AN OUTBREAK OF TETRODOTOXIN POISONING FROM CONSUMING HORSESHOE CRABS IN SABAH.

The horseshoe crab (Carcinoscorpius rotundicauda) is consumed by those residing near the coastal areas of Kota Marudu District in Malaysia, as it is considered a delicacy. During June to August, 2011 thirty cases of tetrodotoxin poisoning were reported from Kota Marudu District following ingestion of horseshoe crabs caught in Kota Marudu Bay. The purpose of this study is to describe this case series in order to determine risk factors to prevent further outbreaks. There were six confirmed and 24 probable cases of tetrodotoxin poisoning identified in the study area during the study period as diagnosed by clinical presentation and laboratory findings. Symptoms included dizziness (80%), circumoral and lingual numbness (80%), hand and feet numbness (63.3%), nausea and vomiting (30%) and weakness and difficulty in breathing (26.6%). Three cases (10%) died while 27 cases recovered. Forty-seven percent of the cases had onset of symptoms within 30 minutes of ingestion and 14% 31-60 minutes after ingestion of horseshoe crab meat. Urine samples were collected from the cases, while horseshoe crabs, cockles and sea water from the epidemic area were also taken for analysis. Tetrodotoxin was detected in the urine of six cases; the highest concentrations recorded were among the three cases who died. High tetrodotoxin concentrations were found in the hepatic cecum and eggs of the tested horseshoe crabs. Dinoflagellates were not detected in the sea water or cockle samples. Intensive health education was initiated quickly to stop other members of the Marudu Bay community from consuming the horseshoe crabs. This is the first documented epidemic of tetrodotoxin poisoning in Sabah.

Tetrodotoxin poisoning outbreak from imported dried puffer fish--Minneapolis, Minnesota, 2014.

On June 13, 2014, two patients went to the Hennepin County Medical Center Emergency Department in Minneapolis, Minnesota, with symptoms suggestive of tetrodotoxin poisoning (i.e., oral paresthesias, weakness, and dyspnea) after consuming dried puffer fish (also known as globefish) purchased during a recent visit to New York City. The patients said two friends who consumed the same fish had similar, although less pronounced, symptoms and had not sought care. The Minnesota Department of Health conducted an investigation to determine the source of the product and samples were sent to the Food and Drug Administration (FDA) Center for Food Safety and Applied Nutrition for chemical and genetic analysis. Genetic analysis identified the product as puffer fish (Lagocephalus lunaris) and chemical analysis determined it was contaminated with high levels of tetrodotoxin. A traceback investigation was unable to determine the original source of the product. Tetrodotoxin is a deadly, potent poison; the minimum lethal dose in an adult human is estimated to be 2-3 mg. Tetrodotoxin is a heat-stable and acid-stable, nonprotein, alkaloid toxin found in many species of the fish family Tetraodontidae (puffer fish) as well as in certain gobies, amphibians, invertebrates, and the blue-ringed octopus. Tetrodotoxin exerts its effects by blocking voltage-activated sodium channels, terminating nerve conduction and muscle action potentials, leading to progressive paralysis and, in extreme cases, to death from respiratory failure. Because these fish were reportedly purchased in the United States, they pose a substantial U.S. public health hazard given the potency of the toxin and the high levels of toxin found in the fish.

Consequences of the increasing prevalence of the poisonous Lagocephalus sceleratus in southern Turkey.

BACKGROUND: The increasing Indo-Pacific migration has affected the biodiversity of the Mediterranean Sea, and the prevalence of the puffer fish (Lagocephalus sceleratus), a well-known poisonous migrant, is increasing. The fish, which contains tetrodotoxin, is lethally poisonous when consumed. As its population increases it becomes more available in the markets of southern Turkey, but local people seem to be unaware of the danger. Probably because of the depressed stocks of the surrounding waters and demand on affordable seafood, local anglers are catching the fish. The situation constitutes an alert for the local emergency medicine organisation and is a public health issue. METHODS: Local fishermen, fish sellers/dealers/brokers, buyers and emergency department physicians were interviewed about the fishery and consumption facts of the puffer fish in the region, the number of cases reported in the regional state run hospitals and the 112 Emergency Medical Response Service, and the knowledge and practice of the doctors in the emergency departments. RESULTS AND CONCLUSIONS: General health organisations are unprepared for the serious health hazards caused by this fish, including fatalities. Health workers should have sufficient knowledge regarding the clinical manifestations, complications and management of puffer fish poisoning. Official authorities should make the public aware of the potential risk of consuming puffer fish.

