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.

Tetrodotoxin (TTX) intoxication resulting from the ingestion of toxic puffer is relatively common in a number of Asian countries. In Japan, 100 annual human fatality due to ingestion of toxic puffer have been reported until 1960. Poisoning incidents, however, decreased in the recent years by imposing quarantine rule and creating public awareness after extensive study of the toxicity and toxin properties of puffer. Generally, the oral paresthesia is the initial symptom of puffer poisoning. The onset of symptoms is rapid. In spite of long history of TTX intoxication, no antidotes or antitoxins to TTX is invented so far. Treatment is supportive.

Puffer poisoning: epidemiology and treatment

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.

Paralytic complications of puffer fish (tetrodotoxin) poisoning.

• Primary care physicians care for large numbers of patients presenting with "food poisoning" or gastroenteritis. When a patient who presents with acute gastrointestinal illness, especially in conjunction with neurologic or cutaneous symptoms, is evaluated, the history should focus on past seafood consumption (particularly raw or undercooked seafood). The infectious syndromes are generally self-limited and respond to supportive care; exceptions are those caused byVibrio choleraeandVibrio vulnificus, which may be fatal in severe cases. The toxic syndromes are uncommon and fall into two categories: the histaminelike syndrome of scombroid poisoning and the neurotoxic syndromes, including ciguatera, paralytic shellfish poisoning, and puffer fish poisoning. Recognition of these clinical entities may lead to more appropriate management and preventive measures. (Arch Intern Med. 1989;149:1735-1740)

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Kuo Weng Wang

Papers

Anticholinesterase drugs in the treatment of tetrodotoxin poisoning.