Download Prevention and Treatment of Toxic Seafoodborne Diseases in

Prevention and Treatment of Toxic
Seafoodborne Diseases in Travelers
Heather M. Barbier and James H. Diaz
More than 5,000 species of marine phytoplankton
are divided into five major botanical divisions: Chlorophyta (green algae), Chrysophyta (golden-brown and
yellow algae and diatoms), Pyrrhophyta (dinoflagellates),
Euglenophyta, and Cyanophyta (blue-green algae).
Approximately 300 species of marine phytoplankton are
able to cause red or brown tides, but only about 40 of
those species, mostly dinoflagellates (Pyrrhophyta) are
capable of producing human toxins.1 The focus of this
review is toxic seafoodborne illnesses, most of which are
dinoflagellate-induced diseases of travelers. Other causes
of toxic seafoodborne illnesses in travelers include toxic
decomposition products, such as scombrotoxin, and toxins endogenous to the mar ine animal, such as
tetrodotoxin.
Most of the red tide-causing dinoflagellates rest as
cysts in the ocean sediments where they remain dormant
for years. When water conditions (temperature, salinity,
light, and nutrients) are suitable, these cysts germinate to
form swimming cells. Swimming cells reproduce by
simple fission and within 1 week, each cell produces several thousand progeny cells, creating an algal bloom and
causing a red (or brown) tide. When marine conditions
are no longer favorable for asexual reproduction, game-
togenesis takes place. Two sexual gametes fuse to form
a zygote, which then encysts and returns to the ocean
floor until appropriate conditions for blooming return.1
Three categories of harmful algal blooms (HAB)
exist. The first type is produced by nontoxic species that
discolor the water and may cause extensive fish kills by
creating hypoxic marine conditions. The second type of
HAB is produced by species that are directly toxic to fish
and shellfish and potentially toxic to humans. The third
type of HAB is caused by species that are not harmful
to man or marine life.1
When humans consume dinoflagellate-contaminated seafood from the type II HAB, they may contract
dinoflagellate toxin poisoning. Since dinoflagellate toxins are heat and salt stable, cooking or salting of dinoflagellate toxin-contaminated fish and shellfish cannot
deactivate the toxins and offer no human protection
from seafood poisoning. The larger, long-lived, predatory
fish are the most toxic to humans because toxins bioaccumulate up the marine food chain. Dinoflagellate toxins cause a variety of symptoms, mainly gastrointestinal
and neurologic when ingested by humans.1
Most toxic seafoodborne illnesses are caused by
toxins produced by dinoflagellates and include (1) ciguatera fish poisoning (CFP), (2) paralytic shellfish poisoning (PSP), (3) diarrhetic shellfish poisoning (DSP), (4)
neurotoxic shellfish poisoning (NSP), and (5) amnesic
shellfish poisoning (ASP). The symptoms of toxic seafood
poisoning range from mild and self-limiting to very
severe and potentially fatal with incubation periods ranging from 15 minutes to 24 hours and illness durations
ranging from 8 hours for scombroid poisoning to months
to years for chronic CFP (Table 1). The management of
toxic seafood poisoning is mostly palliative and supportive. The best management strategies for toxic seafood
poisonings focus on prevention (Table 2). Several other
marine toxins cause human illness unrelated to dinoflagellate-produced toxins. These marine toxins, particularly scombrotoxin and tetrodotoxin, have a significant
impact on public health and will also be addressed in this
review of toxic seafoodborne diseases in travelers.
Heather M. Barbier, BS:Third Year MD-MPH Candidate
Louisiana State University, James H. Diaz, MD, DPH:
Professor of Public Health and Preventive Medicine,
Department of Public Health, and Preventive Medicine,
Louisiana State University Health Sciences Center, New
Orleans, Louisiana.
Support was provided from institutional and/or departmental
sources and by a State Grant to Dr Diaz from the Health
Education Fund (HEF) of the Board of Regents, State of
Louisiana, entitled “Assessment and Remediation of Public
Health Impacts due to Hurricanes and Major Flooding
Events.”
Correspondence: James H. Diaz, MD, DPH, Professor of
Public Health and Preventive Medicine, Department of Public
Health and Preventive Medicine, Louisiana State University
Health Sciences Center, 1600 Canal Street, Suite 800, New
Orleans, LA 70112.
Ciguatera Fish Poisoning
CFP afflicts 10,000 to 50,000 individuals worldwide
each year. This wide incident range is due to combina-
J Travel Med 2003;10:29–37.