[Postmortem distribution of tetrodotoxin in tissues and body fluids of guinea pigs].

OBJECTIVE: To investigate the postmortem distribution of tetrodotoxin in tissues and body fluids of guinea pig, and to provide method and evidence for forensic identification and clinical diagnosis and treatment. METHODS: Guinea pigs were intragastric administrated with 100, 50, 15 microg/kg tetrodotoxin, respectively. The poisoning symptoms were observed. The samples of heart, liver, spleen, lung, kidney, brain, stomach, intestines, bile, heart blood and urine were collected. The concentrations of tetrodotoxin in tissues and body fluids were measured with liquid chromatography-tandem mass spectrometry (LC-MS/MS). RESULTS: After administrated with tetrodotoxin, all guinea pigs came out poisoning signs including tachypnea, weary and dead finally. Tetrodotoxin concentrations in lung, stomach, intestines and urine were higher, followed by blood, heart and brain. The concentration in bile was the lowest. CONCLUSION: Postmortem distribution of tetrodotoxin in guinea pig is uneven. The concentration in the lung, stomach, intestines, urine and heart blood are higher, those tissues could be used for diagnosis of tetrodotoxin poisoning.

[Natural toxin poisoning].

Natural toxin poisoning often occurs when amateur who has no expert knowledge of food collects and cooks the wrong material. In many cases, the symptoms of natural toxin poisoning are mild and the patients recover from illness within a day. However, if the patients have respiratory or neurological symptoms after several hours of intake, the patients must go to hospital immediately. Mushroom poisoning is often reported and puffer fish poisoning is sometimes reported in Japan.

A cluster of tetrodotoxin poisoning in Oman.

INTRODUCTION: Tetrodotoxin (TTX) is a potent sodium channel blocker, with significant neurotoxicity, found in marine animals like pufferfish and blue-ringed octopus. The severity of toxicity depends on the amount of toxin ingested and the outcome depends on the time-lapse to appropriate medical care. CASES REPORT: We report five patients who presented with tetrodotoxin poisoning after consuming fried internal organs of local pufferfish from the coast of Oman. The patients' clinical manifestations were consistent with the expected TTX toxidrome of perioral and generalized paresthesia, weakness of upper and lower extremities, gastrointestinal manifestations, dyspnea, dysarthria, ascending paralysis, hypotension, bradycardia and coma. The severity varied among the patients who recovered completely except one patient who developed a subarachnoid hemorrhage without underlying aneurysms on computed tomography-angiogram. This complication was potentially related to TTX poisoning and has not been previously reported. In addition to standard supportive management, patients with severe illness should potentially receive the intravenous acetylcholinesterase inhibitor neostigmine, and intermittent dialysis. Urine specimens were sent to CDC in Atlanta, where they were analyzed using online solid phase extraction (SPE) with LC-MS/MS and confirmed the diagnosis in all five cases. DISCUSSION: In general, the patients' clinical manifestations were consistent with the expected TTX toxidrome except patient 3 who developed a subarachnoid hemorrhage early during his clinical course. Two patients received neostigmine and underwent dialysis with complete recovery.

Awareness on tetrodotoxin of illegal activity: forensic issue from a rare homicide case report and literature review.

The authors describe an extremely rare case of homicide by injecting tetrodotoxin (TTX) as lethal neurotoxin found in puffer fish. After a thorough investigation, the male victim was found to have a broken stalk from syringe needle in the subcutaneous tissue of left buttock and severe asphyxia confirmed by the main pathological findings at autopsy. During tortuous toxicological analysis，TTX was revealed by ultra high performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) as well as acute intoxication confirmed from forensic examination. The literature of qualitative and quantitative determination of TTX from human fluids was also reviewed to expect widely acceptable detection strategies. This case highlighted the importance of TTX toxicant with chemical formula name purchased through e-commerce，so as to improve particular emphasis and supervision on harmful substances possibly using hidden information or illegal means. Histopathological and toxicological results demonstrated here provided a reference and other useful information to the challenges of forensic casework. In general, the case report illustrates medico-legal issues of more attention to the possibility of TTX poisoning in rapid death and the need of routine postmortem tox screening in future practice.

Seafood intoxication by tetrodotoxin: first case in Europe.

