The following are notes from a talk I gave in Vanuatu.

The most common diseases caused by marine toxins in the United States in order of incidence are:

1. scombrotoxic fish poisoning
2. ciguatera poisoning
3. paralytic shellfish poisoning
4. neurotoxic shellfish poisoning
5. amnesic shellfish poisoning.

•         Marine toxins are naturally occurring chemicals that can contaminate certain seafood. The seafood contaminated with these chemicals frequently looks, smells, and tastes normal. When humans eat such seafood, disease can result.

Scrombotoxic Fish Poisoning

•         Caused by bacterial spoilage of certain (tunas and mackerels)

•         A consequence of the free histidine content of the fresh fish which is broken down by the bacterial enzyme histidine decarboxylase → histamine.

•         Eating spoiled fish that have high levels of these histamines can cause in human disease

•         Symptoms begin within 2 minutes to 2 hours after eating the fish.

•         Rash, diarrhea, flushing, sweating, headache, and vomiting. Burning or swelling of the mouth, abdominal pain, or a metallic taste may also occur. Hypotension in severe.

•         Most have mild symptoms that resolve within a few hours.

•         Treatment is generally unnecessary, but antihistamines or adrenaline may be required.

•         Symptoms may be more severe in patients taking certain medications that slow the breakdown of histamine by their liver, such as isoniazide and doxycycline.

Ciguatera Poisoning

•         Ciguatoxin produced by dinoflagellates.

•         CTX concentrated up food chain and highest in large predatory fish.

•         Eating contaminated fish produces syndrome in humans.

•         CTX not removed by cooking or cleaning fish.

•         Fish found between 35 N and 35 S.

•         Symptoms usually within 6hrs of eating fish, but up to 48hrs.

•         Mixed GI illness and neurocutaneous Sxs.

•         Lasts 1- 4 weeks, in <5% months to years.

Shellfish poisoning

•         Other dinoflagellates are filtered by shellfish, especially during algal blooms.

•         Toxins concentrated in shellfish which are consumed by humans.

•         Sxs in 30mins to 12hrs

•         Starts with numbness, tingling of face and limbs.

•         Muscular paralysis in 24hrs reported.

Ciguatera in depth

•         A widespread ichthyosarcotoxaemia

•         A severe form of fish poisoning which may present with either acute or chronic intoxication syndromes

•         Human ingestion fish that harbour the bioaccumulated ciguatoxins of the photosynthetic dinoflagellates (types of single-celled algae) Gambierdiscus toxicus  and Gymnodinium toxicus.

Peridinium sp. .

History of Ciguatera

•         Galen “Moray eels are dangerous to eat”

•         First European colonists in the islands of the Caribbean encountered the neurological consequences suffered by gourmet victims who had ingested the local gastropod, Livona, called "cigua". Thought that all cases were due to the ingestion of snails, now appreciated that most were in fact due to the eating of ciguatoxic fish.

•         Parra, in 1787 in his "Description de Diferents Piezas" in the Antilles, referred to the neurological symptoms of the clinical intoxication which he called "siguatera"

The detailed neurological effects of ciguatera were first described by Lieutenant William Anderson RN, naval surgeon on Cook's Ship HMS Resolution, in the Pacific in 1786. Cook’s crew poisoned both themselves and their dogs.

Which Fish?

•         muraenids (moray eels)

•         lutjanids (e.g. red snappers)

•         serranids (groupers, coral trout, coral cod)

•         lethrinids (emperors)

•         scombrids (tuna-like fishes)

•         carangids (jacks or trevallies)

•         sphyraenids (barracudas).

When and Where?

•         Anytime of year but outbreaks occur in summer with the increase in dinoflagellates.

•         May be more common in reef systems in poor health.

•         Despite a wide distribution, there are many areas relatively free of ciguatera that are adjacent to areas of high risk. An explanation for such patchiness in the occurrence of ciguatera remains elusive.

Incidence

•         Estimated to affect more than 25,000 persons annually (allowing for under reporting)

•         Fatalities are rare (~ 0.1% of cases). One exception is ciguatera in the Indian Ocean, which is more often fatal.

•         Up to 10% of Pacific Islanders per annum

Ciguatoxins

•         Neurotoxins stored in the viscera of fish that have eaten the dinoflagellate are concentrated upwards throughout the food chain towards progressively larger species, including humans.