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30
Table 1
J o u r n a l o f Tr a v e l M e d i c i n e , Vo l u m e 10 , N u m b e r 1
Toxic Seafoodborne Diseases in Travelers
Disease
Causative
Organism
Toxin
Produced
Ciguatera fish
poisoning
Giamberdicus
Toxicus
Ciguatera
toxin or
maitoxin
Paralytic shellfish
poisoning
Alexandrium spp Saxitoxin
Source
Coral reef
fish, finfish
Incubation
Period
Clinical Manifestations (Duration)
< 24 hours
Perioral numbness and tingling,
reversal of temperature sensation,
perception of loose teeth, headache,
vertigo, acute gastroenteritis,
autonomic and other symptoms
(usually 3 weeks; possibly months
to years)
Mussels, clams, 30 minutes Parasthesia, drowsiness, incoherent
cockles,
to 2 hours
speech, respiratory
scallops
paralysis (2 hrs–2 to 3 days)
Diarrhetic shellfish Dinophysis spp
poisoning
Okadaic acid Mussels, oysters, 30 min to
and others
scallops
15 hours
Nausea, vomiting, diarrhea, abdominal
pain (3 days)
Neurotoxic shellfish Gymnodinium
poisoning
brevis
Brevetoxin
Nearly identical to those seen in CFP
plus asthma-like symptoms and eye
irritation (2 days)
Amnesic shellfish
poisoning
Domoic acid Mussels
Nitzschia
spp
Oysters, clams, 15 min to
aerosolized
3 hours
toxin
< 24 hours
Gastroenteritis, short-term memory
loss, dizziness, headache, disorientation, seizures, respiratory difficulty,
coma
Scombroid (hista
Histidine
-mine) poisoning
converted to
histamine
Scombrotoxin Scombridae
15 to 90
family of fish,
minutes
and others
(usually
1 hour)
Face and neck flushing, headache,
burning sensation in the throat,
palpitations, nausea, diarrhea,
abdominal pain, bronchospasm
(8 to 24 hours)
Tetrodotoxin (fugu) Primary fish
poisoning
toxin(toxin is
endogenous)
Tetrodotoxin Puffer fish,
sunfish,
porcupine
fish
Oral parasthesias, light-headedness,
acute gastroenteritis, ataxia,
weakness, paralysis, lethargy,
dysphagia, seizures, cyanosis,
bronchospasms, respiratory failure,
coma, hypotension (1 week)
10 minutes
to 4 hours
CFP = Ciguatera fish poisoning.
tions of underreporting a self-limiting disorder and misdiagnosis.The incidence is most likely around 25,000 cases
per year worldwide. CFP is mainly diagnosed between
35 degrees north and 35 degrees south latitude near
warm, shallow waters (Fig.).2 It is endemic to tropical and
subtropical areas of the Pacific Ocean, the western Indian
Ocean, and the Caribbean Sea, although it is not limited to these areas (Fig.). CFP is especially prevalent in
many island nations in the Pacific and in the Caribbean,
where the main source of protein is fish. In those areas,
the annual incidence of CFP approaches 10%.3 Most of
the cases in the United States are confined to Florida and
Hawaii; however, cases have been reported in Texas,
Louisiana, Washington DC, Massachusetts, and Maryland.4
CFP is an underrecognized and underreported cause of
morbidity among travelers to endemic areas and is a
global health problem due to the worldwide exportation
of seafood.
CFP is predominately caused by the ciguatera neurotoxin, which is produced by the dinoflagellate,
Gambierdiscus toxicus. CFP can also be caused by maitotoxin, a myotoxin.1 Illness usually results from ingesting
the toxins found in large predacious coral reef fish and
finfish, including groupers, barracudas, snappers, amberjack and other jack fish, mackerel, triggerfish, and kingfish. Ciguatera toxicity can also be caused by some
herbivorous fish, including the surgeonfish and parrotfish; however, this is not as common.5 In addition, moray,
conger, and anguillid eels may contain a ciguatera-like
neurotoxin.6 Fish greater than 10 kg are most likely to
contain the toxin, although there are cases of intoxication from smaller fish.7
B a r b i e r a n d D i a z , P r e v e n t i o n a n d Tr e a t m e n t o f To x i c S e a f o o d b o r n e D i s e a s e s
Table 2
31
The Management of Toxic Seafoodborne Diseases in Travelers
Disease
Prevention
Ciguatera fish
poisoning
Difficult; no commercially avail- Usually self-limiting; less than 1% Symptomatic and supportive;
able detection methods; no
mortality; symptoms are genintravenous rehydration,
antitoxin available; best prevenerally acute to subacute, lasting
antiemetics, antidiarrheals,
tion is avoidance of potentially
a few weeks; chronic symptoms
atropine, anti-depressants;
toxic fish
may occur, lasting months to
possibly intravenous
years
mannitol or gabapentin
Paralytic shellfish
poisoning
Detection of toxin and closure
of harvest beds; no antitoxin;
avoid toxic shellfish
Diarrhetic shellfish
poisoning
No antitoxin; avoid toxic shellfish Usually resolves within 3 days;
no fatalities
Neurotoxic shellfish Monitoring of dinoflagellate cell
poisoning
counts; avoid toxic shellfish;
no antitoxin available
Clinical Course
Treatment
With supportive treatment, survi- Supportive
vors recover fully; without
treatment, death due to respiratory paralysis
Full recovery in 48 hours;
no fatalities
Supportive
Supportive
Amnesic shellfish
poisoning
No antitoxin; avoid toxic shellfish Severe to fatal; can be chronic
