• PSP: paralysis due to saxitoxin and gonyaulatoxins
• NSP: paresthesia due to brevetoxin; also bronchial spasms
• DSP: diarrhoea due to okadaic acid
• ASP: memory disturbances due to domoic acid

• Pfiesteria: skin ulcers and lesions of the central nervous system. Toxins unclear

Many shellfish –certainly bivalves– often filter enormous amounts of seawater (a mussel filters 50-150 litres of seawater each day). The smallest particles of the plankton, including dinoflagellates, algae and diatoms, remain behind as food. In this manner shellfish concentrate toxins. Most shellfish are not themselves sensitive to these toxins. Toxins may be further modified chemically within the shellfish. The toxins are heat-stable and are not destroyed by boiling, although they may leak into the cooking water. They must not be confused with the toxins of some freshwater cyanobacteria, such as Phormidium sp. or the hepatotoxic microcystines of Microcystis aeruginosa which may be found in drinking water.

Mussels, oysters, St. Jacob’s scallops and a number of other molluscs accumulate viruses, bacteria and toxins due to their manner of feeding (filtration of seawater). Sometimes other medical problems are caused by molluscs, such as stings from venomous Conus shells or bites from Hapalochlaena sp. (blue ring octopus).

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• Bacteria: Salmonella, Vibrio
• Viruses: hepatitis A, Norwalk virus
• Allergy
• Toxins: e.g. heavy metal (mercury)
• Toxins: Diarrhoeic shellfish poisoning (DSP)
• Toxins: Paralytic shellfish poisoning (PSP)
• Toxins: Neurotoxic shellfish poisoning (NSP)
• Toxins: Amnesic shellfish poisoning (ASP)

Shellfish poisoning may result from the presence of large numbers of toxic dinoflagellates in the seawater. The species of dinoflagellate which is responsible for human illness depends on the geographical location. In the southern hemisphere Pyrodinium species will be responsible for PSP, while Alexandrium, Gymnodinium and Dinophysis are responsible for PSP, NSP and DSP in the Northern hemisphere. Gonyaulax tamarensis sometimes blooms in the North Sea, while in California Gymnodinium catenatum causes problems. Most clinical cases occur between late spring and early autumn, which corresponds to the bloom season of these photosynthesising organisms. Shellfish poisoning can also occur without an algal bloom, however. If sediments containing dormant cysts are disturbed so that the cysts are brought into suspension (by dredging or storms), they may pass into the food chain.

The "Alaskan Butter Clam" accumulates saxitoxin in its digestive glands, gills and siphon. The toxicity may persist for two years. This is partly explained by a symbiosis between the dinoflagellate and the mollusc. Saxitoxin in mussels (Mytilus sp.) is stored in the animal’s hepatopancreas. The toxin has a half-life of 12 days if the animals are kept in toxin-free salt water at 15-20°. Mussel banks which are not useable in the summer, may thus deliver edible mussels a few months later. The adductor muscles of St. Jacob’s scallops are rarely toxic (generally only this part of the animal is eaten), although the other tissues contain significant amounts of toxins.

Here we will discuss further the medical problems resulting from biotoxins which originate in plankton and are absorbed via eating shellfish or molluscs. We will differentiate between various clinical entities:

• PSP: paralytic shellfish poisoning.      Paralysis is foremost here.
• NSP: neurotoxic shellfish poisoning.      Paresthesia is foremost here.
• DSP: diarrhoeic shellfish poisoning.      Severe diarrhoea is foremost here.
• ASP: amnesic shellfish poisoning.      Memory problems are foremost here.

Paralytic shellfish poisoning (PSP) is the result of ingestion of saxitoxin, a purine alkaloid. Saxitoxin takes its name from the Alaskan butter clam Saxidomus giganteus. This animal can harbour very large amounts of toxin, and is responsible for a great deal of morbidity. Saxitoxin is produced by Alexandrium (Gonyaulax) tamarense, Alexandrium catenella, Pyrodinium bahamense, Gymnodinium catenatum and Cochlodinium catenatum. Many derivatives of saxitoxin are known as gonyautoxins. The name refers to Gonyaulax, the former name of Alexandrium dinoflagellates. The basic chemical stucture of these gonyautoxins is identical, but they are distinguished by chemical side-chains such as: -H, -OSO₃, -CONH₂, -CONHSO₃). Saxitoxin blocks sodium channels, which leads to paralysis. Deaths resulting from saxitoxin are known. Sometimes the patient requires mechanical ventilation. The lethal dose for humans is 0.1 to 1 mg. Consequently the toxin is extremely powerful (as toxic as tetrodotoxin). It is even regulated under the Chemical Weapons Convention. The toxins are heat-stable and water-soluble. Differentiation between PSP, tetrodotoxin poisoning and ciguatera is not easy.

