Clinic: Ciguatera poisoning

Examine for venom effects

Local (gastrointestinal) Effects

• Diarrhoea, nausea, vomiting, abdominal pain,

• Dehydration (!).

Neurological effects (Peripheral and central nervous system including neuropsychiatric symptoms)

Peripheral nervous system

Paraesthesias

• Sensation of numbness, tingling, itching (palms of the hands and the soles of the feet, as well as the lips and oral mucosa). 
• Body regions where contact with cold objects elicits an unpleasant, often acutely painful tingling or burning sensation. 
• Temperature dysaesthesia to cold air and when swallowing cold food or liquid. 

Central nervous system

Vertigo, loss of consciousness, cerebellar syndrome, balance disturbance, hallucinations, depression, memory loss, concentration problems, behavioural disturbance, visual disturbance, multi-tasking problems, giddiness.

Cardiac effects

• Bradycardia, tachycardia, arrhythmia, hypotension, hypertension.

Laboratory method to confirm ciguatera poisoning

There is no specific routine laboratory method to confirm ciguatera poisoning in humans (Perkins et al. 2024).

CTX-detection in fish, see Bian et al. (2024) and related references.

Species-specific envenoming pattern

Friedman et al. (2017) suggested a “Possible universal case definition of ciguatera fish poisoning (CFP) (Box 1)

¹Local (gastrointestinal) effects

(see clinical epidemiology and references of reviews below) 

Diarrhoea, vomiting, nausea, abdominal pain.

Time between ingestion and onset of gastrointestinal symptoms
On average 5.5 h (1–24 h) (Frenette et al. 1988).
Time between ingestion and onset of symptoms (all symptoms)
24 h (96%), <12 h (77%), <6 h (52%). Nausea is the first symptom of poisoning in 29%, diarrhoea in 11%, abdominal pain and vomiting in <1% each (Bagnis and Legrand 1987).

²Neurological effects 

(see clinical epidemiology and references of reviews below)

• Peripheral nervous system
  
  • Paraesthesias
    • Sensation of numbness, tingling, itching are frequently localised to the palms of the hands and the soles of the feet, as well as the lips and oral mucosa. These are the same body regions in which contact with cold objects elicits an unpleasant, often acutely painful tingling or burning sensation. 
    • This sensitivity to cold also appears in the form of temperature dysaesthesia to cold air and when swallowing cold food or liquid. 
    • The sensitivity and specificity of this sign for ciguatera poisoning; 0.78 and 1.00, respectively, and to date has never been seen in a neurological illness that was not associated with fish or shellfish poisoning (Frenette et al. 1988).
    • Heat contact does not normally elicit the opposite reaction (Bagnis et al. 1979). Thus, this phenomenon is not a reversal of temperature perception in the strict sense.

• Central nervous system
  
  • Vertigo, loss of consciousness, cerebellar syndrome, balance disturbance, hallucinations, depression, memory loss, concentration problems, behavioural disturbance, visual disturbance, multi-tasking problems, giddiness (see clinical epidemiology and references of reviews below).
• Time between ingestion and onset of neurological symptoms
  On average 20.5 h (3–72 h) (Frenette et al. 1988) 

• Time between ingestion and onset of symptoms (all symptoms)
  24 h (96%), <12 h (77%), <6 h (52%). The first symptoms of poisoning were perioral paraesthesias and paraesthesias of the extremities in 56%, myalgias and arthralgias in 2% and vertigo in <1% (Bagnis and Legrand 1987).

³Cardiac effects 

(see clinical epidemiology and references of reviews below)

• Bradycardia, tachycardia, arrhythmia which may necessitate emergency medical care, hypotension, hypertension (Morihara et al. 2024).

Pregnancy 

Ciguatera during pregnancy: movements such as those that occur during cerebral seizures have been observed in foetuses (Pearn et al. 1982). No apparent impact on the fetus at the time (Gatti et al. 2008). 

