What is Ciguatera Fish Poisoning. How is it diagnosed. What are the symptoms of Ciguatera toxin exposure. What treatments are available for Ciguatera poisoning. How can Ciguatera Fish Poisoning be prevented.

Understanding Ciguatera Fish Poisoning: A Comprehensive Overview

Ciguatera Fish Poisoning (CFP) is a form of foodborne illness caused by consuming certain reef fish contaminated with ciguatoxins. These potent marine neurotoxins are produced by dinoflagellates, microscopic algae that live on coral reefs. As larger predatory fish consume smaller reef fish, the toxins accumulate up the food chain, reaching potentially dangerous levels in species like barracuda, moray eel, grouper, and red snapper.

CFP is a significant health concern in tropical and subtropical regions worldwide, affecting thousands of people annually. The toxins responsible for CFP are odorless, colorless, and tasteless, making contaminated fish impossible to detect through normal sensory evaluation. This presents unique challenges for prevention and control of the illness.

Key Facts About Ciguatera Toxins

• Ciguatoxin and maitotoxin are the primary toxins involved in CFP
• These are some of the most potent natural toxins known
• Ciguatoxin is lethal to mice at 0.45 μg/kg when injected intraperitoneally
• Maitotoxin is even more potent, with a lethal dose of 0.15 μg/kg in mice
• In humans, as little as 0.1 μg of ciguatoxin can cause illness when ingested orally

Diagnosing Ciguatera Fish Poisoning: From Traditional Methods to Modern Techniques

Accurately diagnosing Ciguatera Fish Poisoning has historically been challenging due to the lack of simple, reliable testing methods. Over the years, various approaches have been developed, ranging from rudimentary bioassays to sophisticated immunological techniques.

Traditional Bioassays

In many island communities, unconventional methods were once employed to detect ciguatoxin-contaminated fish. These included using household pets or even elderly relatives as simple bioassays. While ethically questionable and unreliable, these practices highlight the desperate need for effective detection methods in endemic areas.

More formal bioassays using laboratory animals such as mongoose, rats, and cats were also developed. These methods, while more controlled, were expensive and time-consuming.

Mouse Bioassay

The mouse bioassay has long been considered the standard diagnostic tool for CFP. However, it has limitations, notably its inability to distinguish between ciguatoxin and scaritoxin, another marine toxin.

Immunological Assays

In recent years, more sophisticated diagnostic techniques have been developed:

• Radioimmune assays (RIA)
• Enzyme-linked immunosorbent assays (ELISA)
• Hokama enzyme immunoassay stick test

These methods offer improved sensitivity and specificity compared to traditional bioassays. For instance, Emerson et al. (1983) used counter-immunoelectrophoresis to effectively discriminate between toxic and non-toxic fish extracts, correlating well with human and mouse bioassay results.

Trainer et al. (1990, 1991) developed an assay capable of qualitatively and potentially quantitatively measuring ciguatoxin in fish and possibly human fluids. This represents a significant advancement in CFP diagnostics, although further research is needed to validate its application in clinical settings.

Symptoms and Clinical Presentation of Ciguatera Fish Poisoning

Ciguatera Fish Poisoning can produce a wide range of symptoms, which can vary in severity and duration. Understanding these symptoms is crucial for prompt diagnosis and appropriate management.

Common Symptoms of CFP

• Gastrointestinal distress: nausea, vomiting, diarrhea, abdominal pain
• Neurological symptoms: paresthesias, temperature sensation reversal, headache, dizziness
• Cardiovascular effects: bradycardia, hypotension
• Generalized weakness and fatigue
• Pruritus (itching)
• Myalgia (muscle pain)

One of the hallmark symptoms of CFP is temperature sensation reversal, where cold objects feel hot to the touch and vice versa. This unique symptom can be a key diagnostic indicator.

Acute vs. Chronic Symptoms

CFP symptoms can be categorized into acute and chronic phases:

1. Acute phase: Typically begins within 24 hours of consuming contaminated fish and can last for several days to weeks
2. Chronic phase: Some individuals experience persistent symptoms lasting months or even years

Chronic symptoms often include fatigue, weakness, and recurrent neurological effects. These long-term effects can significantly impact quality of life and may be challenging to manage.

Treatment Strategies for Ciguatera Fish Poisoning

Managing Ciguatera Fish Poisoning involves a combination of supportive care and targeted interventions. While there is no specific antidote for ciguatoxin, several treatment approaches have shown promise in alleviating symptoms and promoting recovery.

Supportive Care and Symptomatic Treatment

The cornerstone of CFP management is supportive care, addressing symptoms as they arise. This may include:

• Intravenous fluids for dehydration
• Antiemetics for nausea and vomiting
• Pain management for headaches and myalgia
• Atropine for bradycardia
• Dopamine or calcium gluconate for shock

It’s important to note that opiates and barbiturates are generally avoided, as they may cause hypotension and potentially interact with maitotoxin.

Mannitol Therapy

Intravenous mannitol has emerged as a promising treatment for acute CFP. Palafox et al. (1988) reported significant success using mannitol infusions:

• Dosage: 1 g/kg of 20% mannitol
• Administration rate: 500 mL/h
• Delivery method: “Piggybacked” to an IV infusion of 5% dextrose in Ringer’s lactate or saline solution

This approach led to complete symptom reversal in the majority of patients treated. Subsequent studies have confirmed these findings, particularly when mannitol is administered within 48-72 hours of toxin ingestion.