There is no antitoxin for PSP. Treatment is based on symptomatic care and the avoidance of complications. Inducing vomiting is dangerous due to the risk of aspiration due to loss of the gag reflex. In case of respiratory depression artificial respiration is necessary. Oxygen should be administered. Whether vitamin B injections are beneficial is still an open question.

Gymnodinium breve (previously known as Ptychodiscus brevis) is found in the Caribbean and the Gulf of Mexico. This dinoflagellate produces at least two brevetoxins. These are fat-soluble complex molecules (polyketides). They disturb neuromuscular transmission. After being inhaled as aerosol they cause bronchial spasms. This may be manifested as an "asthma" crisis, rhinitis, sneezing, cough or burning eyes after walking on the beach while a strong breeze which splashes up water (with the toxin). This kind of aerosol is facilitated by the fact that Gymnodinium is a very fragile organism which easily breaks in the surf, releasing the endotoxins. The Alexandrium sp. in the Pacific or in the North Atlantic are much less fragile and do not cause irritation via aerosol. Brevetoxins may be present in molluscs (oysters, mussels) during an algal bloom, but are not present in fish, crabs or snails. If the toxins are absorbed in the intestine, nausea and vomiting, abdominal pain and diarrhoea occur. There then follows paresthesia around the mouth, which extends further to the throat, trunk and limbs. Ataxia, mydriasis, vertigo, breathing difficulties, headache and bradycardia may follow. As yet no deaths due to NSP have been reported. The diagnosis is clinical. There is no antidote.

Various Dinophysis sp. and Prorocentrum sp. produce okadaic acid and derivatives (polyketides). The substance takes its name from the marine sponge Halichondria okadai, from which it was first isolated. These marine sponges are cultivated in Japan and New Zealand and also contain halichondrine, an antitumoural substance (possibly active against melanoma). Okadaic acid has several derivatives. They are known as dinophysitoxins and pectenotoxins. The toxins are powerful inhibitors of protein phosphatases 1A and 2A. They are possibly carcinogenic. Severe diarrhoea results from acute intoxication. Not all diarrhoea after eating seafood is the result of this toxin. Molluscs can also contain viruses (Norwalk agent) and bacteria (Salmonella, Vibrio sp.).

ASP is caused by domoic acid, a neurotoxic tricarboxylic amino acid structurally related to glutamic acid. It was chemically identified after its isolation in 1958 from the seaweed Chondria armata, found off the coast of Japan. In 1987, more than 100 people became ill and several people died following the consumption of blue mussels caught off Prince Edward Island, Canada. Canadian scientists found that domoic acid had entered the food chain when the mussels fed on a toxic algal bloom of the pennate diatom Pseudonitzschia pungens forma multiseries. This is therefore not a toxin of a dinoflagellate, but from diatoms. Domoic acid is known to occur at low concentrations in various red algae (in Chondria armata, Alsidium corallinum and Digenea simplex). Some bacteria which are present in molluscs may use domoic acid as substrate. Their possible role in detoxification of their host needs further research. If the concentration of domoic acid is more than 20 ppm, the seafood is unsuitable for human consumption. After eating toxic mussels, people experience an initial feeling of nausea and diarrhoea, together with hyperexcitation, followed by symptoms attributable to necrosis of certain parts of the brain such as the amygdala and parts of the hypothalamus. The cerebral lesions may be permanent. Disturbed behaviour and loss of memory, as well as involuntary facial grimaces, convulsions, coma and death may follow. Sometimes the chronic symptoms are similar to those of Alzheimer’s disease.

The conditions of the seawater can be monitored by taking water samples and via satellite pictures. Countries all have their own guidelines for acceptable toxin levels. If these levels are exceeded the government will close commercial mussel and oyster banks, forbid the sale of certain seafood and advise against the use of it. For saxitoxins, for example, the limit is set at more than 500 cells of Pyrodinium bahamense per litre of sea water or more than 40 µg of saxitoxins per 100 gram of mollusc. For brevetoxin there is a guideline that only total absence of the toxin can be accepted. A guideline such as this leads to practical problems. The most frequently used monitoring technique is that of the mouse bioassay. For saxitoxin one mouse unit corresponds to 0.18 µg of saxitoxin. One mouse unit kills a 20 gram mouse within 15 minutes if the toxin is administered into the peritoneum. An in-vitro toxicity test via tissue cell cultures will possibly form a good alternative.