JAccid Emerg Med 1997;14:246-251

REVIEW

Ichthyosarcotoxism: poisoning by edible fish

Iain C Grant

The term ichthyosarcotoxism describes a varietyof conditions arising as the result of poisoningby fish flesh. Poisoning by shellfish and otherinvertebrates is excluded, as is bacterial foodpoisoning from contaminated fish. Althoughmost of the conditions are experienced mainlyin warmer climates than Britain's, one form offish poisoning is relatively common here, andothers may be imported, either throughimported fish or by travellers. The conditionscould present to any accident and emergency(A&E) department, and increased awareness

of these disease entities may improve diagnosisand management.

It has long been known that some normallyedible fish species may from time to time causepoisoning. Many of the early records of theseconditions come from the Royal Navy. BothCaptain Blighl and Captain Cook2 describedillness among their crews after eating fishwhich were known usually to be safe. The firstdetailed medical treatise on fish poisoning inthe West Indies was written by the Surgeon on

a frigate.3 Since the beginning of this century,interest in the conditions and awareness of theconsiderable morbidity they produce has in-creased.

Several different clinical syndromes havebeen described with a variety of gastrointesti-nal, neurotoxic, and cardiotoxic features.The syndromes are not specific to any one

species of fish-some species may at times

Accident andEmergencyDepartment,Derriford Hospital,Plymouth, DevonPL6 8DHI C Grant

Correspondence to:Mr I C Grant, consultant inA&E medicine.

Accepted for publication10 April 1997

cause different syndromes, and even within arecognised single disease entity there may bewide variation in symptoms depending on thefish eaten or the geographical area. All of thismakes classification very difficult and conse-

quently no recognised classification exists.Table 1 shows an attempt to classify the condi-tions by the type of clinical features and symp-toms usually seen. This arrangement is simpli-fied and there is some overlap betweenconditions, but for the physician faced with a

patient with likely fish poisoning it gives some

guidance towards a specific diagnosis.It has been suggested that the features of

ciguatera, tetraodon, and paralytic shellfishpoisoning are similar and that these should beconsidered as a single disease, pelagic paraly-sis.4 However, each of these syndromes pro-duces a recognisable clinical picture, the toxinscausing the conditions have been shown to bedifferent, the fish species implicated vary, themorbidity and mortality are differ greatly, andthere are differences in recommended manage-ment. For these reasons most authorities agreethat the conditions should be considered as

distinct entities.57Most of these conditions are found mainly in

tropical and subtropical regions, but scom-broid is well known and endemic in the UnitedKingdom,8 9 ciguatera has been described inWest Indians returning to Britain and in Britishservicemen,' 1' "exotic" fish are increasingly

Table 1 Classification of ichthyosarcotoxisms

Group 1Mild gastrointestinal symptoms only

Cyclostome (lampreys and hagfish). Probably from slime. Severe but self limiting symptoms.Elasmobranch (shark flesh usually from Greenland sleeper shark). Relatively mild.Gempylid (snake mackerel, castor oil fish, skilfish). Strongly purgative.

Group 2Gastrointestinal and neurological symptoms

Tetraodon (puffer and porcupine fish). See text.Elasmobranch (liver) (shark liver from most sharks). Possibly related to hypervitaminosis A but probably also some toxin involved.Ichthyootoxism (roe or caviar poisoning). Often freshwater fish including sturgeon and salmon. ?Related to saxitoxin, the

cause of paralytic shellfish poisoning.Group 3Gastrointestinal and cardiac symptoms

Clupeotoxin (sardines, anchovies, herring). Episodic outbreaks.Group 4Gastrointestinal, neurological, cardiac, joints, etc

Ciguatera (many fish and symptoms). See text.Gymothorax (Moray eel). Probably severe ciguatera.

Group 5Anaphylactoid

Scombroid (See text)Group 6Hallucinogenic

Chimera (ratfish and elephant fish). Very poorly understood. Avoid these fish!Haliucinogenic fish poisoning (HFP) (mainly mullet). See text.Surgeon fish. Possibly related to one of ciguateric toxins (maitotoxin) but more likely to be indole induced.

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available in British supermarkets, and inter-national cuisine gains popularity making itpossible that tetradotoxication will soon beseen in Europe. These three conditions arecertainly the most important ichthyosarcotox-isms worldwide, but before discussing these inmore detail, two of the less common are worthyof particular mention.

