Quantitative Risk Assessment on the Public Health Impact of Pathogenic Vibrio parahaemolyticus in Raw Oysters

TABLE OF CONTENTS

INTERPRETIVE SUMMARY (also available in PDF)

TECHNICAL DOCUMENT (also available in PDF)

• EXECUTIVE SUMMARY

1. INTRODUCTION
   • Background
   • Scope
   • Risk Assessment Overview
   • Using the Model as a Tool: "What-If" Scenarios
2. HAZARD IDENTIFICATION
   • Vibrio parahaemolyticus
   • Illnesses Caused by Vibrio parahaemolyticus
   • At-Risk Populations
   • Annual Incidence
   • Outbreaks and Sporadic Cases
   • Implicated Foods
   • Seasonality
   • Geographic Distribution of Illness
   • International Reports of Vibrio parahaemolyticus Cases
3. HAZARD CHARACTERIZATION/DOSE-RESPONSE
   • Factors Influencing the Dose-Response Relationship
   • Human Clinical Feeding Studies
   • Animal Studies
   • Epidemiological Data
   • Data Selection and Criteria for the Dose-Response Model
   • Modeling the Dose-Response Relationship
4. EXPOSURE ASSESSMENT
   • Harvest Module
     • Data Selection and Criteria for the Harvest Module
     • Modeling the Harvest Module
     • Output of the Harvest Module
   • Post-Harvest Module
     • Data Selection and Criteria for the Post-Harvest Module
     • Modeling the Post-Harvest Module
     • Output of the Post-Harvest Module
   • Consumption Module
     • Data Selection and Criteria for the Consumption Module
     • Modeling the Consumption Module
     • Output of the Consumption Module
5. RISK CHARACTERIZATION
   • Simulations
   • Predicted Illness Burden
   • Uncertainty Distributions of Predicted Illness
   • Sensitivity Analysis
   • Model Validation
6. WHAT-IF SCENARIOS
   • Mitigation Strategies
   • Mitigations Scenarios
7. INTERPRETATION AND CONCLUSIONS

• REFERENCES

APPENDICES (also available in PDF)

• Appendix 1: Chronology of Technical and Scientific Reviews of the FDA   Vibrio Parahaemolyticus Risk Assessment Document
• Appendix 2: Response to Public Comments
• Appendix 3: The Vibrio Parahaemolyticus Risk Assessment Simulation Model
• Appendix 4:  Details of the Data Analysis for the Hazard Characterization Component of the Vibrio Parahaemolyticus Risk  Assessment Model
• Appendix 5:  Details of the Data Analysis for the Exposure Assessment Component of the Vibrio Parahaemolyticus Risk Assessment Model
• Appendix 6: Regression-Based Sensitivity Analyses to Determine Influential Variability and Uncertainty Parameters
• Appendix 7: Actual Values Predicted by the Risk Assessment Model
• Appendix 8: Additional Uncertainty Analyses
• Appendix 9: Comparison of Model-Predicted Vibrio parahaemolyticus Illnesses and Surveillance Data
• Appendix 10: Additional Information:  What-If Scenarios
• Appendix 11: Data Gaps and Future Research Needs
• Appendix 12: Response to Comments Provided by a Review of the Modeling Techniques Used

