The Food and Drug Administration (FDA) conducted a risk assessment to characterize the public health impact associated with consumption of raw oysters containing pathogenic Vibrio parahaemolyticus. This effort was initiated in January 1999, in response to four outbreaks occurring in the United States in 1997 and 1998 involving over 700 cases of illness, the majority of which were associated with the consumption of raw oysters. These events renewed concern for this pathogen as a serious foodborne threat to public health, given that the last outbreak in the United States occurred in 1981. In two of the 1998 outbreaks a serotype previously reported only in Asia, O3:K6, emerged as a principal cause of illness in the United States for the first time. The outbreaks also introduced uncertainty about the effectiveness of current criteria for closing and reopening shellfish waters to harvesting, and about previous FDA guidance indicating that no more than 10,000 V. parahaemolyticus per gram should be present in shellfish.
Input for this risk assessment was obtained from many sources, including both published and unpublished scientific literature and reports, State shellfish control authorities, the Centers for Disease Control and Prevention (CDC), the shellfish industry, the Interstate Shellfish Sanitation Conference (ISSC), and records from State Health Departments. During the development of this risk assessment model, information that was lacking was identified, and these gaps necessarily required certain assumptions to be made. The National Advisory Committee on Microbiological Criteria for Foods (NACMCF) reviewed each significant assumption included in the risk assessment.
The objectives of the risk assessment were twofold. One was to produce a mathematical model of the risk of illness incurred by consumers of raw oysters containing pathogenic V. parahaemolyticus. The second objective of this quantitative risk assessment was to provide FDA with information that will assist the agency with the review of current programs relating to the regulation of Vibrio parahaemolyticus in raw molluscan shellfish to ensure that such programs protect the public health. To accomplish this, the project sought to achieve the following: (a) evaluate the current criteria used for closing and reopening shellfish waters to harvesting, (b) evaluate preventive and intervention measures for controlling V. parahaemolyticus in oysters after harvest, and (c) evaluate the current guidance of 10,000 viable V. parahaemolyticus per gram of shellfish.
In order to develop the model, the risk assessment was divided into three modules, Harvest, Post Harvest, and Public Health. The Harvest and Post Harvest Modules differentiated two distinct time frames that affect V. parahaemolyticus levels in oysters harvested for raw consumption. Significant differences in oyster harvesting methods, handling practices, and climates in the United States were sufficient to distinguish five separate geographic regions (Northeast Atlantic, Mid-Atlantic, Pacific Northwest, Louisiana Gulf Coast, and the remaining Gulf Coast) and four seasons, and these were treated separately in modeling each of the modules.
The Harvest Module incorporated factors influencing the prevalence of V. parahaemolyticus in oysters up to the time of harvest, and identified the parameters that contribute to the likelihood that shellfish in a growing area will contain pathogenic strains of V. parahaemolyticus. Quantitative modeling in this module used water temperatures as factors influencing and, therefore, potentially predicting the prevalence of pathogenic V. parahaemolyticus in the harvest waters and oysters.
The Post Harvest Module addressed factors associated with handling and processing of oysters after harvest, in particular those that could influence the levels of V. parahaemolyticus in oysters at consumption. Such factors included in the modeling of this module were ambient air temperatures at time of harvest, time from harvest that oysters remained unrefrigerated, time required to cool oysters once placed under refrigeration, and the length of time oysters are stored in refrigeration until consumption. This module also simulated intervention measures that may affect V. parahaemolyticus densities, such as cooling immediately after harvest, freezing, and use of mild heat treatment (5 min at 50°C) .
The Public Health Module estimated the number of illnesses based on the levels of pathogenic V. parahaemolyticus at consumption, which was determined from the Harvest and Post Harvest modules. This module was further subdivided into three segments, epidemiology, consumption, and dose-response. The epidemiology segment included the number of illnesses, the severity and type of illness, the population affected, and the seasonal incidence. The consumption segment considered the number of oyster meals/servings eaten, the quantity of oysters consumed per serving, and the levels of total and pathogenic V. parahaemolyticus in the shellfish at consumption. The dose-response segment related the actual levels of V. parahaemolyticus consumed with frequency and severity of illness.
Outputs from the risk assessment model demonstrated that the single most important factor related to the risk of illness caused by this organism is the level of V. parahaemolyticus in oysters at the time of harvest. However, the model is based on a direct correlation between total and pathogenic V. parahaemolyticus levels at time of harvest. We have also assumed that pathogenic strains of V. parahaemolyticus grow at the same rate as non-pathogenic strains. Consequently, as the level of total V. parahaemolyticus increases so does the number of pathogenic V. parahaemolyticus. Accordingly, intervention measures aimed at controlling or reducing the levels of V. parahaemolyticus in oysters should have a direct bearing on controlling or reducing the risk associated with this pathogen. Water and air temperatures at time of harvest were found to be the major factors influencing the initial levels of this pathogen in oysters. Air temperature was also found to influence the growth of V. parahaemolyticus in oysters after harvest and, thus, the levels in oysters at the time of consumption. In oysters left unrefrigerated after harvest, V. parahaemolyticus rapidly multiply. The model demonstrated that these factors could have a significant impact on the likelihood of illnesses occurring. Model simulations of intervention measures indicated a significant reduction in the probability of illness when the oysters are cooled immediately after harvest and kept refrigerated. During refrigerated storage V. parahaemolyticus densities slowly but steadily decrease. Mild heat treatment (5 min at 50°C) of oysters, which causes at least a 4.5 log decrease in the number of viable V. parahaemolyticus in oysters, practically eliminates the likelihood of illness occurring. Quick-freezing and frozen storage of oysters, which causes a 1 to 2 log decrease in viable V. parahaemolyticus oyster levels, also substantially reduces the probability of illness.
