Ciguatera Fish Poisoning
This information is courtesy of Lora E. Fleming, NIEHS Marine and Freshwater Biomedical Sciences Center
The most commonly reported marine toxin disease in the world is Ciguatera, associated with consumption of contaminated reef fish such as barracuda, grouper, and snapper. Under-diagnosis and under-reporting (especially in endemic areas such as the Caribbean) make it difficult to know the true worldwide incidence of the Marine Toxin Diseases. At least 50,000 people per year who live in or visit tropical and subtropical areas suffer from Ciguatera worldwide. For example, CDC and others estimate that only 2-10% of Ciguatera cases are actually reported in the United States. In the US Virgin Islands, there are an estimated 300 cases per 10,000 or 3% of the population per year; a similar rate is found in the French West Indies. In St. Thomas, a household survey estimated that 4.4% of all households suffered from Ciguatera annually (at least 2640 persons per year or an annual incidence of 600 cases per year); in Puerto Rico, 7% of the residents have experienced at least one episode of Ciguatera in their lifetime.
Ciguatera, especially in the Caribbean, suffer for weeks to months with debilitating neurologic symptoms, including profound weakness, temperature sensation changes, pain, and numbness in the extremities. The dinoflagellate Gambierdiscus toxicus produces ciguatoxin throughout tropical regions of the world.
Ciguatera presents primarily as an acute neurologic disease manifested by a constellation of gastrointestinal (diarrhea, abdominal cramps and vomiting), neurologic (paresthesias, pain in the teeth, pain on urination, blurred vision, temperature reversal) and cardiovascular (arrhythmias, heart block) signs and symptoms within a few hours of contaminated fish ingestion. The pathneumonic symptom of Ciguatera intoxication is hot/cold temperature reversal, although not all patients report this.
The attack rate has been reported to be 73%-100% with ingestion of contaminated fish, without any apparent age-related susceptibility. Acute fatality, usually due to respiratory failure, circulatory collapse or arrhythmias, ranges from 0.1% to 12% of reported cases; presently in the Pacific, the mortality is less than 1%. Lethality is usually seen with ingestion of the most toxic parts of fish (ie. the liver, viscera, roe and other organs).
The clinical picture may be variable among individuals, even with the same food source, different ethnic groups, and possibly with different types of fish and/or geographic location. It appears that ciguatera from consumption of carnivore species may be more toxic than that from consumption of herbivores due to exposure to more than one toxin and/or transformation of the toxin(s) and/or an increased dose response. In Polynesia, Ciguatera is dominated and initiated by neurologic symptoms (90% of patients report paresthesias and dysesthesia), while reports from the Caribbean suggest that Ciguatera initially presents acutely as a gastroenteritis often with associated cardiovascular symptoms, with the gradual onset and dominance of neurologic symptoms over the first 24 hours. This may be due to different toxins mixtures elaborated by Caribbean and Polynesian G. toxicus.
The symptoms of Ciguatera poisoning, especially the paresthesias and weakness, can persist in varying severity for weeks to months after the acute illness. Prolonged itching due to chronic Ciguatera can present as a dermatologic disease when it is really due to ciguatera paresthesias. Chronic ciguatera can also present as a psychiatric disorder of general malaise, depression, headaches, muscular aches, and peculiar feelings in extremities for several weeks. It is reported that those with chronic symptoms seem to have recurrences of their symptoms with the ingestion of fish (regardless of type), ethanol, caffeine, and nuts 3 to 6 months from initial ingestion.
Ciguatera can be sexually transmitted. With exposure of the mother, premature labor and spontaneous abortion have been reported, as well as effects on the fetus and newborn child through placental and breast milk transmission.
In the differential diagnosis of Ciguatera, poisoning with the other marine toxins, especially NSP and PSP should be considered since dysesthesias with nausea, vomiting and diarrhea are the presenting symptoms. Obviously the history of fish versus shellfish consumption should help to differentiate. Type E botulism with ingestion of smoked fish, Scromboid and even Eosinophilic meningitis from helminthic infection of Angiostrongylus cantonensis from ingestion of raw mollusks, crabs and certain fish should be considered. Finally, poisoning with organophosphates pesticides can present initially with a similar clinical picture except for the exposure history.
Using a household pet or even elderly relative as a simple bioasssay was and may still be practiced in many island communities. Otherwise, only expensive ponderous bioassays in such animals as the mongoose, rat and cats were available for screening Ciguatoxin-contaminated fish until ten years ago. The mouse bioassay, while it remains the standard diagnostic tool, does not distinguish between ciguatoxin and scaritoxin.
Over the past few years, radioimmune (RIA) or enzyme linked immunosorbent (ELISA) assays have been developed to investigate Ciguatera, including the Hokama enzyme immunoassay stick test. Emerson et al (1983) using counter-immunoelectrophoresis disclosed precipitin lines with toxic fish extracts and effectively discriminated between samples compared with human and mouse bioassay. However putative immune and nonimmune serum gave equally clear precipitin reactions with toxic extracts therefore the authors could not conclude that they had located a specific antibody. Trainer et al (1990, 1991) developed an assay which can measure Ciguatoxin qualitatively and potentially quantitatively in fish and possibly human fluids. Further work involves the application of these assays to human fluids from persons who have eaten assay-positive fish.
