What are ciguatoxins?
The ciguatoxins (CTXs) are a group of marine biotoxins, which are the cause of a foodborne intoxication known as ciguatera fish poisoning (CFP). CFP is associated with consumption of coral reef fish from tropical and subtropical waters in the Pacific and Indian Oceans and the Caribbean sea. It was first recorded by Spanish explorers some 500 years ago. CFP is the commonest form of marine food poisoning worldwide and is considered to be a significant public health problem.
CTXs accumulate in certain fish species that feed on toxic algae, or prey on toxic herbivorous fish species. They are lipid-soluble polyether compounds made up of 13 or 14 rings fused into rigid ladder-like structures. Multiple forms of CTX with small structural differences have been described and there are important geographic differences. The Pacific ciguatoxin-1 (P-CTX-1) is the most potent and its structure is slightly different from that of the Caribbean ciguatoxin-1 (C-CTX-1). These differences are also reflected in the symptoms produced.
What foods can be contaminated?
CTXs are found in a broad range of fish that live in or around coral reefs in comparatively shallow tropical waters. Over 400 species have been reported to be involved in CFP outbreaks. The toxins tend to concentrate as they move up the food chain, so that large carnivorous fish are more likely to be toxic. Species such as barracuda, grouper, snapper, jack, moray eel, Spanish mackerel and some inshore tuna carry the highest risk, but herbivorous and coral eating species such as parrot fish may also cause CFP outbreaks.
Recently, CTXs have been detected in coastal fish species harvested from Israeli waters in the eastern Mediterranean. There is also evidence that recent CFP outbreaks in Madeira and the Canary Islands were caused by locally caught fish. These findings are causing concerns that the geographic range of CTX production may be extending into more temperate waters.
The highest concentrations of toxins in the fish are found in the viscera, particularly in the liver and kidneys, and levels can be up to 100 times higher than in other tissues. The fish themselves suffer no detectable symptoms even though the toxin is persistent and affected fish can remain toxic for long periods.
In former times, CFP was restricted to indigenous populations in areas where CTXs are endemic, but this has changed in recent years with the increase in global travel and the increasing importation of exotic foodfish species into developed countries.
How do they affect human health?
CTXs cause a wide variety of neurological, gastrointestinal and cardiovascular symptoms. They are extremely powerful toxins and an oral dose of 0.1μg may be enough to cause illness. They act by increasing the sodium ion permeability of the plasma membranes in nerve and muscle cells, causing membrane depolarisation and thus disrupting cell function. Similarly, they affect intracellular calcium transport in gut epithelial cells.
Symptoms may appear within one hour in severe cases, but onset can be delayed for 24 or even 48 hours in milder cases. Gastrointestinal symptoms, including nausea, vomiting, diarrhoea and abdominal pain often occur first, followed by neurological symptoms, such as a tingling of the lips and extremities and severe localised skin irritation. However, there is geographic variation, with neurological symptoms being more common in the Pacific and gastrointestinal in the Caribbean.
Other recorded symptoms include hallucinations, depression and anxiety, fatigue and aching in the muscles and joints. Hypotension, respiratory problems and even paralysis can occur in severe cases, but death is uncommon, with a reported fatality rate of less than 1%. Gastrointestinal symptoms usually resolve within a few days, but where neurological symptoms occur they may last much longer, typically several weeks or months. Individuals can also become sensitised to CTXs so that they may react to eating fish that do not affect others.
The varied nature of the symptoms can result in CFP being misdiagnosed as multiple sclerosis or chronic fatigue disorder in developed countries.
How common is illness?
It is estimated that between 10,000 and 50,000 cases of CFP occur each year. Most of these cases occur in tropical and sub-tropical coastal regions adjoining the Pacific and Indian Oceans and the Caribbean. However, more cases are being reported in temperate developed countries and it is thought that under-reporting could be significant in Europe and North America because of misdiagnosis.
CFP outbreaks have been reported in France, Italy, Germany and the Netherlands. In the USA, 129 outbreaks affecting 508 people were recorded between 1983 and 1992. Most of these occurred in Hawaii and Florida, but outbreaks linked to imported fish were reported elsewhere. A number of outbreaks have occurred in Australia and an annual incidence of 30 cases per 100,000 has been estimated.
Where do they come from?
The principal known source of ciguatoxins is an alga, the marine dinoflagellate Gambierdiscus toxicus, which is associated with seaweeds, sediments and dead coral. It is distributed around the tropics within the latitudes 32oN and 32oS and grows in shallow waters, but its presence and numbers are unpredictable. There is also evidence that other species of dinoflagellates may sometimes be involved.
Certain strains of G. toxicus produce toxins referred to as gambiertoxins – less oxidised and less toxic precursors of CTXs. When the algae are consumed by herbivorous fish, the gambiertoxins accumulate in the fish and a biotransformation begins to occur, in which they are converted to CTXs. Over time, the toxins become transferred to carnivorous fish and the biotransformation is completed. The highest levels of CTXs are found in the largest carnivorous fish. Different strains of G. toxicus are thought to produce different CTX precursors, which are then transformed into the various CTX types.
G. toxicus also produces another type of highly potent toxin called maitotoxins. These occur in the guts of herbivorous fish, but are not now thought to be involved in CFP.
Are they stable in food?
CTXs are temperature-stable and are not destroyed by cooking or by freezing. Other processes, including salting and smoking, also have little or no effect. Affected fish can remain toxic for years, even when their diet ceases to contain toxin or precursors.
How can they be controlled?
CTXs are odourless and tasteless and do not alter the appearance of the fish. They can be detected using a number of techniques following extraction and purification techniques. The most widely used test method is a mouse bioassay, but biomolecular assay methods, such as cytotoxicity, receptor binding and immunoassay can also be applied. An ELISA-based method for CTX detection has recently been developed. The difficulty of detecting CTXs in fish, plus their stability, severely limits the control options available.
The only practical control is to avoid consumption of susceptible fish species from areas where CFP is endemic. Large predatory reef fish, such as barracuda, present a high risk and should be particularly avoided. Parts of the fish where the highest toxin levels accumulate, such as the head, gut, liver and roe should not be eaten. Health Canada advises travellers not to eat large reef fish weighing more than 3kg.
Are there rules and regulations?
There are few specific regulations for CTXs toxins in fish.
In the EU, legislation covering fishery products states that “fishery products containing biotoxins such as ciguatera toxins” cannot be placed on the market, but no methods of analysis are given.
In the USA no action limits have so far been established. However, the Food and Drug Administration (FDA) has proposed guidance levels of less than 0.1 μg/kg C-CTX-1 equivalents and less than 0.01 μg/kg P-CTX-1 equivalents.
The most common legislative control in use around the world is the prohibition of the sale of high risk fish taken from areas where CTXs are known to be present. Such bans have been used with success in Australia, Fiji, Hawaii and Florida.