LIST OF TABLES

• Summary Table 1. Predicted Mean Risk per Serving Associated with the Consumption of Vibrio parahaemolyticus in Raw Oysters
• Summary Table 2. Predicted Mean Annual Number of Illnesses Associated with the Consumption of Vibrio parahaemolyticus in Raw Oysters
• Table II-1.  Clinical Symptoms Associated with Gastroenteritis Caused by Vibrio parahaemolyticus   
• Table II-2. Outbreaks of Illnesses from Vibrio parahaemolyticus Associated with Consumption of Raw Oysters in the United States
• Table II-3.  Culture-confirmed Vibrio parahaemolyticus Illnesses Associated with Consumption of Oysters    
• Table III-1.  Summary of Criteria and Selection of Human Clinical Feeding Studies for Dose-Response Modeling
• Table III-2.  Summary of Data from the Human Feeding Trial Studies Used for the Vibrio parahaemolyticus Dose-Response Model
• Table III-3. Dose-Response Model Equations for the Probability of Illness as a Function of Ingested Dose      
• Table III-4. Probability of Septicemia in Patients with Gastroenteritis from V. parahaemolyticus Infection      
• Table IV-1a.  Summary of Criteria and Selection of Data for the Regional and Seasonal Distribution of Water Temperature
• Table IV-1b.  Summary of Criteria and Selection of Data on the Relationship between Vibrio parahaemolyticus (Vp) Levels in Oysters and Water Temperature
• Table IV-1c.  Summary of Criteria and Selection of Data to Define the Ratio of Pathogenic to Total V. parahaemolyticus (Vp) Levels in Oysters
• Table IV-2. Summary Statistics of Midday Water Temperature Distributions for Different Regions and Seasons
• Table IV-3.  Summary of Data Used for Modeling the Effect of Water Temperature on Total Vibrio parahaemolyticus Densities
• Table IV-4. Estimates of Mean Pathogenic Vibrio parahaemolyticus as a Percentage of Total Vibrio parahaemolyticus
• Table IV-5. Estimate of the Mean of Distributions of Percentage Pathogenic Vibrio parahaemolyticus in Oysters
• Table IV-6.  Predicted Mean Levels of Vibrio parahaemolyticus per gram in Oysters at Harvest        
• Table IV-7. Mean Differences between Air and Water Temperature Distributions from Various Regions at Midday
• Table IV-8. Duration of Oyster Harvesting Operation for Each Region and Season Combination           
• Table IV-9. Discrete Approximation of Variation in the Growth Rate of Vibrio parahaemolyticus during a Cooldown Period of T Hours
• Table IV-10. Cold Storage Time between First Refrigeration and Retail
• Table IV-11.  Predicted Mean Levels of Total and Pathogenic Vibrio parahaemolyticus per Gram in Oysters Post-Harvest
• Table IV-12. Summary of Criteria and Selection of Data Used for the Number of Oysters per Serving   70
• Table IV-13. National Marine Fisheries Service (NMFS) Average Yearly Oyster Landings from 1990 to 1998 73
• Table IV-14.  Annual Number of Raw Oyster Servings Used in the Model for Each Region and Season Combination
• Table IV-15. Predicted Mean Levels of Total and Pathogenic Vibrio parahaemolyticus per Serving of Oysters at Consumption
• Table V-1. Predicted Mean Risk per Serving Associated with the Consumption of Vibrio parahaemolyticus in Raw Oysters
• Table V-2. Predicted Annual Number of Illnessess Associated with the Consumption of Vibrio parahaemolyticus in Raw Oysters
• Table V-3. Predicted Mean Number of Cases of Vibrio parahaemolyticus Septicemia Associated with the Consumption of Raw Oysters
• Table V-4.  Variability Factors from Tornado Plots for Each Region and Season Combination
• Table V-5.  Importance of Selected Uncertainty Factors Based on Reduction in the Variance of the Uncertainty Distribution of the Mean Risk per Serving for the Gulf Coast (Louisiana) Summer Harvest
• Table VI-1.  Summary of Mitigation Strategies and Typical Effectiveness in Reducing Levels of Vibrio parahaemolyticus in Oysters
• Table VI-2.  Predicted Mean Number of Illnesses per Annum from Reduction of Levels of Pathogenic Vibrio parahaemolyticus in Oysters
• Table VI-3. Effect of Overnight Submersion of Oysters during Intertidal Harvest on Predicted Risk in the Pacific Northwest Harvest Region
• Table VII-1. Predicted Mean Levels of Total and Pathogenic Vibrio parahaemolyticus in Raw Oysters At-Harvest
• Table VII-2. Predicted Mean Levels of Pathogenic Vibrio parahaemolyticus per Serving in Raw Oysters At-Harvest and At-Consumption
• Table VII-3. Predicted Mean Annual Number of Illnesses Associated with the Consumption of Vibrio parahaemolyticus in Raw Oysters
• Table VII-4.  Predicted Mean Number of Illnesses per Annum from Reduction of Levels of Pathogenic Vibrio parahaemolyticus in Oysters
• Table VII-5.  Effect of Compliance with Guidance Levels for Vibrio parahaemolyticus In Raw Oysters At-Harvest and At-Retail for the Gulf Coast (Louisiana)/ Summer Harvest

