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EXECUTIVE SUMMARY

Background

The Food and Drug Administration (FDA) conducted a quantitative risk assessment to characterize the factors influencing the public health impact associated with the consumption of raw oysters containing pathogenic Vibrio parahaemolyticus. This effort was initiated in January 1999 and a draft risk assessment was made available for public comment in 2001. The risk assessment was conducted in response to four outbreaks in 1997 and 1998 in the United States involving over 700 cases of illness. These outbreaks renewed concern for this pathogen as a serious foodborne threat to public health and raised new concerns about the effectiveness of risk management guidance available at that time. These outbreaks also raised questions about the criteria used to close and reopen shellfish waters to harvesting and the FDA guidance for the maximum number of V. parahaemolyticus per gram in shellfish.  FDA decided to conduct a quantitative risk assessment to provide new insights into how to better manage the presence of this pathogenic microorganism in shellfish.

This risk assessment focused on raw oysters, because that is the food in the United States predominately linked to illness from this pathogen. The risk assessment gathers available knowledge of V. parahaemolyticus in a systematic manner, and includes sophisticated, mathematical models. The levels of the pathogen in oysters were estimated beginning with harvest of the oysters through post-harvest handling, processing, and storage to predict human exposure from consumption of raw oysters and subsequent illnesses. The number of illnesses (on a per serving and a per year basis) were predicted for six regions in the United States and each season for a total of 24 region/season combinations. Total cases of illness include both gastroenteritis and septicemia.  In addition, the probability of gastroenteritis progressing to septicemia in individuals with underlying medical conditions (such as diabetes, alcoholic liver disease, hepatitis, and those receiving immunosuppressive treatments for cancer or AIDS) was compared to that of healthy individuals. Once developed, the baseline model was used to develop "what-if" scenarios to evaluate the likely impact of potential intervention strategies on the exposure to pathogenic V. parahaemolyticus from consumption of raw oysters.

Vibrio parahaemolyticus is a gram-negative, salt tolerant bacterium that occurs naturally in estuaries. It has been long recognized as an important bacterial seafood-borne pathogen throughout the world. It was first isolated and implicated in an outbreak of food poisoning in Japan in 1950. Vibrio parahaemolyticus has been associated with outbreaks and individual cases of illness in the United States since 1969. These bacteria are normally present in many types of raw seafood, including fish, crustaceans, and molluscan shellfish. The microorganism concentrates, colonizes, and multiplies in the gut of filter-feeding molluscan shellfish such as oysters, clams, and mussels. Not all strains of V. parahaemolyticus cause illness; on the contrary, pathogenic strains represent a small percentage of the total V. parahaemolyticus present in the environment or seafood.

Scope and General Approach

This risk assessment is a quantitative product pathway analysis in which the key steps from harvest through post-harvest handling and processing to consumption were modeled. The likelihood of illness following exposure to pathogenic V. parahaemolyticus from consumption of raw oysters was calculated. The levels of V. parahaemolyticus in oysters at the time of consumption are influenced by the harvest methods and conditions, as well as the handling of oysters after harvest. These practices and conditions vary considerably among different geographic areas and at different times of year. The baseline risk assessment model was also used to estimate the likely impact of intervention strategies (referred to as "what-if" scenarios) on the predicted number of illnesses.

The risk assessment considered six oyster harvest regions and four seasons for a total of 24 region/season combinations. The oyster harvest regions included: Gulf Coast (Louisiana), Gulf Coast (non-Louisiana), Mid-Atlantic, Northeast Atlantic, Pacific Northwest (Dredged) and Pacific Northwest (Intertidal). In the Gulf Coast, the harvest duration (i.e., the time between removal of the oyster from the water to unloading them at the dock) for Louisiana is typically much longer than for other states in that region (Florida, Mississippi, Texas, and Alabama). Since harvest duration can affect the levels of V. parahaemolyticus in raw oysters, the Gulf Coast was divided into two distinct regions. Likewise, the Pacific Northwest was divided into two distinct regions, but in this case it was based on harvest methods, dredging and intertidal. Oysters harvested in intertidal areas are typically exposed to higher temperatures before refrigeration than those harvested using dredging. For the intertidal harvest method, oysters are hand-picked when oyster reefs are exposed during the tide cycle and left in baskets until the tide rises to a sufficient depth to allow a boat to retrieve the basket.

