Seafood Toxins - ACS Publications - American Chemical Society

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Ciguatera Seafood Poisoning Overview EDWARD P. RAGELIS

Downloaded by UNIV OF SYDNEY on November 8, 2016 | http://pubs.acs.org Publication Date: September 19, 1984 | doi: 10.1021/bk-1984-0262.ch003

Food and Drug Administration, Washington, DC 20204 Ciguatera poisoning is an important and serious cause of morbidity in humans that results from the consumption of a large variety of reef associated fishes throughout the circumtropical regions of the world. It is estimated that well over 50,000 people may be afflicted with the disease yearly and the number may be increasing. Besides affecting the public directly, ciguatera has had a dramatic impact on the development, growth, and stability of the in-shore fisheries in tropical and subtropical areas. Moreover, reports of ciguatera, coupled with adverse publicity have led to a ban on the sale of selected fish species, causing huge economic losses. Ciguatera is separate and distinct from human illnesses (botulism and scombroid poisoning) that result from eating seafood that has spoiled because of improper handling and/or processing. Cooking (e.g., frying, baking, broiling, boiling, steaming), smoking, drying, salting, or freezing does not appear to destroy the toxin in the fish flesh, and one cannot t e l l from smell or appearance whether or not a fish is ciguatoxic. The victim usually recovers from ciguatera within a few days (death occasionally occurs), but symptoms may last for several weeks, months, or possibly years. Ciguatera is the most commonly reported poisoning associated with eating fish in the United States and its territories. In spite of the long history of ciguatera, the origin or identity of the toxin(s), the organism(s), and ecological factors responsible for the disease are still not completely known. However, despite an incomplete description of the molecular structure of ciguatera toxin(s), methods are being developed for the detection of ciguatoxic fish. This chapter not subject to U.S. copyright. Published 1984 American Chemical Society

Ragelis; Seafood Toxins ACS Symposium Series; American Chemical Society: Washington, DC, 1984.

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History Ciguatera poisoning, which has been attributed to the agent "ciguatoxin" (1_), occurs throughout the regions between the Tropic of Cancer and the Tropic of Capricorn. The malady probably dates to antiquity. References to f i s h poisoning can be found i n Homer s Odyssey (800 B.C.) and were noted during the time of Alexander the Great (356-323 B.C.), when his soldiers were forbidden to eat f i s h to avoid the accompanying maladies and malaise that could threaten his conquests (2). The term ciguatera i s of Spanish o r i g i n , dating to the eighteenth century. I t was o r i g i n a l l y used to refer to intoxications caused by the ingestion of a marine s n a i l , Turbo Livona pica, known i n the Spanish A n t i l l e s by the Cuban name "cigua" (_2-4_). Current usage of ciguatera refers to human i n t o x i c a t i o n from ingestion of t r o p i c a l and subtropical f i n f i s h (_2). While the name has i t s o r i g i n i n the West Indies, the phenomenon was observed and recorded i n the Indian and P a c i f i c Oceans as early as the sixteenth century (5). The recorded outbreaks of ciguatera, both i n the New Hebrides aboard the vessel of the Portuguese explorer Pedro Fernandez de Queiros i n 1606 and i n 1774 aboard Captain Cook's Resolution, were probably two of the e a r l i e r v i v i d accounts of the i l l n e s s (_5,6) • In general, outbreaks of ciguatera poisoning are sporadic and unpredictable both i n geographic d i s t r i b u t i o n and time. Moreover, of the more than 400 species implicated ( 7_), not a l l of the f i s h of the same species caught at the same time i n the same place are t o x i c . Only a few miles can separate ciguateric and safe f i s h of a given species. Within the t r o p i c a l Western A t l a n t i c , e.g., F l o r i d a and the Caribbean, barracuda, grouper, and snapper are the f i s h most often implicated i n the disease. In the Hawaiian Islands region, the kahala (amberjack) and uluau cr Papio (Hawaiian names for 25 species i n the Carangidae family) are the most common offenders. A general l i s t of the species of f i s h l i k e l y to be toxic and t h e i r d i s t r i b u t i o n has been documented (7-10).