Supportive
Scromboid (histamine) poisoning
Refrigerate fish; prevent bacterial Recovery within 8 to 24 hours
overgrowth
without treatment
Symptomatic plus antihistamines
or subcutaneous epinephine;
may need an antiemetic
Tetrodotoxin (fugu) Avoid affected fish; have fish
poisoning
specially prepared
60% mortality; if survive first
24 hours, patients usually
recover in 1 week
Ciguatera toxin is a potent neurotoxin that binds
sodium channels quasi-irreversibly at site 5, opening
sodium channels, and producing an overall excitatory
effect. Forced opening of the sodium channels increases
the sodium ion permeability of the nerve membrane,
causing spontaneous depolarization with repetitive firing of action potentials.1,7–9
Neurologic symptoms caused by CFP from ciguatoxin and maitotoxin may include perioral numbness and
tingling that may spread to the extremities; pathognomonic reversal of temperature sensation, with hot temperature feeling cold and vice versa; headache, and
vertigo. Extreme sensitivity to cold may also be present.10
Gastrointestinal symptoms include nausea, vomiting, and
diarrhea. Cardiovascular symptoms may include arrhythmia, bradycardia, tachycardia, or hypotension. The contrasting symptoms of bradycardia and tachycardia result
from autonomic imbalance. Which one is present depends
on whether the parasympathetic or sympathetic nervous
system, respectively, is predominately affected. Other
autonomic nervous system-related symptoms may include
sweating and hypersalivation. Myalgia, arthralgia, muscle cramping, weakness, pruritus, skin rash, dental pain,
Gastric lavage with sodium
bicarbonate, activated charcoal,
endotracheal intubation, further
supportive therapy
perception of loose teeth, dyspnea, sore or dry throat,
short-term memory loss, and depression may also be present. Myopathic symptoms of weakness, muscle cramping, and myalgia predominate and coexist with autonomic
imbalance in isolated maitotoxin CFP. Although it is possible to contract both ciguatoxic and maitotoxic CFP, it
is more common to contract either one form or the other
as determined by the bioaccumulation of the predominate dinoflagellate toxin in the local population of baitfish and long-lived predatory reef fish.
Symptoms of CFP appear within 24 hours of ingestion of the toxin. The illness is usually self-limiting and
mortality is usually less than 1%, although much higher
case fatality rates have been reported. A case fatality rate
of 20% was reported from Madagascar where 98 of 500
individuals died after ingesting ciguatoxin-contaminated
shark.11 Two deaths from CFP were also reported in
Hawaii, in1964.12 Symptoms are generally acute or subacute, lasting a few weeks. However, chronic symptoms
may occur, lasting months to years.7 Immunity is not conferred from initial intoxication and subsequent exposures
may actually result in more severe chronic disease. This
chronicity may be due to permanent inactivation of
32
J o u r n a l o f Tr a v e l M e d i c i n e , Vo l u m e 10 , N u m b e r 1
Figure Global distribution of toxic seafoodborne diseases.
sodium channels, inducing sensitivity in previously intoxicated individuals.3 Individuals with CFP should avoid
fish, alcohol, and nuts for 3 to 6 months after the initial
illness as they tend to exacerbate symptoms or precipitate a relapse.13 In an outbreak of CFP in 8 persons on
a scuba diving cruise in Queensland, Australia, 2 of the
victims experienced extreme pruritis after drinking alcohol within 6 months of recovering from CFP. This symptom lasted several months in both cases.10
Several cases of CFP in Australia have been reported
in pregnant women. Ciguatera toxin does not appear to
cause lasting problems if ingested during the first or second trimester.8 However, markedly increased fetal movements were reported in a mother who acquired CFP 2
days prior to Cesarean section.3 The infant was born with
left-sided facial palsy, myotonia of the small muscles of
the hand, and respiratory distress syndrome.3 However,
the infant was developing normally by 6 weeks of age.8
Ciguatera toxin is secreted in breastmilk.7
Laboratory testing methods for CFP are not currently
available and diagnosis is based on clinical presentation
and history. Ciguatera toxicity is often misdiagnosed; thus,
it is important to rule out other marine poisonings. In
addition, the early stages of CFP may be mistaken for
decompression illness, especially in isolated cases. In the
aforementioned outbreak in scuba divers in Queensland,
Australia, 2 of the victims first developed paraesthesia,
arthralgia, weakness, and myalgia followed by gastrointestinal symptoms in 1 patient. The other victim manifested neuromuscular symptoms only, without
gastrointestinal symptoms. Thus, CFP with minimal or
no gastrointestinal symptoms could have easily been
misdiagnosed as decompression illness in the Australian
outbreak.10 Early CFP may mimic decompression sickness causing a diagnostic dilemma, especially when recent
deep-sea divers become ciguatoxic.
