Paralytic Shellfish Poisoning

This information is courtesy of Lora E. Fleming, NIEHS Marine and Freshwater Biomedical Sciences Center

Background

PSP is a marine toxin disease with both gastrointestinal and neurologic symptoms reported worldwide. It is caused predominantly by the consumption of contaminated shellfish.

Gonyaulacoid dinoflagellates are the source of PSP marine toxins.These unicellular dinoflagellates develop algal blooms throughout the world for unknown reasons, although a variety of factors have been studied, including change in weather, upwellings, temperature, turbulence, salinity, and transparency. However, significant epidemics of PSP can occur in humans in the absence of a known red tide (Rodrigue et al. 1990). These dinoflagellates produce at least 12 toxins which are tetrahydropurines, and heat and acid stable. Saxitoxin was the first characterized and the best understood.

The major transvector for PSP are the bivalve molluscs (mussels, clams, oysters, with the Alaskan butterclam having the highest concentrations) (Sommer & Meyer 1937). PSP toxins are also found in certain crabs and snails which feed on coral reef seaweed. The transvectors accumulate the toxins via feeding in their digestive organs and soft tissues, apparently without harm to the transvectors.

Humans, birds and fish can all be affected by PSP toxins. Herbivorous zooplankton is the primary transvector which can in turn transmit the toxin to fish and possibly other marine creatures which consume zooplankton (Baden 1983). The usual route for humans is the consumption of raw or cooked contaminated shellfish. There has been only one case of human contamination through consumption of contaminated fish and bird kills in Indonesia. In this case, the whole fish was consumed including the viscera which could be contaminated with PSP from shellfish consumption by the fish prior to death (MacLean & White 1989, Viviani 1992).

Clinical Presentation:

Ingestion of molluscs contaminated with PSP results in the following clinical picture (Bower et al, 1981, Kao 1993). Five to 30 minutes from consumption, there is slight perioral tingling progressing to numbness which spreads to face and neck to moderate cases. In severe cases, these symptoms spread to the extremities with incoordination and respiratory difficulty. There are medullary disturbances in severe cases evidenced by difficulty swallowing, sense of throat constriction, speech incoherence or complete loss of speech, as well as brain stem dysfunction. Within 2-12 hours, in very severe cases, there is complete paralysis and death from respiratory failure in absence of ventilatory support. After 12 hours, regardless of severity, victims start to recover gradually and are without any residual symptoms within a few days (Bower et al, 1981, ILO 1984, Halstead 1988).

Other symptoms include headache, dizziness, nausea, vomiting, rapid pain, and anuria. There is no loss of consciousness and the reflexes are unaltered except maybe pupillary size and sight may be temporarily lost. As opposed to tetrodotoxin poisoning, there is rarely significant hypotension. Symptomatology is essentially identical for Pacific and Atlantic cases, although gastrointestinal symptoms may be more prominent in the Atlantic (ILO 1984, Halstead 1988).

The overall mortality (case fatality rate) was about 8.5% -9.5% in two large series (Meyer 1953, Ayres and Cullum 1978). However, the Guatemalan 1987 outbreak on Pacific coast had a case fatality rate of 14%, which was even higher in young children (50%). It is possible that children may be more sensitive to PSP toxins than adults (Rodrigue et al. 1990). In addition, the access to emergency medical services in acute cases is crucial to the prognosis.

The differential diagnosis of this clinical scenario of an acute gastrointestinal illness with recent shellfish ingestion would be bacterial or viral gastroenteritis. The neurologic manifestations are more consistent with poisoning by other marine toxins such as NSP and pufferfish poisoning, or even recent organophosphate pesticide poisoning.

Diagnosis:

The clinical scenario is the primary method of diagnosis initially. Recent shellfish ingestion, often but not always associated with known red tide, and an acute gastrointestinal illness with neurologic symptoms are part of the classic presentation. It is imperative to obtain samples of contaminated tissues and their source.

Each PSP epidemic is associated with different mixtures of the PSP toxins; this complicates the laboratory analysis of contaminated tissues. The mouse bioassay (time to death) of food extract is the recommended diagnostic method, (Sommer & Meyer 1937, Association of Official Analytical Chemists 1980) but it cannot distinguish between tetrodotoxin and other PSP toxins. The oral dose in humans for death is 1 to 4 mg (5,000 to 20,000 mouse units) depending upon the age and physical condition of the patient (see below). A mouse unit [MU] is defined as the minimum amount needed to cause the death of an 18 to 22 g white mouse in 15 minutes (Wiberg & Stephenson 1960, Shimizu 1984, Winter et al, 1990).

Radioimmunoassay and indirect enzyme-linked immunoabsorbent assay (ELISA) have been developed for saxitoxin but not all PSP toxins (Carlson et al, 1984). HPLC analysis method for all the PSP toxins has been developed with good correlation with mouse bioassay in terms of quantification (Sullivan et al, 1983, Halstead 1988).

Management and Treatment:

In general, supportive measures are the basis of treatment for PSP, especially ventilatory support in severe cases. In animals, artificial respiration is the most effective treatment. Without supportive treatment, upto 75% of severely affected persons die within 12 hours. Use of anticholinesterase agents are not recommended, and could actually be harmful (Murtha 1960, ILO 1984, Halstead 1988, Brown & Shepherd 1992, Kao 1993).

When the ingestion of contaminated food is recent, gut decontamination by the gastric lavage and administration of activated charcoal or dilute bicarbonate solution is recommended. Care must be taken concerning aspiration with the neurologically compromised patient. Anticurare drugs were ineffective, while DL amphetamine (benzedrine) was most effective in aiding the artificial respiration and decreasing the recovery period. Use of anticholinesterase agents are not recommended, and could actually be harmful (Murtha 1960, Bower et al, 1981, ILO 1984, Halstead 1988, Brown & Shepherd 1992, Kao 1993).

