Ciguatera Fish Poisoning in the Caribbean Sea and Atlantic Ocean: Reconciling the Multiplicity of Ciguatoxins and Analytical Chemistry Approach for Public Health Safety

Ciguatera is a major circumtropical poisoning caused by the consumption of marine fish and invertebrates contaminated with ciguatoxins (CTXs): neurotoxins produced by endemic and benthic dinoflagellates which are biotransformed in the fish food-web. We provide a history of ciguatera research conducted over the past 70 years on ciguatoxins from the Pacific Ocean (P-CTXs) and Caribbean Sea (C-CTXs) and describe their main chemical, biochemical, and toxicological properties. Currently, there is no official method for the extraction and quantification of ciguatoxins, regardless their origin, mainly due to limited CTX-certified reference materials. In this review, the extraction and purification procedures of C-CTXs are investigated, considering specific objectives such as isolating reference materials, analysing fish toxin profiles, or ensuring food safety control. Certain in vitro assays may provide sufficient sensitivity to detect C-CTXs at sub-ppb levels in fish, but they do not allow for individual identification of CTXs. Recent advances in analysis using liquid chromatography coupled with low- or high-resolution mass spectrometry provide new opportunities to identify known C-CTXs, to gain structural insights into new analogues, and to quantify C-CTXs. Together, these methods reveal that ciguatera arises from a multiplicity of CTXs, although one major form (C-CTX-1) seems to dominate. However, questions arise regarding the abundance and instability of certain C-CTXs, which are further complicated by the wide array of CTX-producing dinoflagellates and fish vectors. Further research is needed to assess the toxic potential of the new C-CTX and their role in ciguatera fish poisoning. With the identification of C-CTXs in the coastal USA and Eastern Atlantic Ocean, the investigation of ciguatera fish poisoning is now a truly global effort.

[1]  J. Diogène,et al.  Ciguatoxin-like toxicity distribution in flesh of amberjack (Seriola spp.) and dusky grouper (Epinephelus marginatus). , 2023, Environmental research.

[2]  D. Harwood,et al.  The Effect of Experimental Protocol on the Toxicity of Saxitoxin in Mice , 2023, Toxins.

[3]  C. Fæste,et al.  Algal ciguatoxin identified as source of ciguatera poisoning in the Caribbean , 2023, Chemosphere.

[4]  A. Burlingame,et al.  Characterization of the Ciguatoxin Profile in Fish Samples from the Eastern Atlantic Ocean using Capillary Liquid Chromatography-High Resolution Mass Spectrometry , 2023, Food Chemistry.

[5]  A. Gago-Martínez,et al.  Contribution of Mass Spectrometry to the Advances in Risk Characterization of Marine Biotoxins: Towards the Characterization of Metabolites Implied in Human Intoxications , 2023, Toxins.

[6]  C. González‐Bello,et al.  In Silico Simulations and Functional Cell Studies Evidence Similar Potency and Distinct Binding of Pacific and Caribbean Ciguatoxins , 2022, Exposure and Health.

[7]  S. Murray,et al.  Geographical distribution, molecular and toxin diversity of the dinoflagellate species Gambierdiscus honu in the Pacific region. , 2022, Harmful algae.

[8]  R. Lewis,et al.  Origin of Ciguateric Fish: Quantitative Modelling of the Flow of Ciguatoxin through a Marine Food Chain , 2022, Toxins.

[9]  Christopher R Loeffler,et al.  Identical Ciguatoxin-3C group profiles in Lutjanus bohar from the Pacific and Indian Oceans - indicating the need to re-evaluate geographical CTX classifications , 2022, Frontiers in Marine Science.

[10]  Dazhi Wang,et al.  Gambierdiscus and Its Associated Toxins: A Minireview , 2022, Toxins.

[11]  F. Rise,et al.  Structural Characterization of Maitotoxins Produced by Toxic Gambierdiscus Species , 2022, Marine drugs.

[12]  P. Costa,et al.  Preparation of Ciguatoxin Reference Materials from Canary Islands (Spain) and Madeira Archipelago (Portugal) Fish , 2022, Journal of Marine Science and Engineering.

[13]  C. Miles,et al.  Reductive Amination for LC–MS Signal Enhancement and Confirmation of the Presence of Caribbean Ciguatoxin-1 in Fish , 2022, Toxins.

[14]  R. Litaker,et al.  Comparative Study on the Performance of Three Detection Methods for the Quantification of Pacific Ciguatoxins in French Polynesian Strains of Gambierdiscus polynesiensis , 2022, Marine drugs.

[15]  M. Campàs,et al.  Identification of New CTX Analogues in Fish from the Madeira and Selvagens Archipelagos by Neuro-2a CBA and LC-HRMS , 2022, Marine drugs.