Treatment for CFP currently consists of symptomatic
and supportive therapy, including intravenous (IV) rehydration, antiemetics, antidiarrheals, atropine for bradycardia, and antidepressants.2 Mannitol given by IV has also
been used empirically and appears to immediately resolve
symptoms if given within 24 to 48 hours of ingestion of
the toxin. However, mannitol is not always effective and
in a small outbreak of eight cases in Queensland, Australia, it was administered 8 days after the onset of symptoms and had no benefit.10 Mannitol’s mechanism of
action in CFP is unknown, although its effects may be
related to membrane stabilization.2,7 There are, however, no randomized controlled studies of mannitol therapy in CFP, only anecdotal case reports of its effectiveness.
Mannitol was first used by chance in an undiagnosed case
of CFP in the Marshall Islands.14 A potential side effect
B a r b i e r a n d D i a z , P r e v e n t i o n a n d Tr e a t m e n t o f To x i c S e a f o o d b o r n e D i s e a s e s
of mannitol therapy is orthostatic hypotension from volume depletion with hyponatremia and hypokalemia.
Mannitol should be administered with caution in patients
with congestive heart failure, cardiac arrhythmias, renal
insufficiency, or severe dehydration, and in patients on
antiarrhythmic (especially digitalis) and/or antihypertensive medications.15 If mannitol is administered, it is
important to rehydrate the patient first.
Two patients in the Dominican Republic were
given gabapentin (an antiepileptic drug related to gammaaminobutyric acid) to control neuropathic phenomena
in CFP and showed rapid improvement. In this instance,
the gabapentin was administered 1 month after the onset
of symptoms and was still effective, as opposed to mannitol, which must be administered within 48 hours to have
any effect. However, no randomized control studies exist
to confirm gabapentin’s effectiveness in CFP.16
Prevention of CFP is difficult. No simple and inexpensive methods of detecting ciguatoxin in fish have been
developed. An expensive test kit, the Cigua-Check
(Oceanit Test Sysyems, Inco, Honolulu, Hawaii), is commercially available on the Internet. A box of two singleuse kits costs $20 (US), and a box of five costs $29 (US),
not including the cost of shipping (http://
www.cigua.com). The ciguatera toxin in affected fish can
also be detected by mouse bioassay or enzyme immunoassay, however, the intoxication of the fish is sporadic, and
it is possible that only one fish in an entire school is
affected. CFP outbreaks are also sporadic and regionally
localized.7,8 Ciguatera toxin is not inactivated by cooking, freezing, or stomach acid and cannot be detected by
sight, smell, or taste.16,17 Finally, G. toxicus overgrowth and
CFP outbreaks may be related to the multifactorial
effects of global warming; bleaching and death of coral
(G. toxicus lives in association with microalgae attached
to injured and dead coral); agricultural fertilizer and
pesticide runoff; and contaminated fresh water and soil
sediments entering marine estuaries after earthquakes,hurricanes, dock construction, and rainstorm surge with
untreated sewage runoff.8
Paralytic Shellfish Poisoning
Between 1971 and 1977, there were 12 outbreaks
of PSP in the United States, affecting 68 people. An outbreak in Guatemala in 1987 affected 187 people, resulting in 26 fatalities.17 PSP is a life-threatening illness
caused by more than 20 different structurally related
saxitoxins with varying toxicities produced mainly by the
Alexandrium species of dinoflagellates. The type of toxin
produced depends on the dinoflagellate and the geographic location involved.1 Saxitoxin blocks neuronal and
muscular sodium channels, preventing propagation of
action potentials.1 Illness develops approximately 30 min-
33
utes to 2 hours after ingesting toxin-laden mussels, clams,
cockles, or scallops from affected areas.18 Saxitoxins, as well
as tetrodotoxin and palyotoxin, have also been isolated
from xanthid crabs from the species Atergatis floridus
from the coral reefs in Australia. They can also be found
in Fiji, Okinawa, Taiwan, and Japan.19
Symptoms of PSP are primarily neurologic and
include paresthesia, drowsiness, incoherent speech, and
respiratory paralysis. PSP can be fatal due to respiratory
paralysis, and the severity of symptoms depends on the
amount of toxin ingested and the time until treatment
is administered.17 No clinical testing is available for PSP;
diagnosis is based on clinical presentation and history.
