A Simulation Model to Quantify the Spread of BSE in the United States

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

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 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 • Reproductive constant of the disease (R0) • Extent of human exposure

4. Report History • Grant awarded to Harvard in 1998 • Report completed in November, 2001 • Report reviewed in 2002 under contract with RTI • H. Christopher Frey – University of North Carolina • John C. Galland – Kansas State University • 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) • Revised report accepted by USDA and released in October, 2003

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

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

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

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

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

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

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

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

13. Predicted BSE Spread500 Infected Cattle Introduced • Same type of result when more cattle introduced

14. Probability that Disease is Eliminated Within 20 Years

15. Human Exposure • Total human exposure in 20 years -- 40 Cattle oral ID50s

16. Risk Management Scenarios Analyzed

17. Sensitivity Analysis:Additional Infected Animals

18. Sensitivity Analysis:Potential Human Exposure

19. Findings • Outcome following an introduction • Incidence tends to decrease with time (R0 < 1) • After 20 years, BSE is most likely eliminated from U.S. • Results hold regardless of source (live animals or feed) • Human exposure is limited • Orders of magnitude less than UK • AMR, brain, beef on bone, and spinal cord are responsible for the bulk of the exposure

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

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

22. Live Cattle Imports

23. Contaminated Feed Imports

24. Findings • Timing of introduction matters • Contaminated feed produces more cases than imports of infected animals • 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 • Introduction of feed ban in 1997 reverses growth and starts toward elimination