Sardine poisoningSardine poisoning occurs infrequently and epi-sodically in the tropics and as far north as theMediterranean. For some uncertain reason,suddenly many of the sardines in a local area,usually those caught close to shore, appear tobe toxic at the same time. Sometimes ancho-vies and sprats many also be affected.

CLINICAL FEATURESA violent gastrointestinal illness precedesparaesthesiae, progressive paresis, fits, andtetanic spasms. Cardiovascular effects are oftenmarked, with arrhythmias and even cardiacarrest. Behavioural changes with anxiety andbizarre behaviour are also frequent. Desqua-mation and other skin problems are reported inthose who survive the acute episode. Mortalityis about 40%.

PATHOGENESISIt has been suggested that the occurrence ofsardine poisoning may be associated with algalblooms such as the red tides which cause saxi-toxin problems in shellfish, but this has notbeen established. A hypothetical toxin involv-ing the conversion of eicosapentaeonic acids toa toxin akin to thromboxane A2 has beenpostulated. 12

Given that all the fish involved feed onplankton, it seems likely that a protozoon is theorigin of the toxin (as in ciguatera and paralyticshellfish poisoning), but the exact organism hasyet to be identified.'3

TREATMENTNo effective treatment has been described, andgiven the high mortality, work is required to tryto produce an effective prevention strategy ortreatment. 12

Hallucinogenic fish poisoningWhile sardine poisoning causes bizarre behav-ioural changes, another interesting group ofichthyotoxins is known to produce hallucina-tions without gastrointestinal or other toxicity.Various toxins including indoles akin to LSDhave been implicated, with sources in algae andplankton eaten by the fish.'2 There is some evi-dence that a combination of these toxins withplant and perhaps fungal toxins is the basis forthe "zombies" of Haiti.7

ScombroidThe only indigenous British ichthyosarcotox-ism derives its name from the type of fish inwhich it was originally described. The scom-broid fish are the dark fleshed migratoryspecies such as mackerel, tuna, and bonito.'4Cases of this poisoning have been describedafter the ingestion of non-scombroid fish such

as herring, sardines, anchovies, and salmon.'5-Perhaps therefore the alternative name of"anaphylactoid fish poisoning" should be used.

CLINICAL FEATURESThe clinical picture starts with rapid onset ofsymptoms, sometimes within 10 minutes ofbeginning to eat the fish. Symptoms are usuallymaximal at about two hours after ingestion. Anacute gastrointestinal upset with vomiting,abdominal cramps, and sometimes diarrhoea isassociated with erythema, urticarial patches,and oedema. Although much of the swelling isoften facial, airway compromise is rare. Therecan be tachycardia and palpitations, althoughthese are uncommon. The disease is frighten-ing and distressing but is very seldom if everfatal. Spontaneous recovery within 24 hours isusual without treatment, but appropriate man-agement can dramatically curtail the attacks.'7

AETIOLOGYSmoked Mackerel used to account for most ofthe outbreaks of this condition in the UnitedKingdom," but tinned products, mainly tunaand sardines, now appear to cause more prob-lems. 7

In 1993 thirty two incidents were reported inthe first eight months of the year. Seven ofthese were traced to two batches of importedfresh tuna from Indonesia and Sri Lanka, and10 were from canned products.8There is probably considerable under-

reporting of scombroid for several reasons. Thedisease is self limiting and may not come tomedical attention. Even if it does it may not berecognised, the symptoms being easily con-fused with allergy. There is no legal require-ment to report the condition, although theFood Hygiene Laboratory at PHLS (PublicHealth Laboratory Service) would welcomereports.

PATHOGENESISThe pathogenesis of scombroid remains a mat-ter of some dispute. The flesh of the implicatedfish is rich in histidine, and organisms such asklebsiella and morganella in gut and bileproduce a decarboxylase which converts this tohistamine, and possibly other amines such assaurine. Since the symptoms produced arethose usually associated with histamine release,it is considered by many that histamine is theprincipal toxin.'2'7-20 Some investigators, how-ever, have suggested that since histamine canbe taken by mouth without ill effect, and sincethe symptoms are not necessarily related to theamount of histamine in the fish, a morecomplex mechanism involving the activation ofmast cells by the toxin may be involved.2'22

