Ciguatera fish poisoning

INTRODUCTION — This topic describes the clinical manifestations, diagnosis, and management of ciguatera poisoning. Poisoning caused by ingestion of other seafood (eg, scombroid fish, shellfish, or pufferfish) is discussed in detail separately.

●(See "Overview of shellfish, pufferfish, and other marine toxin poisoning".)

●(See "Scombroid (histamine) poisoning".)

EPIDEMIOLOGY — Ciguatera fish poisoning is a foodborne illness that is caused by ingestion of reef fish (eg, barracuda, amberjack, moray eel, and certain types of grouper, snapper, or parrotfish) that are contaminated with toxins that arise from Gambierdiscus toxicus, a single-celled organism that grows on coral reefs. Ciguatera fish poisoning accounts for approximately 20 percent of the fish-related foodborne disease outbreaks in the United States [1], and is a common fish food poisoning in tropical coastal regions [2]. Approximately 10,000 to 50,000 people develop this poisoning annually worldwide [3,4], although this is not precise and may be an underestimate because of missed diagnoses and underreporting [5,6]. In the United States, an estimated 16,000 cases occur annually, resulting in more than 300 hospitalizations but fewer than five deaths. This may be an underestimate since cases are not rigorously tracked by the United States National Office for Harmful Algal Blooms [6,7].

Most cases originate in the tropics and subtropics, between 35 degrees north latitude and 35 degrees south latitude. However, cases of ciguatera toxicity may also occur in more temperate regions because of increasing tourism, fish exportation, and unusual fish migration. Multiple cases of ciguatera fish poisoning have also been reported after ingestion of imported fish purchased at markets in New York City [8] and in northern Germany [9], as well as fish imported to Paris from Guadeloupe [10]. In addition, two cases of ciguatera fish poisoning have been reported following consumption of fish (barracuda) caught off the coast of South Carolina, well north of the typical location for such poisoning [11]. More recently, cases have been reported in the Canary Islands [12].

More than 400 different fish species have been associated with ciguatera fish toxicity. Reef-dwelling tropical fish such as barracuda, moray eel, amberjack, and certain types of grouper, mackerel, parrotfish, and red snapper are the most common sources. Rare cases exist of ciguatera fish poisoning occurring after the ingestion of temperate fish, including farm-raised salmon [13]. In general, however, toxicity from nontropical fish is extremely rare.

The overall fatality rate from ciguatera fish poisoning is about 0.1 percent, with death usually due to cardiovascular collapse or respiratory failure [3,14-17]. Mortality is lowest in the Caribbean and areas of the world where the healthcare system is able to rapidly treat the rare episodes of coma, bradycardia, or hypotension.

PATHOGENESIS — Ciguatera fish poisoning is caused by several distinct toxins, of which ciguatoxin is the best known. These toxins are formed by dinoflagellates of the genus Gambierdiscus, which are single-celled algae-like organisms that grow on and around coral reefs. Gambierdiscus toxicus, which produces ciguatoxin, tends to proliferate on denuded coral surfaces [18].

The dinoflagellates are consumed by large, predatory fish (eg, barracuda, amberjack, moray eel, snapper, and certain types of grouper) that concentrate the toxin in their organs and flesh but are not affected by it. Ciguatera toxin-containing fish do not taste, smell, or appear unusual. Cooking, marinating, freezing, and stewing fish do not destroy the toxins.

Ciguatoxin is a lipid-soluble, heat-stable, acid-resistant neurotoxin. It opens voltage-dependent sodium channels in cell membranes, triggering membrane depolarization. Ciguatoxin exposure in an animal model has caused long-term disruption of cerebral function in association with upregulation of sodium channel expression in astrocytes [19].

Maitotoxin and scaritoxin, other ciguatera associated toxins, increase calcium ion influx through excitable membranes [14] and permeability of sodium channels resulting in norepinephrine and acetylcholine release, respectively [20].

CLINICAL MANIFESTATIONS — The patient affected with ciguatera fish poisoning frequently develops the following constellation of clinical findings:

●Gastrointestinal – Gastroenteritis, including vomiting, diarrhea, and abdominal cramping, typically begins three to six hours after eating contaminated fish, but can be delayed up to 30 hours [15,16,21,22].

