Ciguatera  fish  poisoning  and  climate  change:  analysis  of  cross-­‐sec8onal  na8onal  poison  center  data  in  the  United  States  2001-­‐2011  

Dan  Gingold,  MD/MPH  Candidate1,  Jeremy  Hess,  MD,  MPH2,3,  MaGhew  Strickland,  PhD,  MPH1,2    

1Emory  University  Rollins  School  of  Public  Health,  Department  of  Epidemiology  2Emory  University  Rollins  School  of  Public  Health,  Department  of  Environmental  Health  

3Emory  University  School  of  Medicine,  Department  of  Emergency  Medicine  

Introduc)on   Ciguatera fish poisoning (CFP) is a significant public health problem in endemic areas, including the Caribbean and Pacific Islands. CFP prevalence in these areas is affected by El Niño and warmer sea surface temperatures (SST). (1,2) Climate change is projected expand the range of suitable habitat for the organisms that cause ciguatera by warming SST and bleaching coral reefs. (3) We hypothesize that CFP incidence in the US is associated with increases in Caribbean SST and severe storm frequency. If true, projections of increased SST and storm frequency from climate change suggest CFP prevalence in the US may increase.

Background   CFP is the most common non-bacterial illness associated with fish consumption, affecting 50,000 - 200,000 people annually. Ciguatera toxin is produced by benthic dinoflagellate plankton in the genus Gambierdiscus, which live on dead coral surfaces and bottom-dwelling algae. Toxin accumulates in tissues of fish that eat the algae and bioaccumulates up the food chain. (2) Humans eating contaminated fish are susceptible to the toxidrome caused by the ciguatera toxin, which includes gastrointestinal upset followed by neurologic symptoms that can include paresthesias and hot-cold reversal. (4) Ciguatera poisoning is most prevalent in tropical regions of warm and stable SST that remains above 24°C. Laboratory studies have shown that water temperatures of 29°C are optimal for Gambierdiscus growth. (2) Increased coral bleaching from higher sea temperatures, more frequent storms, and man-made ocean structures may increase habitat for toxic dinoflagellates. (5)

Materials  and  methods   This is a retrospective observational study. All calls to US poison control centers with substance code “Ciguatera Fish Poisoning” affecting humans during years 2001-2011 were collected from the National Poison Data System (NPDS) run by the American Association of Poison Control Centers (AAPCC). Monthly SST data contained in the Reynolds/NOAA (OI.v2) SST Data Set is available online from the IRI/LDEO Climate Data Library at Columbia University. (6) The Caribbean SST index is the time series of Caribbean SST anomalies compared to SST averages from 1951-1991, and is available online from the Earth System Research Laboratory at NOAA. Data for severe tropical storms, US state populations, and Caribbean fishing yields years 2001-2011 are available online from Unisys Weather, US census, and Food and Agriculture Organization of the United Nations, respectively. Results from descriptive analysis of the location, timing, and severity of these cases standardized by population will be reported. Conditional logistic regression will be used to calculate associations between annual US and regional CFP incidence and the spread of warm SST temperatures, Caribbean SST index, and storm frequency in the Caribbean, Gulf of Mexico, and Atlantic basins, taking into account key confounders such as regional fishing yields and time-lags.

Preliminary  Results  

Implica)ons   Climate change is likely to increase SST in higher latitudes, expanding the range of acceptable habitat for Gambierdiscus northward along the Atlantic coast of the US. (2, 3) Quantification of the association of CFP with climatic variables combined with climate projections could provide predictions regarding future CFP prevalence and range in the US. This can inform adaptation measures such as education of health professionals and enhanced surveillance, and augment projections of the potential public health impacts of unmitigated climate change.

Limita)ons   Ciguatera-related calls to poison control centers are not confirmed cases and are coded based on suspicion. CFP has a substantial underreporting bias even with more active surveillance techniques. Little information about source of contaminated fish is available, and we must assume that fish causing CFP in the US came from the Caribbean. Locations of calls are not necessarily where the toxic fish was consumed. Call incidence may be affected by confounders such as increased awareness of CFP during the study period.

