1. 1 A Simulation Model to Quantify the Spread of BSE in the United States Joshua Cohen and George Gray Harvard Center for Risk Analysis Harvard School of Public Health

2. 2 Contributors Harvard Center for Risk Analysis Harvard Center for Risk Analysis Joshua T. Cohen Joshua T. Cohen Keith Duggar (MIT) Keith Duggar (MIT) George M. Gray George M. Gray Silvia Kreindel Silvia Kreindel Center for Computational Epidemiology, College of Veterinary Medicine, Tuskegee University Center for Computational Epidemiology, College of Veterinary Medicine, Tuskegee University Hatim Gubara Hatim Gubara Tsegaye HabteMariam Tsegaye HabteMariam David Oryang David Oryang Berhanu Tameru Berhanu Tameru Harvard Center for Risk Analysis Harvard Center for Risk Analysis Joshua T. Cohen Joshua T. Cohen Keith Duggar (MIT) Keith Duggar (MIT) George M. Gray George M. Gray Silvia Kreindel Silvia Kreindel Center for Computational Epidemiology, College of Veterinary Medicine, Tuskegee University Center for Computational Epidemiology, College of Veterinary Medicine, Tuskegee University Hatim Gubara Hatim Gubara Tsegaye HabteMariam Tsegaye HabteMariam David Oryang David Oryang Berhanu Tameru Berhanu Tameru

3. 3 What USDA Asked Harvard to Do Identify possible sources for the introduction of BSE (“mad cow disease”) into the U.S. cattle population Identify possible sources for the introduction of BSE (“mad cow disease”) into the U.S. cattle population Identify and quantify the relative importance of pathways by which BSE infectivity might spread among U.S. cattle or contaminate the human food supply Identify and quantify the relative importance of pathways by which BSE infectivity might spread among U.S. cattle or contaminate the human food supply Evaluate implications over time of possible introduction of BSE into U.S. agricultural system Evaluate implications over time of possible introduction of BSE into U.S. agricultural system Reproductive constant of the disease (R 0 ) Reproductive constant of the disease (R 0 ) Extent of human exposure Extent of human exposure

4. 4 Report History Grant awarded to Harvard in 1998 Grant awarded to Harvard in 1998 Report completed in November, 2001 Report completed in November, 2001 Report reviewed in 2002 under contract with RTI Report reviewed in 2002 under contract with RTI H. Christopher Frey – University of North Carolina H. Christopher Frey – University of North Carolina John C. Galland – Kansas State University John C. Galland – Kansas State University Bram E.C. Schreuder – DLO-Institute of Animal Science and Health (Netherlands) Bram E.C. Schreuder – DLO-Institute of Animal Science and Health (Netherlands) John W. Wilesmith – UK Department of the Environment, Food and Rural Affairs (DEFRA) John W. Wilesmith – UK Department of the Environment, Food and Rural Affairs (DEFRA) Revised report accepted by USDA and released in October, 2003 Revised report accepted by USDA and released in October, 2003

5. 5 Why We Chose a Simulation Approach (1) No historical data for U.S. - build understanding up from biology, agriculture, etc. No historical data for U.S. - build understanding up from biology, agriculture, etc. Need to characterize the evolution of the disease over time Need to characterize the evolution of the disease over time Within animals Within animals Across the cattle population Across the cattle population BSE not amenable to conventional epidemic disease modeling BSE not amenable to conventional epidemic disease modeling Spread depends on how and when animal was slaughtered Spread depends on how and when animal was slaughtered

6. 6 Why We Chose a Simulation Approach (2) Allows quantitative comparison of importance of different pathways of spread and different risk management Allows quantitative comparison of importance of different pathways of spread and different risk management Can help focus collection of information Can help focus collection of information

7. 7 Learning from UK Experience We assume the prevailing hypothesis of UK BSE spread is correct:

8. 8 Model Overview Exogenous Sources of Infectivity Cattle Population Slaughter and Death by Other Causes Feed Human Food Uses Posing No Risk to Humans or Cattle Split depends on 1) time since infection, 2) slaughter plant practices, and 3) animal age Split depends on compliance with ban on feeding ruminant materials to cattle