●Neurologic – Neurologic abnormalities usually appear 3 to 72 hours after the meal. Clinical findings include peri-oral paresthesias, pruritus without urticaria or erythema, a metallic taste in the mouth, painful dentition, a feeling that the teeth are loose, painful urination, blurred vision, ataxia, and temperature-related dysesthesias (cold stimuli perceived as hot or producing an abnormal, unpleasant sensation) [21-24]. Temperature-related dysesthesias are regarded by some as a specific finding of ciguatera toxicity although it can also be seen in patients with neurotoxic shellfish poisoning. In the South Pacific, paresis may occur in up to 10 percent of patients [25]. Reversible cerebellar dysfunction also can occur [26].

●Cardiovascular – Cardiovascular signs, including bradycardia, heart block, and hypotension, can occur within hours of consumption [21,22].

The types and frequencies of presenting signs and symptoms vary according to locale and likely reflect geographic differences in the various toxins and local food habits (eg, ingestion of visceral or reproductive organs where the toxin is concentrated) that may increase toxin consumption (table 1) [5]. In Pacific and Indian Ocean regions, patients often display early neurologic, gastrointestinal, and cardiovascular findings with neurologic findings predominating [27]. Mental status changes, such as hallucinations or giddiness, and ataxia may also be noted [28]. Although infrequent, life-threatening signs including coma and respiratory distress have also been described [25,29].

By contrast, in the Caribbean, ciguatera fish poisoning usually presents with gastroenteritis followed by a neurologic illness without mental status changes and is usually not life-threatening [3,5,21,22,30,31].

A number of other clinical findings have been associated with ciguatera toxicity as follows:

●Chronic neuropsychiatric illness with fatigue and malaise [32]

●Fibromyalgia [33]

●Premature labor and spontaneous abortion [14]

●Painful sexual intercourse in men and women [34]

●Painful ejaculation in an affected male, followed by dyspareunia in the previously unaffected female [14]

The course of ciguatera fish poisoning is variable. Gastrointestinal and, if present, cardiovascular signs frequently resolve within 24 to 48 hours and rarely persist beyond four days [5,21]. Neurologic abnormalities typically are more persistent, lasting from a few days to several weeks. About 20 percent of patients have neurologic signs and symptoms that persist for months; and up to 2 percent report findings, such as fatigue, weakness, headache, or depression, that last for years [22,30,35]. However, patients who continue with symptoms beyond one year warrant investigation for other potential etiologies [32].

Several case reports and series describe exacerbation or relapse of ciguatera toxicity in patients who consume alcohol, caffeine, nuts, pork, chicken, or fish, including fish that did not cause poisoning symptoms in other individuals sharing the meal [25,36-38]. In one case, a patient developed neurologic symptoms (perioral paresthesia, myalgia, and malaise) and arthralgia similar to his original ciguatera poisoning symptoms two years later after drinking one beer [36]. Excessive physical exertion or dehydration within six months of original symptoms has also been reported to cause worsening or relapsing symptoms [39].

Pregnant and nursing mothers — Perinatal transmission of ciguatera toxicity may occur. As an example, a baby born by caesarean section to a mother with ciguatera poisoning exhibited left sided facial palsy, possible hand myotonia, and respiratory distress [18]. These symptoms resolved within six weeks.

Toxins can also be transmitted via breast milk [14]. Thus, nursing mothers with ciguatera fish poisoning should be advised to stop breast feeding while symptomatic. To maintain lactation, they can pump and discard breast milk. Though evidence is lacking, resumption of breast feeding is probably safe once the mother's symptoms have completely resolved. However, careful monitoring of the infant is warranted in such situations.

DIAGNOSIS — No clinical test is available to diagnose ciguatera fish poisoning. The diagnosis is established clinically using the following criteria:

●A history of ingestion of a large reef fish commonly associated with ciguatera toxicity (eg, moray eel, amberjack, barracuda, red snapper, or grouper)

●Gastrointestinal and neurologic features consistent with ciguatera fish poisoning, especially temperature-related dysesthesia (see 'Clinical manifestations' above)

●Exclusion of other potential causes (see 'Differential diagnosis' below)

●Confirmation of ciguatoxin in the consumed fish, if possible. The United States National Oceanographic and Atmospheric Administration helped to develop a fluorescent receptor binding assay for detecting ciguatoxins in fish, which is now available commercially [40,41]. If the fish is not available for analysis, ciguatera poisoning in other individuals who consumed the same fish is also supportive.

