Tetrodotoxin (TTX) is a naturally occurring toxin that has been responsible for human intoxications and fatalities. Its usual route of toxicity is via the ingestion of contaminated puffer fish which are a culinary delicacy, especially in Japan. TTX was believed to be confined to regions of South East Asia, but recent studies have demonstrated that the toxin has spread to regions in the Pacific and the Mediterranean. There is no known antidote to TTX which is a powerful sodium channel inhibitor. This review aims to collect pertinent information available to date on TTX and its analogues with a special emphasis on the structure, aetiology, distribution, effects and the analytical methods employed for its detection.

Tetrodotoxin: Chemistry, Toxicity, Source, Distribution and Detection

Tetrodotoxin (TTX) is a potent neurotoxin responsible for many human intoxications and fatalities each year. The origin of TTX is unknown, but in the pufferfish, it seems to be produced by endosymbiotic bacteria that often seem to be passed down the food chain. The ingestion of contaminated pufferfish, considered the most delicious fish in Japan, is the usual route of toxicity. This neurotoxin, reported as a threat to human health in Asian countries, has spread to the Pacific and Mediterranean, due to the increase of temperature waters worldwide. TTX, for which there is no known antidote, inhibits sodium channel producing heart failure in many cases and consequently death. In Japan, a regulatory limit of 2 mg eq TTX/kg was established, although the restaurant preparation of "fugu" is strictly controlled by law and only chefs qualified are allowed to prepare the fish. Due to its paralysis effect, this neurotoxin could be used in the medical field as an analgesic to treat some cancer pains.

Tetrodotoxin, an Extremely Potent Marine Neurotoxin: Distribution, Toxicity, Origin and Therapeutical Uses.

http://www.bidt.ca/j_food_prot_2009_cohen.pdf

Public health response to puffer fish (tetrodotoxin) poisoning from mislabeled product.

Poisoning after eating puffer fish containing highly lethal tetrodotoxin (TTX) is widespread in Asia. In 2008, naive inland populations in Bangladesh were exposed to cheap puffer fish sold on markets. In three outbreaks, 141 patients with history of puffer fish consumption were hospitalized. Symptoms of poisoning included perioral paraesthesia, tingling over the entire body, nausea and vomiting, dizziness, headache, abdominal pain and muscular paralysis of the limbs. Seventeen patients (12%) died from rapidly developing respiratory arrest. Blood and urine samples from 38 patients were analyzed using a TTX-specific enzyme-linked immunoassay (ELISA). Medium to high TTX levels were detected (1.7-13.7 ng/ml) in the blood of 27 patients. TTX was below detection level (< 1.6 ng/ml) in 11 blood samples but the toxin was detected in urine. Ten patients had blood levels above 9 ng/ml and developed paralysis; seven of these died. The remaining patients recovered with supportive treatment. High concentrations of TTX and its analogues 4-epiTTX and 4,9-anhydroTTX were also found in cooked puffer fish by post-column liquid chromatography-fluorescence detection. To prevent future instances of puffer fish poisoning of this magnitude, measures should be implemented to increase awareness, to control markets and to establish toxicological testing. To improve the management of this and other poisoning in Bangladesh, facilities for life-saving assisted ventilation and related training of healthcare personnel are urgently needed at all levels of the health system.

Puffer fish poisoning in Bangladesh: clinical and toxicological results from large outbreaks in 2008

Marine toxins are produced by algae or bacteria and are concentrated in contaminated seafood. Substantial increases in seafood consumption in recent years, together with globalization of the seafood trade, have increased potential exposure to these agents. Marine toxins produce neurological, gastrointestinal, and cardiovascular syndromes, some of which result in high mortality and long-term morbidity. Routine clinical diagnostic tests are not available for these toxins; diagnosis is based on clinical presentation and a history of eating seafood in the preceding 24 h. There is no antidote for any of the marine toxins, and supportive care is the mainstay of treatment. In particular, paralytic shellfish poisoning and puffer fish poisoning can cause death within hours after consuming the toxins and may require immediate intensive care. Rapid notification of public health authorities is essential, because timely investigation may identify the source of contaminated seafood and prevent additional illnesses. Extensive environmental monitoring and sometimes seasonal quarantine of a harvest are employed to reduce the risk of exposure.

Illnesses Caused by Marine Toxins

Introduction: Puffer fish is available in Bangladesh and is occasionally eaten by some people. Ignorance regarding its proper cooking process may lead to serious health hazards, including fatality. Methods: An unusual catastrophic event happened recently in Khulna, Bangladesh that drew nationwide attention. Eight families were affected. Results: Thirty-seven patients were admitted with a history of consumption of puffer fish. Peri-oral paraesthesia (24), weakness of both lower limbs (22), paraesthesia all over the body (18), headache (15), difficulty in respiration (14), nausea and vomiting (8), blurring of vision (7), and vertigo (6) were common clinical presentations. Twentytwo patients developed ascending paralysis of limbs and involved the respiratory muscles in 17 patients. Eight patients died due to respiratory failure while the rest improved. Conclusion: Health personnel should have sufficient knowledge regarding the clinical manifestations, complications and management of puffer fish poisoning. During its preparation, organs that contain the highest level of tetrodotoxin should be removed. Since there is no specific treatment, people should be made aware of the potential risk of eating puffer fish, about the warning symptoms and signs of puffer fish poisoning, and when to seek medical help.

M A Bakar

Papers

Paralytic complications of puffer fish (tetrodotoxin) poisoning.