There is no vaccine or ciguatera specific treatment available. Currently, the medical management of CP remains symptomatic.

 

However, several studies have identified compounds that showed to be able to specifically counteract ciguatoxins activity  (brevenal, monoclonal antibodies, rosmarinic acid…). Complementary studies are still required bto confirm their benefice.

 

Prevention remains the best-known treatment for CP, through combined actions of information/education, protection of coral reefs, integrated management, traceability reinforcement of fisheries, algal blooms (HABs) monitoring and epidemiological surveillance.

 

   ACUTE PHASE EMERGENCIES  

Hemodynamic and hydroelectric disorders, must be treated first. The use of large volumes of isotonic fluids and amines vasopressors may be necessary.

Although very rare, endotracheal intubation may be required in case of coma or acute polyradiculoneuritis.

Finally, to prevent a toxic/anaphylactic shock, administration of corticosteroids may be necessary.

 

   TRAITMENT OF GASTROINTESTINAL SIGNS

In general, gastrointestinal symptoms are the first to appear. Antisecretory anti-diuretics like racecadotril (Tiorfan®) seem to treat diarrhea well; antiemetics for vomiting and antispasmodics for abdominal pains, can also be used.

In severe cases, decontamination with activated charcoal (if administered within 3-4h after the poisoning) and a gastric lavage can be applayed. However, these methods must be avoided in case of intense vomiting.

In general, these disorders resolve after a few days.

 

 TRAITMENT OF CARDIOVASCULAR SIGNS

These symptoms are found in most severe cases and are relevant of an exposure to large amounts of toxins. Their occurrence usually requires emergency hospitalization.

 

Bradycardia and hypotension require IV or IM atropine (0.5 to 1 mg every 5 minutes, if necessary) to maintain a heart rate greater than 60 bpm. Atropine is also known to improve some gastrointestinal disorders (diarrhea, vomiting, nausea, spasms).

 

Cardiotonics (isoprenaline…) can be administered in case of persistent bradycardia, and pralidoxime (Contrathion®…; 200 to 1000 mg, slow infusion) for its cholinesterase reactivator property.

 

 TRAITMENT OF NEUROMUSCULAR SIGNS

PAIN

Myalgia, arthralgia, headaches, etc. are treated with analgesics and nonsteroidal anti-inflammatory drugs (paracetamol, ibuprofene, aspirin, indomethacin…).

 

PRURITUS

Ciguatera pruritus is generally releaved with pure H1 type antihistamine drugs: dexchlorphéniramine (Polaramine®…), mixed H1 type antihistamines: cyproheptadine (Periactin®…), hydroxyzine (Atarax®); cetirizine (Virlix®) and local anesthetics (lidocaine...).

 

PERIPHERAL NEUROPATHY AND ASTHENIA

A multivitamin cocktail of vitamins B (B1, B6, B12) and C associated with calcium gluconate is frequently suggested, although its efficacy has not been officially proved. In the acute phase, the treatment consists of a slow IV infusion (1h) of a glucose solution (250ml), containing 1g of vitamin C, 250mg of vitamin B6 and 1g of calcium gluconate.

It has been shown that vitamin B12 active form (methylcobalamin), when administered at high doses, stimulates regeneration of damaged neural structures. Vitamins B are usually known for their neuroprotective properties. Vitamin C, is used for its anti-asthenic properties and as a chelator of free radicals. Finally, calcium salts are used, as a calcium rich medium, causes a decreased affinity of ciguatoxins for their receptors.

 

CHRONIC DYSESTHESIA AND PARESTHESIA

Amitriptyline (Laroxyl®, Elavil®) and gabapentin (Neurontin®) are recommended for the relief of chronic paresthesia and dysesthesia. Indeed, amitriptyline administered at a dose of approximately 50mg once a day, has shown significant improvements (of neurological symptoms, and even pruritus) in some patients.

Finally, cholestyramine (Questran®…), an anticholesteremic, which seems to be a ciguatoxins-antagonist, demonstrated some efficiency on neurological symptoms improvement in numerous patients.

 

CHRONIC FATIGUE

It has been demonstrated that fluoxetine (Prozac®), a selective serotonin reuptake inhibitor used as an antidepressant drug, leads to a significant improvement of the chronic fatigue syndrome associated with CP.