Literature  cited  1.  Hales S, Weinstein P, Woodward A. Ciguatera (Fish Poisoning), El Niño, and Pacific Sea Surface Temperatures. Ecosystem Health 1999;5(1):20-25. 2.  Tester PA, Feldman RL, Nau AW, Kibler SR, Wayne Litaker R. Ciguatera fish poisoning and sea surface temperatures in the Caribbean Sea and the West Indies. Toxicon : official journal of the International Society on Toxinology 2010;56(5):698-710. 3.  Moore SK, Trainer VL, Mantua NJ, Parker MS, Laws EA, Backer LC, et al. Impacts of climate variability and future climate change on harmful algal blooms and human health. Environmental health: a global access science source 2008;7 Suppl 2:S4. 4.  Friedman MA, Fleming LE, Fernandez M, Bienfang P, Schrank K, Dickey R, et al. Ciguatera fish poisoning: treatment, prevention and management. Marine drugs 2008;6(3):456-79. 5.  Tester PA. Harmful Marine Phytoplankton and Shellfish Toxicity Potential Consequences of Climate Change. Annals of the New York Academy of Sciences 1994;740(1):69-76. 6.  Reynolds RW, Rayner NA, Smith TM, Stokes DC, Wang W. An Improved In Situ and Satellite SST Analysis for Climate. Journal of Climate 2002;15(13):1609-1625. 7.  Crump JA, McLay CL, Chambers ST. Ciguatera fish poisoning. Postgraduate medical journal 1999;75(889):678-9. 8.  Pearn J. Neurology of ciguatera. Journal of neurology, neurosurgery, and psychiatry 2001;70(1):4-8.

Acknowledgements   Thanks to George Luber, Royal Law, and Joshua Schier at CDC/ONDIEH/NCEH for assistance in project development and obtaining ciguatera data from AAPCC with Alvin Bronstein and Elise Baily. This study was presented to the Emory University Institutional Review Board and exempted from review. No informed consent process necessary given that this study involved secondary analysis of a de-identified data set. Please contact Dan Gingold at dbgingo@emory.edu for more information.

Sea  Surface  Temp  Feb  2010   Sea  Surface  Temp  May  2010  

Sea  Surface  Temp  Aug  2010  Sea  Surface  Temp  Nov  2010  

Coral  reef  regions  (grey)  

CFP  endemic  areas  (brown)  

Peréz-Arellano J-L, Luzardo OP, Brito AP, Hernández Cabrera M, Zumbado M, Carranza C, et al. Ciguatera fish poisoning, Canary Islands [letter]. Emerg Infect Dis [Internet serial]. 2005 Dec

Maps  of  seasonal  Caribbean  SST  warming  and  cooling,  data  from  Reynolds/NOAA  (OI.v2)  SST,  2010  

Electron  micrograph  of  Gambierdiscus  toxius  (7)  

intoxication may approach 10% of the popula-tion.10 Ciguatera poisoning is poorly under-stood as a potential global health problem intemperate countries, particularly in NorthAmerica and Europe. The toxin is stored in theviscera of fish that have eaten the photosyn-thetic dinoflagellate; and is progressively con-centrated upwards along the food chain. Thetoxin is stable in the tissue of living fish anddoes them no harm. Larger carnivores havehigher concentrations of the toxin in theirtissues. The practical consequence of this isthat consumption of the largest carnivorousfish—often those gourmet specimens which arefrozen and transported for intercontinentalconsumption— therefore forms the greatestrisk of ciguatera intoxication for the consumer.Pacific ciguatoxins pose a health risk atconcentrations (within ingested fish flesh)above 0.1 ppb.11

Extensive international commerce in frozenfish, and especially that involving trade ingourmet reef species, means that victims of thisdramatic intoxication may now be encounteredin all countries.12 An estimated 10 000–50 000victims have the disease annually.13 Cases havebeen reported in the past decade from theUnited States (Hawaii14 and from RhodeIsland15), Madagascar,16 Hong Kong,17 Eu-rope,12 and extensively from the South Pa-cific.3 4 9 Ciguatera is thus a global health prob-lem from the perspective of preventivemedicine5 and an acute challenge for the clini-cian treating individual cases.

