1	Analyzing Potential Pathways for BSE to Cattle or Human Food
2	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	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	What We Are Doing Characterizing knowledge of BSE and other TSEs Developing tool to help evaluate the robustness of US protection systems Identifying key processes or pathways that influence spread of BSE to animals or humans if it is introduced to the US system Pointing out important data gaps
5	What We are Not Doing Generating estimate of risk of BSE in US Suggesting risk of vCJD in US Making policy recommendations
6	What is BSE? Bovine Spongiform Encephalopathy A Transmissible Spongiform Encephalopathy (TSE) of cattle Fatal neurodegenerative disease characterized by spongiform changes in the brain First recognized in cattle in the Britain in 1986
7	Transmissible Spongiform Encephalopathies Humans Kuru Crutzfeld-Jacob Disease (CJD) (nvCJD) Fatal Familial Insomnia, etc. Animals: BSE (cattle) Scrapie (sheep and goats) Chronic Wasting Disease (CWD) (deer and elk) Transmissible Mink Encephalopathy (mink) Others….
8	Characteristics of TSEs All cause fatal spongiform changes in the brain Long incubation period Pathogenesis poorly understood Infectivity often concentrated in CNS tissues Infective agent unknown, current hypotheses focus on prions
9	Confirmed Cases of BSE in UK (1986-Nov 1998)
10	Theory for BSE in UK
11	Major Assumption Prevailing hypothesis of UK BSE origin and spread is correct: BSE came from scrapie or spontaneous case Spread through oral exposure to infective material derived from diseased animals with some maternal transmission UK case born “after the ban” and other examples indicate some uncertainty in these assumptions
12	Current US BSE Protection Measures Importation ban – cattle and beef UK since 1989 All Europe since 1997 Prohibit all imports of rendered animal products from Europe Interagency Surveillance Program BSE Emergency Response Plan FDA feed ban
13	Challenges for Modeling BSE Latent period between infection and symptoms Changing levels of infectivity Changing sites of infectivity Many pathways of concern involve circumvention of current rules and regulations Numerous sources of uncertainty and gaps in data
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15	Important Attributes of Model Infectivity characterized as cattle oral ID_50s Use linear model of infectivity with no threshold One cattle oral ID₅₀ fed back to cattle will cause 0.5 cases of disease on average No experimental or analytic estimate of threshold “Conservative” model in that true dose-response is unlikely to give higher estimates of risk Characterize average situation across the US
16	Potential Sources of BSE/TSE Importation of infected animals/products Transmission from other species Spontaneous case
17	Sources Summary We consider importation of infectivity to be unlikely but retain the ability to model effects of importing infected animals or feed components We model rendering of sheep as potential routes of other TSEs to cattle feed The evaluate but do not model the potential for CWD as a source through rendering or lateral transmission IF spontaneous BSE does occur it is likely at a low rate (approximately 1 detectable case every 7 years in US) and can be included in model estimates
18	Cattle Population Model different groups of bovines that will have different potential exposure to BSE infectivity or potential to develop disease Beef (production and breeding stock) Dairy (production and breeding stock) Males and females Characterize rates at which different groups are born, die, are slaughtered When BSE is introduced, monitor number of infected and number of clinical animals
19	Pathways to Human Food and Cattle Feed Model pathways by which BSE infectivity could enter the US human or cattle food supply if it were present in a bovine Important for understanding dynamics of process and potential for cattle epidemic or significant human exposure to cattle TSE agent Model passes simulated animal through slaughter, rendering, feed production and farm use of feed
20	Slaughter Model slaughter and processing for points at which infectivity could become available for animal or human exposure Evaluate “potential human exposure” without explicit consideration of consumption, waste, and other factors Infected tissues not taken for human consumption go to rendering
21	Rendering and Feed Production Model progress of infected material through rendering and feed production Some reduction of infectivity in rendering process Consider possibility of noncompliance with FDA feed ban - few data to make confident predictions Mislabeling Contamination Misfeeding on the farm
22	System Dynamics A major concern about occurrence of BSE/TSE is potential for a UK-like epidemic in the US Development of additional cases requires infectivity to get from initial case to others If one case can give rise to more than one new case, an epidemic could develop. If each case gives rise to less than one new case, on average, the disease will die out The model follows US cattle over time and uses the pathways to move infectivity into the population
23	System Dynamics (cont.) The model reflects important attributes for development of BSE/TSE Type of bovine (beef or dairy) Age of animal Susceptibility to infection if exposed Feeding practices Time since infection Development of infectivity Slaughter and death rates The model reports annual counts of animals, animals that are born, die, and are slaughtered as well as number of infected animals
24	System Dynamics - Key Uncertainties Age dependence of susceptibility Time course of development of infectivity and infectious tissues Feeding practices - how much animal protein of what types is fed to cattle? Lesser uncertainties include population demographics
25	Potential Uses of the Model Evaluating the response of the US system to an external challenge Characterization of important gaps in knowledge or data Identification of potential risk management actions
26	Summary We are assessing 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 Our method of analysis involves definition and characterization of pathways by which infectivity could enter the herd or food supply 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
27	Summary Our model allows evaluation of the relative contribution of different pathways to the spread of infectivity to cattle or for potential human exposure The dynamic nature of the model allows characterization of the likelihood of an epidemic or of the disease dying out The model has many potential applications in BSE risk management
28	Thank You!