Ciguatera concerns a form of food poisoning caused by the consumption of certain tropical and subtropical fish which are normally edible, but have become toxic due to ingestion of algae containing poisonous polyethers. The presence of the latter is determined by ecological conditions on coral reefs. This is the most common form of intoxication associated with the marine environment. There are probably some 10,000-50,000 cases each year, but estimates show wide variation. The average incidence in endemic regions varies from 5-50 cases per 100,000 inhabitants per year, but in some years this can reach as high as 500/100,000 in the South Pacific.

The first observations of ciguatera date from the 16^th century. Pedro Martyr D’Anghera worked for the Spanish crown as a rapporteur on board the ships of the great discoverers such as Columbus and Cortez. In his writings he reported on clinical cases and attributed them to intoxication by poisonous fish. According to him, the poison originated from a tree (Hippomane mancinella), the fruits of which fell into the sea. This hypothesis persisted until recent times. In 1675 John Locke, the English philosopher and physician, described the symptoms quite precisely and also reported the effect of an earlier exposure to the poison. James Cook and his crew were poisoned after eating "red pargo" fish (Lutjanidae). It took a month before they recovered. Morrison, on board the Bounty (of mutiny fame), reported ciguatera resulting from eating moray eels in Polynesia, the ship’s doctor being one of those who died. In 1866 in Cuba, Mr. Poey, a lawyer, naturalist and fish expert, reported intoxication due to consumption of a gastropod (Livona pica) which was known locally as "cigua". In this way the name ciguatera was introduced.

The disorder only occurs between latitudes 35° North and 34° South and follows the distribution of the madreporic coral reefs. Many tropical archipelagos are affected. In some regions the disorder is endemic, in other places there are irregular epidemics. Other areas again are completely free (insofar as is known).

Geographical distribution of ciguatera:

• Indian Ocean:

• Réunion, Madagascar, Mauritius, Seychelles.
• To a lesser extent Sri Lanka, the Maldives, Mayotte and the Chagos archipelago.
• Oddly enough, not in the Red Sea, although the pathogen - Gambierdiscus toxicus – is present there.

• South Pacific

• French Polynesia, with significant numbers in Tuamotu (Tahiti and Bora Bora), the Gambier Islands, the Marquesas Islands.
• The Philippines, Fiji, Samoa, Tonga.
• Various other archipelagos such as New Hebrides, Hawaii, Cook Islands, Wallis and Futuna, Marshall Islands.
• Papua New Guinea, New Caledonia and Australia in Queensland, north of Brisbane (Great Barrier Reef).

• Atlantic Ocean

• Florida and the Bahamas.
• Cuba, Jamaica and Hispaniola (Haiti and the Dominican Republic).
• Puerto Rico, Virgin Islands, St Maarten, St Bartholomew, Saba, St Kitts and Nevis, Montserrat, Antigua, Guadeloupe, Martinique.
• Rarely in Trinidad and Tobago.

Gambierdiscus toxicus, a dinoflagellate, was discovered in the Gambier Islands (French Polynesia) during an epidemic of ciguatera in 1976. The cells are brownish green. They are shaped like smarties with a diameter of 80-90 µm and a thickness of 40 µm. This unicellular alga is in fact a benthic organism which grows as an epiphyte on other large algae (compare with a Bromelia in the rain forest). Consequently it is not part of the plankton and plays no part in red tides. The preferred growth site is on the thalli of multi-branched macrophytic seaweeds such as Turbinaria ornata or Jania sp. The cells adhere to the thalli by means of mucus threads or a superficial layer of mucus, but dinoflagellates are also sometimes found under the surface of the seaweed. On this type of substrate intense competition between various algae takes place, including other toxic dinoflagellates (Amphidinium, Ostreopsis, Prorocentrum, Coolea). It results in a dynamic balance between the various species. Gambierdiscus is sometimes found on pieces of floating seaweed helping the organism to spread. This kind of dispersion explains the distribution to new regions. The alga can also grow on dead coral surfaces. The quantity of available surfaces is determined in part by increased turbidity of the sea water, including that caused by humans (building works, dredging, the development of sea ports, explosives, the sinking of ships and so on) and by nature (tsunamis, storms, cyclones). The dinoflagellates avoid bright sunlight or deep shadow. They will be found in the upper 10-15 metres of the sea water, where there is sufficient, but not too much, sunlight.

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The alga is responsible for the production of two kinds of toxins: maitotoxins and ciguatoxins. Large cells contain up to 3 times more poison. The concentration of poison varies greatly, however, from region to region. Whether the presence of certain bacteria plays a part in the ecology is not yet clear. Older and larger fish have more chance of containing greater amounts of poison. Do not forget that the age of tropical fish is very difficult to determine. For fish in regions which have seasons, it is possible to study the growth rings in the otoliths (ear bones) or the skin scales, but these techniques cannot be used in the tropics.

