[Federal Register Volume 64, Number 88 (Friday, May 7, 1999)]
[Notices]
[Pages 24664-24666]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 99-11318]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. 99N-1075]
Risk Assessment on the Potential Public Health Impact of Vibrio
Parahaemolyticus in Molluscan Shellfish; Request for Scientific Data
and Information
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice; request for scientific data and information.
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SUMMARY: The Food and Drug Administration (FDA) is announcing a call
for scientific data and information relevant to the agency's planned
risk assessment on the potential public health impact of pathogenic
Vibrio parahaemolyticus infections resulting from the consumption of
raw molluscan shellfish. The risk assessment will assist FDA by
providing a scientific framework for developing food safety policies
relating to raw molluscan shellfish contaminated with pathogenic V.
parahaemolyticus. FDA plans to hold public meetings to present the
process of the risk assessment, to present information collected, and
to allow interested parties additional opportunities to present data to
facilitate this effort.
DATES: Submit scientific data and information by July 6, 1999.
ADDRESSES: Submit scientific data and information to the Dockets
Management Branch (HFA-305), Food and Drug Administration, 5630 Fishers
Lane, rm. 1061, Rockville, MD 20852.
FOR FURTHER INFORMATION CONTACT: Marianna D. Miliotis, Center for Food
Safety and Applied Nutrition (HFS-327), Food and Drug Administration,
200 C St., SW., rm. 3472, Washington, DC 20204, 202-205-4824, FAX 202-
205-4939, or e-mail mmilioti@bangate.fda.gov.''
SUPPLEMENTARY INFORMATION:
I. Background
A. Vibrio parahaemolyticus
V. parahaemolyticus is a gram-negative, halophilic bacterium that
occurs naturally in estuarine environments and, therefore, can be
present in many fishery products, including molluscan shellfish (Ref.
1). The organism can cause acute gastroenteritis in consumers (Refs. 2,
3, and 4), and in some individuals can also cause septicemia (Ref. 5)
and even death (Ref. 6), though such cases have been reported only
rarely. Worldwide, this organism is one of the leading causes of
foodborne illnesses (Ref. 7). In the United States, the outbreaks
caused by this organism usually have been associated with cooked crabs
(Ref. 8), and illnesses transmitted by raw molluscan shellfish
generally have been limited to sporadic cases (Ref. 9). However, in
1997 V. parahaemolyticus from molluscan shellfish caused a large
outbreak of illness involving a total of 209 individuals in the Pacific
Northwest region, from California to British Columbia (Ref. 10). Many
of these cases implicated oysters from specific growing areas, and the
magnitude of this outbreak was considerably larger than
[[Page 24665]]
any previously caused by shellfish in the United States. In 1998,
outbreaks caused by molluscan shellfish-borne V. parahaemolyticus
occurred again, this time in three different coastal regions of the
United States. Overall, more than 500 individuals from the Gulf Coast
(Ref. 11), the Northeast (Ref. 12), and the Pacific Northwest (Ref. 13)
reportedly became ill after consuming raw molluscan shellfish, and many
of these cases were culture confirmed as attributable to V.
parahaemolyticus.
V. parahaemolyticus has been widely studied for years, and many of
the factors influencing its pathogenicity and natural occurrence have
been reported. For example, the organism is mesophilic, halophilic,
grows optimally in alkaline pH, and causes illnesses and outbreaks
principally during warmer weather months (Refs. 2, 5, and 14). However,
those environmental factors and production practices that influence the
incidence and prevalence of the organism and which would enable
reliable estimates of risks associated with the consumption of seafood,
especially molluscan shellfish, remain unknown.
Investigations of both the 1997 and the June 1998 outbreaks
demonstrated both epidemiological and direct relationships between
illness and raw oyster consumption (Refs. 10 and 11). Moreover,
accounts from some patients indicated that illness may result from the
consumption of a single infected oyster, which suggests the possibility
of a highly virulent strain, or a low infectious dose. A single
serotype of V. parahaemolyticus, that being O3:K6, was identified as
predominant in the June 1998 outbreak (Ref. 11). In September 1998, the
same serotype of V. parahaemolyticus again was identified in a U.S.
outbreak caused by raw oysters, this time in the Northeast region (Ref.
