & 2001• Animal products were reported as products covered in

153 (28.6%) of the notifications.

• The most reported objective or rationale for notifying was animal health 203 (42.2%), followed by food safety 177 (37.8%).

• 192 (59.8%) of the notifications reported the existence of a recommendation, standard, or guideline.

• Foot and mouth was most often the nature of urgency 113 (36.2%), followed by bovine spongiform encephalopathy (BSE) 65 (20.8%).

• New Zealand and the United States reported most frequently with 66 (19.2%) and 54 (15.7%) notifications, respectively.

• Animal products were reported as products covered in 153 (28.6%) of the notifications.

• The most reported objective or rationale for notifying was animal health 203 (42.2%), followed by food safety 177 (37.8%).

• 192 (59.8%) of the notifications reported the existence of a recommendation, standard, or guideline.

• Foot and mouth was most often the nature of urgency 113 (36.2%), followed by bovine spongiform encephalopathy (BSE) 65 (20.8%).

• New Zealand and the United States reported most frequently with 66 (19.2%) and 54 (15.7%) notifications, respectively.

Characteristics of WTO Countries by Reporting Status

Characteristics of WTO Countries by Reporting Status

25.321.241.7†93.5Mean Population (Millions)

―*2448.0―*8301.5Mean Agriculture Imports (Millions, US$)

―*188.9―*459.1Mean GDP (Billions, US$)

2001(N=104)

2000(N=124)

2001(N=39)

2000(N=16)

Year

All countries within the WTO not notifying

All countries within the WTO notifying

* Complete data not available† Population estimates of the European Community and Brunei Darussalam not included

WTO Urgent Measures Preliminary Analysis of an

Event

WTO Urgent Measures Preliminary Analysis of an

Event• All BSE related

norifications selected for 2000

• Product codes imputed to six digits

• Linked to Trade COM data for 1998,1999,2000

• All BSE related norifications selected for 2000

• Product codes imputed to six digits

• Linked to Trade COM data for 1998,1999,2000

• 157 forms included • Net trade value for

products rose from 1998 to 1999

• Fell with restrictions imposed in 2000

• Further validation ongoing

• 157 forms included • Net trade value for

products rose from 1998 to 1999

• Fell with restrictions imposed in 2000

• Further validation ongoing

Trade data contribution to Knowledge of Infectious

events

Trade data contribution to Knowledge of Infectious

events• With unknown infections, urgent

notifications may expand insight into scope of the problem

• With known infections, can study patterns of restrictions to inform the IHR implementation process

• May eventually aid in source identification, determining least disruptive effective measures

• With unknown infections, urgent notifications may expand insight into scope of the problem

• With known infections, can study patterns of restrictions to inform the IHR implementation process

• May eventually aid in source identification, determining least disruptive effective measures

Why is this importantWhy is this important

• Trade related infectious disease is important to human population welfare

• Trade related infections can be very costly

• Trade related infectious disease is important to human population welfare

• Trade related infections can be very costly

• Enhancing cooperation among international assistance organizations for epidemic control

• Assuring “Safe Trade”

• Enhancing cooperation among international assistance organizations for epidemic control

• Assuring “Safe Trade”

In SummaryIn Summary

• Trade related infections in food, biological products have been described

• We are seeing the tip of the iceberg

• Trade is increasing and diversifying

• Trade related infections in food, biological products have been described

• We are seeing the tip of the iceberg

• Trade is increasing and diversifying

• We will see more trade related infections

• Global Surveillance, detection is being enhanced

• Linking trade information with disease occurrence is key

• We will see more trade related infections

• Global Surveillance, detection is being enhanced

• Linking trade information with disease occurrence is key