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Medical, Public Health, and Economic Aspects The symptoms of ciguatera poisoning are complex, involving the digestive, cardiovascular, and neurological systems (see below); the symptoms can occur i n various combinations (11). Symptoms of Ciguatera Poisoning 1.

Digestive -

2.

nausea, vomiting diarrhea, abdominal cramps

Cardiovascular

-

slow pulse rate between 40 and 50 beats/min. i r r e g u l a r or accelerated pulse between 100 and 200 beats/min. reduced blood pressure


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Neurological -


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headache severe pruritus temperature reversal paresthesia arthralgia myalgia convulsions, muscular paralysis audio and v i s u a l hallucinations vertigo and loss of equilibrium

Usually the i l l n e s s begins with g a s t r o i n t e s t i n a l inflammation, which causes severe dehydration and weakness, followed by cardiovascular and neurological syndromes. The d i s t i n c t i v e features of the poisoning are severe pruritus, temperature reversal, and paresthesia — t i n g l i n g and numbness of the extremities. The neurol o g i c a l symptoms may persist for months or years. Victims can develop s e n s i t i z a t i o n , whereby the neurological symptoms can recur with stress, drinking a l c o h o l i c beverages, or eating seemingly non-toxic f i s h (400 (27 deaths) >10,000 yearly (100 yearly (~50% mortality)

Other estimates suggest that as many as 50,000 individuals per year worldwide are a f f l i c t e d with ciguatera poisoning (17). Ciguatera morbidity i n the P a c i f i c averages f i v e cases per 1,000 (8). I t i s a sad commentary that on many islands i n the P a c i f i c , where ciguatera can be endemic, f i s h have to be imported, causing economic loss and hardship both to the island and the commercial and l o c a l fishermen whose l i v e l i h o o d depends on harvesting f i s h (8).


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Most s t a r t l i n g i s the report f o r 1983 of the morbidity rate of ciguatera poisoning f o r southern Queensland, A u s t r a l i a , which averaged 18/1,000 (18). Implicated i n the poisonings has been the Spanish mackerel (Scomberomorus commersoni), a pelagic f i s h economically important (1,000 tons landed annually) to the mackerel f i s h i n g industry i n Queensland (19). Pelagic f i s h are generally considered safe and are not normally associated with ciguatera poisoning (6). Impact of Ciguatera i n the United States. While r e l i a b l e morbidity s t a t i s t i c s have been d i f f i c u l t to obtain because of the lack of a precise diagnostic means to c l e a r l y i d e n t i f y c l i n i c a l cases of ciguatera, information has been gathered which shows that i t i s a widespread public health problem i n the United States and i t s t e r r i t o r i e s (20-22). The number of cases of ciguatera may average over 2,000 per year. Data accumulated from a tu 2e-year study of southern F l o r i d a indicate an average of 1,300 cases per year (23) or f o r Dade County, F l o r i d a , 0.5 cases per 1,000 population (24). Moreover, 1.6-4.4% of the l o c a l population on St. Thomas, U.S. V i r g i n Islands, i s annually a f f l i c t e d with ciguatera, representing a morbidity s t a t i s t i c of 27 cases per 1,000 persons i n a population of about 60,000 (25). In Hawaii, over a period of 82 years (19001981), 653 people have been a f f l i c t e d , with only two reported f a t a l i t i e s , i n d i c a t i n g a low mortality rate f o r ciguatera i n Hawaii (21). In the Commonwealth of Puerto Rico, where ciguatera was e s s e n t i a l l y unrecognized before 1976 (26), i t has recently become a considerable health and economic concern. Between A p r i l and June 1981, 49 persons were stricken with ciguatera. Two f a t a l i t i e s were reported among 22 victims who became i l l from eating freshly caught barracuda (27). [ U n o f f i c i a l estimates (28) indicate that there may be over 100 cases per year on the Island that are unreported or the disease i s misdiagnosed.] This episode and the threat of ciguatera has led to a ban by the Commonwealth i n the buying or s e l l i n g of barracuda, amberjack (medregal), and the urel negro or blackjack. In addition, the "ciguatera scare" caused the Island's demand f o r f i s h to f a l l d r a s t i c a l l y i n 1981, p a r t i c u l a r l y f o r red snapper, which dropped 80%. Red snapper and grouper together represent one-third of the annual catch; and ciguatera continues to be an impediment to the growth and s t a b i l i t y of the f l e d g l i n g Puerto Rican f i s h i n g industry. Two months before the Puerto Rican incident, an outbreak of ciguatera poisoning occurred at nearby St. Croix, U.S. V i r g i n Islands. This outbreak involved at least 69 people, most of whom had eaten red snapper purchased from a l o c a l vendor (29). An u n o f f i c i a l count of those affected may have been as high as 150 (30). Although ciguatera i s a problem limited to circumtropical regions, with the i n t e n s i f i e d commercialization of t r o p i c a l reef f i s h , ciguatera i s increasing i n frequency. Two examples are the outbreak of ciguatera i n Montgomery County, Maryland (31) i n September 1980 involving 12 persons (two seriously i l l with symptoms l a s t i n g a year) and one case i n Boston, Massachusetts (32) i n November 1982. Both events involved the consumption of