9. 9 Key Assumptions (1) Exogenous sources of BSE Exogenous sources of BSE Imported cattle Imported cattle Imported feed Imported feed Sporadic disease Sporadic disease Cross species transmission (e.g. scrapie) Cross species transmission (e.g. scrapie) Spread of disease among cattle – Imperfect compliance with feed ban Spread of disease among cattle – Imperfect compliance with feed ban Contamination of non-prohibited materials Contamination of non-prohibited materials Mislabeling of prohibited materials Mislabeling of prohibited materials Misfeeding Misfeeding

10. 10 Key Assumptions (2) Infection probability Infection probability Exposure and susceptibility high in young animals Exposure and susceptibility high in young animals Disease course Disease course Agent moves from gut to CNS over time Agent moves from gut to CNS over time Total infectivity load grows rapidly in months prior to clinical signs Total infectivity load grows rapidly in months prior to clinical signs Human exposure Human exposure Contamination of AMR Contamination of AMR Consumption of variety meats Consumption of variety meats

11. 11 Model is Probabilistic Initialize Model Run Simulation Record Results Run 3 Run 2 Run 1 … Run 5000 Number of Infected Cattle over 20 Years

12. 12 Predicted BSE Spread Base Case Introduce 10 BSE infected animals Introduce 10 BSE infected animals On average, 4.3 new cases in the 20 years that follow On average, 4.3 new cases in the 20 years that follow

13. 13 Predicted BSE Spread 500 Infected Cattle Introduced Same type of result when more cattle introduced Same type of result when more cattle introduced

14. 14 Probability that Disease is Eliminated Within 20 Years

15. 15 Human Exposure Total human exposure in 20 years -- 40 Cattle oral ID 50 s Total human exposure in 20 years -- 40 Cattle oral ID 50 s Tissue Proportion of Human Exposure Advanced Meat Recovery (AMR) 51% Brain24% Beef on Bone 12% Spinal Cord 9% Other3%

16. 16 Risk Management Scenarios Analyzed Decrease Relative to the Base Case Scenario Number of Additional Infected Cattle Human Exposure Specified Risk Materials (SRM) ban 90%95% Ban on rendering of animals that die prior to slaughter 80%20%

17. 17 Sensitivity Analysis: Additional Infected Animals

18. 18 Sensitivity Analysis: Potential Human Exposure

19. 19 Findings Outcome following an introduction Outcome following an introduction Incidence tends to decrease with time (R 0 < 1) Incidence tends to decrease with time (R 0 < 1) After 20 years, BSE is most likely eliminated from U.S. After 20 years, BSE is most likely eliminated from U.S. Results hold regardless of source (live animals or feed) Results hold regardless of source (live animals or feed) Human exposure is limited Human exposure is limited Orders of magnitude less than UK Orders of magnitude less than UK AMR, brain, beef on bone, and spinal cord are responsible for the bulk of the exposure AMR, brain, beef on bone, and spinal cord are responsible for the bulk of the exposure

20. 20 Findings Risk mitigation measures Risk mitigation measures Eliminate CNS material from animal feed and human food Eliminate CNS material from animal feed and human food Stop rendering of animals that die before slaughter Stop rendering of animals that die before slaughter Key sources of uncertainty Key sources of uncertainty Compliance with feed ban Compliance with feed ban

21. 21 Summer, 2003 Analysis of the Canadian BSE Case Considered various introductions of BSE into the U.S. from Canada Considered various introductions of BSE into the U.S. from Canada Live cattle imports – Five infected bulls Live cattle imports – Five infected bulls Contaminated feed imports – Material from five infected animals (adjusted for processing, etc.) Contaminated feed imports – Material from five infected animals (adjusted for processing, etc.) Time of introduction ranging from 1990 to 1998 Time of introduction ranging from 1990 to 1998 Model run through 2020 Model run through 2020

22. 22 Live Cattle Imports

23. 23 Contaminated Feed Imports

24. 24 Findings Timing of introduction matters Timing of introduction matters Contaminated feed produces more cases than imports of infected animals Contaminated feed produces more cases than imports of infected animals Most infectivity in cattle is not fed back to cattle Most infectivity in cattle is not fed back to cattle Virtually all introductions yield too few clinical cases to be confident that they would be found by surveillance Virtually all introductions yield too few clinical cases to be confident that they would be found by surveillance Introduction of feed ban in 1997 reverses growth and starts toward elimination Introduction of feed ban in 1997 reverses growth and starts toward elimination