Treatment is mostly supportive; there are no antitoxins.
However, with supportive treatment, survivors usually
recover fully within 2 to 3 days.1–20
Like ciguatoxin, saxitoxin is not inactivated by cooking, freezing, or smoking and is undetectable by sight or
smell. Therefore, prevention of PSP lies in detecting the
toxin before the shellfish reach the consumers.17 Alexandrium blooms occur several times each year, between April
and October along the coastal United States, especially
along the New England States, Alaska, California, and
Washington. The shellfish remain toxic for about 2 to
3 weeks after the bloom subsides. In the United States,
surveillance of high-risk harvest areas directs the closing
of those areas when toxin levels surpass 80 mcg/g. The
best method of prevention of PSP is to avoid eating shellfish during red tide toxicity alerts, many of which are promulgated by federal and state governments, especially in
the Americas, Scandinavia, and Western Europe.18
Diarrhetic Shellfish Poisoning
Outbreaks of DSP have occurred in Japan, France,
other parts of Europe, Canada, New Zealand, and South
America. There have not been any confirmed cases of
DSP in the United States. However, the responsible
organisms (Dinophysis species) have been identified in US
coastal waters.18 There are 8 toxins produced by Dinophysis species: (1) okadaic acid, (2) dinophysistoxin 1
and 2, and (3) pectenotoxin 1–5.17 The major toxin in
DSP is okadaic acid, a powerful phosphatase inhibitor.
The inhibition of phosphatase results in increased phosphorylation of many proteins, and the expression of
numerous cell proliferation genes, some of which may
promote neoplasia. Symptoms of DSP occur 30 minutes
to15 hours after ingesting toxic mussels, oysters, or scallops from affected areas.
Symptoms of DSP are entirely gastrointestinal and
include nausea, vomiting, diarrhea, and abdominal pain.
Treatment is supportive; no antitoxin is available. The illness is self-limiting, and individuals recover within 3 days,
with or without medical treatment, and no fatalities
34
have been reported. However, DSP may produce chronic
problems due to benign stomach tumors.1,17 No clinical testing is available for DSP, and diagnosis is based on
clinical presentation and history. The best forms of prevention are to identify the toxin before the shellfish
reach consumers and to avoid eating shellfish during
regional red tide alerts in developed areas.1
Neurotoxic Shellfish Poisoning
NSP occurs in the United States, especially following algal blooms along the Gulf Coast in Florida and
Texas. The dinoflagellate producing the NSP toxins or
brevetoxins is Karenia brevis (formerly Gymnodinium
breve). Brevetoxins act at site 5 of voltage-sensitive sodium
channels (along with ciguatera toxin). Analogous to the
other shellfish poisonings, NSP occurs within 15 minutes to 3 hours after ingesting toxic shellfish (oysters or
clams) from affected areas. However, NSP is unique in
that it can also be contracted via inhalation of wave
action aerosols during a K. brevis bloom.1,17,18
Symptoms of NSP are almost identical to those of
CFP, although the illness is much less severe. The symptoms include numbness and tingling of the perioral
region and the extremities, reversal of temperature sensation, bradycardia, mydriasis, dizziness and ataxia, feeling of inebriation, muscle aches, and gastrointestinal
symptoms. Toxic aerosols may cause eye irritation and
asthma-like respiratory symptoms, with little or no symptoms of autonomic imbalance. Treatment is supportive
and complete recovery usually occurs within 48 hours.
No fatalities have been reported. Diagnosis is based on
clinical presentation and history.1,17,18
Prevention is based on monitoring K. brevis cell
counts, early detection of contaminated shellfish supply,
and avoiding contaminated shellfish consumption. The
symptoms resulting from the aerosolized toxin can be
avoided by staying away from tidal waterways and breaking surf during a bloom.1,17,18
Amnesic Shellfish Poisoning
During 1987 to 1988, an outbreak of ASP in eastern Canada affected 156 people, resulting in 3 fatalities.17
ASP is caused by domoic acid, a toxin produced by the
diatom, Nitzschia pungens. These organisms are found in
coastal waters around the United States in the Atlantic
and Pacific Oceans. They are also found in the Indian
Ocean. Domoic acid acts as an agonist to glutamate
receptors that upregulate sodium channels, resulting in
unopposed depolarization. This depolarization increases
the calcium ion permeability of the nerve cell membrane
and induces cell death.4 Illness develops less than 24 hours
J o u r n a l o f Tr a v e l M e d i c i n e , Vo l u m e 10 , N u m b e r 1
after ingesting toxic mussels from affected areas and can
be severe to fatal.