Morbidity

Ciguatera poisoning is unique amongst the illnesses caused by poisonous animals due to the persistence of sometimes bizarre residual symptoms.
Reliable morbidity data are rare. Only a few prospective studies have been carried out over a sufficiently long period of time (Lawrence et al. 1980, Frenette et al. 1988). Frenette et al. (1988) indicate the mean and median values of the duration of gastrointestinal and neurological symptoms. In total, 90% of the patients studied by Frenette et al. (1988) were free of symptoms after 18 weeks. 
However, residual neurological symptoms can persist for several months and appear to be aggravated by certain influences, e.g. consumption of alcohol. In contrast, gastrointestinal symptoms generally last only a few days.
Around one third of patients with ciguatera poisoning are bedridden, approx. 30% of those at home and approx. 3% in hospital. Gastrointestinal symptoms generally disappear after 24–30 h, frequently with subsequent dehydration if the patient was not sufficiently rehydrated. Cardiovascular symptoms generally take 2–5 days to resolve, while the neurological symptoms, in particular paraesthesias, can persist for weeks, months and in extreme cases years (Bagnis and Legrand 1987). 

Case fatality rate

3/3,009 (0.1%) (Bagnis et al. 1979, Chan 2016).
<0.1% of a total of 12,890 of observed cases of ciguatera (Bagnis and Legrand 1987), although thorough documentation of the fatalities in these studies was not possible due to local circumstances. 
Mortality is possibly confined by the fact that the lethal effect of the ciguatoxins on the fish themselves limits the dose of toxins that they can accumulate (Lewis 1992).
Mortality from certain types of poisoning that are connected with ciguatera, e.g. palytoxin poisoning, can be considerably higher. 

Publications providing guidance for patients and clinicians

Ciguatera Fish Poisoning: Information for Patients

Friedman et al. (2017), page 24

Ciguatera Fish Poisoning: Information for Clinicians

Friedman et al. (2017), page 23

Based upon available evidence and anecdotal experience, the authors provide recommendations for CFP clinicians. Some of these recommendations are specific to public health management procedures within the United States; various other countries and jurisdictions have developed their own respective procedures (Friedman et al. 2017).

Species-specific publications 
see ‘References’ at the end of the file.

Clinical management

See also Clinical Management: poisonous animals

for advice on diagnosis (clinical, laboratory) and treatment (supportive).

First Aid

Induction of vomiting within the first hours of ciguatera poisoning, if the patient cannot vomit spontaneously, and use laxatives. However, the effect of these measures on the course of poisoning has not been documented in controlled clinical studies.

Systemic supportive treatment

A general understanding of emergency medicine is required, or can be found in emergency medicine guidelines, e.g. ABCDE approach, WHO-ICRC Basic Emergency Care.

• Comprehensive ABCDE approach

• ICRC Basic Emergency Care: approach to the acutely ill and injured (SAMPLE  and ABCDE approach: first module)

Obey ciguatera - specific features

see 'Species-specific envenoming pattern' above.

Key issues

Supportive treatment can be lifesaving

Fluid and electrolyte and acid–base balance

Rehydration and correction of electrolyte and acid–base balance Friedman et al. (2017).

Hypotension, bradycardia

IV fluid resuscitation, IV pressor infusion if needed after volume repletion. Symptomatic bradycardia may require IV atropine Friedman et al. (2017). 

Mannitol

During the acute phase of ciguatera poisoning
0.5 to 1g/kg of body weight iv over a 30-45 minute period, administered within 48-72h after the consumption of the toxic fish (generally recommended) Friedman et al. (2008, 2017).
Caution
Patients must be rehydrated before application. Should be avoided for patients with cardiac failure.
Improvement has, however, been observed when applied after longer times post-intoxication.
See Mullins and Hoffman (2017) for critical discussion and Friedman et al. (2008, 2017).

See results in Section ‘Studies’ below.