LIST OF FIGURES

• Figure I-1.  Overview of Vibrio parahaemolyticus Risk Assessment Document
• Figure III-1.  Schematic Representation of the Development of the Vibrio parahaemolyticus Dose-Response Model
• Figure III-2.  Comparison of the Beta-Poisson, Gompertz, and Probit Dose-Response Models Fit to Data from Human Feeding Studies
• Figure III-3.  The Beta-Poisson Dose-Response Model for Vibrio parahaemolyticus Fit to Human Feeding Trials and Adjusted Using Epidemiological Surveillance Data
• Figure III-4.  Vibrio parahaemolyticus Dose-Response Curve and Uncertainty
• Figure IV-1.  Schematic Representation of the Exposure Assessment Component of the Vibrio parahaemolyticus (Vp) Risk Assessment Model
• Figure IV-2. Schematic Depiction of the Harvest Module of the Vibrio parahaemolyticus (Vp) Exposure Assessment Model
• Figure IV-3. Tobit Regression Fit of Vibrio parahaemolyticus Densities in Oysters Versus Water Temperature Using the DePaola et al. (1990) Data Set
• Figure IV-4. Tobit Regression Fit of the Vibrio parahaemolyticus Densities in Oysters Versus Water Temperature Using the FDA/ISSC (2001) Data Set
• Figure IV-5. Tobit Regression Fit of the Vibrio parahaemolyticus Densities in Oysters Versus Water Temperature Using the Washington State Department of Health (2002a) Data Set
• Figure IV-6. Schematic Depiction of the Post-Harvest Module of the Vibrio parahaemolyticus Exposure Assessment Model
• Figure IV-7. Predicted Mean Loglinear Growth of Vibrio parahaemolyticus in Oysters from an Initial Density of 1,000 (3-log₁₀) Vibrio parahaemolyticus per gram as a Function of Ambient Air Temperature    
• Figure IV-8.  Example Beta-PERT Probability Density Distribution for Duration of Oyster Harvesting   
• Figure IV-9. Schematic Depiction of the Consumption Module of the Vibrio parahaemolyticus Exposure Assessment Model
• Figure IV-10. Self-reported Frequency of Number of Oysters Consumed per   Serving.
• Figure V-1. Schematic Representation of the Vibrio parahaemolyticus Risk Assessment Model 
• Figure V-2.  Uncertainty Distributions of the Annual Number of Vibrio parahaemolyticus Illnesses Associated with Spring and Summer Mid-Atlantic Harvests
• Figure V-3. Influence of Water Temperature on Variation of Mean Risk per Serving for Each Region    
• Figure V-4. Tornado Plot of Influential Variability Factors on Vibrio parahaemolyticus (Vp) Illness per Serving of Raw Oysters for the Gulf Coast (Louisiana) Winter Harvest.
• Figure V-5. Tornado Plot of Influential Variability Factors of Vibrio parahaemolyticus (Vp) Illness per Serving of Raw Oysters for the Gulf Coast (Louisiana) Summer Harvest
• Figure V-6. Tornado Plot of Influential Variability Factors on Vibrio parahaemolyticus (Vp) Illness per Serving of Raw Oysters for the Pacific Northwest Coast (Intertidal) Spring Harvest
• Figure V-7. Tornado Plot of Influential Variability Factors on Vibrio parahaemolyticus (Vp) Illness per Serving of Raw Oysters for the Pacific Northwest Coast (Intertidal) Winter Harvest
• Figure V-8. Correlation of Risk per Serving and Total Vibrio parahaemolyticus in Oysters at Harvest for the Gulf Coast (Louisiana) Summer.