TREATMENTIn the past treatment relied on adrenaline andhistamine (HI) antagonists on the assumptionthat the condition was histamine induced.Recent experience has suggested that H2receptors may play some part in the aetiologyand the use of intravenous cimetidine has beenrecommended, producing very rapid resolu-tion of all symptoms.'920

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PREVENTIONThis condition should be completely prevent-able. It is poor handling and storage of fish attoo high a temperature which allows the enzy-matic activity to progress. The reduction in thecases attributed to smoked mackerel is testi-mony to the results possible with improvementin food hygiene. A case can be made for com-pulsory measurement of histamine levels inimported canned products, as is already donein Sweden, but in view of the debate aboutpathogenesis and the difficulty in agreeingwhat a permitted level should be there are cur-rently no plans to introduce this in the UnitedKingdom. Histamine concentrations can, how-ever, be measured in suspect fish. Fresh fishshould be frozen, and all samples (10 g) shouldbe sent, together with details of the productand the incident, to Anne Scoging at the FoodHygiene Laboratory (telephone 0181 2004400).8

TetraodonThe ingestion of toxic pufferfish (and a fewother related species) is most common inJapan, where fugu (raw pufferfish) is consid-ered a great delicacy. Cases from deliberateingestion (usually of ovary) and accidentalconsumption have also been reported. In Japanonly specially licensed chefs are allowed to pre-pare fugu. Nevertheless there are still severaltens of cases every year, and despite muchexperience in managing these cases the overallmortality is still in excess of 50%.7 2324

CLINICAL FEATURES

Shortly after the ingestion of toxic fish, thepatient develops a severe gastrointestinal upsetwith profound vomiting. This is associatedwith paraesthesiae, ataxia, and paresis which isoften rapidly progressive and may lead torespiratory insufficiency. Petechial haemor-rhages and extensive haemorrhagic blisteringof the skin may progress to severe desquama-tion. Patients usually lose consciousness rap-idly and prolonged convulsions may occur.The severity of attacks has been classified intofour grades.25 Death has been reported in aslittle as 17 minutes from the onset ofsymptoms, but is usually within hours.2526

TREATMENT

In severe cases early intensive care is required ifthere is to be any hope of survival. Even in mildcases hospital admission is essential. Supple-mentary oxygen should be given, and ventila-tory support considered if monitoring suggestsrespiratory insufficiency.Profound bradycardia, heart block, and

circulatory failure can occur, necessitating theuse of atropine and inotropes. Emesis can becontrolled by continuous low pressure gastricsuction rather than by drugs. In early casesgastric lavage using a 2% bicarbonate solutionhas been suggested and charcoal has beenused, on the theoretical basis that it shouldbind the toxin, but there is no firm evidence forits efficacy. Crystalloid infusion is recom-mended.242527

PATHOGENESISThe principal toxin, tetrodotoxin (or TTX), isprobably the best understood ichthyotoxin,having been first identified in 1948.28 Othersubstances such as saxitoxin have been foundin the flesh of implicated fish, suggesting thatseveral substances may be involved.'2 Tetrodo-toxin is a powerful axonal blocking agent whichmay react with cytochrome systems. It is themost powerful emetic known, and a powerfulrespiratory depressant, hypotensive agent, andsedative. It causes hypothermia and alterscoagulation, and at high doses is a convul-sant23 24 27

Tetrodotoxin is an extremely potent agentand has excited interest as a potential thera-peutic tool. There is considerable work on itsusefulness in anaesthesia and intensive care,but no standardised preparation or indicationyet exists.

PREVENTIONTheoretically tetraodon poisoning should bepreventable simply by avoiding the knowntoxic species. Avoiding the contamination offlesh with gut contents, visceral, and ovariantissue would go a long way to controlling theseverity of any case, but, as has been shown inJapan, even careful control of preparation can-not completely prevent the disease. Perhapscultural differences will prevent the Europeanpatient population from risking exposure tosuch a potent toxin. As yet, there has been noreported case in the United Kingdom, wherethe sale of fugu is not allowed, but Japaneserestaurants and sushi are growing in popular-ity. There is at least one Japanese licensed chefin this country who has recently been vocifer-ous in the media about his wish to produce this"delicacy" for his London customers. Caseshave been seen in California from fish im-ported from Japan.29 Perhaps fugu in Britainwill be next, unless it remains proscribed.