12). Prior to 1998, with the exception of one isolated case in 1972
(Ref. 15), serotype O3:K6 had been associated only with outbreaks in
Asian countries (Japan, Bangladesh, Laos, and Taiwan) (Ref. 16).
Notably, this serotype has repeatedly been associated with outbreaks,
whereas most other serotypes are primarily associated with sporadic
cases. For example, in Japan there were 43 V. parahaemolyticus
outbreaks involving 1,131 patients during the summer of 1998. Thirty of
the outbreaks (70 percent) were due to serotype O3:K6 (Ref. 16). Based
on all information available, the Centers for Disease Control and
Prevention (CDC) have described the O3:K6 serotype as ``an outbreak
strain'' of V. parahaemolyticus, and FDA concurs with this current
assessment. Other serotypes of the organism, such as O4:K8 currently
seen predominantly in Japan (Ref. 17), may also merit special concern.
FDA therefore believes that the U.S. outbreaks of illness in 1997 and
1998 have identified certain serotypes of V. parahaemolyticus as
important emerging pathogens linked to the consumption of raw molluscan
shellfish, particularly oysters.
However, since not all V. parahaemolyticus strains are
enteropathogenic as determined by their ability to produce a
thermostable direct hemolysin (TDH) (Ref. 18), FDA is concerned that
determining the total concentration of this species in shellfish is
unlikely to be useful for evaluating the risk of illness posed by V.
parahaemolyticus. Other strain characteristics, such as invasion of the
enterocytes (Ref. 19) and production of an enterotoxin (Ref. 20) may
also be important to pathogenicity and thus useful in identification of
pathogenic V. parahaemolyticus, other than the production of TDH.
B. Current Efforts
FDA and the States share responsibility for the safety of molluscan
shellfish for human consumption through the National Shellfish
Sanitation Program (NSSP), a long-standing Federal/State cooperative
program recognized by FDA for the sanitary control of molluscan
shellfish produced and sold for human consumption. To promote safety,
the NSSP has developed and maintained recommended shellfish sanitation
control practices for adoption by member States. These control
practices or guidelines are set out in the ``NSSP Guide for the Control
of Molluscan Shellfish'' (Ref. 21) which also includes State growing
area classification and dealer certification programs, and FDA
evaluation of State shellfish control programs.
In 1984, FDA entered into a Memorandum of Understanding (MOU) with
the Interstate Shellfish Sanitation Conference (ISSC) recognizing the
ISSC as the primary voluntary national organization of State shellfish
regulatory officials that provides guidance and counsel on matters for
the sanitary control of shellfish. The purpose of the ISSC is to
provide a formal structure for State regulatory authorities to
participate in establishing updated regulatory guidelines and
procedures for uniform State application of the program. The ISSC has
adopted formal procedures for State representatives to review shellfish
sanitation issues and develop regulatory guidelines. Following FDA
concurrence, these guidelines are published in revision of the NSSP
guidelines mentioned above (Ref. 21).
Historically, most illness caused by consumption of molluscan
shellfish can be traced back to pathogens resulting from sewage
contaminated water, and the NSSP has focused on control measures to
prevent illnesses caused by pathogens that may occur in fecal material
(Ref. 22). V. parahaemolyticus, however, occurs naturally in estuarine
environments. Thus, there is uncertainty about the effectiveness of
current NSSP measures to control V. parahaemolyticus in molluscan
shellfish.