Earlier human feeding trials conducted in Japan showed that illnesses occurred at levels of V. parahaemolyticus, which were comparable to those of other bacterial strains when administered with antacids, and that the number of illnesses increased with increasing levels of pathogenic V. parahaemolyticus. Three different dose-response distribution models were considered for the purpose of extrapolating from these data the risk of illness associated with lower levels of exposure associated with consumption of raw oysters. Distributions of ingested dose were developed by considering the probabilistic variation of number and meat weight of oysters in a serving or eating occasion in addition to the expected variation of the density of pathogenic V. parahaemolyticus determined in the Harvest and Post Harvest Modules.
On the basis of all available epidemiological data, and in the absence of quantitative data to the contrary, equal virulence among pathogenic strains of V. parahaemolyticus was assumed for modeling purposes. Pathogenic strains of V. parahaemolyticus were defined as those stains possessing the ability to produce a thermostable direct hemolysin (TDH). The assessment of dose-response was developed based on this definition. This may be modified as new data become available that identify new virulence determinants.
Based on all available epidemiological information, it was assumed that all consumers are equally susceptible to infection by V. parahaemolyticus. The probability of illness was determined as an increasing function of ingested dose of pathogenic V. parahaemolyticus. Epidemiological case series data clearly suggest a greater probability of an infection leading to septicemia and death among immune compromised individuals. This is reflected in model-based estimates of severe outcome (i.e. septicemia).
The outputs from this project provide estimates of risk for illness among consumers of raw oysters (average nationwide yearly incidence of 4,750 cases per year, with a range from 1,000 to 16,000 cases - for the Gulf Coast, 25 (winter), 1,200 (spring), 3,000 (summer), and 400 (fall); for the Pacific Northwest, 15 (spring) and 50 (summer); for the Mid-Atlantic, 10 (spring) and 12 (summer); and for the Northeast Atlantic, 12 (spring), 30 (summer) and 7 (fall)). Risks increase with increasing levels of total V. parahaemolyticus and therefore pathogenic strains of V. parahaemolyticus.
Simulations on the rate of illness caused by oyster-servings where the levels of V. parahaemolyticus at harvest are at or above 10,000 cells/g, suggest that approximately 15% of the illnesses are associated with the consumption of oysters containing greater than 10,000 V. parahaemolyticus/g at time of harvest. Comparing the number of servings that cause illness to those that do not, the simulations demonstrate that on average 0.6% of the servings result in illness when V. parahaemolyticus levels are at 10,000 cells/g or above.
Data gaps relevant to the risk assessment have been identified, and further research is needed to narrow risk estimates and reduce the uncertainties associated with these. For example, more definitive information on other potential virulence factors, such as the capacity for invasion of the enterocytes, production of an enterotoxin, and urease production would enable better differentiation of pathogenic and non-pathogenic strains and, thereby, enable more conclusive estimates on the prevalence of pathogenic strains in shellfish waters and oysters. Another special interest for this risk assessment requiring further data is the prevalence and abundance of pathogenic V. parahaemolyticus serotype O3:K6 in oysters at harvest, and also at consumption. In addition, though some studies have suggested that the immune and physiological status of an oyster could be an important factor in the prevalence of total V. parahaemolyticus and, therefore, in the prevalence of pathogenic V. parahaemolyticus, further data on this also is needed. Research needs identified by this risk assessment are summarized for the following areas:
This risk assessment significantly advances our ability to describe our current state of knowledge about this important foodborne pathogen, while simultaneously providing a framework for integrating and evaluating the impact of new scientific knowledge on enhancing public health.
The results of this draft risk assessment on V. parahaemolyticus are influenced by the assumptions and data sets that were used to develop the exposure assessment and hazard characterization. These results, particularly the predicted estimates of risk for illness among consumers of raw oysters, and the most significant parameters, which influence the incidence of illness, could change as a result of future data obtained from the Interim Control Plan and the FDA actively seeking new information, scientific opinions, or data during the public comment period. It is anticipated that periodic updates to the risk model will continue to reduce the degree of uncertainty associated with risk estimates, and that this will assist in making the best possible decisions, policies, and measures for reducing the risk posed by V. parahaemolyticus in raw molluscan shellfish.
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