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.

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.

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.

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 caused by Goby fish consumption in southeast China: a retrospective case series analysis.

OBJECTIVES: To investigate an unusual outbreak of tetrodotoxin poisoning in Leizhou, southeast China, a case series analysis was conducted to identify the source of illness. METHODS: A total of 22 individuals experienced symptoms of poisoning, including tongue numbness, dizziness, nausea and limb numbness and weakness. Two toxic species, Amoya caninus and Yongeichthys nebulosus, were morphologically identified from the batches of gobies consumed by the patients. Tetrodotoxin levels in the blood and Goby fish samples were detected using liquid chromatography-tandem mass spectrometry. RESULTS: The tetrodotoxin levels in the remaining cooked Goby fish were determined to be 2090.12 µg/kg. For Amoya caninus, the toxicity levels were 1858.29 µg/kg in the muscle and 1997.19 µg/kg in the viscera and for Yongeichthys nebulosus, they were 2783.00 µg/kg in the muscle and 2966.21 µg/kg in the viscera. CONCLUSION: This outbreak demonstrates an underestimation of the risk of Goby fish poisoning. Furthermore, the relationships among the toxic species, climates and marine algae present should be clarified in the future.

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.

Tetrodotoxin poisoning caused by Goby fish consumption in southeast China: a retrospective case series analysis

OBJECTIVES: To investigate an unusual outbreak of tetrodotoxin poisoning in Leizhou, southeast China, a case series analysis was conducted to identify the source of illness. METHODS: A total of 22 individuals experienced symptoms of poisoning, including tongue numbness, dizziness, nausea and limb numbness and weakness. Two toxic species, Amoya caninus and Yongeichthys nebulosus, were morphologically identified from the batches of gobies consumed by the patients. Tetrodotoxin levels in the blood and Goby fish samples were detected using liquid chromatography-tandem mass spectrometry. RESULTS: The tetrodotoxin levels in the remaining cooked Goby fish were determined to be 2090.12 µg/kg. For Amoya caninus, the toxicity levels were 1858.29 µg/kg in the muscle and 1997.19 µg/kg in the viscera and for Yongeichthys nebulosus, they were 2783.00 µg/kg in the muscle and 2966.21 µg/kg in the viscera. CONCLUSION: This outbreak demonstrates an underestimation of the risk of Goby fish poisoning. Furthermore, the relationships among the toxic species, climates and marine algae present should be clarified in the future. .

Is neostigmine effective in severe pufferfish-associated tetrodotoxin poisoning?

CONTEXT: Pufferfish-associated tetrodotoxin poisoning occurs occasionally in coastal regions of Asian countries and sporadically elsewhere. While anecdotal reports have suggested neostigmine use, evidence for its clinical effectiveness remains unclear. OBJECTIVE: We sought to determine whether neostigmine was likely to be effective in tetrodotoxin-poisoned patients with acute respiratory failure caused by pufferfish consumption. METHODS: We searched in PubMed, EMBASE, CINAHL, Google Scholar, and other databases to collect cases of acute pufferfish-associated tetrodotoxin poisoning ever published without limiting publishing years. We screened each identified title and abstracts that were published in English language, selected, and reviewed full-text publications that were published in English or Chinese and reported at least one adult case (aged ≥ 16 years) of acute respiratory failure attributable to pufferfish-associated tetrodotoxin poisoning. RESULTS: Overall, we identified 435 titles and retrieved 71 full-text publications for further review. After excluding duplicates, review articles, articles reporting cases of minor severity only, incomplete clinical information or non-tetrodotoxin poisoning, and non-English, non-Chinese articles, we selected 37 citations (23 case series and 14 case reports) for data extraction and evidence synthesis. Clusters of acute pufferfish poisoning were mostly reported from coastal countries in the western Pacific or in the Indian Ocean, whereas sporadic cases have occurred in Mediterranean countries and Puerto Rico. Although 10 of the 14 case series reported neostigmine use in respiratory failure, age of these cases was not separately reported. Group-level outcome reporting irrespective of severity or the universal use of neostigmine in severe cases did not allow separate quantitative synthesis of evidence. In contrast, 32 cases from the other 9 case series and 14 case reports had individual information available for pooled analysis, yet only three of which were given neostigmine. CONCLUSION: Both qualitatively and quantitatively, the current literature was insufficient to provide an evidence base for or against the use of neostigmine in adults with tetrodotoxin-associated respiratory failure. This lack of quality evidence has mainly resulted from poor reporting in published case series. More research in collaborative data collection using standardized reporting and in animal experiments may be needed to tackle this problem. In addition, future case reports should adhere to the CARE guidelines to facilitate experience sharing, evidence synthesis, and consensus forming.

Family tetrodotoxin poisoning in Reunion Island (Southwest Indian Ocean) following the consumption of Lagocephalus sceleratus (Pufferfish).