CiguateraProbably the most prevalent ichthyosarcotox-ism worldwide, and a well recognised cause ofconsiderable morbidity in the tropics and sub-tropics, ciguatera takes its name from "cigua",the Cuban name for a form of sea snail (or tur-ban shell) which was initially linked with thiscondition.30 The true incidence is not known,as many local people do not seek medicalattention. The incidence in Hawaii has beenestimated at about 3/100 000, while a tele-phone survey in Queensland in the 1980s sug-gested an annual incidence of about 1800/100 000.3' The highest risk area appears to bein the eastern Pacific, and particularly inFrench Polynesia, although the disease is wide-spread throughout the tropics and adjacentzones, and is frequently reported in Australia,the United States, and the Caribbean.3'-3The disease has been seen in Britain in peo-

ple who have eaten fish shortly before leavingthe Caribbean to return to this country, and inone case where fish was brought back to theUnited Kingdom.'0 The increasing availability

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of tropical seafish in supermarkets suggeststhat the disease could become more com-mon. 36 38

AETIOLOGYIn each area where ciguatera occurs there isconsiderable variation in the toxicity of fishfrom different reefs, with the toxicity of anygiven reef altering over time.3539 Disturbance,whether by natural events such as earthquakesor by man (beam trawling), appears to allow anincrease of toxicity in the disturbed area.7 Over400 fish species have at one time beenimplicated in the pathogenesis of ciguatera,7but probably only about 50 species, mainly thelarger carnivores, cause most of the problems.Grouper, snapper, barracuda, surgeon fish, andMoray eel are probably the most commonciguatoxic fish (figs 1-3).3 36 Until fairlyrecently Moray eel was thought to cause amuch more serious disease than ciguatera,which was called gymothorax poisoning. It isnow considered that gymothorax is simply amore severe form of ciguatera due to muchhigher concentrations of the toxins in Morayflesh than in any other fish.

It is likely that apparent geographical andethnic differences in the symptoms of ciguaterareflect, at least to some extent, variations indietary preferences.'2

CLINICAL FEATURESThe clinical disease usually starts about four to10 hours after ingestion of toxic fish, with gas-trointestinal effects of nausea, vomiting, anddiarrhoea. It varies considerably in severity, butis often quite mild. The degree of this upsetseems to be correlated with the ingested doseof toxin and may give an early indication of thelikely severity of the episode.Some hours later paraesthesiae, dysaesthe-

siae, headache, malaise, weakness, pruritus,and a host of other symptoms develop. Some300 symptoms and signs have been described.8Cardiotoxicity may also occur, with heart blockthe most common finding.7 11 36 The featurewhich appears to be almost pathognomic ofciguatera is a strange reversal of temperaturediscrimination, such that hot objects feel coldand vice versa. This is often most noticeable inthe mouth, where hot drinks seem cold and ice

"burns", but the symptom does not usuallydevelop for two to five days and is therefore notmuch help in making the diagnosis in the A&Edepartment.7 ' 12 35 39 47The neurotoxic symptoms are long lasting,

with many patients reporting persistent prob-lems three months after the incident. A chronicform of the condition may occur (notably inMelanesia) characterised by remission andrelapse in which ataxia and muscle weaknessare prominent debilitating features.35 39 Duringthe acute episode, patients often describe exac-erbations of symptoms after drinking alcoholand after eating fish known not to be toxic,including fish from European waters. Nuts andshellfish have also been implicated in increas-ing symptoms (Sims JK, personal communica-tion). This may suggest that there is a"cotoxin" in these substances."The high incidence, long duration, and

debilitating nature of this illness makes it animportant condition in endemic areas in termsof morbidity and in its socioeconomic conse-quences. Overall mortality is, however, verylow with the reported death rates being wellbelow 1:1000.

PATHOGENESISIn 1977 a substance was isolated from toxicfish which caused the symptoms of ciguatera inanimals.2340 This substance, ciguatoxin, was

Figure 1 Barracuda (lowest) with red and grey snappers.

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Figure 2 Grouper.