Symptoms of ASP include gastroenteritis, shortterm memory loss, dizziness, headache, disorientation,
seizures, respiratory difficulty, and coma. Short-term
memory loss is usually the most apparent symptom
(hence the name amnesic shellfish poisoning) and can
manifest as severe antegrade memory loss. The illness can
be especially severe in elderly patients, and all fatalities
due to ASP thus far have been in the elderly population.
Diagnosis is based on clinical presentation and history
because no clinical testing is available. Therapy is supportive and no antitoxin is available. After a Canadian outbreak of ASP involving 107 people, Canadian authorities
began to monitor mussels and clams for domoic acid and
to close shellfish beds when levels exceeded 20 mcg/g.21
The only other method of prevention is to avoid eating
contaminated shellfish.1,17,18
Scombroid Poisoning
Scombroid poisoning is a toxic fish poisoning that
is not related to dinoflagellates. Scombroid poisoning
causes nearly 5% of foodborne illnesses reported to the
Centers for Disease Control and Prevention and comprises about 37% of all seafoodborne diseases.17,20 The production of scombrotoxin is initiated by bacterial
overgrowth when harvested fish are improperly stored,
refrigerated, or preserved. The toxin is produced by the
decarboxylation of histidine in the muscle of the fish to
histamine and saurine. This decarboxylation reaction is
catalyzed by bacterial enzymes produced by Proteus morganii, Klebsiella pneumoniae, Escheria coli, and other bacteria during the bacterial decomposition of dead fish.20,22
Scombrotoxin formation is promoted by increased
levels of histamine, other vasoactive amines, and other protein decay products.17
The toxin is so named because of its association with
scombroid fish, which include tuna, albacore, abalone,
saury, mackerel, bonito, needlefish, kingfish, wahoo, and
skipjack. However, the toxin is most commonly associated with nonscombroid fish, such as mahi-mahi, amberjack, kahawai, sardine, herring, bluefish, anchovies, and
Australian ocean salmon.23
Patients present with symptoms similar to those
caused by other histamine reactions. This illness is sometimes referred to as “histamine poisoning” and is often
misdiagnosed as a fish allergy. However, it is unlikely that
histamine alone causes the symptoms as increased doses
of exogenous histamine do not cause the same effects.
Symptoms begin within minutes after ingestion of the
toxin and may include flushing of the face and neck with
a sunburn-like appearance, a feeling of warmth without
an elevated body temperature, headache, burning sensa-
B a r b i e r a n d D i a z , P r e v e n t i o n a n d Tr e a t m e n t o f To x i c S e a f o o d b o r n e D i s e a s e s
tion in the throat, tingling of the mouth, hypotension,
tachycardia, palpitations, nausea, vomiting, diarrhea,
abdominal pain, wheezing with bronchospasm, pruritis,
urticaria, epigastric pain, dysphagia, and dizziness. Diagnosis is based on presentation and physical findings and
can be confirmed by elevated serum or urine histamine
levels. Capillary electrophoretic assay is a new procedure
that allows for prompt detection of histamine in seafood.24
A histamine level of greater than 50 mg per 100 g of fish
is considered unsafe by the US Food and Drug Administration (FDA).25,26
Initial treatment is similar to that for food allergy or
anaphylaxis and includes gastric emptying and administration of epinephrine. Further treatment is symptomatic with antihistamines, including intravenous
H1 blockers, such as diphenhydramine and H2 blockers,
such as cimetidine. The symptomatic treatment may
include metaproterenol, corticosteroids, or epinephrine
(for bronchospasm) and antiemetics. Symptoms usually
resolve within 8 to 24 hours, even without treatment and
no deaths have been reported.17,20,22,27
All humans are susceptible to this illness; however
it can have a severe effect on the elderly and on those
individuals who are concurrently taking isoniazid, which
inhibits gastrointestinal histaminase.20,25,26 If intoxication
is severe, immediate gastric emptying with syrup of
ipecac, or preferably, gastric lavage, followed by oral
administration of activated charcoal are recommended.17,20
Scombroid poisoning can occur anywhere, but in the
United States it occurs most often in coastal areas.