Medical treatment has been to a large extent symptomatic; a variety of agents, including vitamins, antihistamines, anticholinesterases, steroids and tricyclic antidepressants, have been tried with limited results. Gut emptying and decontamination with charcoal is recommended acutely although often the severe ongoing vomiting and diarrhea prevents this. Atropine is indicated for bradycardia, and dopamine or calcium gluconate for shock. It is recommend that opiates and barbiturates be avoided since they may cause hypotension, and opiates may interact with maitotoxin.
With apparent considerable success, at least acutely, mannitol infusions have been used. Palafox et al (1988) administered 1 gm/kg of 20% mannitol at a rate of 500 mL/h "piggybacked" to an iv infusion of 5% dextrose in Ringers lactate or saline solution at 30 mL/h or more depending on fluid requirements with complete reversal of symptoms in the majority of patients tested. Subsequent reports have affirmed his success although mannitol appears to be most effective in completely relieving symptoms when given within the first 48-72 hours from ingestion.
Amitriptyline (25 to 75 mg bid) and similar medications do seem to have some success in relieving the symptoms of chronic Ciguatera, such as fatigue and paresthesias. It is possible that nifedipine may be appropriate as a calcium channel blocker to counteract the effects of maitotoxin. Finally, there are over 64 different local remedies including medicinal teas used in both the Indo-Pacific and West Indies regions. None of these treatments have been evaluated in a controlled clinical trial with the exception of two controlled trials of Mannitol for treatment of acute Ciguatera, so that their true efficacy is impossible to determine.
As mentioned above, there appears to be a sensitivity to certain foods (ie. ingestion of fish (regardless of type), ethanol, caffeine, and nuts) after ciguatera poisoning and these should be avoided for 3 to 6 months after the illnesses. In addition, there is no immunity to this illnesses and recurrences of actual ciguatera in the same individual appear to be worse than the initial illness.
As with many of the marine toxin induced diseases, the initial or index case(s) are often the tip of the iceberg. Therefore any suspected cases of Ciguatera should be reported to the appropriate public health authorities for follow up to ascertain other cases and to prevent further spread. And every effort should be made to obtain contaminated materials and their source.
Obviously persons who live in or travel to endemic areas should never eat barracuda or morey eel, and should be cautious with grouper and red snapper, as well as enquiring about local fish associated with Ciguatera. Since there is no reliable way to "decontaminate" or even to distinguish contaminated fish by smell or appearance, at a minimum, people should be advised to avoid the viscera of any reef fish as well as avoiding consuming unusually large predacious reef fish especially during the reproductive season.
The two most common toxins associated with Ciguatera are Ciguatoxin and Maitotoxin, and they are some of the most lethal natural substances known. In mice, ciguatoxin is lethal at 0.45 ug/kg ip, and maitotoxin at a dose of 0.15 ug/kg ip. Oral intake of as little as 0.1 ug ciguatoxin can cause illness in the human adult (as an extrapolation from fish samples eaten).
Ciguatoxin, a lipid soluble substance, opens voltage dependant sodium channels in cell membranes which induces membrane depolarization. It causes prolonged symptoms indicate nerve blockage or damage requiring regeneration of nervous tissue Maitotoxin, water soluble, specifically increases the calcium ion influx through excitable membrane; this is not affected by tetrodotoxin or sodium. Usually Maitotoxin is less important since it is less present in fish. Scaritoxin is similar to Ciguatoxin. Okadaic Acid is a lipid soluble toxin with a LD50 210 ug/kg ip in mice; it is a sodium ionophore. Palytoxin is a water soluble polyether which causes severe tonic contraction of all muscle groups; it also strong skin irritant and potent tumor activator.
The pharmacologic action of Ciguatoxin is due to its direct effects on excitable membranes. Its potent depolarizing action due to a selective increases in sodium permeability in the nerve cells and striated muscle can be counteracted by calcium ions and tetrodotoxin. The respiratory arrest induced by a lethal dose results mainly from depression of the central respiratory center. It causes biphasic cardiovascular response with hypotension and bradycardia (which can be antagonized with anticholinergics) followed by hypertension and tachycardia (which can be suppressed by adrenergic blockers). The response of smooth muscle to ciguatoxin is complex, depending upon the predominant autonomic innervation and postsynaptic receptor. It causes a potent release of endogenous norepinephrine from adrenergic nerve terminals and a potentiating effect on the post synaptic membrane.
Maitotoxin possesses a specific Ca2+ dependent action which causes a release of norepinephrine from rat pheochromocytoma cells. This action occurs in the absence of Na+ ions and in the presence of tetrodotoxin, precluding the participation of sodium channels; Maitotoxin appears to exert its effects on endogenous membrane calcium channels.
Last updated: July 31, 2012