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Global Trade and Microbial Traffic Ann Marie Kimball, MD., MPH School of Public Health and Community Medicine University of Washington Global 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 “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 Uneven Access to Water/Sanitation Uncontrolled Urbanization International Agricultural Trade, 1961-2000 Fruit & Vegetable 140,000 120,000 Meat & Meat Preparations 100,000 80,000 Dairy Products & Eggs 60,000 40,000 20,000 Live Animals 6 19 1 6 19 4 6 19 7 7 19 0 7 19 3 7 19 6 7 19 9 8 19 2 8 19 5 8 19 8 9 19 1 9 19 4 9 20 7 00 0 19 US Dollars (millions) 160,000 Years Source: UN Food and Agriculture Organization ***Value of food trade in US alone in 1994: $266 billion Global 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 Human Disease as Travelers on the Global Express Examples of Global Epidemics • 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 Eastern Europe Western Europe & Central Asia 560 000 1 millionEast Asia & Pacific North Africa 1 million South & Middle East & South-East Asia 440 000 6.1 million North America 940 000 Caribbean 420 000 Latin America 1.4 million Sub-Saharan Africa 28.1 million Total: 40 million Source: UNAIDS, 12/01 Australia & New Zealand 15 000 HIV 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) • 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 • 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. US Export of Blood Fractions & Modified Immunological Products 1989 – 2000 1,000 US Dollars 1,600,000 1,400,000 1,200,000 1,000,000 Blood Fractions & Modified Immunological Products 800,000 600,000 400,000 1999 1997 1995 1993 1991 0 1989 200,000 Years United States International Trade Commission, Interactive Tariff and Trade DataWeb Sprouts and Enteric Disease • 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 Sprout Production Process • Seeds purchased from a distributor and sprouted locally • Several opportunities for contamination • Provides ideal conditions for bacterial growth Many unexpected cases • Serotype specific CDC surveillance system begun • Salmonella stanley isolates were the cause of numerous reports of gastroenteritis in 1995 Three S. stanley outbreaks • Two states – Michigan – Arizona • SALM-Net – Finland – from Mahon, BE et al, JID 1997;175:876 Identifying a common source • Case control studies conducted in each location • Confirmed the role of alfalfa sprouts in transmitting the variant Salmonella Molecular Epidemiology • PFGE & antibiogram – common source for the three outbreaks – Unique isolate found at all locations outbreak sporadic 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. Tracebacks • 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 threat Year 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 Japan Radish Unknown Nat'l Inst. Infect. Dis. and Infect. Dis. Ctrl Div., Ministry of Health and Welfare of Japan, 1997 1996 . E coli O157:H7 >6,000 1997 S. Meleagrid is 78 Canada Alfalfa Seed Buck et al., 1998 1997 E. coli O157:H7 126 Japan Radish Unkown Gutierrez, 1997 Cylcospora cayetanesis • • • • • Emerging infection First documented case in 1977 Confirmed coccidian parasite in 1993 Received its name in 1994 Outbreaks starting in 1995 Lifecycle • Not completely understood • Humans are only known host • Infectious spores are ingested • Prolonged GI illness • Oocysts excreted in feces “Sentinel” Outbreaks in 1995 • First North American outbreaks • New York and Florida • Three small clusters • Inconclusive investigation • Suggested raspberries and strawberries Difficult 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 Outbreak 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 • Canada and US both experienced clusters of disease • 737 lab confirmed cases clustered seasonally Cultivation Related Contamination • Infected humans contaminate water sources • Water used in crop treatments – Insecticides – Fertilizers • Contaminated raspberries exported Virulence 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 Outbreak 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 Despite measures, 41 new clusters occurred Shipments were stopped from Guatemala end of May, 1997 (voluntary) Outbreak 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 Guatemalan 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 Guatemalan Incident • Unsafe cultivation in resource poor setting of a newly introduced cash crop • Role of surveillance • Is trade restriction the only remedy? BSE/nCJD Disease • 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 30 number of cases 25 20 15 10 5 0 1995 1996 1997 1998 1999 2000 2001 Source: UK, France Bovine Spongiform Encephalopathy, United Kingdom BSE and vCJD: potential exposure through international trade, early 1990s Live