Medications for Chronic Symptoms

For patients experiencing chronic CFP symptoms, certain medications have shown efficacy:

• Amitriptyline (25 to 75 mg twice daily) and similar tricyclic antidepressants can help alleviate fatigue and paresthesias
• Nifedipine, a calcium channel blocker, may potentially counteract the effects of maitotoxin, although further research is needed to confirm its efficacy

Traditional Remedies

In many endemic regions, local communities have long-standing traditional remedies for CFP, including various medicinal teas. While over 64 different local treatments have been documented in the Indo-Pacific and West Indies regions, their efficacy has not been scientifically evaluated in controlled clinical trials.

Preventing Ciguatera Fish Poisoning: Risk Reduction Strategies

Given the challenges in detecting and treating Ciguatera Fish Poisoning, prevention remains the most effective approach to reducing its impact. Several strategies can be employed to minimize the risk of exposure to ciguatoxins.

Avoiding High-Risk Fish Species

Certain fish species are more likely to accumulate ciguatoxins to dangerous levels. In endemic areas, it’s advisable to:

• Never consume barracuda or moray eel, which are high-risk species
• Exercise caution with grouper and red snapper
• Avoid eating unusually large predatory reef fish, especially during their reproductive season
• Refrain from consuming the viscera (internal organs) of any reef fish, as toxins tend to concentrate in these tissues

Local Knowledge and Awareness

When traveling to or living in endemic areas, it’s crucial to:

• Inquire about local fish species associated with CFP
• Stay informed about any recent CFP outbreaks or warnings
• Consult with local fishermen or health authorities about safe fishing areas

Understanding Limitations of Detection

It’s important to recognize that ciguatoxin-contaminated fish cannot be reliably identified by smell, taste, or appearance. Currently, there is no simple, widely available method to test fish for ciguatoxins before consumption. This underscores the importance of avoiding high-risk species and following local advisories.

The Molecular Mechanism of Ciguatoxin Action

Understanding how ciguatoxins affect the body at a molecular level is crucial for developing effective treatments and potentially new diagnostic tools. Ciguatoxin, the primary toxin responsible for CFP, has a unique mechanism of action that explains many of the observed symptoms.

Sodium Channel Activation

Ciguatoxin is a lipid-soluble substance that primarily targets voltage-gated sodium channels in nerve cells. Its effects include:

• Opening sodium channels at resting membrane potential
• Shifting the voltage dependence of sodium channel activation to more negative potentials
• Slowing channel inactivation

These actions lead to persistent activation of sodium channels, resulting in membrane depolarization and spontaneous firing of action potentials. This explains many of the neurological symptoms associated with CFP, such as paresthesias and temperature sensation abnormalities.

Cellular and Systemic Effects

The consequences of ciguatoxin’s action on sodium channels extend beyond individual neurons, affecting various physiological systems:

• Neurotransmitter release: Increased calcium influx due to membrane depolarization leads to enhanced release of neurotransmitters
• Muscle cells: Affects both skeletal and cardiac muscle, contributing to weakness and cardiovascular symptoms
• Epithelial tissues: May explain gastrointestinal symptoms through effects on intestinal epithelium

Understanding these molecular mechanisms provides insight into potential therapeutic targets and explains the diverse symptomatology of CFP.

Public Health Implications and Reporting of Ciguatera Fish Poisoning

Ciguatera Fish Poisoning represents a significant public health challenge, particularly in tropical and subtropical coastal regions. Effective management of CFP outbreaks requires a coordinated approach involving healthcare providers, public health authorities, and the community at large.

Importance of Reporting

Prompt reporting of suspected CFP cases is crucial for several reasons:

• Identifying and preventing further spread of contaminated fish
• Detecting outbreaks early to minimize their impact
• Gathering data to improve understanding of CFP epidemiology and risk factors
• Informing public health policies and interventions

Healthcare providers should be aware that initial CFP cases are often just the “tip of the iceberg,” with more cases likely to follow. Reporting suspected cases to appropriate public health authorities allows for thorough investigation and follow-up.

Outbreak Investigation

When a CFP outbreak is suspected, public health officials typically conduct investigations that may include:

• Interviewing affected individuals to identify common food sources
• Tracing the origin of implicated fish
• Collecting samples of suspected contaminated fish for analysis
• Issuing public health advisories or recalls if necessary

These efforts are crucial for preventing further cases and gathering valuable data on CFP occurrence and distribution.

Long-Term Management and Research

Addressing the public health impact of CFP requires ongoing efforts in several areas:

• Improving diagnostic capabilities, including the development of rapid, field-deployable testing methods
• Conducting controlled clinical trials to evaluate the efficacy of various treatments, including traditional remedies
• Enhancing surveillance systems to better track CFP incidence and identify high-risk areas
• Developing predictive models to forecast CFP risk based on environmental factors
• Educating healthcare providers, fishermen, and the general public about CFP risks and prevention strategies

By addressing these aspects, public health authorities can work towards reducing the burden of Ciguatera Fish Poisoning and improving outcomes for affected individuals.