[16]  P. Otero,et al.  Emerging Marine Biotoxins in European Waters: Potential Risks and Analytical Challenges , 2022, Marine drugs.

[17]  P. McCarron,et al.  Production and stability of Oxygen-18 labeled Caribbean ciguatoxins and gambierones. , 2022, Toxicon : official journal of the International Society on Toxinology.

[18]  J. Diogène,et al.  Ciguatoxin Detection in Flesh and Liver of Relevant Fish Species from the Canary Islands , 2022, Toxins.

[19]  D. Réveillon,et al.  Sulfo-Gambierones, Two New Analogs of Gambierone Produced by Gambierdiscus excentricus , 2021, Marine drugs.

[20]  A. Robertson,et al.  Depuration Kinetics and Growth Dilution of Caribbean Ciguatoxin in the Omnivore Lagodon rhomboides: Implications for Trophic Transfer and Ciguatera Risk , 2021, Toxins.

[21]  P. McCarron,et al.  Selective extraction of gambierone and related metabolites in Gambierdiscus silvae using m-aminophenylboronic acid-agarose gel and liquid chromatography-high-resolution mass spectrometric detection. , 2021, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[22]  M. Chinain,et al.  Screening for Predictors of Chronic Ciguatera Poisoning: An Exploratory Analysis among Hospitalized Cases from French Polynesia , 2021, Toxins.

[23]  Christopher R Loeffler,et al.  Extraction and LC-MS/MS Analysis of Ciguatoxins: A Semi-Targeted Approach Designed for Fish of Unknown Origin , 2021, Toxins.

[24]  S. Rodrigues,et al.  An Update on Ciguatoxins and CTX-like Toxicity in Fish from Different Trophic Levels of the Selvagens Islands (NE Atlantic, Madeira, Portugal) , 2021, Toxins.

[25]  F. Oberhaensli,et al.  Experimental Evidence of Ciguatoxin Accumulation and Depuration in Carnivorous Lionfish , 2021, Toxins.

[26]  C. Fæste,et al.  In Vitro Glucuronidation of Caribbean Ciguatoxins in Fish: First Report of Conjugative Ciguatoxin Metabolites. , 2021, Chemical research in toxicology.

[27]  B. Venables,et al.  Critical Review and Conceptual and Quantitative Models for the Transfer and Depuration of Ciguatoxins in Fishes , 2021, Toxins.

[28]  D. Réveillon,et al.  Deeper insight into Gambierdiscus polynesiensis toxin production relies on specific optimization of high-performance liquid chromatography-high resolution mass spectrometry. , 2021, Talanta.

[29]  T. Yasumoto,et al.  Development and Validation of an LC-MS/MS Method for the Ultra-Trace Analysis of Pacific Ciguatoxins in Fish , 2021, Journal of AOAC International.

[30]  M. Sasaki,et al.  Synthesis and Structural Implication of the JKLMN-Ring Fragment of Caribbean Ciguatoxin C-CTX-1. , 2021, The Journal of organic chemistry.

[31]  Y. Sugita‐Konishi,et al.  Characteristic Distribution of Ciguatoxins in the Edible Parts of a Grouper, Variola louti , 2021, Toxins.

[32]  L. Tartaglione,et al.  Ciguatera Mini Review: 21st Century Environmental Challenges and the Interdisciplinary Research Efforts Rising to Meet Them , 2021, International journal of environmental research and public health.

[33]  R. Hatfield,et al.  Application of Six Detection Methods for Analysis of Paralytic Shellfish Toxins in Shellfish from Four Regions within Latin America , 2020, Marine drugs.

[34]  L. Misery,et al.  Neurological Disturbances of Ciguatera Poisoning: Clinical Features and Pathophysiological Basis , 2020, Cells.

[35]  P. Tester,et al.  Ciguatera poisonings: A global review of occurrences and trends. , 2020, Harmful algae.

[36]  T. Dennis,et al.  Advances in Detecting Ciguatoxins in Fish , 2020, Toxins.

[37]  P. Hess,et al.  Use of Mass Spectrometry to Determine the Diversity of Toxins Produced by Gambierdiscus and Fukuyoa Species from Balearic Islands and Crete (Mediterranean Sea) and the Canary Islands (Northeast Atlantic) , 2020, Toxins.

[38]  H. Darius,et al.  Revisiting the Neuroblastoma Cell-Based Assay (CBA-N2a) for the Improved Detection of Marine Toxins Active on Voltage Gated Sodium Channels (VGSCs) , 2020, Toxins.