• Figure V-9. Observed log₁₀ Density of Total Vibrio parahaemolyticus at Retail (Cook et al., 2002a) Compared to Model Predictions for the Gulf Coast (Louisiana) Harvest.
• Figure V-10. Observed log₁₀ Density of Total Vibrio parahaemolyticus at Retail (Cook et al., 2002a) Compared to Model Predictions for the Gulf Coast (non-Louisiana) Harvest.
• Figure V-11.  Observed log₁₀ Density of Total Vibrio parahaemolyticus at Retail (Cook et al., 2002a) Compared to Model Predictions for the Mid-Atlantic Coast Harvest
• Figure V-12. Observed log₁₀ Density of Total Vibrio parahaemolyticus at Retail (Cook et al., 2002a) Compared to Model Predictions for the Pacific Northwest (Dredged and Intertidal) Region [The error bars indicate one standard deviation above and below either the model predictions (square boxes) or observed values (filled circles).]
• Figure V-13. Observed log₁₀ Density of Total Vibrio parahaemolyticus at Retail (Cook et al., 2002a) Compared to Model Predictions for the Gulf Coast (Lousisana and non-Lousisana) Based on 1998 Fall Temperature [The error bars indicate one standard deviation above and below either the model predictions using average temperatures (open square boxes) model prediction using only 1998 temperature data (filled square box) or observed values (filled circles).]
• Figure V-14. Observed Log₁₀ Density of Total Vibrio parahaemolyticus for the Pacific Northwest (Intertidal) Region (WA State Department of Health, 2002a) Compared to Model Predictions
• Figure VI-1. Schematic Representation from Harvest to Retail Showing Steps at which Evaluated Mitigations Occur
• Figure VI-2. Effect of Potential Mitigations on the Distribution of Probable Number of Illnesses Associated with Vibrio parahaemolyticus in Oysters Harvested from the Gulf Coast (Louisiana) in the Summer    
• Figure VI-3. Effect of Potential Mitigations on Mean Risk of Vibrio parahaemolyticus Illnesses per Serving Associated with the Gulf Coast (Louisiana) Harvest
• Figure VI-4. Effect of Potential Mitigations on Mean Risk of Vibrio parahaemolyticus Illnesses per Serving Associated with the Gulf Coast (Non-Louisiana) Harvest
• Figure VI-5.  Effect of Potential Mitigations on Mean Risk of Vibrio parahaemolyticus Illnesses per Serving Associated with the Mid-Atlantic Harvest
• Figure VI-6. Effect of Potential Mitigations on Mean Risk of Vibrio parahaemolyticus Illnesses per Serving Associated with the Northeast Atlantic Harvest
• Figure VI-7. Effect of Potential Mitigations on Mean Risk of Vibrio parahaemolyticus Illnesses per Serving Associated with the Pacific Northwest (Dredged) Harvest
• Figure VI-8. Effect of Potential Mitigations on Mean Risk of Vibrio parahaemolyticus Illnesses per Serving Associated with the Pacific Northwest (Intertidal) Harvest
• Figure VI-9. Predicted Effectiveness of Rapid versus Conventional Cooling on Vibrio parahaemolyticus Risk for Gulf Coast Summer Harvest
• Figure VI-10.  Predicted Effect of Control of Total Vibrio parahaemolyticus per Gram Oysters at Time of Harvest for the Gulf Coast (Louisiana) Summer Harvest
• Figure VI-11.  Predicted Effect of Control of Total Vibrio parahaemolyticus per Gram Oysters at Retail for the Gulf Coast (Louisiana) Summer Harvest