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Figure 3 Moray eel.

found to be produced by a dinoflagellateprotozoon (Gambierdiscus toxicus)," and theappearance of this organism correlated wellwith the onset of toxicity around particularreefs. Subsequent work has identified at leasttwo other toxins, maitotoxin and scaritoxin,which can be associated with the disease.4243Other dinoflagellate protozoa such as coolia,prorocentrum, and others can also producethese toxins.44 The toxins have been demon-strated in increasing concentrations throughthe food web of vegetarian and carnivorousfish.3645 Some fish appear to be unaffected bythe toxin, simply concentrating it in theirflesh,45-7 while others may themselves bepoisoned.48 These are then ultimately eaten byman, producing the clinical picture of ciguat-era. Variations in the concentration of eachindividual toxin, as well as the total doseingested, probably account for considerablevariations in the severity and overall clinicalpresentation in individuals.

All the toxins share certain common proper-ties. They are extremely stable substances,resistant to all usual forms of food preparation,storage, and cooking, and pass unchanged intoman via the gastrointestinal tract. All the toxinsseem to alter the membrane properties ofexcitable cells in a way that activates voltagedependent sodium channels, which are wide-spread in nerve and muscle.3646

TREATMENT

Some have suggested prevention of toxinabsorption by gastrointestinal tract cleansing(Sims JK, personal communication) but re-

cently the use of magnesium containingcathartics has been implicated in the worseningof symptoms.36 There is theoretical and anec-

dotal evidence for the efficacy of activated

charcoal in limiting absorption, but no control-led trials have been published.Most treatment is supportive and aimed at

relieving the symptoms. Dehydration andhypovolaemia may occur, and intravenous fluidis recommended. There may also be decreasedcardiac output, and correction of bradycardiawith atropine and inotropic support withdopamine have both been used successfully.Calcium salts have been used to try to coun-

ter some of the ion shifts in nerve cells.Calcium has been shown to be effective in vitrobut again only anecdotal evidence for itsefficacy in vivo exists.There are few controlled trials of treatment

in this condition and results are difficult tointerpret. This makes firm recommendationsequally difficult. There are uncontrolled trialsin which both calcium and mannitol appear tobe effective, the latter probably slightly moreso,49 50 and its use is therefore recommended insevere cases.The membrane stabilising effect of ami-

triptyline may relieve the symptoms, especiallydysaesthesiae and pruritus, and it may also bebeneficial in the chronic form.5' Non-steroidalanti-inflammatory drugs may also be of benefitin the early stages (Sims JK, personal commu-nication). Many other drugs have been used,with varying effects, but there is a need forcontrolled trials to find a specific treatmentwith minimal side effects.

PREVENTION

Given the variety of potentially toxic fish andthe difficulties in identifying toxic reefs andfish, prevention is very difficult. Several assayshave been tried52 and a rapid "stick" test forciguatoxin based on enzyme immunoassay iscommercially available and has some use inhighly endemic areas.53 There have beendifficulties in validating this test, however,3"and even in fish markets it is only economicallypossible to batch-test catches from specificareas, rather than detecting the problem inindividual fish. In the USA many ciguatoxicfish are caught by sport fishermen and do notpass through commercial premises where sucha test might be possible.54Some investigators have suggested that unu-

sually large specimens of any given fish arelikely to harbour greater concentrations of thetoxins and should be avoided.5556 This, how-ever, does not make economic sense to thefisherman or vendor.Much work is in progress in the attempt to

find a cheap reliable way of detecting cigua-toxin in fish flesh. Until this becomes available,however, the advice to travellers in endemicareas should be:(1) Be circumspect about eating fish;(2) Never eat Moray eel or scaleless fish, andavoid anything which the locals don't eat;(3) Avoid particularly big specimens;(4) Don't eat the head, liver, gonads, or visceraof any fish;(5) If you become ill after eating fish seekmedical attention.

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SummaryThe ichthyosarcotoxisms are a varied andcomplex group of conditions which cause awide variety of symptoms after the ingestion offish. The diagnosis is largely clinical and all areprobably underrecognised and underreported.They pose considerable challenges to clini-cians, ecologists, biologists, and others. Thereis a need for further research into methods ofprevention as well as treatment. With increas-ing air travel and holidays further afield,together with changing eating habits at home,these conditions may become more prevalentin the United Kingdom. I would be interestedto hear from anyone who has encountered anyof these conditions, and ciguatera in particular.