•         Pacific (P-CTX-1) and Caribbean (C-CTX-1) ciguatoxins.

•         Heat stable polyether toxins, pose a health risk at concentrations above 0.1 ppb.

•         Ciguatoxins are potent, lipophilic sodium channel activator toxins which bind to the voltage sensitive (site 5) sodium channel on the cell membranes of all excitable tissues.

•         Tasteless and odourless. Not affected by cooking or freezing.

•         Do not harm the fish!

•         Bind to Na channel of somatic and autonomic nerves.

•         Resistant to washout from receptor site and high lipid solubility explain chronicity of illness.

•         The severity, number and duration of symptoms reflect the combined influence of dose, toxin profile, and individual factors.

Ciguatera Poisoning

•         Neurotoxic in 80%

•         Nausea, abdo pain and diarrhea in 50%

•         Pathognomonic features of postingestion paraesthesiae, dysaesthesiae, pruritis and heightened nociception, temp reversal.

•         Metallic taste and dental pain 30%.

•         Cerebellar dysfunction.

•         Autonomic dysfunction.

•         Weakness from neuropathy and polymyositis.

•         Profound fatigue in 90% (confusion with CFS).

•         Arthralgia and myalgia in 70%

•         Mood disorders in 50%

•         Relapses in response to certain foods or alcohol reported.

•         In the Pacific Ocean, neurological symptoms predominate.

•         In the Caribbean Sea gastrointestinal symptoms predominate.

•         A third class of ciguatoxins (yet to be chemically defined) is likely to explain the different symptomology observed in the Indian Ocean – most severe form.

Cardiovascular effects of CTX

•         Bradycardia, hypotension, and S-T segment changes. Occasionally HT.

•         CTX impairs cardiac nerve conduction and increase the opening probability of Na+ channels in intracardiac ganglions.

•         Induce swelling of the cells and alterations of cellular organelles ? Role for mannitol.

Diagnosis

•         Remains a clinical diagnosis in the absence of a readily available lab test.

•         Analytical methods with the required sensitivity have been developed, but are unlikely to be cost-effective for routine screening.

•         The toxin is so potent that high performance liquid chromatography and mass spectroscopy are not sufficiently sensitive to detect clinically relevant concentrations of ciguatoxin in crude extracts of fish

•         A diagnostic kit exists for use by fishermen called “Cigua-Check” . $US4.00 each. ?effective

Traetment?

•         Essentially supportive

•         Rehydration important

•         ??Mannitol

•         ?Tricyclic antidepressants

•         ??? IV calcium + vitamins B6 and C

•         Good communication about disease and explanation of chronicity may help alleviate secondary depression and fatigue.

MANNITOL

•         First decribed in Marshall Islands by Palafox

•         JAMA. 1988 May 13;259(18):2740-2.
Successful treatment of ciguatera fish poisoning with intravenous mannitol.

Palafox NA, Jain LG, Pinano AZ, Gulick TM, Williams RK, Schatz IJ.
Armer Ishoda Memorial Hospital, Majuro, Marshall Islands.

•         Then supported by Pearn…

•         Pearn JH. (QLD) “We conclude that an intravenous infusion of 1.0 g/kg of mannitol which is given over 45 minutes, after rehydration if required, can be of significant benefit to at least some acutely intoxicated victims…”

•         Hyperosmotic mannitol infusions may reduce Schwann cell oedema which is a feature of acute ciguatera.

•         Hyperosmolar D-mannitol reverses the increased membrane excitability and the nodal swelling caused by Caribbean ciguatoxin-1 in single frog myelinated axons.

•         We present a case series of four adult tourists who developed ciguatera poisoning after consuming contaminated fish in Vanuatu. All responded well to intravenous mannitol.

•         Stewart MP. Mannitol had little effect upon gastrointestinal manifestations, but a marked reduction was observed in the expected duration of neurological symptoms …

And…

“Twenty-four patients with acute ciguatera fish poisoning were treated with intravenous mannitol, and each patient's condition improved dramatically. All exhibited marked lessening of neurologic and muscular dysfunction within minutes of the administration.”