Ciguatera Fish Poisoning

Using a household pet or even elderly relative as a simple bioasssay
was and may still be practiced in many island communities. Otherwise,
only expensive ponderous bioassays in such animals as the mongoose,
rat and cats were available for screening Ciguatoxin-contaminated
fish until ten years ago. The mouse bioassay, while it remains the
standard diagnostic tool, does not distinguish between ciguatoxin and
scaritoxin.

Over the past few years, radioimmune (RIA) or enzyme linked
immunosorbent (ELISA) assays have been developed to investigate
Ciguatera, including the Hokama enzyme immunoassay stick test.
Emerson et al (1983) using counter-immunoelectrophoresis disclosed
precipitin lines with toxic fish extracts and effectively
discriminated between samples compared with human and mouse bioassay.
However putative immune and nonimmune serum gave equally clear
precipitin reactions with toxic extracts therefore the authors could
not conclude that they had located a specific antibody. Trainer et
al (1990, 1991) developed an assay which can measure Ciguatoxin
qualitatively and potentially quantitatively in fish and possibly
human fluids. Further work involves the application of these assays
to human fluids from persons who have eaten assay-positive fish.

Management and Treatment:

Medical treatment has been to a large extent symptomatic; a variety
of agents, including vitamins, antihistamines, anticholinesterases,
steroids and tricyclic antidepressants, have been tried with limited
results. Gut emptying and decontamination with charcoal is
recommended acutely although often the severe ongoing vomiting and
diarrhea prevents this. Atropine is indicated for bradycardia, and
dopamine or calcium gluconate for shock. It is recommend that
opiates and barbiturates be avoided since they may cause hypotension,
and opiates may interact with maitotoxin.

With apparent considerable success, at least acutely, mannitol
infusions have been used. Palafox et al (1988) administered 1 gm/kg
of 20% mannitol at a rate of 500 mL/h “piggybacked” to an iv infusion
of 5% dextrose in Ringers lactate or saline solution at 30 mL/h or
more depending on fluid requirements with complete reversal of
symptoms in the majority of patients tested. Subsequent reports have
affirmed his success although mannitol appears to be most effective
in completely relieving symptoms when given within the first 48-72
hours from ingestion.

Amitriptyline (25 to 75 mg bid) and similar medications do seem to
have some success in relieving the symptoms of chronic Ciguatera,
such as fatigue and paresthesias. It is possible that nifedipine may
be appropriate as a calcium channel blocker to counteract the effects
of maitotoxin. Finally, there are over 64 different local remedies
including medicinal teas used in both the Indo-Pacific and West
Indies regions. None of these treatments have been evaluated in a
controlled clinical trial with the exception of two controlled trials
of Mannitol for treatment of acute Ciguatera, so that their true
efficacy is impossible to determine.

As mentioned above, there appears to be a sensitivity to certain
foods (ie. ingestion of fish (regardless of type), ethanol, caffeine,
and nuts) after ciguatera poisoning and these should be avoided for 3
to 6 months after the illnesses. In addition, there is no immunity
to this illnesses and recurrences of actual ciguatera in the same
individual appear to be worse than the initial illness.

As with many of the marine toxin induced diseases, the initial or
index case(s) are often the tip of the iceberg. Therefore any
suspected cases of Ciguatera should be reported to the appropriate
public health authorities for follow up to ascertain other cases and
to prevent further spread. And every effort should be made to obtain
contaminated materials and their source.

Obviously persons who live in or travel to endemic areas should never
eat barracuda or morey eel, and should be cautious with grouper and
red snapper, as well as enquiring about local fish associated with
Ciguatera. Since there is no reliable way to “decontaminate” or
even to distinguish contaminated fish by smell or appearance, at a
minimum, people should be advised to avoid the viscera of any reef
fish as well as avoiding consuming unusually large predacious reef
fish especially during the reproductive season.

CFP Chemical Structure

Molecular Mechanism of Action:

The two most common toxins associated with Ciguatera are Ciguatoxin
and Maitotoxin, and they are some of the most lethal natural
substances known. In mice, ciguatoxin is lethal at 0.45 ug/kg ip, and
maitotoxin at a dose of 0.15 ug/kg ip. Oral intake of as little as
0.1 ug ciguatoxin can cause illness in the human adult (as an
extrapolation from fish samples eaten).

Ciguatoxin, a lipid soluble substance, opens voltage dependant sodium
channels in cell membranes which induces membrane depolarization. It
causes prolonged symptoms indicate nerve blockage or damage requiring
regeneration of nervous tissue Maitotoxin, water soluble,
specifically increases the calcium ion influx through excitable
membrane; this is not affected by tetrodotoxin or sodium. Usually
Maitotoxin is less important since it is less present in fish.
Scaritoxin is similar to Ciguatoxin. Okadaic Acid is a lipid soluble
toxin with a LD50 210 ug/kg ip in mice; it is a sodium ionophore.
Palytoxin is a water soluble polyether which causes severe tonic
contraction of all muscle groups; it also strong skin irritant and
potent tumor activator.