Specific treatment (antidots)

No antidotes available.
Mannitol is not an "antidote" in the strict sense.
Mannitol most likely works through reduction of neuronal oedema (Pearn 2001).

Rehabilitation

For chronic ciguatera symptoms numerous drugs have been used; controlled trials to establish their effectiveness are, however, lacking
(see Friedman et al. 2017).
Avoiding recurrence
(see Friedman et al. 2017)

References

Reviews

• Anagnostou A, Abrams E. Is it food poisoning or allergy?: A diagnostic challenge revisited.Ann Allergy Asthma Immunol. 2023 Apr;130(4):403-404. PMID: 37005046. https://doi.org/10.1016/j.anai.2022.12.019
• Bian Y, Zhang Y, Feng XS, Gao HY.Marine toxins in seafood: Recent updates on sample pretreatment and determination techniques. Food Chem. 2024 Apr 16;438:137995. Epub 2023 Nov 20. PMID: 38029684. https://doi.org/10.1016/j.foodchem.2023.137995
• Patel P, Komorowski AS, Mack DP. An allergist's approach to food poisoning. Ann Allergy Asthma Immunol. 2023 Apr;130(4):444-451. Epub 2022 Nov 2. PMID: 36334721. https://doi.org/10.1016/j.anai.2022.10.021
• Friedman MA, Fleming LE, Fernandez M, Bienfang P, Schrank K, Dickey R, Bottein MY, Backer L, Ayyar R, Weisman R, Watkins S, Granade R, Reich A. Ciguatera fish poisoning: treatment, prevention and management. Mar Drugs. 2008;6(3):456-79. Epub 2008 Aug 21. PMID: 19005579; PMCID: PMC2579736. https://doi.org/10.3390/md20080022
• Friedman MA, Fernandez M, Backer LC, Dickey RW, Bernstein J, Schrank K, Kibler S, Stephan W, Gribble MO, Bienfang P, Bowen RE, Degrasse S, Flores Quintana HA, Loeffler CR, Weisman R, Blythe D, Berdalet E, Ayyar R, Clarkson-Townsend D, Swajian K, Benner R, Brewer T, Fleming LE. An Updated Review of Ciguatera Fish Poisoning: Clinical, Epidemiological, Environmental, and Public Health Management. Mar Drugs. 2017 Mar 14;15(3):72. PMID: 28335428; PMCID: PMC5367029. https://doi.org/10.3390/md15030072
• L'Herondelle K, Talagas M, Mignen O, Misery L, Le Garrec R. Neurological Disturbances of Ciguatera Poisoning: Clinical Features and Pathophysiological Basis. Cells. 2020 Oct 14;9(10):2291. PMID: 33066435; PMCID: PMC7602189. https://doi.org/10.3390/cells9102291
• Loeffler CR, Tartaglione L, Friedemann M, Spielmeyer A, Kappenstein O, Bodi D. Ciguatera Mini Review: 21st Century Environmental Challenges and the Interdisciplinary Research Efforts Rising to Meet Them. Int J Environ Res Public Health. 2021 Mar 15;18(6):3027. PMID: 33804281; PMCID: PMC7999458. https://doi.org/10.3390/ijerph18063027
• Patel P, Komorowski AS, Mack DP. An allergist's approach to food poisoning. Ann Allergy Asthma Immunol. 2023 Apr;130(4):444-451. Epub 2022 Nov 2. PMID: 36334721. https://doi.org/10.1016/j.anai.2022.10.021
• Pearn J. Neurology of ciguatera. J Neurol Neurosurg Psychiatry. 2001 Jan;70(1):4-8.  PMID: 11118239; PMCID: PMC1763481. https://doi.org/10.1136/jnnp.70.1.4