The accumulation of poison via the food chain passes through five stages:

1. Degradation or destruction of the coral reef ecosystem. This may be both due to human activities (e.g. excavation and building works) and due to natural causes (heavy storms with destruction of coral reefs). These events play a large part in the changing geographical and seasonal risks of ciguatera. One island may be without danger, while a nearby island is at risk. There is often 5 to 6 months between the destruction of the reef and a ciguatera outbreak, reflecting the time needed for recolonisation of the exposed surfaces.
2. The substrates released are covered with new plants, including seaweeds and toxic dinoflagellates. Proliferation of the dinoflagellates may lead to large areas on which fish can graze and ingest toxins.
3. Since algae serve as food for plant-eating animals low in the food chain (invertebrates and herbivorous fish), the latter animals will absorb the poison. They will generally have a small amount of poison in their bodies. Maitotoxins are concentrated in the intestine of the herbivores and eliminated with the faeces of these animals. Therefore the importance of the toxin in the clinical course of ciguatera is limited. In contrast, ciguatoxin is accumulated chiefly in the liver, the eggs and the skin. Some fish have large amounts of poison in the muscles (e.g. Scaridae). Many species of fish can contain the poison. Of importance here are Acanthuridae (surgeon fish), Scaridae (parrot fish), Balistidae (trigger fish) and Malacanthidae. The latter feed on annelids, molluscs and crustacea. Surgeon fish can be recognised by the sharp moveable spines near the tail (they can cause serious mechanical injuries). The lips of parrot fish are fused into a beak and these animals nibble coral. Their faeces also contain large amounts of sand and lime grains and are an important source of sand on coral reefs. They have the unusual habit of secreting a mucus coccoon around their bodies in the evening, a kind of sleeping bag to spend the night in. Trigger fish have two special dorsal spines towards the front of its back. In exceptional cases molluscs also accumulate the poison (e.g. the original "cigua").
4. Fish concentrate the toxins in their bodies and may modify them chemically. Piscivorous fish then accumulate more toxins and are more dangerous if consumed by humans. Notorious examples are Muraenidae (moray eels), Sphyraenidae (barracudas), Serranidae (groupers), Lutjanidae (snappers), Carangidae (jacks). It is not so much the taxonomic relationship of the animals which is important, but their feeding habits. Pelagic piscivorous fish which can swim long distances, e.g. barracudas, may take the poison outside the regions of coral reefs.
5. If these fish are eaten by humans, intoxication may follow.

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Ciguatoxin was originally isolated by Scheuer in Hawaii in 1967. The structural formula of ciguatoxin was discovered on the basis of 350 µg of poison originating from 830 kg of Javanese giant moray eels (Gymnothorax javanicus). The toxin is present in low concentrations, but is extremely powerful. The toxins form a family of very closely related structures with a molecular weight of 941-1117 Dalton. There are a number of variants, depending on whether certain chemical groups (-H, -CH₃, etc) are present or not. It is a heat-resistant, fat-soluble polyheterocyclic molecule structurally related to brevetoxin. The poison binds to voltage-dependent sodium channels in muscle and nerve cells, so that they remain open.

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This toxin was isolated in 1976 in Tahiti from a parrot fish (Scarus gibbus). It is a metabolite of ciguatoxin, but dinoflagellates are also said to be able to produce the poison in in-vitro culture. More research is needed.

The symptoms usually follow eating toxin-containing fish, rarely after eating gastropods, crustaceans or sea urchins. The fish does not differ as regards to colour, taste or smell. The poison is not destroyed by baking or boiling, or broken down by gastric acid, pickling, drying freezing, smoking or processing in canned foods. The symptoms depend on the amount of poison (the quantity of fish and type of tissue eaten), as well as the body weight of the patient and possibly individual sensitivity. Previous exposure to sub-clinical amounts also play a role in the symptomatology due to accumulation.