BACKGROUND: Tetrodotoxin is considered the most lethal toxin in the marine environment. Prior cases of intoxication previously described correspond to consumption of tetrodotoxin in tropical or subtropical regions of Asia or the Pacific Islands. OBJECTIVES: We present the first European case of tetrodotoxin intoxication in a patient who ingested part of a trumpet shellfish (Charonia sauliae) from the Atlantic Ocean in Southern Europe. CASE REPORT: Our patient suffered general paralysis, including the respiratory muscles, a few minutes after the consumption of a few grams of C. sauliae. Intubation and mechanical ventilation were necessary for 52 h after the intoxication. The corresponding electrophysiologic studies showed complete non-excitability, with no recordable sensory or motor nerve conduction. We detected the presence of tetrodotoxin in the mollusk and the patient's blood and urine by means of high-performance liquid chromatography-mass spectrometry analysis technique. A previous bioassay showed extremely high quantities of the toxin in the mollusk. CONCLUSIONS: This case alerts us to the possibility of a very harmful biotoxin in European coastal waters. This now should be included in the differential diagnosis of similar cases in Europe, and we must be vigilant for its possible presence in Europe.

[Deep non-reactive reversible coma after a Mediterranean neurotoxic fish poisoning]. / Coma profond aréactif réversible après intoxication par des abats d'un poisson méditerranéen.

INTRODUCTION: Neurotoxic fish poisoning appears to be a recent phenomenon in the Mediterranean Sea. We report a case of deep non-reactive reversible coma after ingestion of Mediterranean fish innards. CASE REPORT: An 80 year-old man, heavy smoker who had a previous cerebral infarct in the posterior territory, was admitted for rapid deterioration of his neurological condition. He started having perioral tingling, then dysarthria, then became quadriparetic, then developed respiratory and hemodynamic failure and within 3-4h, entered a state of deep non-reactive coma with absence of all brainstem reflexes. He started to improve after 20 h and recovered his neurological baseline within 36 h. Later on, he stated that all his symptoms started after he ingested the gonads of a toxic fish, Lagocephalus scleratus. DISCUSSION: Tetrodotoxin blocks voltage-gated sodium channels and inhibits the production and propagation of action potentials. This toxin is highly concentrated in the liver, gonads, intestines and skin of this fish that is well-known in Japan (where it is considered as a delicacy) and South-East Asia and seems to have migrated recently to the Mediterranean Sea. There is no known antidote to tetrodotoxin but intensive supportive treatment can be life-saving.

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

Tetrodotoxin is a neurotoxin that occurs in select species of the family Tetraodontidae (puffer fish). It causes paralysis and potentially death if ingested in sufficient quantities. In 2007, two individuals developed symptoms consistent with tetrodotoxin poisoning after ingesting home-cooked puffer fish purchased in Chicago. Both the Chicago retailer and the California supplier denied having sold or imported puffer fish but claimed the product was monkfish. However, genetic analysis and visual inspection determined that the ingested fish and others from the implicated lot retrieved from the supplier belonged to the family Tetraodontidae. Tetrodotoxin was detected at high levels in both remnants of the ingested meal and fish retrieved from the implicated lot. The investigation led to a voluntary recall of monkfish distributed by the supplier in three states and placement of the supplier on the U.S. Food and Drug Administration's Import Alert for species misbranding. This case of tetrodotoxin poisoning highlights the need for continued stringent regulation of puffer fish importation by the U.S. Food and Drug Administration, education of the public regarding the dangers of puffer fish consumption, and raising awareness among medical providers of the diagnosis and management of foodborne toxin ingestions and the need for reporting to public health agencies.

Human poisoning after ingestion of puffer fish caught from Mediterranean Sea.

Puffer fish poisoning is due to a powerful neurotoxin produced by bacteria living in this kind of fish. Though the sea of Lebanon (Mediterranean) is not endemic of puffer fish and incidence of its serious poisoning is rare, yet occasional incidences do occur. The purpose of this presentation is to raise the awareness of fishermen, fish-restaurant frequenters, public health organizations and the Ministry of Health, of its serious symptomology and to seek medical help as soon as possible.

Blow: a case of pufferfish intoxication in South Florida.

We report the case of a 43-year-old African American man with a history of hypertension and chronic kidney disease presenting with hypertensive emergency and bulbar paralysis in a descending fashion, which ultimately led to acute respiratory failure. He ingested pufferfish liver during the preceding 4 hours prior to presentation, as well as canned foods and cocaine over the prior 3 days. He had a complicated hospital course requiring intubation and mechanical ventilation, as well as the development of acute respiratory distress syndrome and acute renal failure requiring haemodialysis. This case exemplifies the classic manifestations of tetrodotoxin poisoning with some unique overlapping features, in the setting of an interesting social history.