Original publications

• Bagnis, R. A., A. M. Legrand (1987) Clinical features on 12,890 cases of ciguatera (fish poisoning) in French Polynesia. In Gopalakrishnakone, P., C. K. Tan: Progress in Venom and Toxin Research. Proceedings of the first Asia-Pacific Congress on animal, plant and microbial toxins held in Singapore, june 24-27, 1987. Faculty of Medicine, National University of Singapore: 372-384
• Bagnis R, Kuberski T, Laugier S. Clinical observations on 3,009 cases of ciguatera (fish poisoning) in the South Pacific. Am J Trop Med Hyg. 1979 Nov;28(6):1067-73. PMID: 574366.https://doi.org/10.4269/ajtmh.1979.28.1067
• Chan TY. Characteristic Features and Contributory Factors in Fatal Ciguatera Fish Poisoning--Implications for Prevention and Public Education. Am J Trop Med Hyg. 2016 Apr;94(4):704-9. Epub 2016 Jan 19. PMID: 26787145; PMCID: PMC4824207. https://doi.org/10.4269/ajtmh.15-0686
• Frenette, Charles, J. Dick MacLean, Theresa W. Gyorkos, A Large Common-Source Outbreak of Ciguatera Fish Poisoning,
• Gatti, C.; Oelher, E.; Legrand, A.M. Severe seafood poisoning in French Polynesia: A retrospective analysis of 129 medical files. Toxicon 2008, 51, 746–753  https://doi.org/10.1016/j.toxicon.2007.11.025
• Lawrence DN, Enriquez MB, Lumish RM, Maceo A. Ciguatera fish poisoning in Miami. JAMA. 1980 Jul 18;244(3):254-8.PMID: 7189797.
• Lewis RJ. Ciguatoxins are potent ichthyotoxins. Toxicon. 1992 Feb;30(2):207-11PMID: 1557790. https://doi.org/10.1016/0041-0101(92)90474-j
• L'Herondelle K, Talagas M, Mignen O, Misery L, Le Garrec R. Neurological Disturbances of Ciguatera Poisoning: Clinical Features and Pathophysiological Basis. Cells. 2020 Oct 14;9(10):2291. PMID: 33066435; PMCID: PMC7602189. https://doi.org/10.3390/cells9102291
• Loeffler CR, Tartaglione L, Friedemann M, Spielmeyer A, Kappenstein O, Bodi D. Ciguatera Mini Review: 21st Century Environmental Challenges and the Interdisciplinary Research Efforts Rising to Meet Them. Int J Environ Res Public Health. 2021 Mar 15;18(6):3027. PMID: 33804281; PMCID: PMC7999458. https://doi.org/10.3390/ijerph18063027
• Morihara C, Yinadsawaphan T, Capirig CJ, Fujiuchi B, Hirao Y, Hu J, Malone RM, Neuendorf J, Neuendorf S, Ongsupankul S, Shiraishi K, Benavente K, Nishimura Y. Clinicoepidemiological Profile of Ciguatera Cardiotoxicity: A Systematic Review. Am J Trop Med Hyg. 2024 Jul 9;111(3):671-675. PMID: 38981507; PMCID: PMC11376153. https://doi.org/10.4269/ajtmh.24-0207
• Mullins ME, Hoffman RS. Is mannitol the treatment of choice for patients with ciguatera fish poisoning? Clin Toxicol (Phila). 2017 Nov;55(9):947-955. Epub 2017 May 23. PMID: 28535116. https://doi.org/10.1080/15563650.2017.1327664
• Pearn J, Harvey P, De Ambrosis W, Lewis R, McKay R. Ciguatera and pregnancy. Med J Aust. 1982 Jan 23;1(2):57-8. PMID: 7070322. https://doi.org/10.5694/j.1326-5377.1982.tb132142.x
• Perkins, J.C., Zenger, K.R., Liu, Y., Strugnell, J.M., 2024. Ciguatera poisoning: a review of the ecology and detection methods for Gambierdiscus and Fukuyoa species. Harmful Algae 139, 102735  https://doi.org/10.1016/j.hal.2024.102735
• Warrell DA. Venomous and poisonous animals. In: Farrar J, Garcia PJ, Hotez T, Junghanss T, Kang G, Laloo D (eds.).Manson’s tropical diseases. 24th ed. Elsevier; 2023.