[39]  P. Hess,et al.  Liquid Chromatography Coupled to High-Resolution Mass Spectrometry for the Confirmation of Caribbean Ciguatoxin-1 as the Main Toxin Responsible for Ciguatera Poisoning Caused by Fish from European Atlantic Coasts , 2020, Toxins.

[40]  C. Miles,et al.  LC–HRMS and Chemical Derivatization Strategies for the Structure Elucidation of Caribbean Ciguatoxins: Identification of C-CTX-3 and -4 , 2020, Marine drugs.

[41]  Yim Ling Mak,et al.  Uptake and Depuration Kinetics of Pacific Ciguatoxins (P-CTXs) in Orange-spotted Grouper (Epinephelus coioides). , 2020, Environmental science & technology.

[42]  A. Venâncio,et al.  Detection Methods for Aflatoxin M1 in Dairy Products , 2020, Microorganisms.

[43]  P. Costa,et al.  Global impact of ciguatoxins and ciguatera fish poisoning on fish, fisheries and consumers. , 2020, Environmental research.

[44]  E. Berdalet,et al.  Climate change and harmful benthic microalgae. , 2020, Harmful algae.

[45]  T. Yasumoto,et al.  Caribbean Ciguatoxin-1 stability under strongly acidic conditions: Characterisation of a new C-CTX1 methoxy congener , 2019, Food additives & contaminants. Part A, Chemistry, analysis, control, exposure & risk assessment.

[46]  H. Darius,et al.  Intraspecific Variability in the Toxin Production and Toxin Profiles of In Vitro Cultures of Gambierdiscus polynesiensis (Dinophyceae) from French Polynesia , 2019, Toxins.

[47]  R. Litaker,et al.  Ciguatoxin Occurrence in Food-Web Components of a Cuban Coral Reef Ecosystem: Risk-Assessment Implications , 2019, Toxins.

[48]  T. Yasumoto,et al.  Chemiluminescent Receptor Binding Assay for Ciguatoxins and Brevetoxins Using Acridinium Brevetoxin-B2 , 2019, Toxins.

[49]  J. Diogène,et al.  Predictive score and probability of CTX-like toxicity in fish samples from the official control of ciguatera in the Canary Islands. , 2019, The Science of the total environment.

[50]  T. Yasumoto,et al.  Implementation of liquid chromatography tandem mass spectrometry for the analysis of ciguatera fish poisoning in contaminated fish samples from Atlantic coasts. , 2019, Food chemistry.

[51]  A. Gago-Martínez,et al.  Emerging Marine Biotoxins in Seafood from European Coasts: Incidence and Analytical Challenges , 2019, Foods.

[52]  J. Diogène,et al.  An Attempt to Characterize the Ciguatoxin Profile in Seriola fasciata Causing Ciguatera Fish Poisoning in Macaronesia , 2019, Toxins.

[53]  J. F. Lawrence,et al.  Evaluation of the new European Union reference method for paralytic shellfish toxins in shellfish: A review of twelve years regulatory monitoring using pre-column oxidation LC-FLD , 2019, TrAC Trends in Analytical Chemistry.

[54]  S. Rodrigues,et al.  New Insights into the Occurrence and Toxin Profile of Ciguatoxins in Selvagens Islands (Madeira, Portugal) , 2018, Toxins.

[55]  M. Sasaki,et al.  Studies toward the Total Synthesis of Caribbean Ciguatoxin C-CTX-1: Synthesis of the LMN-Ring Fragment through Reductive Olefin Cross-Coupling. , 2018, Organic letters.

[56]  A. Gago-Martínez,et al.  Design of experiments for the optimization of electrospray ionization in the LC-MS/MS analysis of ciguatoxins. , 2018, Journal of mass spectrometry : JMS.

[57]  Y. Fukuyo,et al.  Identification of Causative Ciguatoxins in Red Snappers Lutjanus bohar Implicated in Ciguatera Fish Poisonings in Vietnam , 2018, Toxins.

[58]  M. Roué,et al.  Detection of pacific ciguatoxins using liquid chromatography coupled to either low or high resolution mass spectrometry (LC-MS/MS). , 2018, Journal of chromatography. A.

[59]  F. Oberhaensli,et al.  Experimental evidence of dietary ciguatoxin accumulation in an herbivorous coral reef fish. , 2018, Aquatic toxicology.

[60]  T. Smith,et al.  Ciguatoxin prevalence in 4 commercial fish species along an oceanic exposure gradient in the US Virgin Islands , 2018, Environmental toxicology and chemistry.

[61]  R. Litaker,et al.  Toxicological Investigations on the Sea Urchin Tripneustes gratilla (Toxopneustidae, Echinoid) from Anaho Bay (Nuku Hiva, French Polynesia): Evidence for the Presence of Pacific Ciguatoxins , 2018, Marine drugs.

