Predicting human dose-response relationships from multiple biological models: Issues with Cryptosporidium parvum

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Predicting human dose-response relationships from
multiple biological modelsIssues with
Cryptosporidium parvum
Risk Assessment Consortium
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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

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Outbreaks of Cryptosporidiosis Associated with
Drinking Water - United States, 1984 - 1995
WASHINGTON
WAWALLA WALLA
READING
1994 (113)
1991 (551)
OREGON
MEDFORD
WISCONSIN

MILWAUKEE
TALENT
1993 (400,000)
1992 (3,000)
PENNSYLVANIA
NEVADA
LAS VEGAS
1993 ( ? )
CARROLLTON
1987 (13,000)
NEW MEXICO
GEORGIA
TEXAS
SAN ANTONIO
1984 (2,000)
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Foodborne Outbreaks of Cryptosporidiosisin the
United States
Suspect Food
Est. Cases
How Contaminated
Location
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
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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

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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

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Dose-response Introduction

• Pathogen, host and environment are all factors
• Complex relationship to predict

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What is the RAC?

• An inter-agency, interdisciplinary group
• Working collectively to enhance communication and
  coordination between federal agencies

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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.

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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 Womens Health, FDA

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Understanding Microbial Dose-Response

• Efforts of the RAC
• Dose-response workgroup
• Interest in development of plausible
  dose-response models

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Understanding Microbial Dose-Response

• Efforts of the RAC
• Dose-response workgroup
• Cooperative Agreements
• Relating Numbers of Foodborne Pathogens to Human
  Illness

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Why are we here today?

• Cryptosporidium was selected for this meeting
  because the body of evidence is extensive

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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?