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

Acute flaccid paralysis (AFP) is a clinical syndrome characterized by rapid onset of weakness, including (less frequently) weakness of the muscles of respiration and swallowing, progressing to maximum severity within several days to weeks. The term "flaccid" indicates the absence of spasticity or other signs of disordered central nervous system motor tracts such as hyperreflexia, clonus, or extensor plantar responses (1). When applied to voluntary muscles, "paralysis" means loss of contraction due to interruption of motor pathways from the cortex to the muscle fiber. It is preferable to use the term "paresis" for slight loss of motor strength and "paralysis" or "plegia" for severe loss of motor strength (1). The differential diagnosis of AFP varies considerably with age. No single operational clinical case definition of AFP or paralytic poliomyelitis that combines both high sensitivity and high specificity has emerged (2-4). The currently used case definition increases sensitivity in detecting the existence of AFP but tends to decrease specificity in detecting paralytic poliomyelitis.

Differential Diagnosis of Acute Flaccid Paralysis and its Role in Poliomyelitis Surveillance

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.

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.

P K Mah

Papers

Puffer fish (tetrodotoxin) poisoning: clinical report and role of anti-cholinesterase drugs in therapy.