Fish can be tested using a mouse bioassay and an IgG immunoassay, but these tests are costly and time consuming and are not widely used [20]. Alternatively, cytotoxicity assays or liquid chromatography-mass spectrophotometry can be employed although these techniques are also not widely or rapidly available, other than through the US Food and Drug Administration (FDA) or similar government agency in other countries [21,42].

Reporting of ciguatera poisoning is variable depending upon region. In the United States, ciguatera is a reportable condition in many states, including California, Florida, Hawaii, North Carolina, New York, Rhode Island, and South Carolina, as well as the US Virgin Islands [43]. Regardless of region, suspected cases should be reported to public health authorities when diagnosed so that outbreaks can be identified and investigated. Ciguatera fish poisoning is believed to be widely under-reported [43].

DIFFERENTIAL DIAGNOSIS — Ciguatera fish poisoning has a distinct clinical presentation and is often readily identified once a careful food history is obtained. However, several other illnesses may have similar features as follows [21]:

●Neurotoxic shellfish poisoning – Ingestion of shellfish contaminated by dinoflagellate species Karenia brevis (formerly Gymnodinium breve), which is associated with red tides in temperate waters, can produce gastrointestinal distress and neurologic symptoms such as paresthesias of the face, mouth, and extremities, dizziness, ataxia, and muscle aches. Patients may also experience temperature-related dysesthesia and seizures. All symptoms, including neurologic toxicity, typically resolve within three days. The development of symptoms soon after ingestion of shellfish helps to differentiate neurotoxic shellfish poisoning from ciguatera poisoning. However, the diagnosis may be clouded if the patient has also ingested reef fish. (See "Overview of shellfish, pufferfish, and other marine toxin poisoning", section on 'Neurotoxic shellfish poisoning'.)

●Paralytic shellfish poisoning – Paralytic shellfish poisoning is caused by ingestion of bivalve mollusks, such as mussels, clams, scallops, and oysters, as well as crabs and snails that are contaminated with dinoflagellates of the genus Alexandrium. These algae are also associated with red tides in temperate waters. Physical findings occur within hours of ingestion and include neurologic symptoms ranging from perioral tingling, ataxia, difficulty swallowing, dizziness, paresthesias, weakness, paralysis, brainstem dysfunction, and respiratory failure. The rapid onset of weakness and paralysis distinguishes paralytic shellfish poisoning from ciguatera fish poisoning. (See "Overview of shellfish, pufferfish, and other marine toxin poisoning", section on 'Paralytic shellfish poisoning'.)

●Pufferfish poisoning – Pufferfish poisoning results in paresthesias of the face and extremities, nausea, dizziness, weakness, loss of reflexes, paralysis, and hypotension caused by tetrodotoxin, which blocks sodium channels. This poisoning is primarily encountered in Japan where "Fugu" or blowfish is considered a delicacy. As with paralytic shellfish poisoning, the development of weakness and paralysis differentiates pufferfish poisoning from ciguatera fish poisoning. (See "Overview of shellfish, pufferfish, and other marine toxin poisoning", section on 'Pufferfish poisoning (tetrodotoxin)'.)

●Scombroid fish poisoning – Signs and symptoms of scombroid toxicity usually begin within an hour of eating contaminated fish. The symptoms resemble an IgE-mediated allergic reaction. The patient may suddenly experience flushing, a sensation of warmth, an erythematous rash, palpitations, and significant tachycardia. The rash often is especially prominent on the upper torso and face. Although the timing of symptoms after eating fish is similar to ciguatera toxicity, scombroid otherwise shares very few of its clinical features. (See "Scombroid (histamine) poisoning", section on 'Clinical manifestations'.)

●Foodborne botulism – Ingestion of preformed botulinum toxin, typically found in home canned foods, causes vomiting, diarrhea, abdominal pain, cranial nerve dysfunction, and descending paralysis beginning hours to days after consumption. The disease presentation can vary from mild complaints to death within the first 24 hours of symptoms. Demonstration of the toxin in the blood is diagnostic. The lack of sensory changes helps to distinguish foodborne botulism from ciguatera fish poisoning. (See "Botulism", section on 'Clinical manifestations'.)