[62]  R. Garnier,et al.  Incidence and clinical characteristics of ciguatera fish poisoning in Guadeloupe (French West Indies) between 2013 and 2016: a retrospective cases-series , 2018, Scientific Reports.

[63]  P. Asthana,et al.  Pacific Ciguatoxin Induces Excitotoxicity and Neurodegeneration in the Motor Cortex Via Caspase 3 Activation: Implication for Irreversible Motor Deficit , 2018, Molecular Neurobiology.

[64]  H. Uchida,et al.  Analytical challenges to ciguatoxins , 2017 .

[65]  T. Yasumoto,et al.  Quantification of Representative Ciguatoxins in the Pacific Using Quantitative Nuclear Magnetic Resonance Spectroscopy , 2017, Marine drugs.

[66]  R. Litaker,et al.  Gambierdiscus and Fukuyoa species in the greater Caribbean: Regional growth projections for ciguatera-associated dinoflagellates , 2017 .

[67]  D. T. Harwood,et al.  Sample Preparation Prior to Marine Toxin Analysis , 2017 .

[68]  R. Lewis,et al.  Analysis of Food Toxins and Toxicants , 2017 .

[69]  M. Campàs,et al.  Identification of ciguatoxins in a shark involved in a fatal food poisoning in the Indian Ocean , 2017, Scientific Reports.

[70]  T. Yasumoto,et al.  Biooxidation of Ciguatoxins Leads to Species-Specific Toxin Profiles , 2017, Toxins.

[71]  R. E. Bowen,et al.  Association of Cardiometabolic Genes with Arsenic Metabolism Biomarkers in American Indian Communities: The Strong Heart Family Study (SHFS) , 2016, Environmental health perspectives.

[72]  I. Vetter,et al.  Multiple sodium channel isoforms mediate the pathological effects of Pacific ciguatoxin-1 , 2017, Scientific Reports.

[73]  I. Vetter,et al.  Rapid Extraction and Identification of Maitotoxin and Ciguatoxin-Like Toxins from Caribbean and Pacific Gambierdiscus Using a New Functional Bioassay , 2016, PloS one.

[74]  E. Orive,et al.  Characterization of a Strain of Fukuyoa paulensis (Dinophyceae) from the Western Mediterranean Sea , 2016, The Journal of eukaryotic microbiology.

[75]  M. Roué,et al.  Evidence of the bioaccumulation of ciguatoxins in giant clams (Tridacna maxima) exposed to Gambierdiscus spp. cells. , 2016, Harmful algae.

[76]  D. Baden,et al.  Fluorescent Receptor Binding Assay for Detecting Ciguatoxins in Fish , 2016, PloS one.

[77]  L. Meyer,et al.  An updated ciguatoxin extraction method and silica cleanup for use with HPLC-MS/MS for the analysis of P-CTX-1, PCTX-2 and P-CTX-3. , 2015, Toxicon : official journal of the International Society on Toxinology.

[78]  J. Diogène,et al.  Contribution to the risk characterization of ciguatoxins: LOAEL estimated from eight ciguatera fish poisoning events in Guadeloupe (French West Indies). , 2015, Environmental research.

[79]  L. Botana,et al.  First Report of Ciguatoxins in Two Starfish Species: Ophidiaster ophidianus and Marthasterias glacialis , 2015, Toxins.

[80]  J. Diogène,et al.  Prevalence of ciguatoxins in lionfish (Pterois spp.) from Guadeloupe, Saint Martin, and Saint Barthélmy Islands (Caribbean). , 2015, Toxicon : official journal of the International Society on Toxinology.

[81]  I. Vetter,et al.  Ciguatera fish poisoning: a first epidemic in Germany highlights an increasing risk for European countries. , 2014, Toxicon : official journal of the International Society on Toxinology.

[82]  M. Campàs,et al.  Alternative Methods for the Detection of Emerging Marine Toxins: Biosensors, Biochemical Assays and Cell-Based Assays , 2014, Marine drugs.

[83]  L. Epelboin,et al.  Two clusters of ciguatera fish poisoning in Paris, France, related to tropical fish imported from the French Caribbean by travelers. , 2014, Journal of travel medicine.

[84]  D. Baden,et al.  Development and utilization of a fluorescence-based receptor-binding assay for the site 5 voltage-sensitive sodium channel ligands brevetoxin and ciguatoxin. , 2014, Journal of AOAC International.

[85]  T. Smith,et al.  Invasive Lionfish (Pterois volitans): A Potential Human Health Threat for Ciguatera Fish Poisoning in Tropical Waters , 2013, Marine drugs.

[86]  Jia Jun Wu,et al.  Pacific ciguatoxins in food web components of coral reef systems in the Republic of Kiribati. , 2013, Environmental science & technology.