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grouper shipped from F l o r i d a to the l o c a l restaurants where the incidents occurred. A t h i r d but c o n f l i c t i n g account occurred i n October 1980, involving f i v e persons i n east Tennessee who became i l l (one seriously) a f t e r eating a combination of s h e l l f i s h (hard clams and scallops) and King mackerel. The poisonings were i n i t i a l l y attributed to the consumption of the clams (33), but analysis of the King mackerel showed that i t was ciguatoxic (34). The economic loss to the Florida/Caribbean/Hawaiian seafood industry from constraints i n harvesting p o t e n t i a l l y ciguatoxic f i s h , coupled with the adverse p u b l i c i t y , has not been c l e a r l y determined. I t i s estimated that over $10,000,000 i s lost annually (17); this does not include the higher price of l i a b i l i t y insurance being paid by the industry or recent court cases of ciguatera poisoning and pending l i t i g a t i o n (35). Origin of Toxin(s) In spite of the long history of ciguatera, the o r i g i n or i d e n t i t y of the toxin(s) i s s t i l l not completely known. Lewis (8) has referenced a number of theories that have been put f o r t h . These have included the e f f e c t s of p o l l u t i o n , the presence of heavy metals such as copper, c l i m a t i c changes, and diseased f i s h . Also, a food chain theory (36) was proposed, whereby f i s h become toxic through the food web, beginning with the benthic and d e t r i t a l herbivorous f i s h feeding on a toxic organism (either an algae, fungus, protozoan, or a bacterium), and the toxin(s) i s transmitted to the higher t r o p i c omnivores and carnivores that prey on the herbivores (Figure 1). We now believe, as with PSP (37-39), that the genesis of ciguatera toxin(s) i s a toxic d i n o f l a g e l l a t e ( s ) (Figure 1). P a c i f i c Organism. In the course of examining the food habits of the d e t r i t a l feeder Ctenochaetus s t r i a t u s , a surgeonfish that has been implicated i n numerous cases of ciguatera i n T a h i t i (40), i t was discovered that the d e t r i t a l f r a c t i o n of coral rubble i n a ciguatera-endemic area i n the Gambier Islands i n French Polynesia was toxic (41). Further examination of the d e t r i t a l material revealed the presence of a benthic d i n o f l a g e l late that was shown to bear a d i r e c t relationship to the occurrence of ciguateric f i s h (41,42). This epiphytic d i n o f l a g e l l a t e was recognized as a new species, Gambierdiscus toxicus (43), which was l a t e r found and i d e n t i f i e d i n Hawaii (44,45). The organism appears to spawn and f l o u r i s h following major natural or human-contrived disturbances and destruction of c o r a l reefs, e.g., by dredging and construction (41,43). Caribbean Organism. P a r a l l e l to this discovery, the Food and Drug Administration (FDA) i n 1979 supported work at the University of Southern I l l i n o i s , Carbondale, to i d e n t i f y the organisms(s) responsible for ciguatera poisoning i n the Caribbean. Over 70 d i f f e r e n t s i t e s i n the B r i t i s h and U.S. V i r g i n Islands were examined for epiphytic/benthic f l o r a , e s p e c i a l l y the presence of d i n o f l a g e l l a t e s . A c o l l e c t i o n of 65 strains representing 18 species of the most common d i n o f l a g e l l a t e s was established,