The pharmacologic action of Ciguatoxin is due to its direct effects
on excitable membranes. Its potent depolarizing action due to a
selective increases in sodium permeability in the nerve cells and
striated muscle can be counteracted by calcium ions and tetrodotoxin.
The respiratory arrest induced by a lethal dose results mainly from
depression of the central respiratory center. It causes biphasic
cardiovascular response with hypotension and bradycardia (which can
be antagonized with anticholinergics) followed by hypertension and
tachycardia (which can be suppressed by adrenergic blockers). The
response of smooth muscle to ciguatoxin is complex, depending upon
the predominant autonomic innervation and postsynaptic receptor. It
causes a potent release of endogenous norepinephrine from adrenergic
nerve terminals and a potentiating effect on the post synaptic
membrane.

Maitotoxin possesses a specific Ca2+ dependent action which causes a
release of norepinephrine from rat pheochromocytoma cells. This
action occurs in the absence of Na+ ions and in the presence of
tetrodotoxin, precluding the participation of sodium channels;
Maitotoxin appears to exert its effects on endogenous membrane
calcium channels.

Poison Control Marine Hotline: 1-888-232-8635

Food Poisoning from Ciguatera

The Full Story

What you can’t smell can’t hurt you, right? Wrong! Eating some kinds of fish can cause some pretty unusual and dramatic symptoms.

Ciguatoxin is produced by a type of algae associated with coral reefs. Small plant-eating fish eat the algae, and are then eaten by larger fish, again by yet larger fish, and so on up the food chain. This causes ciguatoxin to concentrate in larger fish. More than 400 species of fish are known to have caused ciguatera poisoning, but the most common are older, larger fish which have been eating contaminated fish during their life spans: grouper, barracuda, snapper, jack, mackerel, triggerfish, and others. Even though contaminated fish are from tropical and sub-tropical fish, ciguatera poisoning occurs anywhere these fish are shipped for consumption.

Ciguatoxin usually causes symptoms within a few hours of eating the fish, but symptoms can be delayed up to 24 hours. Patients can experience nausea, vomiting, diarrhea, muscle weakness, joint aches, headache, dizziness, and low blood pressure. Ciguatoxin can also cause unusual neurologic symptoms because of swelling and dysfunction of nerves. One characteristic and surprising symptom is “hot-cold reversal”; hot items feel cold and cold items feel hot. Imagine drinking iced coffee that feels warm! Other patients have reported numbness around the mouth and even the sensation that their teeth are falling out. Most people are better in a few days, but in some cases symptoms last for months or even years. Symptoms may recur after eating fish, alcohol, nuts, caffeine, chocolate, chicken and eggs.

Most patients recover without treatment; however, those with significant dehydration require treatment with fluids and medications for nausea. Available treatment options for neurologic symptoms are not always effective.

There is no specific way to prevent ciguatera, but avoiding eating larger tropical fish may reduce the chance of exposure to ciguatoxin. Recurrence of symptoms can be prevented by avoiding fish, alcohol, nuts, caffeine, chocolate, chicken, and eggs for several months after the diagnosis. Individuals have reported pain following intercourse with infected individuals, suggesting the toxin may be sexually transmitted. For this reason, it is recommended to use barrier protection for patients with active symptoms. Also, ciguatoxin is secreted in breast milk and has caused diarrhea and facial flushing in breastfed infants. Mothers should consider pumping and dumping their breastmilk if they are actively symptomatic.

Keep others safe, too. If anyone develops symptoms of ciguatera poisoning from fish from a store or restaurant, be sure to let the facility and the health department know. That might prevent someone else from becoming sick from eating the same fish.

For questions about ciguatera poisoning, or if you think someone is having a reaction to fish, go online to www.poison.org or call 1-800-222-1222.  Both options are free for the public, and available 24 hours a day.

Rose Ann Gould Soloway, RN, BSN, MSEd, DABAT emerita
Clinical Toxicologist

Maryann Amirshahi, PharmD, MD, MPH, PhD
Medical Toxicologist

Poisoned?

Call


1-800-222-1222


or

HELP ME online

Prevention Tips

• Avoid eating large fish, at or near the top of the food chain, as they are most likely to cause ciguatera poisoning.
• Avoid foods known to trigger recurrence for several months after a diagnosis of ciguatera.
• Use barrier protection to prevent sexual transmission in symptomatic ciguatera patients.  
• Breastfeeding mothers with active symptoms should consider pumping and dumping to avoid transmission of ciguatera to the baby.  

This Really Happened

A 56-year-old woman ate barracuda while on vacation in Aruba. Eight hours after eating the fish, she developed nausea, vomiting, abdominal cramping, and itching. She then developed numbness around her mouth and a tingling sensation in her arms and legs. The following day, she noted that when she washed her hands under cold water, she felt as though her hands were “on fire”. She experienced the same feeling in her feet when she walked on a cold floor. She returned home to the United States, and presented to an Emergency Department where ciguatera was diagnosed. At a follow-up visit with her primary care doctor one month later, she reported that nearly all of her previous symptoms had resolved, with the exception of pain in her legs.

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If you have a question about adverse reactions from itch mites or other bites or stings, get help with webPOISONCONTROL or call 1-800-222-1222. Both options are free for the public, and available 24 hours a day.

References

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. 

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.

Patel M, Jutzy K. A Curious Case of Ciguatera Fish Poisoning in the Midwest and a Review for Clinicians. J Emerg Med. 2020 Mar;58(3):e109-e111.