RESPONSE TO PUBLIC COMMENTS

A notice of availability of the Food and Drug Administration (FDA) draft risk assessment on the relationship between Vibrio parahaemolyticus in raw molluscan shellfish and public heath was published in the Federal Register of January 19, 2001 (66 FR 5517).  A comment period was established during which FDA actively sought comments, suggestions, and additional data sources.  The results of the draft risk assessment were presented for clarification during a public meeting on March 20, 2001 (66 FR 13544).  Comments were submitted to the FDA Docket (No. 99N-1075) from nine institutions or individuals.  The data and information acquired during the comment period were reviewed and used, as appropriate, to further enhance the risk assessment. 

We appreciate the time and effort expended to submit these comments, and have addressed these in this revised risk assessment to the best of our ability.  A summary of the modifications made to the draft risk assessment in response to the comments, new data and modeling techniques is provided below.  A more detailed discussion of our response to the public comments can be found in Appendix 2.

Modifications Made to the 2001 Draft Vibrio parahaemolyticus Risk Assessment

Topic	Modifications
Assumptions	Additional information was obtained that further the following assumptions: Growth rates of pathogenic and non-pathogenic V. parahaemolyticus are similar; Time required for refrigerated oysters to cool down to temperatures that do not support the growth of V. parahaemolyticus is variable and may range from 1 to 10 hours.
Additional Data/ Information	Prevalence of total and pathogenic V. parahaemolyticus at harvest for Pacific Northwest region (PNW) and Gulf Coast regions; Relationship between water temperature and V. parahaemolyticus levels in oysters; Time-to-refrigeration after harvest for the PNW region.
Modeling techniques	Included intertidal harvesting in the PNW as an additional harvest region; Evaluated mitigation effect of specific reduction levels of  V. parahaemolyticus in addition to types of interventions; Included regression-based sensitivity analysis; Added two additional uncertainty parameters (total V. parahaemolyticus in oysters based on water temperature and dose-response relationship) to the examination of factors that influence risk predictions; Oyster meat weights at retail were used rather than those at harvest; Comparison of the model-predicted number of illnesses using both retail survey and epidemiological data

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CONTRIBUTORS (2004 Version)

Team Leader:	Marianne Miliotis
Project Manager:	Marianne Miliotis
Risk Analysis Coordinator:	Sherri Dennis
Scientific Advisor:	Robert Buchanan

Team Members

Modeling:

• John Bowers
• Mark Walderhaug

Exposure Assessment:

• David Cook
• Angelo DePaola
• Elisa Elliot
• Charles Kaysner
• Marleen Wekell
• William Watkins

Hazard Characterization:

• Donald Burr

Epidemiology:

• Karl Klontz
• Marianne Ross

Technical Editing:

• Robert Buchanan
• Sherri Dennis
• Louise Dickerson
• Lori Pisciotta

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ACKNOWLEDGEMENTS (2004 Version)

The Vibrio parahaemolyticus  Risk Assessment team greatly appreciates the efforts of the following individuals who provided us with comments, information and assistance for this risk assessment:

• Linda Andrews (Mississippi State University)
• Enrico Buenaventura and Klaus Schalle (Canadian food Inspection Agency)
• Colleen Crowe, Patti Griffin, Arthur Liang, John Painter, Donald Sharp, Cynthia (Stover) Smith, and Robert Tauxe (CDC)
• Jessica DeLoach, Kathryn Lofi, Ned Therien, Jennifer Tibaldi, and Patti Waller (Washington State Department of Health)
• Robin Downey (Pacific Coast Shellfish Growers Association)
• Jeffrey Farber (Health Canada)
• Lee Hoines (Washington State Department of Fish and Wildlife)
• Mahendra Kothary (FDA/CFSAN)
• Donald Kraemer (FDA/CFSAN)
• Jeanette Lyon (FDA/CFSAN)
• Sherri McGarry (FDA/CFSAN)
• Michael Morrissey (Oregon State University)
• Lori Pisciotta (FDA/CFSAN)
• John Schwarz (Texas A&M University at Galveston)
• Jessica Tave (FDA)
• Ben Tall (FDA/CFSAN)
• FDA Regional Shellfish Experts (Marc Glatzer, Jeremy Mulnick, Tim Sample)
• Kirk Wiles (Texas State Health Department)