Systemic supportive treatment

• WHO ABCDE Approach. https://cdn.who.int/media/docs/default-source/integrated-health-services-(ihs)/csy/bec-quick-cards/becp-edu29-pdf-en-finl.pdf?sfvrsn=2532d61b_2
• WHO-ICRC Basic Emergency Care: approach to the acutely ill and injured. https://www.who.int/publications-detail-redirect/basic-emergency-care-approach-to-the-acutely-ill-and-injured. https://cdn.who.int/media/docs/default-source/integrated-health-services-(ihs)/csy/bec-quick-cards/becp-edu29-pdf-en-finl.pdf?sfvrsn=2532d61b_2

Internet links providing specific information

Regional Centers

• INSTITUT LOUIS MALARDE (ILM)
  Papeete, Tahiti, French Polynesia
  http://www.ciguatera.pf
  https://www.youtube.com/watch?v=kvDxVFVHEf0&t=305s

• CDC  
  https://www.cdc.gov/yellow-book/hcp/environmental-hazards-risks/food-poisoning-from-marine-toxins.html

• U.S. National Office for Harmful Algal Blooms  
  https://hab.whoi.edu/about/

Species-specific evidence

Studies

1. Review of studies by Friedman et al (2017)

“Reported Frequency (%) of Clinical Symptoms of Ciguatera Fish Poisoning (CFP) at Time of Diagnosis” (Table 2)

comparing Caribbean, Atlantic, Pacific, Indian Ocean CFPs.

The following symptoms have been evaluated:

Local (gastrointestinal) effects

Diarrhoea, vomiting, nausea, abdominal pain.

Neurological effects

Peripheral nervous system
Paraesthesia (extremities), temperature dysaesthesia, circumoral dysaesthesia, dental pain/feeling like tooth are loose, myalgia, arthralgia, pruritus.
Central nervous system
Vertigo, loss of consciousness, cerebellar syndrome, balance disturbance, hallucinations, depression, memory loss, concentration problems, behavioural disturbance, visual disturbance, multi-tasking problems, giddiness.

Cardiac effects 

Bradycardia, hypotension, hypertension, tachycardia, arrhythmia.

2. Review of studies (T. Junghanss)

Signs and symptoms of ciguatera poisoning: comparison of various studies (comments on the reasons for the variability of the symptoms of ciguatera poisoning, see below)

 

 

 

 

 Studies included in the review

• Bagnis R, Kuberski T, Laugier S. Clinical observations on 3,009 cases of ciguatera (fish poisoning) in the South Pacific. Am J Trop Med Hyg. 1979 Nov;28(6):1067-73. PMID: 574366. https://doi.org/10.4269/ajtmh.1979.28.1067
  Retrospective study, N = 3,009, questionnaire, period of investigation 1964–1977. Inclusion criteria: patient history and clinical findings suggest ciguatera poisoning. No data regarding the toxin content of the consumed fish.

• Bagnis, R. A., A. M. Legrand (1987) Clinical features on 12,890 cases of ciguatera (fish poisoning) in French Polynesia. In Gopalakrishnakone, P., C. K. Tan: Progress in Venom and Toxin Research. Proceedings of the first Asia-Pacific Congress on animal, plant and microbial toxins held in Singapore, june 24-27, 1987. Faculty of Medicine, National University of Singapore: 372-384
  Retrospective study, N = 12,890, standardised 1-page questionnaire covering 25 signs and symptoms, period of investigation 1964–1986. Inclusion criterion: clinical suspicion of ciguatera poisoning. In 25 ciguatera outbreaks (99 patients) estimation of ciguatoxin concentration in fish remains from meals through the use of cat, mouse and mosquito bioassays. This study is an extension of the study of Bagnis et al. 1979, above.