1 Steinfeld AD, Steinfeld HJ. Ciguatera and the voyage ofCaptain Bligh. JAMA 1974;228:1270-1.

2 Forster JR. Resolution. Thejournal ofJohann Rheinhold Forster1772-75, vol 4. London: Hakluyt Society, 1982:649-51.

3 Chisholm C. On the poison of fish. Edinburgh Med Surg J1808;4:393-422.

4 Mills AR, Pasmore R. Pelagic paralysis. Lancet 1988;i:161-4.

5 Bagnis R. Poisoning from eating fish. Med Int 1984;2:47-50.

6 Bagnis R, Kuberski T, Laugier S. Clinical observations on3009 cases of ciguatera (fish poisoning) in the SouthPacific. Am J Trop Med Hyg 1979;28:1067-73.

7 Halstead BW Poisonous and venomous marine animals of theworld. Princeton NJ: Darwin Press, 1978.

8 Scombrotoxic (histamine) fish poisoning. Commun Dis Rep(CDR Weekly) 1993;3(36).

9 Gilbert RJ, Hobbs G, Murray CK, Cruickshank JG, YoungSE. Scombrotoxic fish poisoning: features of the first 50incidents to be reported in Britain (1976-9).BMJ 1980;281:71-2.

10 Tatnall FM, Smith HG, Welsby PD, Turnbull PCB. Ciguat-era poisoning. BMJ 1980;281:948-9.

11 Grant IC. Ciguatera poisoning. J R Nav Med Serv 1984;70:82-6.

12 Sims JK. A theoretical discourse on the pharmacology oftoxic marine ingestions. Ann Emerg Med 1987;16:1006-15.

13 Melton RJ, Randell JE, Fusetani N, Weiner RS, Couch RD,Sims JK. Fatal sardine poisoning. Hawaii Med J 1984;43:114-20.

14 Teach SJ. Scombroid fish poisoning. Clin Toxicol Rev 1993;15:1.

15 Mack RB. Dorma con pesce: scombroid ichthyotoxicosis.North Carolina Med J 1993;54:452-3.

16 Dickinson G. Scombroid fish poisoning syndrome. AnnEmerg Med 1982;1 1:487.

17 Bartholomew BA, Berry PR, Rodhouse JC, Gilbert RJ,Murray CK Scombrotoxic fish poisoning in Britain:features of over 25 suspected incidents from 1976 to 1986.Epidemiol Infect 1987;99:775-82.

18 Morrow JD, Margolies GR, Rowland BS, Roberts U.Evidence that histamine is the causative toxin of scombroidfish poisoning. N Engl J Med 1991;324:716-20.

19 Hughes JM, Potter ME. Scombroid-fish poisoning-frompathogenesis to prevention. N Engl J Med 1991;324:766-8.

20 Blakeley ML Scombroid poisoning: prompt resolution ofsymptoms with cimetidine. Ann Emerg Med 1983;12:104-6.

21 Clifford MN, Walker R, Wright J, Ijomah P, Hardy R, Mur-ray CK, et al. Scombroid fish poisoning [letter]. N Engl JMed 1991;325:515-6.

22 Arnold SH. Histamine(?) toxicity from fish products. AdvFood Res 1978;24:113-54.

23 Scheuer PJ. Marine toxins. Accounts of Chemical Research1977;10:33-9.

24 Sims JK. Pufferfish poisoning: emergency diagnosis andmanagement ofmild human tetrodotoxication. Ann EmergMed 1986;15:1094-8.

25 Fukudu T, Tani I. Records of puffer fish poisoning. ReportI. Kyushu University Medical News 1937; 1 1:7-13.

26 Lau FC, Wong CK, Yip SH. Puffer fish poisoning. J AccidEmerg Med 1995:12:214-5.

27 Russell FE. Venomous animal injuries. Curr Probl Pediatr1973;3: 1-47.

28 Hashimoto K, Fusetani N. Toxins occurring in marineorganisms important as food sources in the Indo-Pacificregion. Bull Jpn Soc Sci Fisheries, 1985.

29 Tetrodotoxin poisoning associated with eating puffer fishtransported from Japan to California 1996. MMWR 1996:45:389-91.

30 Poey F. Ciguatera, memoria sobre la enfermedad occazi-onada por los peces venemos. Rep Fiscio Natural, IslaCuba, Havana 1866:2:1-39.

31 Lewis ND. Ciguatera in the Pacific. In: Seafood toxins.American Chemistry Society Symposia, series 262. Wash-ington DC: Food and Drug Administration, 1984:293-5.