We are also deeply grateful to Sharon Edelson Mammel for evaluating the quality of data used in the model and to Louis Michael Thomas, Linda Shasti, and Aesha Minter, JIFSAN student interns, for assembling the references cited in the document.  We also thank CDC staff for their assistance in providing the epidemiological data used for the dose-response model and the data analysis used to compare the model predictions to the epidemiological data.  Our appreciation also goes to David Acheson (FDA), Robert Buchanan (FDA), Don Kraemer (FDA), Angela Ruple (NOAA Fisheries), and Richard Whiting (FDA) for reviewing and providing suggestions to improve the risk assessment documents.  The team is also appreciative of the in depth review and evaluation of the model conducted by Clark Carrington (FDA) and Darrel Donahue (University of Maine).

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CONTRIBUTORS (2001 Version)

The Vibrio parahaemolyticus risk assessment team members:

Team Leaders: Marianne Miliotis and William Watkins

Exposure Assessment - Harvest Module:
Marleen Wekell (Section Lead), Atin Datta, Elisa Elliot, Walter Hill, Charles Kaysner, Brett Podoski

Exposure Assessment - Post-Harvest Module:
Angelo DePaola and David Cook (Section Co-leads), George Hoskin, Susan McCarthy, William Watkins

Exposure Assessment - Consumption Module:
Michael DiNovi

Epidemiology:
Marianne Ross (Section Lead), Karl Klontz, Debra Street, Babgaleh Timbo

Hazard Characterization/Dose-Response:
Donald Burr (Section Lead), John Bowers, Mahendra Kothary, Wesley Long, Marianne Miliotis, Ben Tall, Mark Walderhaug

Modeling:
John Bowers (Section Lead), Mark Walderhaug

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ACKNOWLEDGEMENTS (2001 Version)

The following people provided the V. parahaemolyticus team with comments, information and assistance we needed to accomplish this risk assessment:

• Haejung An (Oregon State University)
• Fred Angulo, Mary Evans, Nicholas Daniels, Paul Mead and Malinda Kennedy (Centers for Disease Control)
• Robert Buchanan (FDA/CFSAN)
• Mercuria Cumbo (Department of Marine Resources, Maine)
• Sherri Dennis (FDA/CFSAN)
• Paul Distefano (FDA/CFSAN)
• Robin Downey (Pacific Coast Shellfish Growers Association)
• Jan Gooch (National Oceanographic Service)
• Michael Kelly (University of British Columbia)
• Bill Kramer (Environmental Protection Agency)
• Ken Moore, Sandra Sharp (Interstate Shellfish Sanitation Conference)
• Mitsuaki Nishibuchi (Kyoto University, Japan)
• Gary Richards (USDA/ARS)
• Tina Rouse (FDA/CFSAN)
• Angela Ruple (National Marine Fisheries Service)
• Patricia Schwartz (FDA/CFSAN)
• FDA Regional Shellfish Experts
• FDA Shellfish Sanitation Team
• Molluscan Shellfish Institute
• National Advisory Committee for Microbiological Criteria for Food (NACMCF)
• Shellfish Industry
• State Shellfish Experts
• State Health Departments

The team would especially like to thank the FDA/CFSAN Offices and Risk Assessment Consortium members for intensive review of the document in December, as well as Federal employees from other agencies, and Special Government Experts, for review of the document in May.  We are also deeply grateful to Lauren Posnick for her outstanding contribution in preparing the interpretive summary of this document, Carolyn Jeletic for excellent technical editing of this document, and Faye Feldstein for assisting with assembling all the references.