Some Current Research Approaches

on Ciguatera Fish Poisoning*


 By J. P. McMillan
 Associate Professor of Biology
 Director, Ciguatera Research Project
 College of the Virgin Islands

 Ciguatera fish poisoning is a human health problem which
has for centuries afflicted people living near the tropical seas
around the world. The poisoning is caused by a neurotoxin called,
appropriately enough, ciguatoxin (CTX). Interestingly, however,
the name "ciguatera" originated as "siguatera" in the eighteenth
century when it applied to an illness found in Cuba that resulted
from eating the "cigua" or "sigua," the top shell. The term was
evidently then extended to poisoning produced by eating fish,
although the two diseases are apparently unrelated. The symptoms
of ciguatera fish poisoning usually occur within six hours and are
primarily neurological, though gastrointestinal symptoms, nausea
and diarrhea, may be the first to appear. Characteristic neuro-
logical symptoms include tingling of the lips, mouth, and tongue;
itching of the skin; a reversal of temperature sensation, cold objects
feel hot and hot objects feel cold; aching in muscles and joints;
and exhaustion and muscular weakness, particularly of the legs.
The severity of the intoxication depends upon the toxicity of the
fish, the amount consumed, and the body size of the victim. Very
severe cases of ciguatera have resulted from eating viscera, especi-
ally the liver, since CTX is much more concentrated in these organs
than in the flesh of the contaminated fish.

 Over the last 25 years, scientific researchers have slowly put
together the pieces of the ciguatera puzzle. The latest and possibly
the most important piece was the recent discovery of the biological
source of CTX. Working in the Society Islands in French Polynesia,
a team of scientists tracked the toxin down the food chain to its
biological source, a dinoflagellate which resides on various sub-
strates on or near coral reefs. The dinoflagellate was given the
scientific name Gambierdiscus toxicus; "Gambier" after the
islands where it was first discovered, "discus" after its shape,
and "toxicus" because it is the biogenitor of CTX and at least
one other toxin. For many years prior to this discovery it was
known that herbivorous fish grazing on or near coral consumed
something in their diet which contained CTX. There was at that
time much speculation as to which microorganism was the culprit.
Many hypotheses were advanced and all were rejected. Gambierdis-
cus toxicus (G.t.) was not known to biological science prior to its
recent identification. G.t. has since been found in many tropical
areas of the Indo-Pacific Ocean, the Caribbean Sea, the Gulf of
Mexico, and the Atlantic Ocean. Herbivorous fish which consume
it store the CTX in their flesh and organs and if they are eaten
by carnivorous fish, the accumulated toxin passes to this link in
the food chain. Carnivorous fish concentrate more and more CTX
as they ingest contaminated herbivores. Fish-eating fish which hunt
in reefs therefore may be many times more toxic than their prey.
Large, presumably older carnivorous fish cause most of the severe
ciguatera poisonings when consumed by humans, who are at the
top of the food chain.


* Funding for the Ciguatera Research Project at C.V.I. has been provided
 by the Food and Drug Administration, the National Marine Fisheries
 Service, and the Agricultural Experiment Station of the College.


 The discovery of G.t. not only answers the question of the
source of CTX, it also presents an opportunity for many new
approaches to the ciguatera problem. Studies of the dinoflagellate
in its natural environment may lead to an understanding of several
long-standing questions: Why do some areas harbor ciguatoxic fish
while other similar areas do not? What causes a ciguatera outbreak?
Can areas likely to harbor toxic fish be identified or outbreaks
predicted by monitoring the environment? Answers to these intri-
guing questions would be most helpful in attempting to reduce the
frequency of ciguatera cases. But the problem would be far from
solved. For example, fish, especially the large carnivores, might
become contaminated in one area and then migrate to another
where G.t. may be absent. And, despite the folklore and legends
which abound in all parts of the world afflicted with ciguatera,
toxic fish can not be discriminated from nontoxic ones by appear-
ance, smell, texture or taste.


Fig. 1 A line drawing taken from scanning electron micrographs
of Gambierdiscus toxicus, the dinoflagellate recently implicated
in the biogenesis of ciguatoxin (after Dr. F.J. R. Taylor, University
of British Columbia).

 Anyone who thinks about the ciguatera problem for very
long quickly realizes, "Aha, what we need is a test to determine
whether or not a particular fish is ciguatoxic." "Aha" indeed, but
this is probably the most formidably challenging facet of the
problem, for several reasons. First, the molecular structure of CTX
has yet to be determined. Why? Because there has never been
enough highly purified CTX available. (A possible solution to the
CTX supply problem will be discussed later.) CTX is known to be
a heat stable, polar lipid with a molecular weight around 1500;
useful information but insufficient to devise a test. Another
problem for testing is that, even if you had a test, say orange paper
turning green when it contacts a CTX solution, contaminated fish
flesh contains a very, very small absolute amount of CTX, 5 to 10
parts per million (ppm) or less. CTX is indeed a very potent neuro-
toxin. Detection of CTX may thus require a very sensitive test.
Furthermore, the test should be quite reliable. If the test misses a
percentage of the toxic fish, people could be poisoned. If the test
falsely identifies fish as ciguatoxic when they are not (false
positives), these will not be marketable although, in fact, perfectly
safe to consume. This would have undesirable economic con-
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