• Engleberg NC, Morris JG Jr, Lewis J, McMillan JP, Pollard RA, Blake PA. Ciguatera fish poisoning: a major common-source outbreak in the U.S. Virgin Islands. Ann Intern Med. 1983 Mar;98(3):336-7. PMID: 6830078. https://doi.org/10.7326/0003-4819-98-3-336
  Retrospective study, N = 47. Ciguatera outbreaks were determined by identifying patients who visited the emergency department between 25.2. and 20.3.1981 with a combination of gastrointestinal symptoms and one neurological clinical sign after eating fish. The index patients and all persons who had eaten the same fish were contacted and questioned.
• Gillespie NC, Lewis RJ, Pearn JH, Bourke AT, Holmes MJ, Bourke JB, Shields WJ. Ciguatera in Australia. Occurrence, clinical features, pathophysiology and management. Med J Aust. 1986 Dec 1-15;145(11-12):584-90. PMID: 2432386.
  Retrospective study, N = 527. No data regarding the toxin content of the consumed fish.
• Kodama AM, Hokama Y. Variations in symptomatology of ciguatera poisoning. Toxicon. 1989;27(5):593-5. doi: 10.1016/0041-0101(89)90121-9. PMID: 2749758. https://doi.org/10.1016/0041-0101(89)90121-9
  Retrospective study, N = 172. Evaluation of ciguatera poisoning protocols. Inclusion criteria: presence of gastrointestinal symptoms plus one or more of the neurological, general or cardiovascular findings considered typical; samples of fish available. No data regarding the toxin content of the consumed fish.

• Morris JG Jr, Lewin P, Hargrett NT, Smith CW, Blake PA, Schneider R. Clinical features of ciguatera fish poisoning: a study of the disease in the US Virgin Islands. Arch Intern Med. 1982 Jun;142(6):1090-2. PMID: 7201299.
  Retrospective study, N = 33. Ciguatera outbreaks were identified by contacting patients who had been diagnosed with fish poisoning in the emergency department of the Knud Hansen Memorial Hospital on the island of St. Thomas. Outbreaks in which patients only had gastrointestinal symptoms and no neurological symptoms were excluded from the study.

• Charles Frenette, J. Dick MacLean, Theresa W. Gyorkos, A Large Common-Source Outbreak of Ciguatera Fish Poisoning, The Journal of Infectious Diseases, Volume 158, Issue 5, November 1988, Pages 1128–1131 https://doi.org/10.1093/infdis/158.5.1128
  Prospective study, N = 57. Longitudinal observation until patients were free of symptoms. Data collection with the help of interviews. Inclusion criteria: onset of illness within 48 h, with gastrointestinal and/or neurological symptoms. No data regarding the toxin content of the consumed fish.

• Katz AR, Terrell-Perica S, Sasaki DM. Ciguatera on Kauai: investigation of factors associated with severity of illness. Am J Trop Med Hyg. 1993 Oct;49(4):448-54. PMID: 8214273. https://doi.org/10.4269/ajtmh.1993.49.448
  Prospective "follow-up" study of 15 cases (of varying age and weight) from a single ciguatera outbreak. Ciguatoxin was detected by ELISA in the remains of the consumed fish.
• Lawrence DN, Enriquez MB, Lumish RM, Maceo A. Ciguatera fish poisoning in Miami. JAMA. 1980 Jul 18;244(3):254-8. PMID: 7189797.
  Prospective study, N = 129. Longitudinal observation. No data regarding the toxin content of the consumed fish.