[87]  Jia Jun Wu,et al.  Simultaneous quantification of Pacific ciguatoxins in fish blood using liquid chromatography–tandem mass spectrometry , 2013, Analytical and Bioanalytical Chemistry.

[88]  I. Vetter,et al.  Ciguatoxins activate specific cold pain pathways to elicit burning pain from cooling , 2012, The EMBO journal.

[89]  S. Rastelli,et al.  Evaluation and Improvement of Extraction Methods for the Analysis of Aflatoxins B1, B2, G1 and G2 from Naturally Contaminated Maize , 2012, Food Analytical Methods.

[90]  H. Granade,et al.  Caribbean ciguatoxin profile in raw and cooked fish implicated in ciguatera , 2012 .

[91]  T. Yasumoto,et al.  Detailed LC-MS/MS analysis of ciguatoxins revealing distinct regional and species characteristics in fish and causative alga from the Pacific. , 2011, Analytical chemistry.

[92]  R. Woesik,et al.  Ciguatera poisoning in Rarotonga, southern Cook Islands , 2011 .

[93]  Jia Jun Wu,et al.  Validation of an accelerated solvent extraction liquid chromatography–tandem mass spectrometry method for Pacific ciguatoxin-1 in fish flesh and comparison with the mouse neuroblastoma assay , 2011, Analytical and bioanalytical chemistry.

[94]  L. D. Boada,et al.  Ciguatera fish poisoning on the West Africa Coast: An emerging risk in the Canary Islands (Spain). , 2010, Toxicon : official journal of the International Society on Toxinology.

[95]  P. Tester,et al.  Ciguatera fish poisoning and sea surface temperatures in the Caribbean Sea and the West Indies. , 2010, Toxicon : official journal of the International Society on Toxinology.

[96]  M. A. Faust,et al.  Global distribution of ciguatera causing dinoflagellates in the genus Gambierdiscus. , 2010, Toxicon : official journal of the International Society on Toxinology.

[97]  R. Lewis,et al.  Analysis of Caribbean ciguatoxin-1 effects on frog myelinated axons and the neuromuscular junction. , 2010, Toxicon : official journal of the International Society on Toxinology.

[98]  T. Yasumoto,et al.  Ciguatera incidence and fish toxicity in Okinawa, Japan. , 2010, Toxicon : official journal of the International Society on Toxinology.

[99]  H. Darius,et al.  Growth and toxin production in the ciguatera-causing dinoflagellate Gambierdiscus polynesiensis (Dinophyceae) in culture. , 2010, Toxicon : official journal of the International Society on Toxinology.

[100]  G. Shaw,et al.  Establishing a public health analytical service based on chemical methods for detecting and quantifying Pacific ciguatoxin in fish samples. , 2010, Toxicon : official journal of the International Society on Toxinology.

[101]  R. Dickey,et al.  Ciguatera: a public health perspective. , 2010, Toxicon : official journal of the International Society on Toxinology.

[102]  C. Vale,et al.  First toxin profile of ciguateric fish in Madeira Arquipelago (Europe). , 2010, Analytical chemistry.

[103]  S. Fraga,et al.  Update on Methodologies Available for Ciguatoxin Determination: Perspectives to Confront the Onset of Ciguatera Fish Poisoning in Europe [] , 2010, Marine drugs.

[104]  F. Macnutt,et al.  de Orbe Novo, the Eight Decades of Peter Martyr D'Anghera , 2009 .

[105]  R. Lewis,et al.  Rapid extraction combined with LC-tandem mass spectrometry (CREM-LC/MS/MS) for the determination of ciguatoxins in ciguateric fish flesh. , 2009, Toxicon : official journal of the International Society on Toxinology.

[106]  E. Levin,et al.  Repeat exposure to ciguatoxin leads to enhanced and sustained thermoregulatory, pain threshold and motor activity responses in mice: relationship to blood ciguatoxin concentrations. , 2008, Toxicology.

[107]  H. Darius,et al.  Ciguatera risk assessment in two toxic sites of French Polynesia using the receptor-binding assay. , 2007, Toxicon : official journal of the International Society on Toxinology.

[108]  P. Arena,et al.  Neuropsychological study of ciguatera fish poisoning: a longitudinal case-control study. , 2007, Archives of clinical neuropsychology : the official journal of the National Academy of Neuropsychologists.

[109]  R. Lewis Ciguatera: Australian perspectives on a global problem. , 2006, Toxicon : official journal of the International Society on Toxinology.

[110]  R. Lewis,et al.  Ciguatoxins: Cyclic Polyether Modulators of Voltage-gated Iion Channel Function , 2006, Marine Drugs.