●Guillain-Barré syndrome – The acute inflammatory demyelinating polyneuropathy variant of Guillain-Barré syndrome produces extremity paresthesias followed by ascending weakness with associated hypo- or areflexia. In some patients, the paresthesias may precede signs of weakness and suggest the diagnosis of ciguatera fish poisoning. The diagnosis of Guillain-Barré syndrome is based upon the clinical features of the characteristic development of weakness. Lack of pleocytosis on examination of the cerebrospinal fluid and nerve conduction studies consistent with a demyelinating polyneuropathy provide confirmation of the clinical impression. (See "Guillain-Barré syndrome in adults: Pathogenesis, clinical features, and diagnosis", section on 'Clinical features' and "Guillain-Barré syndrome in adults: Pathogenesis, clinical features, and diagnosis".)

●Multiple sclerosis – Sensory symptoms of multiple sclerosis (MS) can include paroxysmal onset of extremity paresthesias, pruritus dysesthesia, ataxia, fatigue, and alteration of facial sensation that may be mistaken for early signs of ciguatera toxicity. However, unlike ciguatera fish poisoning, MS causes vertigo, bowel and bladder dysfunction, transverse myelopathy, and weakness. However, clinical findings vary significantly in patients with MS and considerable overlap with neurologic symptoms of ciguatera fish poisoning may occur. The diagnosis of MS is based upon clinical findings and demonstration of demyelinating central nervous system lesions distributed over space and time. (See "Manifestations of multiple sclerosis in adults" and "Evaluation and diagnosis of multiple sclerosis in adults".)

●Eosinophilic meningitis – Similar to findings of ciguatera toxicity, patients with eosinophilic meningitis commonly have nausea, vomiting, and paresthesias. Paresthesias with residual areas of hyperesthesia can persist for several weeks, even after other symptoms have resolved. However, unlike ciguatera fish poisoning, these patients typically have suggestive features of meningitis including neck stiffness and excruciating headache, which is usually frontal, occipital, or bitemporal. The diagnosis of eosinophilic meningitis is made based upon clinical presentation and cerebral spinal fluid eosinophilia, defined as the presence of more than 10 eosinophils/mm³ in the cerebrospinal fluid (CSF) and/or eosinophils accounting for more than 10 percent of CSF leukocytes. (See "Eosinophilic meningitis".)

●Organophosphate poisoning – Organophosphate poisoning has some features in common with ciguatera toxicity including vomiting, diarrhea, and abdominal pain. It can also uncommonly cause delayed neurotoxicity consisting of "stocking-glove" paresthesias and ascending flaccid weakness after acute toxicity has resolved. However, unlike ciguatera fish poisoning, organophosphate toxicity also has additional cholinergic findings of salivation, bronchorrhea, and bronchospasm with accompanying nicotinic features of muscle fasciculations, weakness, and paralysis. Lack of anticholinergic response to atropine challenge and decreased red blood cell acetylcholinesterase activity support the clinical diagnosis of organophosphate poisoning. (See "Organophosphate and carbamate poisoning", section on 'Clinical features' and "Organophosphate and carbamate poisoning", section on 'Diagnosis'.)

●Acute arsenic poisoning – Gastrointestinal symptoms, including diarrhea, vomiting, and abdominal pain, are common early findings in acute arsenic poisoning and may be accompanied by mental status changes and prolongation of the QT interval on electrocardiogram. A sensorimotor peripheral neuropathy may occur one to three weeks following acute exposure. Unlike ciguatera, however, arsenic poisoning may be associated with excessive salivation, rash, acute kidney injury, and respiratory failure. Acute exposure is usually established through urinary arsenic testing. (See "Arsenic exposure and chronic poisoning", section on 'Arsenic concentrations'.)

In addition to the above diagnoses, chronic fatigue syndrome (CFS), also known as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS); or depression may develop as comorbidities after ciguatera fish poisoning. (See "Clinical features and diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome" and "Unipolar depression in adults: Assessment and diagnosis".)

TREATMENT

Gastrointestional decontamination — Although some experts have suggested activated charcoal (AC) administration to bind ciguatoxins [21], vomiting frequently prevents its use and most patients seek medical attention more than one hour after fish ingestion. Thus, activated charcoal is not warranted. Similarly, because vomiting is a prominent feature of ciguatera fish poisoning, syrup of ipecac also has no role in its treatment.