The risk assessment had two main objectives:

• determine the factors that contribute to the risk of becoming ill from the consumption of pathogenic V. parahaemolyticus in raw oysters; and
• evaluate the likely public health impact of different control measures, including the effectiveness of current and alternative microbiological standards.

Data for this risk assessment were obtained from many sources, including both published and unpublished scientific literature and reports produced by various organizations such as State shellfish control authorities, the Centers for Disease Control and Prevention (CDC), the shellfish industry, the Interstate Shellfish Sanitation Conference (ISSC), and State Health Departments. In some instances the conduct of the risk assessment required that assumptions be made when data were incomplete. To the extent possible, research was specifically undertaken during the period between issuing the original draft and the current version to address data gaps previously identified. These new data have been incorporated into the risk assessment.

Results

The model predicts illnesses (gastroenteritis alone and gastroenteritis followed by septicemia) associated with the consumption of V. parahaemolyticus in raw oysters for the 24 region/season combinations. Summary Table 1 provides the risk on a "per serving basis" (i.e., the risk of becoming ill per serving of raw oysters) and Summary Table 2 provides the risk on a "per annum basis" (i.e., the predicted number of illnesses per year).

Below are the responses to the questions that the risk assessment team was charged with answering.

What is known about the dose-response relationship between consumption of Vibrio parahaemolyticus and illnesses?

• Although an individual may become ill from consumption of low levels of V. parahaemolyticus, it is much more likely that he or she will become ill if the level is high. The probability of illness is relatively low (<0.001%) for consumption of 10,000 V. parahaemolyticus cells/serving (equivalent to about 50 cells/gram oysters). Consumption of about 100 million V. parahaemolyticus cells/serving (500 thousand cells/gram oysters) increases the probability of illness to about 50%.
• Anyone exposed to V. parahaemolyticus can become infected and develop gastroenteritis. However there is a greater probability of gastroenteritis developing into septicemia (and possibly death) among the subpopulation with concurrent underlying chronic medical conditions.
• The model predicts about 2,800 V. parahaemolyticus illnesses from oyster consumption each year. Of infected individuals, approximately 7 cases of gastroenteritis will progress to septicemia each year for the total population, of which 2 individuals would be from the healthy subpopulation and 5 would be from the immunocompromised subpopulation.

What is the frequency and extent of pathogenic strains of Vibrio parahaemolyticus in shellfish waters and in oysters?

• Levels of pathogenic V. parahaemolyticus usually occur at low levels in shellfish waters.
• Levels of pathogenic V. parahaemolyticus in oysters at the time of harvest are only a small fraction of the total V. parahaemolyticus levels.

What environmental parameters (e.g., water temperature, salinity) can be used to predict the presence of Vibrio parahaemolyticus in oysters?

• The primary driving factor to predict the presence of V. parahaemolyticus in oysters is water temperature. Salinity was a factor evaluated but not incorporated into the model. Salinity is not a strong determinant of V. parahaemolyticus levels in the regions that account for essentially all the commercial harvest. Other factors such as oyster physiology and disease status may also be important but no quantifiable data were available to include these factors in the model.
• There are large differences in the predicted levels of V. parahaemolyticus in oysters at harvest among regions and seasons. For all regions, the highest levels of V. parahaemolyticus were predicted in the warmer months of summer and spring and the lowest levels in the fall and winter.
• Overall, the highest levels of total and pathogenic V. parahaemolyticus were predicted for the Gulf Coast (Louisiana) and the lowest levels in the Pacific Northwest (Dredged) harvested oysters.
• After harvest, air temperature is also an important determinant of the levels of V. parahaemolyticus in oysters. Vibrio parahaemolyticus can continue to grow and multiply in oysters until they are adequately chilled.
• Levels of V. parahaemolyticus are lower in oysters after harvest in the cooler vs. warmer months. This means that reducing the time between harvest and cooling will be more important in the summer and spring than in the fall and winter.