Patient Page about ciguatera fish poisoning (The Journal of American Medical Association)

Poisoned?

Call


1-800-222-1222


or

HELP ME online

Prevention Tips

• Avoid eating large fish, at or near the top of the food chain, as they are most likely to cause ciguatera poisoning.
• Avoid foods known to trigger recurrence for several months after a diagnosis of ciguatera.
• Use barrier protection to prevent sexual transmission in symptomatic ciguatera patients. 
• Breastfeeding mothers with active symptoms should consider pumping and dumping to avoid transmission of ciguatera to the baby.  

This Really Happened

A 56-year-old woman ate barracuda while on vacation in Aruba. Eight hours after eating the fish, she developed nausea, vomiting, abdominal cramping, and itching. She then developed numbness around her mouth and a tingling sensation in her arms and legs. The following day, she noted that when she washed her hands under cold water, she felt as though her hands were “on fire”. She experienced the same feeling in her feet when she walked on a cold floor. She returned home to the United States, and presented to an Emergency Department where ciguatera was diagnosed. At a follow-up visit with her primary care doctor one month later, she reported that nearly all of her previous symptoms had resolved, with the exception of pain in her legs.

Causes, Symptoms, Diagnosis and Treatment

Ciguatera is a disease that occurs when certain types of reef fish are eaten. The most common symptoms are neurological manifestations, such as paresthesia of the face, limbs, hallucinations, headache, loss of consciousness, delirium. Neuropsychological, cardiovascular, gastrointestinal disturbances are not uncommon. Diagnosis consists in the detection of a toxin in food, the characteristic symptoms of the disease. Treatment is pathogenetic and symptomatic; etiotropic therapy of ciguatera has not been developed, therapeutic measures are aimed at detoxification of the body.

General information

Ciguatera (fish food poisoning) – toxicosis associated with the action of the biological poison ciguatoxin. For the first time, the symptoms of ciguatera are found in the written sources of doctors of Ancient China (VII century AD), the clinic was described in more detail by the Englishman Locke in 1675. The toxin was isolated by the Hawaiian professor Scheuer (1967). More often, poisoning occurs in regions with a tropical, subtropical climate, water areas of the Indian, Pacific Oceans, and the Caribbean. It is believed that no more than 20% of cases of ciguatera are recorded annually, the real number of poisonings is not known for certain.

Ciguatera

Causes

The source of infection is phytoplankton, the dinoflagellate Gambierdiscus toxicus, which is food for small fish, which, in turn, are eaten by predatory relatives. The poison accumulates mainly in the liver and other internal organs of fish. Ciguatoxin is odorless and tasteless, and is not neutralized by heat treatment and freezing. To date, three species are known: Indian, Caribbean and Pacific ciguatoxin; the latter is more common and studied.

Main risk factors: eating reef fish species larger than 10 kg caught after the storm; viscera and heads are especially toxic. The destruction of reefs caused by typhoons and hurricanes significantly increases the toxicity of fish. The most dangerous include Spanish mackerels, yellow moray eels, sea bass, barracudas, sea basses, hamfeads. The danger of ciguatera increases significantly for the elderly, those with heart and arterial diseases, and obesity.

Pathogenesis

The pathogenesis is not fully understood. The main action of toxins (ciguatoxin, meitotoxin) is associated with disruption of the sodium channels of cell membranes, neuronal edema, blockage of potassium channels, which ultimately leads to impaired conduction of the nerve impulse. Uncontrollable and repetitive action potentials occur due to a single stimulus. Ciguatoxin is implicated in calcium channel dysregulation, nitrous oxide induction by cells.

Peripheral nervous system, sensory neurons, skeletal muscle, heart, gray matter become targets for exposure. It has been shown in an animal model that venom administration can lead to neuronal excitotoxicity of the cerebral cortex. It has been suggested that polyneural edema caused by the activity of the toxin and leading to degradation of the myelin sheath may be the cause of autoimmune neuronal aggression.

Symptoms

The incubation period of ciguatera is 1-24 hours. In a typical course, there is a feeling of numbness in the mouth, toothache, burning of the skin upon contact with cold water, a feeling of “loose” teeth. The disease is accompanied by nausea, spastic abdominal pain, vomiting, loose stools, severe muscle weakness. Often there is temperature dysesthesia – hot seems cold, and vice versa.

The severity of symptoms depends on the amount of toxin that has entered the body, and the duration of the disease usually does not exceed 4 days. There are frequent cases of a prolonged drop in blood pressure, accompanied by weakness and the impossibility of active actions in an upright position. In severe cases, shortness of breath appears, a decrease in the patient’s contact reaction to stimuli.

If the symptoms of the disease last 2-6 months or more, it is possible to talk about chronic ichthyotoxicosis. Manifestations of chronic ciguatera are mainly neurological (paresthesia, dysesthesia, cold allodynia, pruritus, headache), psychiatric (cognitive dysfunction, sleep disturbance, anxiety, memory loss, depression) and systemic (myalgia, severe asthenia, arthralgia).