[111]  L. D. Boada,et al.  Ciguatera Fish Poisoning, Canary Islands , 2005, Emerging infectious diseases.

[112]  M. Dechraoui,et al.  Use of two detection methods to discriminate ciguatoxins from brevetoxins: application to great barracuda from Florida Keys. , 2005, Toxicon : official journal of the International Society on Toxinology.

[113]  R. Lewis,et al.  Identification of slow and fast-acting toxins in a highly ciguatoxic barracuda (Sphyraena barracuda) by HPLC/MS and radiolabelled ligand binding. , 2003, Toxicon : official journal of the International Society on Toxinology.

[114]  J. Vernoux,et al.  [Evaluation of Antilles fish ciguatoxicity by mouse and chick bioassays]. , 2003, Bulletin de la Societe de pathologie exotique.

[115]  R. Lewis,et al.  Analysis of toxin profiles in three different fish species causing ciguatera fish poisoning in Guadeloupe, French West Indies , 2002, Food additives and contaminants.

[116]  R. Lewis,et al.  Multiple ciguatoxins present in Indian Ocean reef fish. , 2002, Toxicon : official journal of the International Society on Toxinology.

[117]  J. Vernoux,et al.  Muscarinic effects of the Caribbean ciguatoxin C-CTX-1 on frog atrial heart muscle. , 2002, Toxicon : official journal of the International Society on Toxinology.

[118]  R. Lewis,et al.  Characterisation of multiple Caribbean ciguatoxins and congeners in individual specimens of horse-eye jack (Caranx latus) by high-performance liquid chromatography/mass spectrometry. , 2002, Toxicon : official journal of the International Society on Toxinology.

[119]  R. Lewis,et al.  Isolation and characterisation of Indian Ocean ciguatoxin. , 2002, Toxicon : official journal of the International Society on Toxinology.

[120]  M. Milad,et al.  A Pilot Study for the Detection of Acute Ciguatera Intoxication in Human Blood , 2002, Journal of toxicology. Clinical toxicology.

[121]  J. Pearn Neurology of ciguatera , 2001, Journal of neurology, neurosurgery, and psychiatry.

[122]  R. Lewis,et al.  Ciguatera: recent advances but the risk remains. , 2000, International journal of food microbiology.

[123]  M. Chinain,et al.  Structural Elucidation of Ciguatoxin Congeners by Fast-Atom Bombardment Tandem Mass Spectroscopy , 2000 .

[124]  L. Lehane,et al.  Ciguatera update , 2000, The Medical journal of Australia.

[125]  M. A. Faust,et al.  MORPHOLOGY AND MOLECULAR ANALYSES OF THREE TOXIC SPECIES OF GAMBIERDISCUS (DINOPHYCEAE): G. PACIFICUS, SP. NOV., G. AUSTRALES, SP. NOV., AND G. POLYNESIENSIS, SP. NOV. , 1999 .

[126]  J. Crump,et al.  Ciguatera fish poisoning , 1999, Postgraduate medical journal.

[127]  Y. Ishida,et al.  Effects of epiphytic bacteria on the growth of the toxic dinoflagellate Gambierdiscus toxicus (Dinophyceae) , 1999 .

[128]  R. Lewis,et al.  Structure of Caribbean Ciguatoxin Isolated from Caranx latus , 1998 .

[129]  N. Harada,et al.  The Absolute Configuration of Ciguatoxin , 1997 .

[130]  R. Lewis,et al.  Isolation and characterisation of Caribbean ciguatoxins from the horse-eye jack (Caranx latus). , 1997, Toxicon : official journal of the International Society on Toxinology.

[131]  R. Lewis,et al.  Identification of Caribbean ciguatoxins as the cause of an outbreak of fish poisoning among U.S. soldiers in Haiti. , 1997, Toxicon.

[132]  R. Lewis,et al.  Characterization of ciguatoxins and ciguatoxin congeners present in ciguateric fish by gradient reverse-phase high-performance liquid chromatography/mass spectrometry. , 1997, Toxicon : official journal of the International Society on Toxinology.

[133]  M. Satake,et al.  Isolation and structure of ciguatoxin-4A, a new ciguatoxin precursor, from cultures of dinoflagellate Gambierdiscus toxicus and parrotfish Scarus gibbus. , 1996, Bioscience, biotechnology, and biochemistry.

[134]  Jiang-Ping Wu,et al.  Complete Relative Stereochemistry of Maitotoxin , 1996 .

[135]  J. Quod,et al.  Ciguatera in Réunion Island (SW Indian Ocean): epidemiology and clinical patterns. , 1996, Toxicon : official journal of the International Society on Toxinology.