Increased awareness of the neurotoxiceVects of ciguatera will aid in earlier diagno-sis.3 This in turn will facilitate earlier treat-ment18 and the shortening of convalescence.The earlier identification of sentinel patientshas the potential to prevent secondary casesand thus reduce the clinical clusters or micro-epidemics of victims.

CiguatoxinsCiguatoxins are potent heat stable, non-protein, lipophilic sodium channel activatortoxins that bind quasi-irreversibly to thevoltage sensitive sodium channel at site five.19

The molecular targets are found on allmembranes of excitable tissues but withvarying tissue specific aYnity. The receptor siteoverlaps the receptor site for brevitoxin,another food chain paralytic toxin.20 BothPacific and Caribbean ciguatoxin8 have as theirbasic structure unique molecular chains of 13and 14 joined ether rings (c62H92O19) respec-tively. Nine of these transfused rings form aladder which is very similar in all ciguatoxins(figure).11 18 The toxins are tasteless andodourless and are relatively heat stable to thetemperatures usually employed in cooking.Both Pacific ciguatoxins (P-CTX-1) andCaribbean ciguatoxins (C-CTX-1) are stablefor at least 6 months at commercial freezingtemperatures.19

Clinical evidence suggests that the toxinbinds to sodium channel receptor sites of bothsomatic and autonomic nerves. The chronicityof symptoms (months or years in somevictims)21 22 and the exquisite sensitivity of con-valescent victims accidentally subjected torechallenge4 18 suggests that the sodium chan-nel receptors are inactivated permanently; andthat convalescence from severe intoxicationmay depend on the generation of new recep-tors.

Extensive experimental studies of Pacificciguatoxins, using rat dissociated dorsal rootganglion neurons in whole cell patch clamptechniques, have shown that P-CTX-1 causestetrodotoxin sensitive (TTX-S) sodium chan-nels to open closer to their normal restingmembrane potential. By contrast, tetrodotoxinresistant (TTX-R) sodium channels recoverfrom inactivation more quickly, enabling earlier

Molecular structure of the Pacific (P-CTX-1) and the Caribbean (C-CTX-1) ciguatoxins. These toxins are heat stablepolyether molecules of 1023–1157 Da and post a health risk at concentrations above 0.1 ppb. Structure courtesy ofAssociate Professor Richard Lewis, University of Queensland, with acknowledgements.

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Neurology of ciguatera 5

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Caribbean  Ciguatoxin  (8)  

A  barracuda,  a  commonly  ciguatoxic  fish,  aGacks  prey  

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Jan   Feb   Mar   Apr   May   Jun   Jul   Aug   Sep   Oct   Nov   Dec  

Number  of  ciguatera  calls  by  month,  2001-­‐2011  

Characteris)cs  of  ciguatera-­‐related  calls  Total  calls  2001-­‐2011   1,272  Yearly  total  range   74  -­‐  152  Placed  from  health  care  facility  (%)   323  (25)  Placed  from  residence  (%)   900  (71)  Affected  individual  female  (%)   640  (52)  Median  age  in  years  of  affected  individual  (IQR)   40  (28-­‐51)  

Moderate  or  major  effect  (%)   459  (36)  Deaths  (%)   1  (0.08)  Calls  from  Florida  (%)   471  (37)  

Characteristics and age charts contain missing data. AK and HI are included in “West” region. Map provided by stunningpresentations.com.

58  5%  

70  6%  

170  15%  

242  21%  

271  24%  

192  17%  

95  9%  

35  3%  

Number  and  percent  of  ciguatera  calls  by  age  of  affected  individual,  2001-­‐2011  

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60-­‐69  years  

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Ciguatera fish poisoning

John A Crump, Colin L McLay, Stephen T Chambers

SummaryCiguatera fish poisoning is one of a varietyof non-bacterial forms of human seafoodpoisoning. Consuming large predatoryfish from tropical reef ecosystems may behazardous. We describe a case that is typi-cal of the disease, and illustrates thepersistence of neurological symptoms thatoccur in some patients.