Complications

The most common complication of ciguatera is acute cardiovascular failure, less often respiratory failure. With large fluid losses, dehydration shock and renal dysfunction develop. In severe cases, cerebral edema rapidly increases with the danger of wedging into the foramen magnum. Among 20% ​​of patients, there is a long course and subsequent chronicity of the pathology.

Due to the accumulation of toxin in adipose tissue and the slow rate of its excretion, recurrence of the disease is possible. Most often this is due to repeated intake of fish dishes, caffeine, chicken, nuts, alcohol, prolonged dehydration, stress. To the probable complications of the long course of ciguatera, modern infectology includes multiple sclerosis, chronic fatigue syndrome and brain tumors.

Diagnosis

Verification of the diagnosis of toxicosis and treatment is carried out by infectious disease specialists, often in intensive care units. Other medical specialists are involved according to indications. It is important to collect an epidemiological history, including stay in endemic areas, the nature of nutrition (eating fish). The main clinical, instrumental and laboratory signs of ciguatera are:

• Physical data. Physical examination reveals symptoms of dehydration, diffuse abdominal tenderness, bradycardia, hypotension, severe muscle weakness, less commonly dyspnoea, and forced posture. The degree of impaired consciousness can change to coma, dysphoria is detected. Be sure to evaluate the presence of meningeal symptoms, the nature of vomiting and feces, the amount of urine.
• Laboratory tests . There are no specific laboratory markers for ciguatera. With pronounced fluid losses in the general blood test, symptoms of hemoconcentration increase, the ratio of electrolytes changes, the activity of ALT, AST increases. General clinical analysis of urine – with signs of toxic damage in the form of proteinuria, microhematuria, increased concentration of urinary sediment.
• Detection of infectious agents . There is only a toxicological analysis of probably toxic fish products; in some cases, a biological test on laboratory animals is used for differential diagnosis. A bacteriological examination of feces, washings, preserved suspicious food should be carried out.
• Instrumental methods . Ultrasound examination of the internal organs is shown to exclude urgent surgical pathology, abdominal radiography to confirm or refute the symptoms of an acute abdomen; ECG, EEG – with a differential diagnosis with a gastric form of myocardial infarction and neurological pathologies, respectively.

Differential diagnosis is carried out with various poisonings, in which the only way to determine the source of the toxin is laboratory analysis. Pathologies of the central nervous system are rarely associated with a particular food. The clinic of ciguatera is similar with food poisoning, gastrointestinal salmonellosis, in which there is no neuronal dysfunction, and botulism, characterized by transient “top-down” lesions of the cranial nerves.

Treatment

There are currently no established protocols for the management of patients with ciguatera symptoms. Patients who are indicated for inpatient treatment are the elderly, pregnant women, people with chronic pathology of the heart and blood vessels, children, people with severe dehydration. Before contacting a doctor, it is recommended to wash the stomach, take medicinal sorbents, and perform siphon enemas to get rid of toxic food residues, provided that the patient is conscious.

Bed or semi-bed rest is prescribed. Specific nutrition for ciguatera has not been developed, it is recommended to exclude alcohol, nicotine, heavy, indigestible food, especially saturated with fats. The use of large amounts of water, detoxifying polyionic oral solutions is required for detoxification purposes, as well as to replenish fluid losses – which can be done in the absence of contraindications.

Conservative therapy

Treatment of ciguatera non-specific; many groups of pharmaceuticals have been proposed, while etiotropic agents have not yet been developed. It is necessary to start supportive measures in the first hours and days after the patient presents with suspected ciguatera; thus, manifest symptoms of severe damage to the heart muscle occur among 43% of patients. Most often, poisoning therapy is carried out with the help of:

1. Pathogenetic treatment. It is carried out using infusion detoxification measures with succinate-containing, glucose-salt, polyionic solutions, cardioactive, vasopressor agents. In chronic course, antidepressants, cholestyramine, antiepileptic drug formulas, as well as non-steroidal anti-inflammatory drugs are indicated. Calcium channel blockers have proven themselves well. For the treatment of shock, plasma substitutes, dopamine preparations are used.
2. Symptomatic therapy. Antiemetic, antispasmodic drugs are used, with severe diarrhea – astringents, sorbents; B vitamins are widely used. With skin itching, sedatives, antihistamines and desensitizing agents are indicated. Treatment with steroid hormones, opiates, barbiturates has little therapeutic potential with ciguatera.

Previously widely recommended and highly effective in vitro studies, mannitol should be administered within 24 hours of symptom onset, according to current research. When intravenous mannitol is administered later, its effect is comparable to the introduction of saline, respectively, the risk of side effects of the drug also increases.

Mannitol has been shown to help reduce swelling of nerve cells due to exposure to ciguatoxins and also acts as a scavenger of free radicals generated when cells are exposed to these poisons. Treatment of symptoms of paresthesia with ciguatera is carried out by physiotherapeutic methods (diadynamic currents, electrophoresis, magnetotherapy), course use of antihypoxants and antioxidants.

Experimental treatment

Local people in the South Pacific traditionally use a decoction of the leaves of the silver argusia (Heliotropium foertherianum) to treat the symptoms of ciguatera. In vitro studies have shown that this herbal preparation has the ability to compete with ciguatoxins, limiting their fixation on biological targets, so the remedy is considered most effective only when taken immediately after the first signs of poisoning.