[136]  S. Musser,et al.  Improvements in the sensitivity of inverse-detected heteronuclear correlation spectra using micro inverse probes and micro cells: HMQC and HMBC spectra of caribbean ciguatoxin — preliminary structural inferences , 1995 .

[137]  M. Wekell,et al.  Detection of sodium channel toxins: directed cytotoxicity assays of purified ciguatoxins, brevetoxins, saxitoxins, and seafood extracts. , 1995, Journal of AOAC International.

[138]  B. Ho,et al.  A tetrodotoxin neutralizing system in the haemolymph of the horseshoe crab, Carcinoscorpius rotundicauda. , 1994, Toxicon : official journal of the International Society on Toxinology.

[139]  R. Lewis,et al.  Purification and characterisation of large and small maitotoxins from cultured Gambierdiscus toxicus. , 1994, Natural toxins.

[140]  R. Lewis,et al.  Ionspray mass spectrometry of ciguatoxin-1, maitotoxin-2 and -3, and related marine polyether toxins. , 1994, Natural toxins.

[141]  R. Lewis,et al.  Origin and transfer of toxins involved in ciguatera. , 1993, Comparative biochemistry and physiology. C, Comparative pharmacology and toxicology.

[142]  M. Wekell,et al.  Tetrazolium-based cell bioassay for neurotoxins active on voltage-sensitive sodium channels: semiautomated assay for saxitoxins, brevetoxins, and ciguatoxins. , 1993, Analytical biochemistry.

[143]  R. Lewis,et al.  Ciguatera and mannitol: in vivo and in vitro assessment in mice. , 1993, Toxicon : official journal of the International Society on Toxinology.

[144]  R. Norton,et al.  Ciguatoxin-2 is a diastereomer of ciguatoxin-3. , 1993, Toxicon : official journal of the International Society on Toxinology.

[145]  M. Satake,et al.  The structure of CTX3C, a ciguatoxin congener isolated from cultured Gambierdiscus toxicus , 1993 .

[146]  T. Iwashita,et al.  Structure of maitotoxin , 1993 .

[147]  T. Matsui,et al.  Occurrence of tetrodotoxin-binding high molecular weight substances in the body fluid of shore crab (Hemigrapsus sanguineus). , 1992, Toxicon : official journal of the International Society on Toxinology.

[148]  S. Hahn,et al.  Ciguatoxin-protein association in skeletal muscle of Spanish mackerel (Scomberomorus commersoni). , 1992, Toxicon : official journal of the International Society on Toxinology.

[149]  R. Lewis,et al.  Multiple ciguatoxins in the flesh of fish. , 1992, Toxicon : official journal of the International Society on Toxinology.

[150]  R. Lewis,et al.  Ciguatoxins are potent ichthyotoxins. , 1992, Toxicon : official journal of the International Society on Toxinology.

[151]  T. Yasumoto,et al.  Structures and Configurations of Ciguatoxin from the Moray Eel Gymnothorax javanicus and Its Likely Precursor from the Dinoflagellate Gambierdiscus toxicus , 1990 .

[152]  T. Yasumoto,et al.  Structures of ciguatoxin and its congener , 1989 .

[153]  T. Yasumoto,et al.  Isolation and some properties of ciguatoxin , 1989, Journal of Applied Phycology.

[154]  R. Lewis,et al.  Ciguatera in Australia. Occurrence, clinical features, pathophysiology and management. , 1986, The Medical journal of Australia.

[155]  J. Vernoux,et al.  Hétérogénéité des ciguatoxines extraites de poissons péchés aux Antilles françaises. , 1986 .

[156]  J. Vernoux,et al.  A study of the distribution of ciguatoxin in individual Caribbean fish. , 1985, Acta tropica.

[157]  M. Lazdunski,et al.  Ciguatoxin is a novel type of Na+ channel toxin. , 1984, The Journal of biological chemistry.

[158]  J. Clardy,et al.  Isolation and structure of brevetoxin B from the "red tide" dinoflagellate Ptychodiscus brevis (Gymnodinium breve) , 1981 .

[159]  D. Lawrence,et al.  Ciguatera Fish Poisoning in Miami , 1980 .

[160]  S. Chanteau,et al.  Purification de la ciguatoxine de la loche Epinephelus microdon (Bleecker) , 1976 .

[161]  J. Vernoux,et al.  Fractionnement d'extraits lipidiques ciguatoxiques en milieu alcalin , 1976 .

[162]  J. Vernoux,et al.  [Ciguatoxin and edible reef fishes]. , 1975, Bulletin de la Societe de pathologie exotique et de ses filiales.

[163]  T. Yasumoto,et al.  Marine toxins of the Pacific. VIII. Ciguatoxin from moray eel livers. , 1969 .