Initial supportive care — Initial treatment of ciguatera fish poisoning is primarily supportive and consists of the following [21,44]:

●Airway and breathing – In the rare patients with respiratory distress, coma, or weakness, the airway should be assessed and if not maintainable, secured by endotracheal intubation [21,44]. (See "Rapid sequence intubation in adults for emergency medicine and critical care" and "Rapid sequence intubation (RSI) in children for emergency medicine: Approach".)

●Circulation – Hemodynamic instability caused by dehydration is frequently seen in patients with ciguatera fish poisoning. Bradycardia and toxin-induced hypotension also occur infrequently in some patients. Management for these conditions is as follows [21]:

•Dehydration – Dehydration from vomiting and diarrhea warrants rapid fluid repletion with isotonic saline (eg, 20 mL/kg normal saline, intravenously, maximum initial volume, 1 L). Further fluid therapy should be guided by the degree of dehydration and serum electrolyte values. (See "Treatment of hypovolemia (dehydration) in children in resource-abundant settings" and "General principles of disorders of water balance (hyponatremia and hypernatremia) and sodium balance (hypovolemia and edema)".)

•Bradycardia – Intravenous atropine, including atropine infusion has been used to treat symptomatic bradycardia. Dosing in these cases varies, but anecdotal evidence from case reports suggests that high doses may be required (eg, 0.5 mg atropine intravenously every five minutes to maintain a goal heart rate ≥60 beats per minute in adults with no maximum total dosage) [22,45,46].

Management according to Advanced Cardiac Life Support (ACLS) and Pediatric Advanced Life Support (PALS) guidelines is appropriate for patients who do not respond to atropine (algorithm 1 and algorithm 2). (See "Temporary cardiac pacing".)

•Hypotension – In the rare patient for whom hypotension does not respond to initial fluid resuscitation, vasopressors may be administered.

●Vomiting and diarrhea – Vomiting can be treated with antiemetics (eg, ondansetron). Because diarrhea may be beneficial in removing ingested toxin and is typically self-limited, antimotility agents should be avoided [21].

●Pruritus – Pruritus may be intense after ciguatera fish poisoning and can be treated with antihistamines (eg, diphenhydramine, hydroxyzine, or cetirizine) [21].

Neurologic symptoms — Neurologic symptoms of ciguatera fish poisoning can be prolonged and debilitating. Although several treatments have been proposed, evidence is limited regarding benefit of any specific medical regimen.

●Paresthesias (polyneuropathy) – Ciguatoxins have complex actions on ion channels in cell membranes which may explain some of the neuropathic pain in ciguatera fish poisoning. Medications used to treat ciguatera fish poisoning are as follows:

•Mannitol – We suggest that fluid-repleted patients with significant neurologic symptoms caused by ciguatera fish poisoning receive a single dose of mannitol (1 g/kg infused over one hour) [47]. Because mannitol can cause additional volume loss, it should not be given to patients with significant dehydration or signs of shock.

The use of mannitol for the treatment of ciguatera fish poisoning is controversial. Mannitol is known to reverse prolonged opening of sodium channels and to reduce Schwann cell periaxonal edema in animal models [48]. Multiple uncontrolled trials have found that intravenous mannitol, given at a dose of 0.5 to 1 g/kg, reduces neurologic symptoms when given within the first 48 hours [21,49]. In addition, case reports describe significant benefit from mannitol administration several weeks after onset of symptoms [50,51].

However, the only randomized, placebo-controlled trial, conducted in 50 patients with ciguatera fish poisoning, found that treatment with a single intravenous dose of mannitol was no better in alleviating the acute signs and symptoms of ciguatera poisoning than intravenous normal saline, and was associated with increased local discomfort at the infusion site [52]. Significant improvement (50 percent reduction on a subjective symptoms scale) was seen in both treatment groups with equal frequency at 1, 3, and 24 hours after the infusion. However, the small size of this study may have prevented detection of a clinically important difference.

Taken together, although the evidence base is weak and contradictory, a single dose of mannitol is unlikely to be harmful if given to patients who are not dehydrated or in shock and may be beneficial.

•Gabapentin – Gabapentin was reported to improve polyneuropathic symptoms in two patients approximately one month after onset of symptoms [53]. However, it is a relatively expensive therapy which limits its usefulness in the tropical regions where ciguatera fish poisoning is most prevalent.

•Amitriptyline – Small case series suggest that amitriptyline can provide relief for chronic paresthesias and pruritus but may not be effective for temperature-related dysesthesias [39,54,55].