Scombrotoxin is heat and salt-stable, not inactivated by cooking or marinating, and not detected by
color, odor, or appearance. The affected fish may have
a sharp metallic or peppery taste. Scombroid poisoning
occurs sporadically, but predictably, and is therefore easy
to prevent. Prevention involves immediately refrigerating harvested fish or eating them soon after being captured. Fish that have been left in the sun for more than
2 hours or that have a foul odor or necrotic color should
be discarded.17,20,22,27
Tetrodotoxin Poisoning
Tetrodotoxin poisoning is another toxic fish poisoning that is unrelated to dinoflagellates. Tetrodotoxin
is an inherent neurotoxin found in all puffer fishes (balloon fish, swellfish, fugu fish, blowfish, toadfish, and
globefish), porcupine fish, and marine sunfish. Puffer
fish, porcupine fish, and sunfish are all tropical and subtropical fish found throughout the Pacific, Atlantic, and
Indian Oceans. The tetrodotoxin is distributed throughout the flesh, gonads, skin, intestine, liver, and bile of the
fish. Female fish species have a higher concentration of
toxin than males, with highest tetrodotoxin concentra-
35
tions in the ovaries. The toxin is present in even higher
concentrations during spawning season between March
and June. Tetrodotoxin poisoning can have up to 60%
mortality in some area, especially in Japan, where fugu
fish is considered a delicacy.20,22,27
Tetrodotoxicity can also result from the bite of the
blue-ringed octopus Hapalochlaena maculosa, which has
occurred in Japan and Australia. The tetrodotoxic venom
of the blue-ringed octopus is contained in the salivary
glands and contains tetrodotoxin and several other toxins. Symptoms include profound and rapid hypotension, decreased respiratory rate, and decreased heart rate.
If this envenomation is suspected, respiratory support must
be initiated as soon as possible.28 However, the bite of the
blue-ringed octopus is usually painless, making the diagnosis difficult. A careful history, especially one of wading in small, shallow pools near the coast, handling the
octopus, or decanting a juvenile octopus from a favorite
hiding spot in a discarded bottle or container are necessary elements in confirming the diagnosis of octopus
bite.29
Tetrodotoxin acts by blocking nerve action potentials consequently interfering with central and peripheral neurotransmission. The toxin works by interfering
with sodium conductance and basically has the same
action on the nerve terminal as saxitoxin. Symptoms begin
within 10 minutes to 15 hours after ingestion of the toxin
and initially include circumoral paraesthesia, nausea,
vomiting, and diarrhea. Other symptoms that follow
include light-headedness, headache, unusual taste sensation, hypotension, cardiac arrhythmia (especially sinus
bradycardia), hypersalivation, sweating, lethargy, muscle
weakness, floating sensation, ataxia, incoordination,
tremor, paralysis, twitching, abdominal pain, dysphagia,
loss of voice, convulsions, seizures, cyanosis, dyspnea,
bronchospasm, respiratory failure, coma, and death.20,22,27
The differential diagnosis includes PSP, CFP, and
organophosphate poisoning.22 Tetrodotoxin poisoning
may also present with disseminated intravascular coagulation. Most of the victims that die do so within the first
6 hours. If patients survive past 24 hours they will likely
recover, usually within 1 week.20
Although controversial and disputed by others, some
authorities recommend immediate induced vomiting
by syrup of ipecac in witnessed home or on-site
tetrodotoxin poisoning in remote areas, without access
to emergency care because of (1) the lethality of the toxin;
(2) the delay in interventional gastric emptying by orogastric lavage; and (3) the delay in gastric decontamination by oral activated charcoal administration.30 Induced
vomiting after neurotoxic poisoning remains controversial in patients who may lose airway protective reflexes
after neurotoxic envenomations with seizures and/or
paralysis and is recommended only in immediate first-
36
response situations attended by emergency first responders skilled in airway protection by endotracheal intubation. In most situations of tetrodotoxin poisoning,
especially in developed nations, such as Japan, the management of tetrodotoxin poisoning includes (1) suspicion
of neurotoxic poisoning; (2) summoning of highly trained
emergency medical response services; (3) provision of a
secure upper airway; (4) evacuation to a tertiary care facility offering short-term mechanical ventilation; and (5)
immediate emergency department gastric emptying by
orogastric lavage with a sodium bicarbonate solution
within 3 hours of ingestion, as tetrodotoxin is gastric acid
stable and is partially inactivated by alkaline solutions.22
Orogastric lavage should be followed by gastric decontamination by one (1.0 g/kg) or more (0.5g/kg) doses
of orogastric tube-administered activated charcoal slurry.30
Additional treatment consists of supportive measures,
including ventilatory support for respiratory failure, IV
fluids and vasopressors for volume restoration and
inotropic support, and atropine for bradycardia. Death
from tetrodotoxin is usually due to hypoxic brain injury
making ventilatory support especially important.31
Anticholinesterase drugs have also appeared to be
effective in restoring muscle power when administered
early and during recovery, suggesting that tetrodotoxin
may cause a competitive reversible block at the motor
end plate. However, no clinical studies have been conducted to determine the effectiveness of this therapy.32
There are no antitoxins or specific antidotes for
tetrodotoxin poisoning.20,22
Prevention consists of avoiding inherently toxic fish,
especially from March through June. Deaths from
tetrodotoxin poisoning in Japan are usually associated with
home-cooked meals. If one does decide to eat fugu fish,
it should be eaten at a restaurant, where chefs have completed training in fugu fish cleaning, filleting, and preparation before being licensed as fugu fish preparers.33 The
US FDA prohibits personal importation of fugu into the
United States; however, three cases of tetrodotoxin poisoning occurred in San Diego after ingestion of contaminated fish illegally imported from Japan. All three
victims survived the intoxication after reporting to local
emergency departments and receiving ventilatory support, IV hydration, gastric lavage, and activated charcoal.34
General Approach to a Patient
with a Toxic Seafoodborne Illness
A good history is the first and most important element of diagnosis of toxic marine poisonings. The patient
may present with a recent history of fish or shellfish ingestion, in which case the diagnosis will be more apparent.
