1. Name of the Organism: |
Tetrodotoxin (anhydrotetrodotoxin
4-epitetrodotoxin, tetrodonic acid) |
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2. Nature of Acute Disease: |
Pufferfish Poisoning, Tetradon Poisoning, Fugu
Poisoning |
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3. Nature of Disease: |
Fish poisoning by consumption of members of the order
Tetraodontiformes is one of the most violent intoxications from
marine species. The gonads, liver, intestines, and skin of
pufferfish can contain levels of tetrodotoxin sufficient to produce
rapid and violent death. The flesh of many pufferfish may not
usually be dangerously toxic. Tetrodotoxin has also been isolated
from widely differing animal species, including the California
newt, parrotfish, frogs of the genus Atelopus, the blue-ringed
octopus, starfish, angelfish, and xanthid crabs. The metabolic
source of tetrodotoxin is uncertain. No algal source has been
identified, and until recently tetrodotoxin was assumed to be a
metabolic product of the host. However, recent reports of the
production of tetrodotoxin/anhydrotetrodotoxin by several bacterial
species, including strains of the family Vibrionaceae,
Pseudomonas sp., and Photobacterium phosphoreum, point toward
a bacterial origin of this family of toxins. These are relatively
common marine bacteria that are often associated with marine
animals. If confirmed, these findings may have some significance in
toxicoses that have been more directly related to these bacterial
species. |
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4. Diagnosis of Human Illness: |
The diagnosis of pufferfish poisoning is based on the
observed symptomology and recent dietary history. |
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5. Associated Foods: |
Poisonings from tetrodotoxin have been almost
exclusively associated with the consumption of pufferfish from
waters of the Indo-Pacific ocean regions. Several reported cases of
poisonings, including fatalities, involved pufferfish from the
Atlantic Ocean, Gulf of Mexico, and Gulf of California. There have
been no confirmed cases of poisoning from the Atlantic pufferfish,
Spheroides maculatus. However, in one study, extracts from fish of
this species were highly toxic in mice. The trumpet shell Charonia
sauliae has been implicated in food poisonings, and evidence
suggests that it contains a tetrodotoxin derivative. There have
been several reported poisonings from mislabelled pufferfish and at
least one report of a fatal episode when an individual swallowed a
California newt. |
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6. Relative Frequency of
Disease: |
From 1974 through 1983 there were 646 reported cases
of pufferfish poisoning in Japan, with 179 fatalities. Estimates as
high as 200 cases per year with mortality approaching 50% have been
reported. Only a few cases have been reported in the United States,
and outbreaks in countries outside the Indo-Pacific area are
rare. |
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7. Course of Disease and
Complications: |
The first symptom of intoxication is a slight
numbness of the lips and tongue, appearing between 20 minutes to
three hours after eating poisonous pufferfish. The next symptom is
increasing paraesthesia in the face and extremities, which may be
followed by sensations of lightness or floating. Headache,
epigastric pain, nausea, diarrhea, and/or vomiting may occur.
Occasionally, some reeling or difficulty in walking may occur. The
second stage of the intoxication is increasing paralysis. Many
victims are unable to move; even sitting may be difficult. There is
increasing respiratory distress. Speech is affected, and the victim
usually exhibits dyspnea, cyanosis, and hypotension. Paralysis
increases and convulsions, mental impairment, and cardiac
arrhythmia may occur. The victim, although completely paralyzed,
may be conscious and in some cases completely lucid until shortly
before death. Death usually occurs within 4 to 6 hours, with a
known range of about 20 minutes to 8 hours. |
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8. Target Populations: |
All humans are susceptible to tetrodotoxin poisoning.
This toxicosis may be avoided by not consuming pufferfish or other
animal species containing tetrodotoxin. Most other animal species
known to contain tetrodotoxin are not usually consumed by humans.
Poisoning from tetrodotoxin is of major public health concern
primarily in Japan, where "fugu" is a traditional delicacy. It is
prepared and sold in special restaurants where trained and licensed
individuals carefully remove the viscera to reduce the danger of
poisoning. Importation of pufferfish into the United States is not
generally permitted, although special exceptions may be granted.
There is potential for misidentification and/or mislabelling,
particularly of prepared, frozen fish products. |
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9. Food Analysis: |
The mouse bioassay developed for paralytic shellfish poisoning (PSP) can be
used to monitor tetrodotoxin in pufferfish and is the current
method of choice. An HPLC method with post-column reaction with
alkali and fluorescence has been developed to determine
tetrodotoxin and its associated toxins. The alkali degradation
products can be confirmed as their trimethylsilyl derivatives by
gas chromatography/mass spectrometry. These chromatographic methods
have not yet been validated. |
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10. Selected Outbreaks: |
Literature references can be found at the links
below. |
MMWR 45(19):1996 |
On April 29, 1996, three cases of tetrodotoxin
poisoning occurred among chefs in California who shared
contaminated fugu (puffer fish) brought from Japan by a co-worker
as a prepackaged, ready-to-eat product. The quantity eaten by each
person was minimal, ranging from approximately 1/4 to 1 1/2 oz.
Onset of symptoms began approximately 3-20 minutes after ingestion,
and all three persons were transported by ambulance to a local
emergency department. |
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Pufferfish poisoning is a continuing problem in
Japan, affecting 30 - 100 persons/year. Most of these poisoning
episodes occur from home preparation and consumption and not from
commercial sources of the pufferfish. Three deaths were reported in
Italy in 1977 following the consumption of frozen pufferfish
imported from Taiwan and mislabelled as angler fish. |
Morbidity and Mortality Weekly Reports |
For more information on recent outbreaks see the Morbidity and Mortality Weekly Reports from CDC. |
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11. Education and Background
Resources: |
Literature references can be found at the links
below. |
Loci index for genome
Tetraodontidae (Pufferfish family) |
Available from the GenBank
Taxonomy database, which contains the names of all organisms
that are represented in the genetic databases with at least one
nucleotide or protein sequence. |
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12. Molecular Structural Data: |
This structure was created by Fred Fry, Ph.D,
CFSAN. |
![Tetrodotoxin](https://webarchive.library.unt.edu/eot2008/20090117032352im_/http://www.cfsan.fda.gov/molcule3.gif) |
Tetrodotoxin |
M. Walderhaug
January 1992 with periodic updates