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Figure 1. Pood chain theory.



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including G. toxicus, which i s associated i n these waters with other planktonic d i n o f l a g e l l a t e s and l i t e r a l l y "glues" i t s e l f to macroalgae (46,47). Five of the species, namely, G. toxicus, Prorocentrum concavum, P. rhathymum, Gymnodinium sanquineum, and Gonyaulax polyedra, elaborate one or more toxic i s o l a t e s that k i l l mice within 48 hours (46). Extracts from P. concavum were more potent than those from G. toxicus, containing an unknown, very potent, fast-acting toxin. Chromatographic analysis of extracts from G. toxicus indicates the presence of ciguatoxin, one other l i p i d - s o l u b l e toxin, and maitotoxin, findings s i m i l a r to those with c e l l s of G. toxicus collected i n the P a c i f i c (13). Maitotoxin i s associated with ciguatoxin and s c a r i t o x i n i n c i g u a t e r i c f i s h (5). These observations suggest that more than one organism may produce a combination of toxins contributing to ciguatera poisoning i n the Caribbean and i n the P a c i f i c (21,48), which may account for the bizarre and diverse syndromes accompanying the illness• Chemistry The p r i n c i p a l active agent of ciguatera i n carnivores i s s t i l l thought to be ciguatoxin (49), and attempts to elucidate i t s molecular structure are currently based on the toxin i s o l a t e d from the viscera of moray eels, Lycodontis (Gymnothorax) javanicus (1_, 49,50). The y i e l d of toxin has been extremely low, on the order of 2 X 10~ % or 1.3 mg from 62 kg of eel viscera (49,51). Ciguatoxin i s a highly oxygenated, white s o l i d l i p i d (LD^Q 0.45 ug/kg, in mice) with a molecular weight of 1111.7+0.3 determined by Cf plasma desorption mass spectrometry. Scheuer (49) proposes a molecular formula of ^^^77^2^ ^54^78^24* ^ * basis of extensive H-nuclear magnetic resonance spectroscopic studies at 360 and 600 MHz, the toxin contains four o l e f i n i c , f i v e hydroxyl, and f i v e methyl groups; the bulk of the oxygen atoms are present as ether linkages (49). These features c l o s e l y resemble those of brevetoxin C (51), i s o l a t e d from Florida's red tide organism, Ptychodiscus brevis (39), and okadaic acid, a toxin i s o l a t e d from marine sponges (52) and the d i n o f l a g e l l a t e Prorocentrum lima (53). I t s t i l l has not been unequivocally established whether the toxin i s o l a t e d from moray eel v i s c e r a i s the same as that produced by G. toxicus, but incomplete data seem to indicate a d i r e c t s i m i l a r i t y (13,45). b

o

r

n t

ie

Other Toxins. Much less i s known concerning the molecular s t r u c tures of the secondary or associated toxins, maitotoxin and s c a r i t o x i n , which coexist with ciguatoxin i n toxic f i s h C5)• They have been found together i n the grazing Okinawan turban s h e l l , Turbo argyrostoma (54). Scaritoxin, a l i p i d - s o l u b l e toxin i s o lated from the muscular tissue of p a r r o t f i s h , Scarus gibbus (55), produces symptoms p h y s i o l o g i c a l l y s i m i l a r to ciguatoxin i n mice but i s chromatographically d i f f e r e n t (56). I t i s speculated to be a metabolite of ciguatoxin (5). Maitotoxin, with increased water-solubility (insoluble i n acetone), was f i r s t i s o l a t e d from the surgeonfish, C. s t r i a t u s , and i s a major toxic component elaborated by G. toxicus (46,57). I t i s a potent marine