Prognosis and prevention

The prognosis is favorable in most cases. Ciguatera rarely leads to death, however, with a burdened premorbid background and a high dose of toxin that has entered the body, untimely treatment, the lethality of this poisoning is 0.04-0.1%. The duration of neurological symptoms – paresthesia, depression, headaches, memory loss – after recovery can be weeks and months.

No specific prophylaxis of ciguatera has been developed. Non-specific measures are considered to be abstinence from the consumption of meat and viscera (liver, milk, caviar) of large predatory reef fish, especially in periods after natural disasters, spawning; it is necessary to exclude the purchase of fish from private individuals. In endemic zones, states carry out toxicological studies of fish products supplied for official sale.

Causes, Symptoms, Diagnosis and Treatment

Ciguatera is a disease that occurs when certain reef fish are eaten. The most common symptoms are neurological manifestations, such as paresthesia of the face, limbs, hallucinations, headache, loss of consciousness, delirium. Neuropsychological, cardiovascular, gastrointestinal disturbances are not uncommon. Diagnosis consists in the detection of a toxin in food, the characteristic symptoms of the disease. Treatment is pathogenetic and symptomatic; etiotropic therapy of ciguatera has not been developed, therapeutic measures are aimed at detoxification of the body.

General information

Ciguatera (fish food poisoning) – toxicosis associated with the action of the biological poison ciguatoxin. For the first time, the symptoms of ciguatera are found in the written sources of doctors of Ancient China (VII century AD), the clinic was described in more detail by the Englishman Locke in 1675. The toxin was isolated by the Hawaiian professor Scheuer (1967). More often, poisoning occurs in regions with a tropical, subtropical climate, water areas of the Indian, Pacific Oceans, and the Caribbean. It is believed that no more than 20% of cases of ciguatera are recorded annually, the real number of poisonings is not known for certain.

Ciguatera

Causes

The source of infection is phytoplankton, the dinoflagellate Gambierdiscus toxicus, which is food for small fish, which, in turn, are eaten by predatory relatives. The poison accumulates mainly in the liver and other internal organs of fish. Ciguatoxin is odorless and tasteless, and is not neutralized by heat treatment and freezing. To date, three species are known: Indian, Caribbean and Pacific ciguatoxin; the latter is more common and studied.

Main risk factors: eating reef fish species larger than 10 kg caught after the storm; viscera and heads are especially toxic. The destruction of reefs caused by typhoons and hurricanes significantly increases the toxicity of fish. The most dangerous include Spanish mackerels, yellow moray eels, sea bass, barracudas, sea basses, hamfeads. The danger of ciguatera increases significantly for the elderly, those with heart and arterial diseases, and obesity.

Pathogenesis

The pathogenesis is not fully understood. The main action of toxins (ciguatoxin, meitotoxin) is associated with disruption of the sodium channels of cell membranes, neuronal edema, blockage of potassium channels, which ultimately leads to impaired conduction of the nerve impulse. Uncontrollable and repetitive action potentials occur due to a single stimulus. Ciguatoxin is implicated in calcium channel dysregulation, nitrous oxide induction by cells.

Peripheral nervous system, sensory neurons, skeletal muscle, heart, gray matter become targets for exposure. It has been shown in an animal model that venom administration can lead to neuronal excitotoxicity of the cerebral cortex. It has been suggested that polyneural edema caused by the activity of the toxin and leading to degradation of the myelin sheath may be the cause of autoimmune neuronal aggression.

Symptoms

The incubation period of ciguatera is 1-24 hours. In a typical course, there is a feeling of numbness in the mouth, toothache, burning of the skin upon contact with cold water, a feeling of “loose” teeth. The disease is accompanied by nausea, spastic abdominal pain, vomiting, loose stools, severe muscle weakness. Often there is temperature dysesthesia – hot seems cold, and vice versa.

The severity of symptoms depends on the amount of toxin that has entered the body, and the duration of the disease usually does not exceed 4 days. There are frequent cases of a prolonged drop in blood pressure, accompanied by weakness and the impossibility of active actions in an upright position. In severe cases, shortness of breath appears, a decrease in the patient’s contact reaction to stimuli.

If the symptoms of the disease last 2-6 months or more, it is possible to talk about chronic ichthyotoxicosis. Manifestations of chronic ciguatera are mainly neurological (paresthesia, dysesthesia, cold allodynia, pruritus, headache), psychiatric (cognitive dysfunction, sleep disturbance, anxiety, memory loss, depression) and systemic (myalgia, severe asthenia, arthralgia).

Complications

The most common complication of ciguatera is acute cardiovascular failure, less often respiratory failure. With large fluid losses, dehydration shock and renal dysfunction develop. In severe cases, cerebral edema rapidly increases with the danger of wedging into the foramen magnum. Among 20% ​​of patients, there is a long course and subsequent chronicity of the pathology.

Due to the accumulation of toxin in adipose tissue and the slow rate of its excretion, recurrence of the disease is possible. Most often this is due to repeated intake of fish dishes, caffeine, chicken, nuts, alcohol, prolonged dehydration, stress. To the probable complications of the long course of ciguatera, modern infectology includes multiple sclerosis, chronic fatigue syndrome and brain tumors.