Lessepsian migration and tetrodotoxin poisoning due to Lagocephalus sceleratus in the eastern Mediterranean.

BACKGROUND: The Suez Canal permits migration of fish from the Indo-Pacific Ocean to the Mediterranean Sea. This phenomenon (Lessepsian migration) has enabled poisonous fish species to colonize the Mediterranean Sea. OBJECTIVE: To report clinical tetrodotoxin poisoning after consumption of the Lessepsian immigrant fish Lagocephalus sceleratus caught on the Israeli coast of the eastern Mediterranean. CASE SERIES: Thirteen patients aged 26-70years were admitted after consuming L. sceleratus. Signs of toxicity appeared within 1h. The main manifestations included vomiting, diarrhea, headache, paraesthesias, slurred speech, muscle weakness, dyspnea, hypertension, tachycardia, respiratory arrest, seizures and coma. Treatment was supportive, including mechanical ventilation (two patients). Patients recovered within 4days. All fish were identified as L. sceleratus, a species known to contain tetrodotoxin. DISCUSSION: The diagnosis of tetrodotoxin poisoning was suggested by typical clinical manifestations together with temporal proximity to consumption of tetrodotoxin-containing fish. To the best of our knowledge, this is the first case series of tetrodotoxin poisoning reported from the eastern Mediterranean and due to L. sceleratus. Man made disruption of the ecological balance has resulted in the spread of tetrodotoxin-containing fish from the Indo-Pacific region to the Mediterranean Sea. Increased awareness is required to identify tetrodotoxin poisoning in an atypical fauna.

Tetrodotoxin poisoning evidenced by solid-phase extraction combining with liquid chromatography-tandem mass spectrometry.

The toxicity and toxin component of gastropod Niotha clathrata implicated to a food paralytic poisoning incident in Kaohsiung, Taiwan in November 2006 were studied. The highest scores of average toxicity in the digestive gland and other portions from collected gastropods were 62+/-24 (mean+/-S.D.) and 32+/-16 microg/g according to tetrodotoxin (TTX) bioassay, respectively. The toxin from these gastropods was large amount and easily identified as tetrodotoxin by traditional method of HPLC-FLD. The toxin of patient's blood serum was trace amount and analyzed by a new developed method LC-MS/MS. LC-MS/MS was contracted by the LC system interfaced with the MS/MS system with a turbo ion spray interface. Positive ion detection and multiple reaction monitoring mode were used for TTX of patient serum. It was found that linearity in serum was observed within concentration ranged of 1-100 ng/ml and limit of detection was 0.1 ng/ml. The LOQ was reproducible at 1 ng/ml in serum. The blood serum showed to contain TTX of 3.30+/-0.08 ng/ml. It indicated that LC-MS/MS was more lower detectable and believable method for TTX determination than LC-MS reported previously. Furthermore, the causative agent of gastropod food poisoning was identified as TTX.

An odd pilgrim in the Holy Land.

Fugu is a delicate dish prepared from Lagocephalus scleratus, a poisonous fish that contains tetrodotoxin--a very potent neurotoxin. It is usually confined to the Indo-Pacific Ocean where it is responsible for many accidental deaths each year. This very weird case report is about an Israeli couple that was poisoned by this fish caught for the first time in the eastern Mediterranean Sea. The prompt identification of the yet unrecognized fish by professional zoologists enabled an immediate effective treatment. This case represents another interesting manifestation of the globalization process our world undergoes and emphasizes, once again, the need of present emergency physicians to be aware of remote overseas medical problems. The article discusses the possible presumptions of the ways the fish arrived to the Mediterranean Sea and elaborates a review on tetrodotoxin from historical, structural, biologic activity as well as the diagnostic and treatment means available today.

Tetrodotoxin--distribution and accumulation in aquatic organisms, and cases of human intoxication.