In addition, FDA has previously indicated that V. parahaemolyticus
in raw molluscan shellfish should not exceed a level of 10,000 cells
per gram. This limit was based on data and reports from human volunteer
studies (Refs. 2, 3, 14 and 23) conducted more than 25 years ago, and
on investigations of U.S. outbreaks caused predominantly by cross
contamination of cooked crabs (Ref. 8), which supported an estimation
of minimum infectious dose of about 105 cells. However, the
overall levels of V. parahaemolyticus found in oysters from harvest
sites implicated during the 1997 and 1998 U.S. outbreaks suggest that
the number of pathogenic cells required to cause illness is probably
far less than previously believed, and it may be as low as 100 and
1,000 cells. FDA now believes the 10,000 cells per gram level may be
inadequate to protect the public health and did not rely on this level
during the recent outbreaks. Instead, during the recent U.S. outbreaks,
closing shellfish waters to harvesting was based on the occurrence of
human illness. Reopening was based primarily on two factors: (1) Change
in a season and/or conditions, particularly temperature, to those which
historically have not been associated with illness, and (2) absence of
the particular strains of V. parahaemolyticus associated with the
outbreak. However, it is not certain that these measures are the most
appropriate or effective.
II. Questions to be Considered by the Risk Assessment
FDA is requesting scientific data and information that will allow
it to respond to the following questions:
1. What is the frequency of occurrence of pathogenic strains of V.
parahaemolyticus in the shellfish waters? What parameters (e.g., water
temperature, salinity, turbidity, and nutrient profiles) can be used as
indicators of the presence of the organism in growing waters?
[[Page 24666]]
2. What is the frequency of occurrence of pathogenic strains of V.
parahaemolyticus in molluscan shellfish, and what are the numbers of
viable pathogenic organisms at time of consumption? How are levels
present in the bivalves at the time of consumption related to the
initial levels in the growing waters?
3. What is known about the dose-response relationship from
outbreak, epidemiological, animal and other studies? What are the
differences in dose-response relations among different strains and
serotypes of V. parahaemolyticus, and among the different human
susceptible subpopulations?
4. What is the role of postharvest handling that may be influencing
the numbers of V. parahaemolyticus in oysters? What reductions in risks
can be achieved by intervention strategies such as depuration or
relaying?
5. What is the adequacy of current scientific knowledge, and where
should future research be focused to reduce the uncertainty in the risk
estimate?
III. Scope of the Risk Assessment
Risk assessment is separate from risk management and risk
communication. Thus, FDA's risk assessment will determine the
relationships between molluscan shellfish, V. parahaemolyticus and
illnesses; it will not determine an acceptable level of pathogenic V.
parahaemolyticus.
To accurately assess the exposure to pathogenic V.
parahaemolyticus, the consumption of raw molluscan shellfish,
especially oysters, will be considered. Exposure is a function of the
V. parahaemolyticus prevalence in the shellfish and the consumption
patterns of the population. The number of pathogenic V.
parahaemolyticus in raw molluscan shellfish at consumption is the
critical exposure information. Modeling will be used when V.
parahaemolyticus data are collected during outbreaks, and at retail
outlets to estimate actual exposure.
The risk assessment will produce estimates of illness for levels of
pathogenic V. parahaemolyticus likely to be consumed by different
subpopulations. All assumptions and uncertainties will be identified
and documented.
FDA expects the risk assessment to provide the scientific
underpinnings FDA needs to develop food safety policies that reduce the
risk of disease resulting from ingestion of V. parahaemolyticus in
molluscan shellfish, and other seafood consumed raw. Among other
things, FDA anticipates that the data from the risk assessment will
assist in determining the principal factors that should be considered
in developing criteria for closing of shellfish waters to harvest in
order to prevent illness and reopening waters after outbreaks of V.
parahaemolyticus are over.
IV. Request for Data and Information
FDA is requesting scientific data and information that will allow
it to respond to the questions under section II of this document. The
purpose of this request for data is to gather relevant information to
facilitate a valid risk assessment of V. parahaemolyticus with the
larger goal of providing a sound scientific basis for the food safety
policies relating to raw molluscan shellfish contaminated with V.
parahaemolyticus. FDA does not intend to utilize the submitted data and
information to support future enforcement activity against seafood
producers submitting the data. Accordingly, it is acceptable that data
submitted in response to this notice be ``blinded'' in the sense that
the data need not identify the particular seafood producer or processor
that was the source of the samples underlying the results.