How do levels of Vibrio parahaemolyticus in oysters at harvest compare to levels at consumption?

• With no mitigation treatments, levels of V.  parahaemolyticus are higher in oysters at consumption than at harvest. The difference between V. parahaemolyticus densities at-harvest versus at-consumption is largely attributable to the extent of growth that occurs before the oysters are cooled to no-growth temperatures.
• Levels of V. parahaemolyticus in oysters vary by region and season and are highest during the summer.
• During intertidal harvest, oysters are exposed to ambient air temperatures for longer times, allowing additional growth of V. parahaemolyticus in oysters and leading to higher predicted risk of illness.
• Preventing growth of V. parahaemolyticus in oysters after harvest (particularly in the summer) will lower the levels of V. parahaemolyticus in oysters and, as a consequence, lower the number of illnesses associated with the consumption of raw oysters.

What is the role of post-harvest handling on the level of V. parahaemolyticus in oysters?

• Post-harvest measures aimed at reducing the V. parahaemolyticus levels in oysters reduced the model-predicted risk of illness associated with this pathogen.
• Reducing the time between harvest and chilling has a large impact on reducing levels of Vibrio parahaemolyticus in oysters and the number of illnesses. Predicted reductions were greater for shorter times to refrigeration and ice (oysters reach no-growth temperature in 1 hour) compared to cooling under conventional refrigeration (which may take up to 10 hours until oysters reach a no-growth temperature).

What reductions in risk can be anticipated with different potential intervention strategies?

• Overall. The most influential factor affecting predicted risk of illness is the level of total V. parahaemolyticus in oysters at the time of harvest.  Intervention strategies should be aimed at reducing levels of V. parahaemolyticus and/or preventing its growth in oysters after harvest. These strategies, either at-harvest or post-harvest, may need to consider regional/seasonal differences.
• Regional/seasonal Differences. The risk of V. parahaemolyticus illness is increased during the warmer months of the year, with the magnitude of this increase a function of the extent to which the growing waters (and ambient air temperatures) are at temperatures that support the growth of the pathogen (e.g., temperatures above 10°C). For each region, the predicted numbers of illnesses are much higher for the summer compared to the winter months. Intervention measures that depend on cooling oysters to no-growth temperatures for V. parahaemolyticus may be more important in warmer seasons and regions.

  The risk of V. parahaemolyticus illness is substantial in the Gulf Coast region where water temperatures are warm over a large part of the year as compared to the Northeast Atlantic region where water temperatures support the growth of Vibrio parahaemolyticus only during a relatively small portion of the year. A difference is seen among the regions due to different harvesting methods. Within the Gulf Coast, the predicted number of illnesses is much higher in Louisiana compared to other states in this region because the harvest boats in Louisiana are typically on the water longer, i.e., leading to a longer time from harvest to refrigeration. Harvest volume is also a determining factor; in the summer, Louisiana accounts for approximately 77% of the Gulf Coast harvest. This is also seen in the Pacific Northwest by comparing intertidal versus dredged harvesting. Intertidal harvesting accounts for 75% of the Pacific Northwest harvest and exposes oysters to higher temperatures longer, allowing greater growth of V. parahaemolyticus. Overnight submersion for a single tidal cycle, reduces levels of V. parahaemolyticus in oysters and the risk of illness.