SEAFOOD TOXINS

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toxin with a minimum l e t h a l dose (ip) i n mice of 0.2 ug/kg (58,59). Maitotoxin i s considered to be a non-peptidic material with a molecular weight of >10,000 as determined by u l t r a f i l t r a t i o n (59,60). The i n f r a r e d spectra of the toxin indicate numerous hydroxyl functions and the presence of an amide group (42). With i t s large molecular weight, maitotoxin could be a precursor of ciguatoxin 05). Besides these three toxins, other u n i d e n t i f i e d toxins have been detected i n c i g u a t e r i c f i s h (50). These could be a l t e r a t i o n or degradation products of either maitotoxin, ciguatoxin, or s c a r i t o x i n , or e n t i r e l y d i f f e r e n t toxins accumulated from a variety of toxic organisms (46).


Detection of Ciguatoxin Presently, there i s no validated quantitative method for the determination of ciguatoxin, because of the scarcity and unknown structure of the toxin. A variety of bioassays including feeding suspect f i s h to cats and mongooses (61-62), i n j e c t i n g extracts into mice (63-65), using brine shrimp (66) and guinea pig atrium (67), have been used for the detection of ciguatoxic f i s h . None of these procedures have achieved the s p e c i f i c i t y , s e n s i t i v i t y , and p r a c t i c a l i t y necessary for quantitative routine t e s t i n g , although the guinea pig atrium procedure does appear to d i f ferentiate between maitotoxin and ciguatoxin. However, a recent bioassay (68), using the smooth muscle of the guinea pig ileum, appears to be able to d i s t i n g u i s h three separate l i p i d - s o l u b l e toxins at the nanogram l e v e l i n isolates from cultures of G. toxicus, and has the p o t e n t i a l to be a screening method for these toxins. A more promising method for the detection of ciguatoxin includes a radioimmunoassay (RIA) procedure, which was developed at the University of Hawaii (69). Through support received from the FDA and the National Marine Fisheries Service, this RIA was extensively evaluated for i t s potential as a p o s i t i v e screening test for ciguatoxic f i s h . During a two-year study ( A p r i l 197981), the RIA was used to detect and remove p o t e n t i a l l y toxic kahalas or amberjacks (Seriola dumerili) from the Hawaiian market. F i f t e e n percent of the 5,529 f i s h examined (approximately 45 tons) was rejected (70). During this period, no incident of ciguatera poisoning due to marketed S. dumerili occurred, although p o i sonings (71) due to other f i s h species were reported to the Hawaii Department of Health (30 cases involving 88 i n d i v i d u a l s ) . Furthermore, the RIA was shown to be applicable and useful for developing and surveying f i s h i n g grounds i n areas where ciguatera outbreaks occur (72). It also proved to be h e l p f u l i n i d e n t i f y i n g the toxic snappers and groupers implicated i n the previously cited (29) episodes of ciguatera poisoning i n St. Croix and Tennessee (34). However, the RIA was too costly and time consuming for routine t e s t i n g . Also, the procedure i s s p e c i f i c for polyether l i p i d residues and cross reacts with okadaic acid, brevetoxin, monensin, and other polyether-containing l i p i d soluble residues (71,73,74). For these reasons, the RIA was converted to a simpler enzymeimmunoassay (EIA), which gives results that compare favorably with the RIA method and the mouse bioassay (P

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