Two copies of the scientific data and information are to be
submitted, except that individuals may submit one copy. Scientific data
and information should be addressed to the Dockets Management Branch
(address above) and be identified with the docket number found in
brackets in the heading of this document. Received materials may be
seen in the Dockets Management Branch between 9 a.m. and 4 p.m., Monday
through Friday.
V. References
The following references have been placed on display in the Dockets
Management Branch (address above) and may be seen by interested persons
between 9 a.m. and 4 p.m., Monday through Friday.
1. Roderick, G. E., M. A. Hood, and N. J. Blake, Medical
Clinics of North America, 66:665-673, 1982
2. Takikawa, I., Yokohama Medical Bulletin, 9:313-322, 1958.
3. Aiiso, K. and K. Fujiwara, Annual Report of the Institute of
Food Microbiology, Chiba University, 15:34-38 1963.
4. Chai, T-J. and J. Pace, Goodborne Disease Handbook, p. 395
to 425, Marcel Dekker, NY, 1993.
5. Hlady, W. G. and K. C. Klontz, Journal of Infectious
Diseases, 173:1176-1183, 1996.
6. Hally, R. J., R. A. Rubin, H. S. Fraimow, and M. L. Hoffman-
Terry, Digestive Disease and Sciences, 1995.
7. Olson, Jr., J. C., International Symposium on Vibrio
parahaemolyticus, Saikon Publishing Co., Tokyo, pp. 259-261, 1974.
8. Barker, W. H., Jr., Lancet, 1:551-554, 1974.
9. Nolan, C. M. et al, Diagnostic Microbiology Infectious
Disease, 2:119-128, 1984.
10. CDC, Journal of the American Medical Association, 280:126-
127, 1998.
11. Angulo, F., P. M. Griffin, and R. V. Tauxe, CDC, personal
communication, 1998.
12. CDC, Morbidity and Mortality Weekly Report, vol. 48, 1999.
13. Sample, T. and M. Goza, FDA, personal communication, 1998.
14. Sanyal, S. C. and P. C. Sen, International Symposium on
Vibrio parahaemolyticus, p. 227 to 230, Saikon Publishing Co.,
Tokyo, 1974.
15. Fishbein, M., B. Wentz, W. L. Landry, and B. MacEachern,
International Symposium on Vibrio parahaemolyticus, p. 53 to 58,
Saikon Publishing Co., Tokyo, 1974.
16. Japanese National Institute of Infectious Diseases,
Infectious Agents Survey Report, vol. 20, No. 1, 1999.
17. Japanese National Institute of Infectious Diseases,
Infectious Agents Survey Report, vol. 17, No. 7, 1996.
18. Miyamoto, Y. et al., Journal of Bacteriology, 100:1147-
1149, 1969.
19. Akeda, Y., K. Nagayama, K. Yamamoto, and T. Honda, Journal
of Infectious Diseases, 176:822-824, 1997.
20. Honda, T., M. Shimizu, Y. Takeda, and T. Miwatani,
Infection and Immunity 14:1028-1033, 1976.
21. ISSC and FDA, Guide for the Control of Molluscan Shellfish,
U.S. DHHS, Washington, DC. p. 406, 1997.
22. Fisher, L. M., Shellfish Sanitation, Public Health Reports
No. 1178, U.S. Public Health Service, Washington, D.C., 1927.
23. Doyle, M. P., Lancet, 336:1111-1115, 1990.
Dated: April 29, 1999.
William K. Hubbard,
Acting Deputy Commissioner for Policy.
[FR Doc. 99-11318 Filed 5-6-99; 8:45 am]
BILLING CODE 4160-01-F