•Pregabalin – Two Australian travelers were treated with pregabalin titrated from 75 mg daily to a maximal dose of 150 mg twice daily, with resolution of their painful peripheral neuropathy and cold dysesthesia after 17 weeks [56]. As with gabapentin, pregabalin is expensive. It has numerous side effects, most notably sedation, and a risk for dependency and abuse. If used, it should be tapered slowly [57].

●Headaches – Acetaminophen has been used for the treatment of headaches associated with ciguatera toxicity [21]. Limited evidence from case reports suggest that nifedipine also may provide benefit [55,58]. However, nifedipine should be avoided during the acute phase of illness as it may cause or exacerbate hypotension.

●Chronic fatigue syndrome (CFS) and symptoms of depression – Although one case report suggests that fluoxetine may benefit ciguatera patients suffering from CFS, insomnia, and depression [58,59], these conditions may reflect comorbidity rather than chronic ciguatera toxicity and warrant careful evaluation by a clinician with expertise in their diagnosis and treatment [21]. (See "Clinical features and diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome" and "Unipolar depression in adults: Assessment and diagnosis".)

Diet and activity modification — Patients should be counseled that consumption of fish, alcohol, caffeine, and nuts within six months of poisoning may trigger a recurrence of symptoms and elimination of these foods from their diet is prudent [3,60,61]. Patients should understand that future attacks of ciguatera fish poisoning might be worse than the initial illness. Ciguatera is not an infectious disease, and individuals do not develop immunity to the toxin [25].

Given the potential for painful sexual intercourse, including dyspareunia in previously unaffected female sexual partners, the male patient should curtail sexual activity until symptoms resolve [34]. Although not specifically studied, the use of condoms may present an alternative to abstinence [62].

Overexertion with dehydration may also cause a relapse of ciguatera symptoms and should be avoided until toxicity has resolved. The patient should then gradually increase activity over time.

PREVENTION — The best way to prevent ciguatera fish poisoning is to avoid eating all high-risk fish, such as barracuda, moray eel, and certain types of grouper, red snapper, and amberjack. Unfortunately, no accurate analytical field test for caught fish is available [63]. Development of such tests is difficult because of the lack of effect of ciguatoxin on live fish and the minute amounts of ciguatoxin necessary to render a fish poisonous.

Traditional methods of identifying toxic fish, such as excessive hemorrhage when cutting into a fish (bleeding test) and lack of rigor mortis several hours after the death of a fish (rigor mortis test), can identify some fish that contain toxic levels of ciguatoxin in selected regions (eg, French Polynesia), but have significant interobserver variability and poor discrimination [63].

Fish mislabeling is common, and conscientious consumers may be unaware of the type of fish they are consuming. DNA testing of more than 1200 commercially purchased fish samples found that a third were mislabeled. Fish sold as snapper was the most commonly mislabeled [64].

When in the tropics, it may be less risky to eat smaller fish and avoid eating fish organs, such as the liver and the head, where the toxin concentrates [3]. Recreational fishermen should also travel with experienced local guides who often know which reefs to avoid [65].

Community outreach and education can also help to warn travelers and increase recognition and investigation of ciguatera fish poisoning outbreaks [21,66]. Some mass ciguatera fish poisonings with mortalities occur when ciguatoxic fish species are shared in gatherings or parties. Monitoring reef fish toxicity is particularly important when reef fish are collected following large storms [67].

Upon diagnosis of ciguatera fish poisoning, clinicians should contact their local health department and, if applicable, their regional poison control center so that investigation of the fish source can prevent consumption of other toxic fish from the same reef.

ADDITIONAL RESOURCES

Regional poison control centers — Regional poison control centers in the United States are available at all times for consultation on patients with known or suspected poisoning, and who may be critically ill, require admission, or have clinical pictures that are unclear (1-800-222-1222). In addition, some hospitals have medical toxicologists available for bedside consultation. Whenever available, these are invaluable resources to help in the diagnosis and management of ingestions or overdoses. Contact information for poison centers around the world is provided separately. (See "Society guideline links: Regional poison control centers".)

Society guideline links — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Envenomation by snakes, arthropods (spiders and scorpions), and marine animals".)