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The symptoms are gastro-intestinal, cardiological and neurological in nature and are generally self-limiting. After an incubation period of 3-8 hours (range 1 - 20 hours) the patient does not feel well. There is congestion of the face. Muscle and joint pain, headache and dizziness follow. The patient has nausea, together with abdominal pain, possibly vomiting and diarrhoea. Sometimes there is oliguria. Some tingling around the mouth can arise, which then becomes generalised. There may be a metallic taste in the mouth, together with sweating, lacrimation and hypersalivation. Rarely mydriasis, strabismus or paralysis develop. The dysaesthesia and paresthesia are exacerbated by cold and there is sometimes an inversion of the cold-heat sensation. This may be expressed by a burning feeling when touching cold water or drinking a cold drink. Somewhat later a pronounced generalised pruritus appears. This may persist for weeks. Later still there may be skin rash and desquamation. The gastro-enteric and cardiac symptoms usually last 1 to 5 days, but the nervous symptoms and feeling of fatigue may persist for several weeks. Sometimes the symptoms become worse when drinking alcohol. Combined with alcoholic intoxication, there is irregular heart rate and bradycardia, hypotension with or without AV-block. Mortality is low (0.1 to 4%) and death follows respiratory arrest or cardiovascular shock. The poison is probably excreted in breast milk.

The diagnosis is made clinically. There are no typical biochemical or haematological parameters which can support the diagnosis. The following are important to differential diagnosis:

• Common gastro-enteritis
• Tetrodotoxin intoxication (e.g. from eating porcupine fish or fugu)
• Scombridae ichthyotoxism (symptoms of histamine release)
• Haff disease (rhabdomyolysis)
• Acute vitamin A intoxication (eating the liver of predators, including sharks or polar bears)
• Botulism from food (type E)
• Allergy to fish (symptoms of urticaria – also think of urticaria secondary to anisakiasis)
• Neurotoxic or paralytic poisons originating from shellfish
• Intolerance to sulphite, tartrazine, glutamate
• Decompression sickness (caisson disease, the bends)
• Sea sickness
• Post-alcohol hangover

Various endemic countries have set up a monitoring programme to identify high risk periods. If fewer than 10 cells of G. toxicus per gram of seawater are detected, the danger is considered to be very low. If more than 100, there is a threat. However, more research is needed into the various elements of the ecological requirements of this toxic dinoflagellate.

Although dinoflagellates are found on red algae (Rhodophyta), brown algae (Phaeophyta) and green algae (Chlorophyta), a specific association exists between well-defined macro-algae and certain dinoflagellates. Dinoflagellates occur more on branched species than on broad-leaved seaweeds. The density is higher in the lee of the wind, certainly if there is moderate runoff of water from the land. Both organic and inorganic nutrients, as well as lower sea salt concentrations have a role in this.

Control of the fish stocks together with monitoring of phycotoxins are required, certainly a few months after heavy storms or hurricanes. Eating groupers, jacks, barracudas, moray eels and other known dangerous fish should be systematically avoided. Similar advice is more difficult if the fish species are only sporadically toxic. If there is uncertainty as to the identity of a fish in endemic regions it is best to avoid eating part of a large fish (small fish which may be served whole are generally not dangerous). In endemic zones local people often first give a piece to the cat. If the animal does not vomit, the fish is regarded as safe. The extent to which this is reliable is as yet unclear. Remember that pelagic fish may absorb toxins on a coral reef and then are able to cover great distances (e.g. from the Caribbean to New York). Also, fish living in the deep sea may contain poison even if they live far away from the coral reef.

Toxins are detected via several techniques, including bio-assays. There are various animal tests of variable reliability (a mouse assay is the best to date). Sometimes a mosquito assay is used. After intrathoracic injection of Aedes aegypti with 0.5 µl of poisonous extract, the mosquitoes die of ciguatoxins. There are tests for measuring toxin concentrations using HPLC or detecting the toxicity on tissue cultures. Colorimetric stick tests (Ciguacheck), radio-immunoassays, ELISA, capillary electrophoresis, mass spectrometry and other tests have all been developed, but there is as yet no good and easy test available.

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More than 400 fish species have been described which may contain ciguatoxin. They belong to the following families:

• Murenidae: Moray eels often live in holes in coral reefs. Active at night.
• Sphyraenidae: Barracudas. Fast swimming carnivorous fish with a characteristic shape.
• Lutjanidae: Snappers. Carnivorous fish on coral reefs.
• Serranidae: Groupers. Carnivorous fish on coral reefs and elsewhere.
• Carangidae: Jacks. Carnivorous fish with a pelagic existence.
• Acanthuridae: Surgeon fish. Small shallow water fish which are chiefly herbivorous.
• Balistidae: Trigger fish. Small shallow water fish. Omnivorous, can swim long distances.
• Scaridae: Parrot fish. Typical beak, herbivorous – coral eaters.

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To a lesser extent:

• Belonidae: Needlefish. They are recognisable by their long narrow snouts.
• Holocentridae: Soldierfish and squirrelfish
• Labridae: Wrasses. Prominent "lips"
• Mugilidae: Mullets
• Mullidae: Surmullets, goatfish
• Scombridae: mackerels and their allies