Diagnosis

Verification of the diagnosis of toxicosis and treatment is carried out by infectious disease specialists, often in intensive care units. Other medical specialists are involved according to indications. It is important to collect an epidemiological history, including stay in endemic areas, the nature of nutrition (eating fish). The main clinical, instrumental and laboratory signs of ciguatera are:

• Physical data. Physical examination reveals symptoms of dehydration, diffuse abdominal tenderness, bradycardia, hypotension, severe muscle weakness, less commonly dyspnoea, and forced posture. The degree of impaired consciousness can change to coma, dysphoria is detected. Be sure to evaluate the presence of meningeal symptoms, the nature of vomiting and feces, the amount of urine.
• Laboratory tests . There are no specific laboratory markers for ciguatera. With pronounced fluid losses in the general blood test, symptoms of hemoconcentration increase, the ratio of electrolytes changes, the activity of ALT, AST increases. General clinical analysis of urine – with signs of toxic damage in the form of proteinuria, microhematuria, increased concentration of urinary sediment.
• Detection of infectious agents . There is only a toxicological analysis of probably toxic fish products; in some cases, a biological test on laboratory animals is used for differential diagnosis. A bacteriological examination of feces, washings, preserved suspicious food should be carried out.
• Instrumental methods . Ultrasound examination of the internal organs is shown to exclude urgent surgical pathology, abdominal radiography to confirm or refute the symptoms of an acute abdomen; ECG, EEG – with a differential diagnosis with a gastric form of myocardial infarction and neurological pathologies, respectively.

Differential diagnosis is carried out with various poisonings, in which the only way to determine the source of the toxin is laboratory analysis. Pathologies of the central nervous system are rarely associated with a particular food. The clinic of ciguatera is similar with food poisoning, gastrointestinal salmonellosis, in which there is no neuronal dysfunction, and botulism, characterized by transient “top-down” lesions of the cranial nerves.

Treatment

There are currently no established protocols for the management of patients with ciguatera symptoms. Patients who are indicated for inpatient treatment are the elderly, pregnant women, people with chronic pathology of the heart and blood vessels, children, people with severe dehydration. Before contacting a doctor, it is recommended to wash the stomach, take medicinal sorbents, and perform siphon enemas to get rid of toxic food residues, provided that the patient is conscious.

Bed or semi-bed rest is prescribed. Specific nutrition for ciguatera has not been developed, it is recommended to exclude alcohol, nicotine, heavy, indigestible food, especially saturated with fats. The use of large amounts of water, detoxifying polyionic oral solutions is required for detoxification purposes, as well as to replenish fluid losses – which can be done in the absence of contraindications.

Conservative therapy

Treatment of ciguatera non-specific; many groups of pharmaceuticals have been proposed, while etiotropic agents have not yet been developed. It is necessary to start supportive measures in the first hours and days after the patient presents with suspected ciguatera; thus, manifest symptoms of severe damage to the heart muscle occur among 43% of patients. Most often, poisoning therapy is carried out with the help of:

1. Pathogenetic treatment. It is carried out using infusion detoxification measures with succinate-containing, glucose-salt, polyionic solutions, cardioactive, vasopressor agents. In chronic course, antidepressants, cholestyramine, antiepileptic drug formulas, as well as non-steroidal anti-inflammatory drugs are indicated. Calcium channel blockers have proven themselves well. For the treatment of shock, plasma substitutes, dopamine preparations are used.
2. Symptomatic therapy. Antiemetic, antispasmodic drugs are used, with severe diarrhea – astringents, sorbents; B vitamins are widely used. With skin itching, sedatives, antihistamines and desensitizing agents are indicated. Treatment with steroid hormones, opiates, barbiturates has little therapeutic potential with ciguatera.

Previously widely recommended and highly effective in vitro studies, mannitol should be administered within 24 hours of symptom onset, according to current research. When intravenous mannitol is administered later, its effect is comparable to the introduction of saline, respectively, the risk of side effects of the drug also increases.

Mannitol has been shown to help reduce swelling of nerve cells due to exposure to ciguatoxins and also acts as a scavenger of free radicals generated when cells are exposed to these poisons. Treatment of symptoms of paresthesia with ciguatera is carried out by physiotherapeutic methods (diadynamic currents, electrophoresis, magnetotherapy), course use of antihypoxants and antioxidants.

Experimental treatment

Local people in the South Pacific traditionally use a decoction of the leaves of the silver argusia (Heliotropium foertherianum) to treat the symptoms of ciguatera. In vitro studies have shown that this herbal preparation has the ability to compete with ciguatoxins, limiting their fixation on biological targets, so the remedy is considered most effective only when taken immediately after the first signs of poisoning.

Prognosis and prevention

The prognosis is favorable in most cases. Ciguatera rarely leads to death, however, with a burdened premorbid background and a high dose of toxin that has entered the body, untimely treatment, the lethality of this poisoning is 0.04-0.1%. The duration of neurological symptoms – paresthesia, depression, headaches, memory loss – after recovery can be weeks and months.

No specific prophylaxis of ciguatera has been developed. Non-specific measures are considered to be abstinence from the consumption of meat and viscera (liver, milk, caviar) of large predatory reef fish, especially in periods after natural disasters, spawning; it is necessary to exclude the purchase of fish from private individuals.