 

MANNITOL

Mannitol is usually indicated for the treatment of neurological symptoms during the acute phase of CP, and may prevent the development of chronic symptoms. The dose of mannitol generally recommended is 10ml/kg over a 30-45 minutes period, administered within 48-72h after the consumption of the toxic fish, for maximum efficiency. However, improvements have been observed, even up to several weeks after intoxication.

 

Please note: As mannitol causes intracellular dehydration, it should be administered once the patient is correctly rehydrated, especially if one suffer from severe diarrhea or vomiting. In addition, mannitol should be avoided for patients with cardiac failure.

 

Many hypotheses have been suggested to explain the mechanisms of action of mannitol: its osmotic properties, a chelator of free radicals and/or an inhibitor of successive depolarizations induced by ciguatoxins.

 

Although controversial, the use of mannitol in the acute phase is recommended in most studies.

 

 DIET

In order to avoid the recurrence or worsening of CP related symptoms, it is important that the patient follows a specific diet, free of marine products, animal proteins, alcohol, coffee and nuts during a period of one minimum month.

It may be that this "intolerance" to certain foods developed by CP patients persists over time (several months, even years). It is therefore recommended to keep a diary of "sensitive" foods and to note the nature of reactions and their intensity. These foods will need to be avoided for several weeks, then reintroduced one by one.

This phenomenon of hypersensitivity will disappear over time

In some cases, this intolerance can extend to other food products, such as vegetable source proteins, high-fat products, dairy products, foods rich in histamines, etc.

The diet must be adapted on a case-by-case basis.


 TRADITIONNAL REDEMIES

 

In response to the lack of effective treatment that the conventional medicine can offer, many Pacific islanders prefer to rely on traditional medicine.

 

Hence, ethnobotanical studies carried out in the Pacific region established of a list of some 100 plants used in traditional medicine to combat CP symptoms. These plants may contain active substances, that could act on the symptoms and for some, may improve CTXs  “detoxification”.

 

Among all the remedies listed, the one based on Heliotropium foertherianum (Boraginaceae, vernacular name: "Octopus bush", "faux tabac" in New Caledonia, "tahinu" or "tohonu" in French Polynesia) leaves, have been studied up to the isolation of its active substance, the rosmarinic acid.

 

 

Faux tabac abcd TR 

 

Heliotropium foertherianum or "Octopus bush". a) shrub; b) tree; c) leaves; d) flowers and buds. ‘'Octopus bush" plants usually grow by the seashore, on the sand.© D. Laurent, C. Gatti et F Rossi

 

 

How “Octopus bush” or “Tahinu” traditional remedy is made?

This remedy is still frequently used in French Polynesia, especially in islands with poor medical ressources.

Islanders collect ten yellow leaves. After cleaning them, they boil the leaves  in 1 liter of water until the latter has been reduced to ½ liter. The beverage obtained is then drink hot or cold, in a single or several intakes. According to local custom, this remedy should not be taken more than 3 consecutive days.

 

To be effective, this remedy should be taken as early as possible after the poisoning. Note that the effectiveness may vary from one tree to another, as they do not all contain the same concentration of Rosmarinic acid.

 

Caution: this remedy does not tolerate conservation and should preferably be taken the same day of its preparation.

 

Beneficial effect of this remedy, widely used in the South Pacific and even in Japan, has been demonstrated by various pharmacological studies, including an in vivo test on mice and several electrophysiology, neurophysiology, cellular physiology and neurotoxicity in vitro tests. These tests have shown that this traditional remedy counteracted the toxic effects of ciguatoxins.

 

Rosmarinic acid is one of the main products found in the infusion of H. foertherianum leaves. This phenolic compound that presents no significant toxicity, shows antioxidant as well as anti-inflammatory properties. Its known beneficial effects on the cardiovascular system and on neurodegenerative diseases could also be of a great interest for the treatment of ciguatera. Its “detoxifying” capacity has been studied on cultured neuroblastoma cells and with a receptor-ligand detection test (displacement of the toxin from its action site).

 

Rosmarinic acid, but also the traditional remedy made from H. foertherianum leaves could therefore be a promising alternative treatment for ciguatera poisoning

     
 

 

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