• Post-Harvest Treatments. Post-harvest treatments that reduce levels of V. parahaemolyticus by 2 to 4.5-logs were found to be effective for all seasons and regions, with the most pronounced effects seen for regions and seasons with higher baseline risk. The model shows that any treatment that causes at least a 4.5-log decrease in the number of V. parahaemolyticus bacteria reduces the probability of illness to such an extent that few illnesses would be identified by epidemiological surveillance. However, some outbreak strains (e.g., O3:K6) are more resistant to mitigations than endemic pathogenic V. parahaemolyticus strains, and the duration or extent of treatment may need to be more stringent to achieve an equivalent degree of reduction. Studies have shown that both V. parahaemolyticus and V. vulnificus respond similarly to control measures such as ultra high pressure, mild heat treatment, and freezing. Therefore, mitigations aimed at decreasing levels of V. parahaemolyticus will also likely decrease levels of V. vulnificus.

  The model also demonstrated that if oysters are not refrigerated soon after harvest, Vibrio parahaemolyticus rapidly multiply resulting in higher levels. For example, the model indicates that for the Gulf Coast there is a significant reduction (~10-fold) in the probability of illness when the oysters are placed in a refrigerator immediately after harvest. Less pronounced reductions are predicted for the other regions. Predicted reduction in illness is less in colder seasons because oysters harvested in cooler weather are already at or below the temperature threshold for V. parahaemolyticus growth and as such refrigeration has little additional impact on levels of V. parahaemolyticus.

• At-Harvest and At-Retail Controls. Controlling the levels of V. parahaemolyticus in oysters at-harvest or at-retail (after refrigeration and storage) drastically reduces the number of predicted illnesses but would require diversion of oysters from the raw market or modification of handling practices to reduce post-harvest V. parahaemolyticus growth. For the Gulf Coast (Louisiana) region in the summer, excluding all oysters with at least 10,000 V. parahaemolyticus/g at-harvest would reduce illness by approximately 16% with an impact of approximately 3% of the total harvest; and this same control level at-retail would reduce illness by about 99% with a 43% loss from the raw consumption market. The effectiveness of the control level either at-harvest or at-retail to reduce illnesses depends on the extent of compliance with that control level.

  In a sample-based control strategy, a reasonable surrogate for pathogenic V. parahaemolyticus may be total levels of this microorganism. Criteria for rejection of oysters based on the levels of this surrogate might have to vary by region. For example, an at-harvest control criterion based on total V. parahaemolyticus levels in the Pacific Northwest might need to be more stringent than in the Gulf Coast because the incidence of pathogenic strains appears to be higher in the Pacific Northwest.  However, in an outbreak, the ratio of pathogenic to total V. parahaemolyticus may not be the same or consistent, and the model does not evaluate how well total Vibrio parahaemolyticus would serve as a surrogate for pathogenic V. parahaemolyticus in an outbreak situation.

Conclusions

Although the risk assessment modeled sporadic V. parahaemolyticus illnesses, steps taken to reduce sporadic cases from TDH⁺ strains could also proportionally reduce the size of outbreaks. However, some outbreak strains (e.g., O3:K6) may be more resistant to mitigations than endemic V. parahaemolyticus strains and may also require fewer cells to cause illness. The risk assessment illustrates that the levels of V. parahaemolyticus at-harvest play an important role in causing human illness. However, other factors that either reduce or allow growth of V. parahaemolyticus in oysters are also important in determining the number of illnesses. For example, shortening the time-to-refrigeration of oysters in the summer controls growth of V. parahaemolyticus in oysters and subsequently reduces illnesses associated with this microorganism.

The results of this risk assessment are influenced by the assumptions and data sets that were used to develop the Exposure Assessment and Dose-Response models. The predicted risk for illness among consumers of raw oysters and the most significant factors which influence the incidence of illness could change as a result of future data obtained from continuing surveillance studies. It is anticipated that periodic updates to the model when new data and knowledge become available will continue to reduce the degree of uncertainty associated with the factors that influence the risk, and that this will assist in making the best possible decisions, policies, and measures for reducing the risk posed by V. parahaemolyticus in raw oysters. This risk assessment provides an understanding of the relative importance and interactions among the factors influencing risk. It will hopefully provide a useful tool to facilitate the formulation of effective guidance and requirements and the evaluation of risk mitigation strategies.

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