In most cases, the diagnosis is solely based on history and
symptoms.Important information to obtain in the history,
J o u r n a l o f Tr a v e l M e d i c i n e , Vo l u m e 10 , N u m b e r 1
in addition to the chief complaints, include exactly what
seafood was ingested, how the seafood was prepared, how
much was ingested, when it was ingested, and when the
symptoms began. Were other seafood diners affected in a
similar fashion? Were those diners not ingesting seafood
spared from acute gastrointestinal or neurologic illness? If
history suggests an outbreak of seafood-related toxicity,local
or governmental public health authorities should be notified in order to conduct epidemiologic outbreak investigations and to alert regional health care providers.
Time may be of the essence in many cases and life
support measures, such as ventilatory support for
tetrodotoxin poisoning, and other emergency treatments
should be started as soon as possible, including gastric
lavage, activated charcoal therapy, and intravenous
inotropic support depending on the symptoms. Most
intoxications share gastrointestinal symptoms particularly nausea, vomiting, and abdominal pain. Headache and
malaise are also relatively constant, nonspecific presenting complaints. Other symptoms may be specific to a particular intoxication and should be used to differentiate
the poisonings.35 Pathognomonic symptoms should be
sought and may include sensation of loose teeth for
CFP and flushing and sun-burn-like appearance in scombroid poisoning.
Conclusion
More than 300 fish species and numerous shellfish
species cause toxic poisonings. Puffer fish, sunfish, porcupine fish, and blue-ringed octopus have the most
powerful toxin (tetrodotoxin) with a case fatality rate from
envenomation of 50 to 60%. The CFP from other fish
poisonings ranges from about 1 to 10%. Most fish and
shellfish poisonings affect the autonomic and central
nervous systems and/or the gastrointestinal system and
cause a variety of symptoms, ranging from fairly mild gastrointestinal illness to severe and possibly fatal respiratory
arrest. Toxic fish and shellfish poisonings tend to occur
in warmer tropical areas and in coastal regions. Marine
animals that are extremely toxic in one geographic area
may be completely harmless in another area.27
Diagnosis of toxic seafood poisoning in travelers is
highly dependent upon precise history taking for pathognomonic symptoms, as there are few current ways to
detect the toxins in the clinical laboratory. Treatment
depends on severity of illness and often involves gastric
emptying and supportive treatment. No antitoxins are
available for any of the toxic seafood poisons. These
toxins are not inactivated by cooking, freezing, salting,
or gastric acid. In addition, there are only a few commercially available tests to detect these toxins in contaminated seafood, such as the Cigua-Check for ciguatoxin.
Prevention of toxic seafood poisoning in travelers con-
B a r b i e r a n d D i a z , P r e v e n t i o n a n d Tr e a t m e n t o f To x i c S e a f o o d b o r n e D i s e a s e s
sists mainly of monitoring for the occurrence of red or
brown tides from dinoflagellate HAB type II; avoiding
spoiled and potentially toxic fish and shellfish; and adhering to local restrictions and advisories on fish and shellfish harvesting, preparation, and human consumption, if
available. Such advisories are routine throughout the
developed world, especially in island nations (Japan, Taiwan, Philippines) and in other coastal nations (Canada,
France, Italy, Spain, and the United States), where seafood
consumption is popular. Advisories may not be available
in undeveloped or remote areas of the world, and travelers to these areas should seek safe seafood consumption advice from local health care authorities and providers
and tour and hotel operators.
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