Prevention and Treatment of Toxic Seafoodborne Diseases in Travelers

Transcription

1 Prevention and Treatment of Toxic Seafoodborne Diseases in Travelers Heather M. Barbier and James H. Diaz 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 J Travel Med 2003;10: 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 marine 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, gametogenesis 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. Ciguatera Fish Poisoning CFP afflicts 10,000 to 50,000 individuals worldwide each year. This wide incident range is due to combina- 29

2 30 Journal of Travel Medicine, Volume 10, Number 1 Table 1 Toxic Seafoodborne Diseases in Travelers Causative Toxin Incubation Clinical Manifestations (Duration) Disease Organism Produced Source Period Ciguatera fish Giamberdicus Ciguatera Coral reef < 24 hours Perioral numbness and tingling, poisoning Toxicus toxin or fish, finfish reversal of temperature sensation, maitoxin perception of loose teeth, headache, vertigo, acute gastroenteritis, autonomic and other symptoms (usually 3 weeks; possibly months to years) Paralytic shellfish Alexandrium spp Saxitoxin Mussels, clams, 30 minutes Parasthesia, drowsiness, incoherent poisoning cockles, to 2 hours speech, respiratory scallops paralysis (2 hrs 2 to 3 days) Diarrhetic shellfish Dinophysis spp Okadaic acid Mussels, oysters, 30 min to Nausea, vomiting, diarrhea, abdominal poisoning and others scallops 15 hours pain (3 days) Neurotoxic shellfish Gymnodinium Brevetoxin Oysters, clams, 15 min to Nearly identical to those seen in CFP poisoning brevis aerosolized 3 hours plus asthma-like symptoms and eye toxin irritation (2 days) Amnesic shellfish Nitzschia Domoic acid Mussels < 24 hours Gastroenteritis, short-term memory poisoning spp loss, dizziness, headache, disorientation, seizures, respiratory difficulty, coma Scombroid (hista Histidine Scombrotoxin Scombridae 15 to 90 Face and neck flushing, headache, -mine) poisoning converted to family of fish, minutes burning sensation in the throat, histamine and others (usually palpitations, nausea, diarrhea, 1 hour) abdominal pain, bronchospasm (8 to 24 hours) Tetrodotoxin (fugu) Primary fish Tetrodotoxin Puffer fish, 10 minutes Oral parasthesias, light-headedness, poisoning toxin(toxin is sunfish, to 4 hours acute gastroenteritis, ataxia, endogenous) porcupine weakness, paralysis, lethargy, fish dysphagia, seizures, cyanosis, bronchospasms, respiratory failure, coma, hypotension (1 week) 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

3 Barbier and Diaz, Prevention and Treatment of Toxic Seafoodborne Diseases 31 Table 2 The Management of Toxic Seafoodborne Diseases in Travelers Disease Prevention Clinical Course Treatment Ciguatera fish Difficult; no commercially avail- Usually self-limiting; less than 1% Symptomatic and supportive; poisoning able detection methods; no mortality; symptoms are gen- intravenous rehydration, antitoxin available; best preven- erally 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 Detection of toxin and closure With supportive treatment, survi- Supportive poisoning of harvest beds; no antitoxin; vors recover fully; without avoid toxic shellfish treatment, death due to respiratory paralysis Diarrhetic shellfish No antitoxin; avoid toxic shellfish Usually resolves within 3 days; Supportive poisoning no fatalities Neurotoxic shellfish Monitoring of dinoflagellate cell Full recovery in 48 hours; Supportive poisoning counts; avoid toxic shellfish; no fatalities no antitoxin available Amnesic shellfish No antitoxin; avoid toxic shellfish Severe to fatal; can be chronic Supportive poisoning Scromboid (hista- Refrigerate fish; prevent bacterial Recovery within 8 to 24 hours Symptomatic plus antihistamines mine) poisoning overgrowth without treatment or subcutaneous epinephine; may need an antiemetic Tetrodotoxin (fugu) Avoid affected fish; have fish 60% mortality; if survive first Gastric lavage with sodium poisoning specially prepared 24 hours, patients usually bicarbonate, activated charcoal, recover in 1 week endotracheal intubation, further supportive therapy 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, 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, in 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

4 32 Journal of Travel Medicine, Volume 10, Number 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

5 Barbier and Diaz, Prevention and Treatment of Toxic Seafoodborne Diseases 33 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 ( 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 minutes 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 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 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

6 34 Journal of Travel Medicine, Volume 10, Number 1 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 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-

7 Barbier and Diaz, Prevention and Treatment of Toxic Seafoodborne Diseases 35 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 H 1 blockers, such as diphenhydramine and H 2 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 concentrations 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-

8 36 Journal of Travel Medicine, Volume 10, Number 1 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, 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-

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