But then some science…

•         Neurology. 2002 Mar 26;58(6):873-80. s  
Ciguatera fish poisoning: a double-blind randomized trial of mannitol therapy.
Schnorf H, Taurarii M, Cundy T.
50 pts in Cook Islands

“Mannitol was not superior to normal saline in relieving symptoms and signs of CP at 24 hours in this study population but had more side effects. These results do not support single-dose mannitol as standard treatment for CP.”

And…

•         “….these ciguatoxin-treated animals showed that mannitol did not reverse the effects of ciguatoxin on nerve conduction in any of the parameters measured.”

•         In mice, mannitol (1 g/kg i.v.) administered before or after i.p. ciguatoxin did not influence the signs of intoxication or the time to death

Shellfish Poisoning in depth

•         Infectious agents cause most shellfish-associated illness.

1. Hepatitis A
2. Norwalk virus
3. Vibrio parahaemolyticus, Vibrio vulnificus

•         Marine toxins cause  another group of syndromes.

Classification of phytoplanktonic shellfish poisoning:

•         Paralytic shellfish poisoning (PSP)

•         Neurologic shellfish poisoning (NSP)

•         Diarrheal shellfish poisoning (DSP)

•         Amnestic shellfish poisoning (ASP)

The toxins responsible are water-soluble, heat and acid-stable, and are not inactivated

by ordinary cooking methods.

•         PSP - Saxitoxin

•         NPS - Brevetoxin

•         DSP - Okadaic acid

•         ASP - Domoic acid

•         All 4 syndromes share some common features and primarily are associated with bivalve mollusks (eg, mussels, clams, oysters, scallops).

•         These shellfish are filter feeders and, therefore, accumulate toxins produced by microscopic algae in the form of dinoflagellates and diatoms.

Saxitoxin (PSP)

Saxitoxin is 1,000 times more toxic than

the potent nerve gas sarin

•         Saxitoxin was used by the CIA in the 1950's as suicide pills for its agents.

•         President Nixon ordered the painstakingly collected STX stock of the CIA to be destroyed in concordance with the United Nations Agreement on Biological Weapons.

•         Saxitoxins act by blocking sodium ion movement through voltage-dependent sodium channels in nerve and muscle cell membranes. Conduction block occurs principally in motor neurons and muscle.

•          The toxin is made by dinoflagellates of the Gonyaulax species (red tide).

Brevitoxins (NSP)

•         Brevetoxins are polycyclic ethers that, like ciguatoxin, bind to and stimulate sodium flux through voltage-gated sodium channels in nerve and muscle.

•         Brevetoxins are made by the dinoflagellate Ptychodiscus brevis.

Okadaic Acid (DSP)

•         Okadaic acid binds to intestinal epithelial cells and increases their permeability.

•         This toxin is made by dinoflagellates of the species Dinophysis and Prorocentrum.

•          A group of these toxins associated with diarrheal shellfish poisoning has collectively been called pectenotoxins.

Domoic Acid (ASP)

•         Domoic acid is structurally similar to the excitatory neurotransmitter glutamate. Domoic acid binds to and stimulates the kainic acid glutamate receptor, - neuronal depolarization results.

•         Domoic acid is produced by the diatom Nitzschia pungens.

Amnesic shellfish poisoning

•         A rare syndrome

•         Gastrointestinal distress within 24 hours after eating the contaminated shellfish

•         Dizziness, headache, disorientation, and permanent short-term memory loss. In severe poisoning, seizures, focal weakness or paralysis, and death may occur. 

How dangerous are shellfish poisonings?

•         Mostly a problem of temperate regions (esp northern USA).

•         Sporadic outbreaks have been reported in Europe, Asia, Africa, and the Pacific Islands

•         Fatality rates from PSP, the most severe of the 4 syndromes, ranges from 1-12%

•         Its high mortality rate in some areas is caused by poor access to advanced life support capabilities.

•         The mortality rate in the only known outbreak of ASP was 3%.

•         To date, no deaths have been reported for NSP or DSP.

Diagnosis

•         Essentially clinical

•         Direct human serum assays for shellfish toxins are not yet available to clinicians.

Treatment

•         Therapy for all shellfish poisonings is supportive and symptom-driven.

•         Gastrointestinal decontamination with activated charcoal is recommended for patients that present within 4 hours of ingestion. Nasogastric or orogastric lavage may be performed if the patient presents within 1 hour of ingestion, but this is often unnecessary.