The lactic acidosis of unknown origin seen in experimental animals and possibly humans can be treated by assisted ventilation, fluid therapy and periodic monitoring of the blood pH. It is possibly that the fluid therapy will also assist in the renal excretion of toxin (Kao 1993).

Many endemic areas have traditionally used local treatments with variable success. In the Philippines, a drink of coconut and brown sugar is administered; demonstrations in mice show that these ingredients may have active detoxification substances (Viviani 1992).

As with many of the marine toxin induced diseases, the initial or index case(s) are often the tip of the iceberg. Therefore any cases of PSP 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 the most effective form of PSP prevention is to eliminate human contact with contaminated shellfish and other transvectors. Surveillance and closures of commercial shellfish beds by monitoring the amount of PSP using the mouse assay are common practice throughout the world. For example, in the USA, PSP levels in edible shellfish greater than 800 ug PSP/kg by mouse assay means that commercial beds will be closed until they are monitored below this level; this action level is more than 10 times lower than the lowest level associated with human outbreaks [Anon 1965, ILO 1984]. Furthermore, there is active monitoring of algal blooms with fish and bird kills.

Ozonation can remove low levels of toxins from soft-shell clams but not if the clams have retained toxin for long periods of time; some industrial canning processes may lead to a decrease in PSP concentration (Halstead 1988, Viviani 1992). Biological controls such as using parasitic dinoflagellates to attack the red tide (for example Amoebophrya ceratii parasitizes a variety of dinoflagellates responsible for PSP) have been considered (Viviani 1992).

PSP Chemical Structure

Molecular Mechanism of Action:

Saxitoxin is the most well known of the PSP associated toxins. It is a heat stable neurotoxin. In mice, the saxitoxin LD50 parentally is 3-10 ug/kg body weight and orally is 263 ug/kg body weight (death within minutes of respiratory failure). Humans are the most sensitive to saxitoxin; the oral dose in humans for death is 1 to 4 mg (5,000 to 20,000 mouse units) depending upon the ge and physical condition of the patient. It is rapidly absorbed through the gastro-intestinal tract and excreted in the urine.

Saxitoxin inhibits the temporary permeability of Na+ ions by binding tightly to a receptor site on the outside surface of the membrane very close to the external orifice of the sodium channel. In fact, neurophysiologic studies using saxitoxin as a probe helped to show that Na+ and K+ act independently with separate membrane channels. It is a blocking agent that reduces the number of conducting Na+ channels by occupying some site near the outer opening in a 1:1 high affinity specific receptor binding. This prevents sodium ions from passing through the membranes of nerve cells, thus interfering with the transmission of signals along the nerves. The resulting widespread blockade prevents impulse-generation in peripheral nerves and skeletal muscles. Saxitoxin has a direct effect on skeletal muscle by blocking the muscle action potential without depolarizing cells; it abolishes peripheral nerve conduction but with no curare-like action at the neuromuscular junction.

References:

  • ASSOCIATION OF OFFICIAL ANALYTICAL CHEMISTS (AOAC). Paralytic Shellfish Poison Biological Method. In: Official Methods of Analysis. Washington, AOAC (1980) 289-299.

  • AYRES, P.A. and M. CULLUM: Paralytic Shellfish Poisoning. London Ministry of Agriculture, Fisheries and Food (Fisheries Research Technical Report #4) (1978) 23.

  • Baden D, Fleming LE, Bean JA. Chapter: Marine Toxins. in: Handbook of Clinical Neurology: Intoxications of the Nervous System Part II. Natural Toxins and Drugs. FA deWolff (Ed). Amsterdam: Elsevier Press, 1995. pgs. 141-175.

  • CHENG, H.S., S.O. CHUA, J.S. HUNG and K.K. YIP: Creatinine kinase MB elevation in paralytic shellfish poisoning. Chest 99 (1991) 1032-3.

  • FRANZ, D.R. and R.D. LECLAIRE: Respiratory effects of brevetoxin and saxitoxin in awake guinea pigs. Toxicon 27 (1989) 647-654.

  • HALSTEAD, B.W. and E.J. SCHANTZ: Paralytic Shellfish Poisoning. Geneva, World Health Organization (1984) 60.

  • KAO, C.Y.: Paralytic Shellfish Poisoning. In: IR Falconer (ed), Algal Toxins in Seafood and Drinking Water. London: Academic Press (1993)

    75-86.

  • LONG, R.R, J.C. SARGENT and K. HAMMER: Paralytic Shellfish Poisoning: A case report and serial electrophysiologic observations. Neurology 40 (1990) 1310-1313.

  • MEE, L.D., M. ESPINOSA and G. DIAZ: Paralytic Shellfish Poisoning with a Gymnodinium catenatum Red tide on the Pacific Coast of Mexico. Marine Environmental Research (1986) 141-1136.

  • RODRIGUE, D.C., R.A. ETZEL, S. HALL, E. DE PORRAS, O.H. VELASQUEZ, R.V. TAUXE, E.M. KILBOURNE and P.A. BLAKE: Lethal Paralytic Shellfish Poisoning in Guatemala. American Journal of Tropical Medicine and Hygiene 42 (1990) 267-271.

  • SHIMIZU, Y.: Paralytic shellfish poisons. Forthscritte Der Chemie Organischer Naturstoffe 45 (1984) 235-64.

  • SULLIVAN, J.J., M.G. SIMON and W.T. IWAOKA: Comparison of HPLC and mouse bioassay methods for determining PSP toxins in shellfish. Journal of Food Science 48 (1983) 1312-1314.


Last updated: July 31, 2012