1. Harvard Center for Risk Analysis Evaluation of the Potential for BSE in the United States Joshua T. Cohen Keith Duggar George M. Gray Silvia Kreindel Harvard Center for Risk Analysis Harvard School of Public Health Hatim Abdelrahman Tsegaye HabteMariam David Oryang Berhanu Tameru Center for Computational Epidemiology College of Veterinary Medicine Tuskegee University

2. Harvard Center for Risk Analysis What USDA Asked Us to Do Identify and characterize possible sources for BSE (or a TSE disease with similar clinical and pathologic signs as BSE - will refer to as BSE for brevity) infectivity in U.S. cattle Identify and characterize pathways for cattle-derived BSE infectivity in the U.S. cattle herd or human food supply Evaluate implications over time of possible introduction of BSE into US system

3. Harvard Center for Risk Analysis How We Got Involved HSPH/HCRA Group with long history in risk analysis of hazards to human health and the environment Expertise in methods of risk analysis Multidisciplinary approach TU/CCE Expertise in the integration of quantitative modeling, expert systems and operations research methods in studying the epidemiology of health systems Strong record of work on animal health issues

4. Harvard Center for Risk Analysis Our Approach Understand the science Describe potential pathways of BSE infectivity to U.S. herd or food supply Build quantitative model Characterize the response of the US system BSE

5. Harvard Center for Risk Analysis Learning from UK Experience We assume the prevailing hypothesis of UK BSE spread is correct: Rendering Feed BSE Cattle Scrapie? Spontaneous ?

6. Harvard Center for Risk Analysis Cattle Population Number Infected Number Clinical Slaughter Rendering and Feed Production Infectivity Sources Human Food Disposal Death and Disposal Other Uses and Elimination from System Other Protein Sources Feed Administered to Cattle Death and Rendering Simulation Overview

7. Harvard Center for Risk Analysis Important Attributes of Model Built up from knowledge of science and agriculture system Probabilistic - results are distributions Infectivity characterized as cattle oral ID 50 s Characterize average situation across the US

8. Harvard Center for Risk Analysis Key Assumptions

9. Harvard Center for Risk Analysis Relationship between time since infection and the fraction of maximal level of ID 50 s Key Assumptions

10. Harvard Center for Risk Analysis Inspection 3.1.2.9 Tissues for Possible Human Consumption 5.2.10 AMR/ Spinal Cord/DRG 3.1.2.7 Processing 3.1.2.9 The Slaughter Process Out

11. Harvard Center for Risk Analysis Analyses Base Case Assume BSE not currently present in US Introduce 10 BSE infected animals (also simulated importation of 1 to 500 BSE infected cows) Follow for 20 years Example Risk Management Options Ban on rendering cattle that die on farm UK-style “Specified Risk Material” ban Test with introduction of 10 infected animals and follow for 20 years Others Potential for pre ‘89 imports from England to introduce BSE to US Switzerland Spontaneous Scrapie as source

12. Harvard Center for Risk Analysis Results: Introduction of 10 Infected Cattle after 20 Years Few new cases of BSE (mean 2.9, 95 th 11) Primarily through feed ban leaks 40% of animals predicted to die on farm introduce 96% of infectivity to system BSE gone within 20 years of introduction Little infectivity for potential human exposure (mean 35 cattle oral ID 50 s, 95 th 170) Brain26% Beef on bone11% AMR meat56% Spinal Cord 5% Conservative assumptions (e.g, no change if case detected)

13. Harvard Center for Risk Analysis

17. Other Importations

18. Harvard Center for Risk Analysis Key Uncertainties

19. Harvard Center for Risk Analysis Results: Risk Management Options Evaluate 2 potential risk management options - test with 10 imported BSE cows UK-style ban on specified risk material (brain, spinal cord, etc) in human and animal food Reduces BSE cases by 80% Reduces potential human exposure by 95% Ban on rendering cattle that die on the farm Reduces BSE cases by 77% Reduces potential human exposure by 20% Managing risk upstream makes feed ban compliance less important

20. Harvard Center for Risk Analysis

24. Imports from England before 1989 Evaluated potential for 173 (of 334) English imports not known to have been destroyed to introduce infectivity to US cattle and implications Used information on birth year, export year, animal type and sex, last sighting and more to estimate likelihood and potential magnitude of introductions of BSE infectivity to US cattle feed Used model to look at new BSE cases if introduction of different sizes did occur

25. Harvard Center for Risk Analysis Results: Introduction of Infectivity through UK Imports 82% chance of no introduction Most introduction give no new cases Surveillance rules out big introductions If introduced, is on course for elimination

26. Harvard Center for Risk Analysis Cumulative Distribution for U.S. Cattle Exposure to Cattle Oral ID 50 s from Animals Imported from England during the 1980s

27. Harvard Center for Risk Analysis Cumulative Distribution for the Number of BSE-Clinical Cattle in the Year 2000 for Different Levels of Infectivity Introduced via Import of UK Cattle During the 1980s

28. Harvard Center for Risk Analysis Other Results: Switzerland Test of model plausibility Reasonably reproduces time course and size of Swiss BSE outbreak Spontaneous If true would result in mean of 2 cases per year and <100 cattle oral ID 50s to humans over 20 years Test in absence of feed ban casts some doubt of plausibility of this hypothesis Scrapie If transmission possible (no American scrapie can infect cattle) predict mean of 2 BSE cases/yr <100 cattle oral ID 50s to humans over 20 years

29. Harvard Center for Risk Analysis Summary We have assessed the potential for BSE/TSE infectivity to spread in the US dairy/beef cattle population and in the U.S. food supply if it were to arise here We have constructed a simulation model to explore the dynamics of BSE following an introduction and to quantitatively evaluate the relative risk of specific pathways

30. Harvard Center for Risk Analysis Summary We find that the US is highly resistant to BSE and any plausible introduction yields few new cases of disease and dies out within 20 years. Human exposure to infectious cattle tissues is quite low Spread in cattle herd Mostly due to leaks in FDA feed ban and some maternal transmission Animals that die on farm with provide greatest infectivity to animal feed system Potential human exposure Handling of brain and spinal cord in processing very important Primary routes of exposure are cattle brain, spinal cord, beef on bone and AMR meat

31. Harvard Center for Risk Analysis Summary Cattle imported from UK between 1980 and 1989 have small chance of having put BSE into US herd - would be on the way to elimination if introduced Our approach supported by ability to reasonably mimic Swiss BSE outbreak Cross-species transmission of Scrapie or Spontaneous BSE, if real would result in a couple of cases of BSE and fewer than 5 cattle oral ID 50 s for potential human exposure each year Our model is useful for evaluating potential further risk management strategies

32. Harvard Center for Risk Analysis Thank You!