[164]  A. H. Banner,et al.  OBSERVATIONS ON CIGUATERA‐TYPE TOXIN IN FISH * , 1960, Annals of the New York Academy of Sciences.

[165]  J. Hungerford,et al.  Marine toxins. , 2014, Journal of AOAC International.

[166]  R. Lewis,et al.  Flow cytometric-membrane potential detection of sodium channel active marine toxins: application to ciguatoxins in fish muscle and feasibility of automating saxitoxin detection. , 2014, Journal of AOAC International.

[167]  J. Ramsdell,et al.  Optimization of ciguatoxin extraction method from blood for Pacific ciguatoxin (P-CTX-1). , 2007, Toxicon : official journal of the International Society on Toxinology.

[168]  J. Masson,et al.  Mechanisms involved in the swelling of erythrocytes caused by Pacific and Caribbean ciguatoxins. , 2006, Blood cells, molecules & diseases.

[169]  R. Lewis Detection of toxins associated with cigutera fish poisoning , 2003 .

[170]  T. Yasumoto The chemistry and biological function of natural marine toxins. , 2001, Chemical record.

[171]  M. Dechraoui,et al.  Ciguatoxins and brevetoxins, neurotoxic polyether compounds active on sodium channels. , 1999, Toxicon : official journal of the International Society on Toxinology.

[172]  R. Lewis,et al.  HPLC/tandem electrospray mass spectrometry for the determination of Sub-ppb levels of Pacific and Caribbean ciguatoxins in crude extracts of fish. , 1999, Analytical chemistry.

[173]  R. Lewis,et al.  Strain dependent production of ciguatoxin precursors (gambiertoxins) by Gambierdiscus toxicus (Dinophyceae) in culture. , 1991, Toxicon : official journal of the International Society on Toxinology.

[174]  R. Norton,et al.  Purification and characterization of ciguatoxins from moray eel (Lycodontis javanicus, Muraenidae). , 1991, Toxicon : official journal of the International Society on Toxinology.

[175]  R. Lewis,et al.  Toxicity of Australian and French polynesian strains of Gambierdiscus toxicus (Dinophyceae) grown in culture: characterization of a new type of maitotoxin. , 1990, Toxicon : official journal of the International Society on Toxinology.

[176]  J. Vernoux,et al.  Fractionation and purification of some muscular and visceral ciguatoxins extracted from Carribean fish. , 1989, Comparative biochemistry and physiology. B, Comparative biochemistry.

[177]  J. Vernoux La ciguatera dans l'île de Saint-Barthélémy: aspects épidémiologiques, toxicologiques et préventifs , 1988 .

[178]  H. Durst,et al.  Seasonal frequency of ciguatoxic barracuda in southwest Puerto Rico. , 1988, Toxicon : official journal of the International Society on Toxinology.

[179]  P. Scheuer,et al.  Two interchangeable forms of ciguatoxin. , 1984, Toxicon : official journal of the International Society on Toxinology.

[180]  H. Granade,et al.  The mouse ciguatoxin bioassay: a dose-response curve and symptomatology analysis. , 1983, Toxicon : official journal of the International Society on Toxinology.

[181]  S. Chanteau,et al.  Origins of ciguatera fish poisoning: a new dinoflagellate, Gambierdiscus toxicus Adachi and Fukuyo, definitively involved as a causal agent. , 1980, Toxicon : official journal of the International Society on Toxinology.

[182]  Y. Fukuyo,et al.  The Thecal Structure of a Marine Toxic Dinoflagellate Gambierdiscus toxicus gen. et sp. nov. Collected in a Ciguatera-endemic Area , 1979 .

[183]  T. Yasumoto,et al.  Finding of a dinoflagellate as a likely culprit of ciguatera. , 1977 .

[184]  S. Chanteau,et al.  [Significance of the various toxins present on dead coral substrata in the origin of ciguatera]. , 1977, Bulletin de la Societe de pathologie exotique et de ses filiales.

[185]  Y. Hashimoto,et al.  Isolation of two toxins from a parrotfish Scarus gibbus. , 1977, Toxicon : official journal of the International Society on Toxinology.

[186]  T. Yasumoto,et al.  Toxicity of the surgeonfishes. II. Properties of the principal water-soluble toxin. , 1976 .

[187]  A. H. Banner,et al.  Toxicity of the Surgeonfishes , 1971 .

[188]  Y. Hashimoto,et al.  Ciguatera in the Ryukyu and Amami Islands , 1969 .

[189]  J. E. Randall Food habits of reef fishes of the West Indies , 1967 .

[190]  Y. Hashimoto A Note on the Poison of a Barracuda, Sphyraena picuda BLOCH & SCHNEIDER , 1956 .