Many pufferfish of the family Tetraodontidae possess a potent neurotoxin, tetrodotoxin (TTX). In marine pufferfish species, toxicity is generally high in the liver and ovary, whereas in brackish water and freshwater species, toxicity is higher in the skin. In 1964, the toxin of the California newt was identified as TTX as well, and since then TTX has been detected in a variety of other organisms. TTX is produced primarily by marine bacteria, and pufferfish accumulate TTX via the food chain that begins with these bacteria. Consequently, pufferfish become non-toxic when they are fed TTX-free diets in an environment in which the invasion of TTX-bearing organisms is completely shut off. Although some researchers claim that the TTX of amphibians is endogenous, we believe that it also has an exogenous origin, i.e., from organisms consumed as food. TTX-bearing animals are equipped with a high tolerance to TTX, and thus retain or accumulate TTX possibly as a biologic defense substance. There have been many cases of human intoxication due to the ingestion of TTX-bearing pufferfish, mainly in Japan, China, and Taiwan, and several victims have died. Several cases of TTX intoxication due to the ingestion of small gastropods, including some lethal cases, were recently reported in China and Taiwan, revealing a serious public health issue.

Tetrodotoxin poisoning following ingestion of the toxic eggs of the horseshoe crab Carcinoscorpius rotundicauda, a case series from 1994 through 2006.

Between 1994 and 2006, a total of 280 cases of varying degrees of tetrodotoxin poisoning following ingestion of the toxic eggs of the horseshoe crab, Carcinoscorpius rotundicauda, were admitted to the medical service of Chon Buri Hospital. The severity of the poisoning was classified into four stages based on clinical signs and symptoms of human tetrodotoxication. Of 245 available medical records; 100 were in stage 1, 74 were in stage 2, 3 were in stage 3 and 68 were in stage 4. The frequencies of symptoms and signs included the following : circumoral and lingual numbness (98%), hands and feet numbness (94.7%), weakness (59.6%), dizziness and vertigo (54.3%), nausea and vomiting (52.6%), transient hypertension (39.6%), respiratory paralysis (27.7%), fixed dilated pupils (14.7%), ophthalmoplegia (12.2%), blood pressure lower than 90/60 mmHg (5.7%), and polyuria (0.4%). All patients received symptomatic and supportive treatment. Endotracheal intubation and mechanical ventilation were considered when paralysis was progressing rapidly. The results of treatment are as follows: 239 patients (97.5%) showed complete recovery, 5 patients (2%) died, and 1 patient (0.4%) suffered anoxic brain damage. Horseshoe crab poisoning occurs both sporadically and epidemically in Chon Buri. Seasonal variation in the number of cases of poisoning was observed with a peak from December through March.

Genetic structure of the grey side-gilled sea slug (Pleurobranchaea maculata) in coastal waters of New Zealand.

Pleurobranchaea maculata is a rarely studied species of the Heterobranchia found throughout the south and western Pacific-and recently recorded in Argentina-whose population genetic structure is unknown. Interest in the species was sparked in New Zealand following a series of dog deaths caused by ingestions of slugs containing high levels of the neurotoxin tetrodotoxin. Here we describe the genetic structure and demographic history of P. maculata populations from five principle locations in New Zealand based on extensive analyses of 12 microsatellite loci and the COI and CytB regions of mitochondrial DNA (mtDNA). Microsatellite data showed significant differentiation between northern and southern populations with population structure being associated with previously described regional variations in tetrodotoxin concentrations. However, mtDNA sequence data did not support such structure, revealing a star-shaped haplotype network with estimates of expansion time suggesting a population expansion in the Pleistocene era. Inclusion of publicly available mtDNA sequence sea slugs from Argentina did not alter the star-shaped network. We interpret our data as indicative of a single founding population that fragmented following geographical changes that brought about the present day north-south divide in New Zealand waters. Lack of evidence of cryptic species supports data indicating that differences in toxicity of individuals among regions are a consequence of differences in diet.

Food poisoning.

Food poisoning is encountered throughout the world. Many of the toxins responsible for specific food poisoning syndromes are no longer limited to isolated geographic locations. With increased travel and the ease of transporting food products, it is likely that a patient may present to any emergency department with the clinical effects of food poisoning. Recognizing specific food poisoning syndromes allows emergency health care providers not only to initiate appropriate treatment rapidly but also to notify health departments early and thereby prevent further poisoning cases. This article reviews several potential food-borne poisons and describes each agent's mechanism of toxicity, expected clinical presentation, and currently accepted treatment.

Puffer fish (Tetrodotoxin) poisoning: an analysis and outcome of six cases.

On 24 July 2005, six members of a single family were admitted to the Medicine and Pediatrics Department of Khulna Medical College Hospital, Khulna, Bangladesh, with a history of ingestion of puffer fish. All patients developed toxic manifestations. The cases were clinically analysed with successful outcomes.