SUMMARY AND RECOMMENDATIONS

●Pathogenesis – Ciguatera fish poisoning is caused by consumption of fish contaminated with several distinct toxins (eg, ciguatoxin, saitotoxin, scaritoxin) that are formed by dinoflagellates of the genus Gambierdiscus, single-celled algae-like organisms that grow on and around coral reefs. These toxins are concentrated in the organs and flesh of large, predatory reef fish (eg, moray eel, amberjack, barracuda, red snapper, or grouper). Ciguatera toxin-containing fish do not taste, smell, or appear unusual. Cooking, marinating, freezing, and stewing fish do not destroy the toxins. (See 'Pathogenesis' above.)

●Clinical manifestations – Although signs and symptoms vary according to locale (table 1), the patient affected with ciguatera fish poisoning frequently develops the following constellation of clinical findings (see 'Clinical manifestations' above):

•Gastrointestinal – Gastroenteritis, including vomiting, diarrhea, and abdominal cramping.

•Neurologic – Neurologic abnormalities include peri-oral paresthesias, a metallic taste in the mouth, painful dentition, a feeling that the teeth are loose, painful urination, blurred vision, and temperature-related dysesthesias (cold stimuli perceived as hot or producing an abnormal, unpleasant sensation). Temperature-related dysesthesias are regarded as a specific finding of ciguatera toxicity. In the South Pacific, paralysis may occur in up to 10 percent of patients.

•Cardiovascular – Less commonly bradycardia, heart block, and hypotension may occur.

The course of ciguatera fish poisoning is variable. Gastrointestinal and, if present, cardiovascular signs frequently resolve within 24 to 48 hours and rarely persist beyond four days. Neurologic abnormalities typically are more persistent, lasting from a few days to several weeks. Ingestion of alcohol, caffeine, nuts, or fish as well as excessive physical exertion can cause exacerbation or recurrence of ciguatera toxicity.

●Diagnosis – The diagnosis of ciguatera fish poisoning is made using the following clinical criteria (see 'Diagnosis' above):

•A history of ingestion of a large reef fish commonly associated with ciguatera toxicity (eg, moray eel, amberjack, barracuda, red snapper, or grouper).

•Signs and symptoms consistent with ciguatera poisoning, especially temperature-related dysesthesia (see 'Clinical manifestations' above)

•Exclusion of other potential causes (see 'Differential diagnosis' above)

•Confirmation of ciguatoxin in the consumed fish, if possible. If the fish is not available for analysis, ciguatera fish poisoning in other individuals who consumed the same fish is also supportive.

There is no clinical diagnostic test for ciguatera fish poisoning. Toxins can be detected in cooked fish, but the various techniques are costly and not widely available. (See 'Diagnosis' above.)

●Management

•Initial supportive care – Initial treatment of ciguatera fish poisoning is primarily supportive and consists of expectant management of dehydration, pruritus, and hemodynamic instability. (See 'Initial supportive care' above.)

•Treatment of neurologic symptoms – In a patient with significant neurologic symptoms caused by ciguatera fish poisoning who is fluid repleted, we suggest administering a single dose of mannitol (1 g/kg infused over one hour) (Grade 2C). Neurologic symptoms of ciguatera fish poisoning can be prolonged and debilitating. Agents that have been effective in the treatment of other painful neuropathic syndromes (eg, gabapentin, pregabalin, or amitriptyline) may improve symptoms of chronic polyneuropathy, but should be used cautiously with close monitoring. (See 'Neurologic symptoms' above.)

•Diet and activity modification – In addition to avoiding excessive physical exertion, patients with ciguatera toxicity should be counseled that consumption of fish, alcohol, caffeine, and nuts within six months from onset of illness may trigger a recurrence of symptoms and that it is prudent to avoid these foods. The male patient should curtail sexual activity until symptoms resolve or, alternatively, may use condoms. (See 'Diet and activity modification' above.)

●Prevention – The best way to prevent ciguatera fish poisoning is to avoid eating all high-risk fish, such as barracuda, moray eel, and certain types of grouper, red snapper, and amberjack. No accurate analytical field test for caught fish is available. When in the tropics, it may be less risky to eat smaller fish and avoid eating fish organs where the toxin is concentrated. Recreational fishermen should also travel with experienced local guides who often know which reefs to avoid. (See 'Prevention' above.)

Upon diagnosis of ciguatera fish poisoning, clinicians should contact their local health department and, if applicable, their regional poison control center so that investigation of the fish source can prevent consumption of other toxic fish from the same reef. (See 'Prevention' above and 'Regional poison control centers' above.)