Pufferfish poisoning has rarely been reported in the southwestern Indian Ocean and in the French overseas territories. In Reunion Island, the last notified documented case occurred in 1989 and people are no longer aware of the potential toxicity of pufferfish. We report a family hospitalized for a tetrodotoxin poisoning following the consumption of Lagocephalus sceleratus caught on the coast of Reunion Island in September 2013. Two patients presenting acute vital functions failures were admitted in an ICU. Ten people were admitted simultaneously to the emergency department after consuming L. sceleratus with signs of toxicity appearing within 2 hours. Treatment was supportive, but included the need for mechanical ventilation for two patients. All those affected had complete and uneventful recoveries within a few days. The fish consumed was identified as L. sceleratus, a species known to contain tetrodotoxin. The diagnosis of tetrodotoxin poisoning was suggested by typical clinical manifestations together with the history of very recent consumption of tetrodotoxin-containing fish. Tetrodotoxin was later detected at high levels in food remnants. To the best of our knowledge, there has been no documented case series of tetrodotoxin poisoning reported from Reunion Island for the last 25 years and from the entire Indian Ocean area since 1998. Pufferfish intoxication is one of the most common causes of poisoning among people in coastal regions of Asia but it has also recently been reported in areas where it was previously unknown, particularly along the Mediterranean shores and in Spain. Public health education in French overseas territories and along the Mediterranean shores should be adapted to include increased awareness of the danger of consuming pufferfish. Health teams must be aware of such clinical presentations.

Poisoning after ingestion of pufferfish in Brazil: report of 11 cases

In this brief communication the authors report eleven cases of human poisoning caused by ingestion of pufferfish meat. Three patients (two children and one adult) were seriously affected. The circumstances that precipitated the poisoning are discussed as well as the clinical aspects observed. No deaths were registered and the patients did not present sequelae after the episode.

Acute paralysis after seafood ingestion.

The first European case of tetrodotoxin intoxication is reported in a patient who ingested a trumpet shellfish from the Atlantic Ocean in Southern Europe. He suffered general acute paralysis with respiratory failure necessitating ventilation. Early neurophysiologic studies showed complete peripheral nerve inexcitability, with no recordable sensory or motor responses, and normal electroencephalography. Tetrodotoxin was detected in high quantities in the patient's blood and urine through high performance liquid chromatography-mass spectrometry analysis. Seventy-two hours after admission the patient recovered normal strength, reflexes and sensation.

Poisoning by toxic animals in China--18 autopsy case studies and a comprehensive literature review.

Although exposure to animal venom and poison, such as snakebites, bee stings, and contact, with toads, is a common problem, reported deaths are rare. The present report discusses 18 fatal cases in China. Causes of death were grouped into 6 categories, including 1 case of tetrodotoxin poisoning, 1 case of gallbladder poisoning, 3 cases of snake venom toxicity, 4 cases of melittin toxicity, 4 cases of cantharidin poisoning and 5 cases of venenum bufonis poisoning. The epidemiology of each venom-induced death, the mechanism of exposure to venom, and the target organs and tissues affected by these toxic animals were here systematically reviewed. Such details are important to even suspected cases of venom damage. The associated problems related to forensic medicine, such as manner of death and possible attribution to the toxic effects of various animals, are also discussed herein.

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.

[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.

[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.

Tetrodotoxin poisoning due to smooth-backed blowfish, Lagocephalus inermis and the toxicity of L. inermis caught off the Kyushu coast, Japan.

Food poisoning due to ingestion of a puffer fish occurred in Nagasaki Prefecture, Japan, in October 2008, causing neurotoxic symptoms similar to those of tetrodotoxin (TTX) poisoning. In the present study, we identified the species, toxicity, and toxins using the remaining samples of the causative puffer fish. The puffer fish was identified as smooth-backed blowfish Lagocephalus inermis by nucleotide sequence analysis of the 16S rRNA and cytochrome b gene fragments of muscle mitochondrial DNA. The residual liver sample showed toxicity as high as 1,230 mouse unit (MU)/g by bioassay and TTX was detected by liquid chromatography/mass spectrometry analysis. We therefore concluded that the food poisoning was due to TTX caused by consumption of the toxic liver of L. inermis. This is the first report that the liver of L. inermis caught in Japanese waters is strongly toxic, with levels exceeding 1,000 MU/g. In this context, we re-examined the toxicity of L. inermis collected off the coast of Japan. Of 13 specimens assayed, 12 were toxic, although the toxicity varied markedly among individuals and tissues. Because the intestine and ovary of L. inermis have been considered non-toxic, it is particularly noteworthy that these organs were determined to be toxic, with a maximum toxicity of 43.6 MU/g and 10.0 MU/g, respectively. Furthermore, kidney, gallbladder, and spleen, whose toxicity has been unknown, were frequently found to be weakly toxic with levels ranging from 10 to 99 MU/g. Therefore, further study is needed to re-examine the toxicity of smooth-backed blowfish L. inermis in the coastal waters of Japan.

Postmortem distribution of tetrodotoxin in tissues and body fluids of guinea pigs / 法医学杂志

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.