1. Predicting human dose-response relationships from multiple biological models: Issues with Cryptosporidium parvum Risk Assessment Consortium

2. Cryptosporidiosis: Introduction Cryptosporidium parvum –coccidian protozoan –recognized as human pathogen in 1976 In the 1990s –one of the leading known causes of waterborne disease outbreaks –important OI among HIV (+) persons –important cause of diarrhea outbreaks in day care centers

3. Outbreaks of Cryptosporidiosis Associated with Drinking Water - United States, 1984 - 1995 OREGON WASHINGTON TEXAS WISCONSIN GEORGIA NEVADA PENNSYLVANIA CARROLLTON 1987 (13,000) LAS VEGAS 1993 ( ? ) READING 1991 (551) 1994 (113) WAWALLA WALLA 1992 (3,000) MEDFORD TALENT & MILWAUKEE 1993 (400,000) 1984 (2,000) SAN ANTONIO NEW MEXICO

4. Foodborne Outbreaks of Cryptosporidiosis in the United States Suspect Food Est. Cases Location How Contaminated Chicken Salad Green Onions Green/Fruit Salad Apple Cider (homemade) Apple Cider (commercial) Minnesota Washington Washington DC Maine New York 15 54 101 160 31 Food Handler ? Food Handler / Field Food Handler Cattle Feces in Field ? Rinse Water

6. Dose-response Introduction The determination of the relationship between the magnitude of exposure (dose) to a chemical, biological or physical agent and the severity and/or frequency of associated adverse health effects (response). Relate the level of a biological agent ingested with the frequency of infection or disease

7. Dose-response Introduction Relate the level of a biological agent ingested with the frequency of infection or disease A variety of endpoints may be considered

8. Dose-response Introduction Pathogen, host and environment are all factors Complex relationship to predict

9. What is the RAC? An inter-agency, interdisciplinary group Working collectively to enhance communication and coordination between federal agencies

10. What is the RAC? An inter-agency, interdisciplinary group Promoting the conduct of scientific research that will facilitate risk assessments and assist the regulatory agencies in fulfilling their specific food-safety risk management mandates.

11. Who are the members of the RAC? U.S. Department of Agriculture Animal and Plant Health Inspection Service Cooperative State Research, Education, and Extension Service Agricultural Research Service Economic Research Service Food Safety and Inspection Service Office of Risk Assessment and Cost Benefit Analysis Environmental Protection Agency Office of Water Office of Prevention, Pesticides and Toxic Substances Office of Research and Development Department of Commerce National Marine Fisheries Service Department of Defense Veterinary Service Activity Department of Health and Human Services Center for Veterinary Medicine, FDA National Center for Food Safety and Technology, FDA National Center for Toxicological Research, FDA Centers for Disease Control and Prevention National Institutes of Health Center for Food Safety and Applied Nutrition, FDA Office of Women’s Health, FDA

12. Understanding Microbial Dose- Response Efforts of the RAC Dose-response workgroup Interest in development of plausible dose-response models

13. Understanding Microbial Dose- Response Efforts of the RAC Dose-response workgroup Cooperative Agreements Relating Numbers of Foodborne Pathogens to Human Illness

14. Why are we here today? Cryptosporidium was selected for this meeting because the body of evidence is extensive

15. Why are we here today? What lessons can we learn from Cryptosporidium dose-response modeling that can inform model systems for other pathogens? How useful are different biological models as a source of data for modeling human dose-response relationships?