cattle Meat and bone meal Human and bovine tissue used in biologicals Food containing beef Blood and blood products Pharmaceuticals UK Beef Exports 1970 - 1999 1,000 US Dollars 900,000 800,000 700,000 600,000 500,000 UK Bovine UK Beef an 400,000 300,000 200,000 1997 1994 1991 1988 1985 1982 1979 1976 1973 0 1970 100,000 Years Food and Agriculture Organization of the United Nations, FAOSTAT Contaminated 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 US Meat Exports 1989 – 2000 1,000 US Dollars 7,000,000 6,000,000 5,000,000 4,000,000 US Bovine Meat 3,000,000 Total US Meat and Edible Offal 2,000,000 1999 1997 1995 1993 1991 0 1989 1,000,000 Years United States Department of Agriculture, Foreign Agriculture Service E. Coli in Meat, BSE analogies Changes in production to dramatically increase yield, and economize in expense predated outbreak emergent infections linked to meat products for human consumption. Was Global Trade a driver? Addressing Direct Trade Related Infections • “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? Public Health and Trade WHO •Improve health WTO •Establish trade rules •Solve trade problems •Prevent/control disease •Provides health input to Codex Alimentarius standards •Develops and manages health regulations (IHR) IHR •WHO establishes IHR under Constitution Codex Alimentarius •Sets food standards SPS Agreement •Recognizes Codex Alimentarius standards as the reference for food safety requirements when they affect health and international trade Evolution of the WTO • 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 Application of the International Health Regulations, 1969 Strengthen the global framework Formal Country Disease notification (cholera, plague or yellow fever) National containment of disease Notification of cases in Weekly Epidemiologial Record & recommendation by WHO of pre-set public health measures Application of International Health Regulations, proposed revision Strengthen the global framework Public health risk reporting from WHO alert and response network Public health risk reporting by countries Decision-tree analysis to determine if of urgent international public health importance YES NO National containment of public health risk National containmen t of public health risk Collaborative risk-based public health measures identified and recommended by WHO Global surveillance of infectious diseases: Network of networks Detect and respond to the unexpected WHO Regional & Country Offices WHO Collaborating Centres/Laboratories MOH/National Disease Control Centres Epidemiology and Surveillance Networks Military Laboratory Networks UN Sister Agencies GPHIN NGOs Media Electronic Discussion sites FORMAL INFORMAL Global Public Health Intelligence Network, Canada Detect and respond to the unexpected 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 Notification Format - example 1. Member to Agreement notifying: If applicable, name of local government involved: 2. Agency responsible: 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: 4. Title and number of pages of the notified document: 5. Description of content: 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 7. Nature of the urgent problem(s): 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: 9. Relevant documents and language(s) in which these are available: 10. Date of entry into force/period of application (as applicable): 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: 350 319 300 250 200 150 100 50 0 6 8 10 25 28 19 96 19 97 19 98 19 99 20 00 20 01 Number of Reports Number of Reports by Year Year Nature of Urgency by Year Human & Animal Diseases Plant Diseases 4% 18% 78% Human & Plant Diseases Plant Diseases Contaminants 65% GMOs 22% 2% 7% 1% 3% 2000 Contaminants 2001 Regulation of Pesticide Residues Other Objective for Notifying by Year Food Safety 200 180 160 Animal Health 140 120 Plant Protection 100 80 60 40 20 0 1996 1997 1998 1999 2000 2001 Protect Humans from Pest/Disease Protect Territory from Pests Other Results 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. Characteristics of WTO Countries by Reporting Status All countries within the WTO notifying All countries within the WTO not notifying 2000 2001 2000 2001 (N=16) (N=39) (N=124) (N=104) Mean GDP (Billions, US$) 459.1 ―* 188.9 ―* Mean Agriculture Imports (Millions, US$) 8301.5 ―* 2448.0 ―* 93.5 41.7† 21.2 25.3 Year Mean Population (Millions) * Complete data not available † Population estimates of the European Community and Brunei Darussalam not included 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 • 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 • 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 important • 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” In Summary • 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