Keywords: ciguatera fish poisoning; ichthyosarcotoxae-mia; poisoning; biotoxins

Humans who eat large predatory reef fish in thetropics risk the acute and sometimes severeneurological and gastrointestinal symptomsassociated with ciguatera fish poisoning. Acutemanagement is symptomatic and supportive.Intravenous mannitol may be of use. Sequelaeinclude chronic dysesthesia, which may berelieved by amitriptyline.

Ciguatoxin is a lipid-soluble polyethercompound1 that is probably synthesised byspecific bacteria after phagocytosis by the ben-thic dinoflagellate Gambierdiscus toxicus (figure1). The organism adheres to dead coralsurfaces and bottom-associated algae. Thetoxin is then concentrated in the food web asthe dinoflagellates are eaten by herbivorous fishspecies that graze on algae and detritus. Thesefish are in turn eaten by the larger marine car-nivores, which may then be eaten by humans.As the toxin concentration is elevated along thefood chain, larger fish are likely to contain

larger concentrations of toxin. We present acase illustrating the acute and chronic manifes-tations of ciguatera fish poisoning in humans.

Case report

A 42-year-old man presented 3 weeks afterreturning from Fiji complaining of insomnia,lethargy, dysesthesia of hands and feet, occa-sional cramps in the calves, light-headednesson standing, and a dry mouth. While in Fiji hehad eaten barbecued fish, and fed the remainsto a local cat. Within three hours of eating thefish, he developed abdominal pain, waterydiarrhoea, and developed a burning sensationof the skin overnight that became very severethe next day while swimming. He thendeveloped increasing shortness of breath andnoticed that the cat that ate the fish remainshad died. The patient summoned the help of alocal who viewed the fish remains, and notedthem to be of a species commonly associatedwith fish poisoning, and suggested he goimmediately to hospital. On arrival he was inmarked respiratory distress, weak, and experi-encing cramps. He required a period ofrespiratory supportive therapy. The followingday he was maintaining adequate oxygenationwithout support, and was discharged. Hereturned to his home country. A diagnosis ofichthyosarcotoxaemia, clinically consistentwith ciguatera fish poisoning, was made.Dysesthesia of the hands and feet persisted forweeks, but resolved after 5 days on amitriptyl-ine 100 mg daily.

Discussion

Ciguatera fish poisoning can occur in anyregion where humans eat carnivorous, andoccasionally herbivorous, fish derived fromtropical reef ecosystems. The toxin is unaf-fected by cooking, and no protective immunityis conferred by past exposure. In Fiji, Lutjanusspp, the Red Snapper or Red Bass (figure 2),and Plectropomus spp complex, the CoralTrout, are commonly implicated. The patientidentified the Red Snapper as similar in colourand morphology to the fish he had eaten. Spe-cies which have been associated with ciguaterapoisoning derive from the families Serranidae(groupers), Lutjanidae (snappers), Scaridae(parrot fish), Scombridae (mackerel), Murae-nidae (moray eels), Sphyraenidae (barracu-das), and Carangidae (jacks). Generally thedisease occurs in a circumglobal belt betweenapproximately 350 north and 350 south lati-tude, and is endemic in the tropical Indo-

Figure 1 Electron micrograph of the benthic dinoflagellate Gambierdiscus toxicus.Actual diameter 60 µm. Reproduced with permission of CSIRO, Australia fromHallegraeV11

678 Crump, McLay, Chambers

Department ofInfectious Diseases,Christchurch Hospital,Private Bag 4710,Christchurch, NewZealandJ A CrumpS T Chambers

Department ofZoology, University ofCanterbury, PrivateBag 4800,Christchurch, NewZealandC L McLay

Correspondence toDr John A Crump, Fellow,Department of ClinicalMicrobiology, DukeUniversity Medical Center,Box 3879, Durham, NC27710, USA

Accepted 13 May 1999