Mannitol studies

• Palafox NA, Jain LG, Pinano AZ, Gulick TM, Williams RK, Schatz IJ. Successful treatment of ciguatera fish poisoning with intravenous mannitol. JAMA. 1988 May 13;259(18):2740-2.PMID: 3128666.
• Pearn JH, Lewis RJ, Ruff T, Tait M, Quinn J, Murtha W, King G, Mallett A, Gillespie NC. Ciguatera and mannitol: experience with a new treatment regimen. Med J Aust. 1989 Jul 17;151(2):77-80. PMID: 2500582. https://doi.org/10.5694/j.1326-5377.1989.tb101165.x
• Schnorf H, Taurarii M, Cundy T. Ciguatera fish poisoning: a double-blind randomized trial of mannitol therapy.Neurology. 2002 Mar 26;58(6):873-80. PMID: 11914401. https://doi.org/10.1212/wnl.58.6.873
• Palafox et al.(1988) report on 24 patients who all improved dramatically under mannitol treatment, 2 of whom were comatose and 1 who was in shock. The neurological and muscular symptoms improved within minutes, while the gastrointestinal symptoms responded more slowly. 21/24 received mannitol within 10 h, 3 within 82 h after the onset of symptoms (Palafox et al. 1988).

In the pilot study by Pearn et al. (1989), 5 patients who received 1–2 doses of mannitol in the acute phase of poisoning improved significantly. In 3 of these patients the symptoms disappeared completely. Treatment was commenced a maximum of 15 h after the onset of symptoms. If the symptoms had already been present longer than 24 h, mannitol treatment appeared not to be effective (Pearn et al. 1989).

A double-blind, randomized trial of mannitol therapy of 50 patients with ciguatera poisoning on Raratonga, Cook Island, found non difference between mannitol and normal saline (Schnorf et al. 2002).

Critical assessment

• Mullins ME, Hoffman RS. Is mannitol the treatment of choice for patients with ciguatera fish poisoning? Clin Toxicol (Phila). 2017 Nov;55(9):947-955. Epub 2017 May 23. PMID: 28535116. https://doi.org/10.1080/15563650.2017.1327664

For study design issues 

• Friedman MA, Fleming LE, Fernandez M, Bienfang P, Schrank K, Dickey R, Bottein MY, Backer L, Ayyar R, Weisman R, Watkins S, Granade R, Reich A. Ciguatera fish poisoning: treatment, prevention and management. Mar Drugs. 2008;6(3):456-79. Epub 2008 Aug 21. PMID: 19005579; PMCID: PMC2579736. https://doi.org/10.3390/md20080022

Historical
South Pacific 

• Doherty MJ. Captain Cook on poison fish. Neurology. 2005 Dec 13;65(11):1788-91. PMID: 16344524. https://doi.org/10.1212/01.wnl.0000187128.80551.1b

Comments on ciguatera 

Reasons for the great variability in the signs and symptoms of documented ciguatera cases:

1. To date there is still no clinical diagnostic test that can confirm a diagnosis of ciguatera fish poisoning based solely on anamnestic-clinical criteria. Thus it is not possible to include a patient in a study based on objective criteria. Detection of ciguatoxin and related polyethers in fish tissue only supports the clinical diagnosis indirectly, and, besides, this is not available in many studies.

2. Ciguatera poisoning is not caused by a single substance, but rather by different components that contribute in varying amounts to the composition of the poison (ciguatoxin, maitotoxin, ciguaterin, scaritoxin, palytoxin). It is thus conceivable that the types of poisoning that are currently included under the term ciguatera syndrome or ciguatera fish poisoning could be further subdivided if there were better correlation between individual toxins and their corresponding signs and symptoms of poisoning.
There are already 2 cases in which such differentiation appears to be justified. Poisoning caused by Scarus gibbus of the Gambier Islands, which in the initial stage displays the clinical characteristics of ciguatera syndrome, has a second phase that occurs after 5–10 days and which distinguishes it clearly from the normal picture of ciguatera poisoning. Marked cerebellar symptoms occur during this phase, last for about 1 week and require a further 4 weeks to resolve completely (Chungue et al. 1977, Bagnis et al. 1974). The toxin responsible for this second phase of the illness is also a polyether and is most probably scaritoxin.
A further toxin that stands out clearly from the group of poison components that cause ciguatera poisoning is palytoxin. This toxin is also related to ciguatoxin and is likewise a polyether. It has been held responsible for causing particularly serious cases of poisoning. These patients suffer from severe dyspnoea, which can progress to respiratory failure, and severe muscle spasms that lead to damage of the musculature (CK, LDH, GOT increased in serum, myoglobinuria) (Kodama et al. 1989, Noguchi et al. 1987). One of 2 patients died after consuming Parrotfish (Noguchi et al. 1987). In contrast to ciguatoxin and related polyethers, palytoxin has also been found in crabs (Demania reynaudii) and has caused fatalities in the Philippines (Alcala et al. 1988).