32 Banner AH, Helfrich P. Distribution ofciguatera in the tropicalPacific. Hawaii Institute ofMarine Biology, technical reportNo 3. Honolulu: University of Hawaii, 1964.

33 Barton ED, Tanner P, Turchen SG, Tunget CL, ManoguerraA, Clark RF. Ciguatera fish poisoning: a Southern Californiaepidemic. West J Med 1995; 163:31.

34 Glaziou P, Legrand A-M. The epidemiology of ciguaterafish poisoning. Toxicon 1994;32:863-73.

35 Bagnis R. Les empoissonnements par le poisson en Polyne-sie Francaise: etude clinique et epidemiologique. Rev HygMed Soc 1967;15:619-46.

36 Juranovic LR, Park DL. Foodborne toxins of marine origin:ciguatera. Rev Environ Contam Toxicol 1991;1 17:51-94.

37 Lawrence DN, Enriquez MB, Lumish RM, Maceo A.Ciguatera fish poisoning in Miami. JAMA 1980:244:254-8.

38 Fish poisoning [editorial]. BMJ 1980;281:890.39 Sorokin M. Ciguatera poisoning in North West Viti Levu,

Fiji Islands. Hawaii MedJ 1975:34:207-10.40 Scheuer PJ, Takahashi W, Tsutsumi J. Ciguatoxin: isolation

and chemical nature. Science 1967; 155:1267-8.41 Yasumoto T, Nakajima I, Bagnis R, Adachi R. Finding of a

dinoflagellate as a likely culprit of ciguatera. Bull Jpn SocSci Fisheries 1977;43:1021-6.

42 Yasumoto T, Bagnis R, Vernoux JP. Toxicity of thesurgeonfishes-II. Properties of the principal water-solubletoxin. Bull Jpn Soc Sci Fisheries 1976;42:359-65.

43 Legrand AM, Galonnier M, Bagnis R. Studies on the modeof action of ciguateric toxins. Toxicon 1982;20:311-5.

44 Besada EG, Loeblich LA, Loeblich AR. Observations ontropical benthic dinoflagellates from ciguatera-endemicareas: Coolia, Gambierdiscus and Ostreopsis. Bull MarineSci 1982;32:723-35.

45 Yasumoto T, Bagnis R, Thevenin S, Garcon M. A survey ofthe comparative toxicity in the food chain of ciguatera. BullJpn Soc Sci Fisheries 1977;43:1015-9.

46 Rayner MD. The mode of action of ciguatoxin. Fed Proc1972;31:1139-45.

47 Russell FE. Poisonous and venomous marine animals andtheir toxins. Ann NY Acad Sci 1975;245:57-64.

48 Lewis RJ. Ciguatoxins are potent ichthyotoxins. Toxicon1992;30:207-1 1.

49 Bagnis R, Spiegel A, Boutin JP, Burucoa C, Nguyen L, Car-tel JP, et al. Evaluation of the efficacy of mannitol in thetreatment of ciguatera in French Polynesia. Med Trop1992;52:67-73.

50 Palafox NA, Jain LG, Pinano AZ, Gulick TM, Williams RK,Schatz IJ. Successful treatment of ciguatera fish poisoningwith intravenous mannitol. JAMA 1988;259:2740-2.

51 Davis RT, Villar L. Symptomatic improvement withamitriptyline in ciguatera fish poisoning [letter]. N Engl JMed 1986;315:65.

52 Kimura LH, Hokama Y, Abad MA, Oyama M, Miyahara JT.Comparison of three different assays for the assessment ofciguatoxin in fish tissues: radioimmunoassay, mousebioassay, and in vitro guinea pig atrium assay. Toxicon1982;20:907-12.

53 Hokama Y. A rapid simplified enzyme immunoassay sticktest for the detection of ciguatoxin and related polyethersfrom fish tissues. Toxicon 1985;23:939-46.

54 Gollop JH, Pon EW. Ciguatera: a review. Hawaii Med J1992;51:90.

55 Craig CP. It is always the big ones that should get away [edi-torial]. JAMA 1980;244:272-3.

56 Hessel DW, Halstead BW, Peckham NH. Marine biotoxinsI. Ciguatera poisoning: some biological and chemicalaspects. Ann NY Acad Sci 1960;90:788-97.

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