• Alcala AC, Alcala LC, Garth JS, Yasumura D, Yasumoto T. Human fatality due to ingestion of the crab Demania reynaudii that contained apalytoxin-like toxin. Toxicon. 1988;26(1):105-7. PMID: 2894726. https://doi.org/10.1016/0041-0101(88)90142-0
• Noguchi,T., D. F. Hwang, O. Arakawa, D. Daigo, S. Sato, H. Ozaki, N. Kawai, M. Ito, K. Hashimoto (1987)Palytoxinas the causative agent in the parrotfish poisoning. In Gopalakrishnakone, P., C. K. Tan: Progress in Venom and Toxin Research. Proceedings of the first Asia-Pacific Congress on animal, plant and microbial toxins held in Singapore, june 24-27, 1987. Faculty of Medicine Natonal University of Singapore: 325-335
• Kodama AM, Hokama Y, Yasumoto T, Fukui M, Manea SJ, Sutherland N. Clinical and laboratory findings implicatingpalytoxinas cause of ciguaterapoisoning due to Decapterus macrosoma (mackerel). Toxicon. 1989;27(9):1051-3. PMID: 2572075. https://doi.org/10.1016/0041-0101(89)90156-6

One of the most important reasons for the characterisation of subgroups of ciguatera poisoning or ciguatera syndrome on the basis of the main or sole toxin involved is the area of differential therapeutics. Although the toxins associated with ciguatera poisoning that have been isolated to date are all polyethers and all affect ion channels in membranes, they do differ considerably with regard to high specificity for particular ion channels.

3. Different species of fish appear to accumulate the poison components that are considered responsible for the ciguatera syndrome in variable compositions, so that the clinical picture may contain a species-specific component (Kodama and Hokama 1989). In contrast to herbivorous fish, carnivorous fish appear to cause ciguatera poisoning that has a severe course and causes significantly more cardiovascular signs and symptoms (Glaziou and Martin 1993, Kodama and Hokama 1989). Moreover, the toxins responsible for ciguatera poisoning are not evenly distributed in individual fish. The liver and gonads contain considerably higher toxin concentrations than other internal organs or muscle tissue.

4. Interindividual differences in the amount of venom ingested, with a corresponding dose-effect relationship.

5. Ethnic differences with regard to the clinical picture, which may be due to different diets or susceptibility to particular poison effects (Bagnis et al. 1979).

6. Differences in the severity of recurrent ciguatera poisoning. Recurrent ciguatera poisoning is said to be more severe (Glaziou and Martin 1993; Katz et al. 1993).

7. Differences in the severity of poisoning with greater age and body weight of the patients. Severity and duration of symptoms reported to increase significantly with age and body weight (Glaziou and Martin 1993, Katz et al. 1993).

8. Problems distinguishing the ciguatera syndrome from other differential diagnoses (other forms of fish and shellfish poisoning, infectious illnesses that can be transmitted via fish, shellfish and crabs, including type E botulism, organophosphate-containing insecticides, eosinophilic meningitis).

9. Differences in study design. Most studies are retrospective and based on evaluation of questionnaires. The few prospective studies available had only short observation periods, with 3 exceptions (Frenette et al. 1988, Lawrence et al. 1980, Katz et al. 1993).

Thus, the terms ciguatera poisoning or ciguatera syndrome represent umbrella terms. It is not yet clear to what extent the toxicological, biological and geographical variables will make a subdivision possible.