Shellfish Toxicity


Article Author:
Matthew Smith


Article Editor:
Henry Swoboda


Editors In Chief:
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Phillip Hynes
Tehmina Warsi


Updated:
4/2/2019 1:55:06 AM

Introduction

Many toxins can accumulate in shellfish and cause disease in humans. The four shellfish poisoning syndromes are paralytic shellfish poisoning (PSP), amnesic shellfish poisoning (ASP), diarrhetic shellfish poisoning (DSP), and neurotoxic shellfish poisoning (NSP). The most well-known paralytic shellfish toxin is saxitoxin. Domoic acid causes amnesic shellfish poisoning. Okadaic acid causes diarrhetic shellfish poisoning. Brevetoxins are the cause of neurotoxic shellfish poisoning. Shellfish toxins are often associated with the presence of harmful algal blooms. [1]

Etiology

Saxitoxin was first isolated from the butter clam. The toxin can be produced by dinoflagellates as well as by cyanobacteria. The toxin then accumulates in filter-feeding shellfish such as mussels, clams, oysters, and scallops over time. From May to August, these organisms are the primary food source for filter-feeders. There are dozens of toxins related to saxitoxin that have small structural differences but produce similar physiologic effects in humans; examples include neosaxitoxin and gonyautoxin. Domoic acid is produced by a type of algae called diatoms, and it also accumulates in filter-feeding shellfish. Okadaic acid is another dinoflagellate product that accumulates in shellfish as well as marine sponges. Brevetoxins are lipid-soluble heat-stable polyether toxins made by the dinoflagellate Karenia brevis, which is the organism that is responsible for the so-called “red tides” of the Gulf of Mexico. [2][3] [4]

Epidemiology

In the United States, cases of PSP have been reported in Alaska, New England, and the West Coast. Cases have also occurred in Europe, Asia, New Zealand, Australia, and South Africa. Some shellfish may store saxitoxin for several weeks, while others may store the toxin for up to two years. There have been cases of ASP in humans in Japan and Canada, and ASP has also been implicated in strange behavior of seabirds in California. Outbreaks of DSP have been documented in the Netherlands and Japan. Florida and the Gulf of Mexico are the most commonly impacted areas of NSP outbreaks. [2] [5] [6] [7] [8] [9] [10] [11] [12] [13] 

Pathophysiology

Saxitoxin and the related paralytic shellfish toxins are selective sodium channel blockers that reversibly bind the voltage-gated sodium channels of neurons. The toxin binds to the channel of the protein and blocks the flow of sodium ions. Saxitoxin is water soluble and both heat-stable and acid-stable. Thus standard cooking methods do not eliminate the toxin. Domoic acid damages the hippocampus and the amygdala by activating the AMPA and kainate receptors of neurons, starting an uncontrolled influx of calcium that causes the cells to degenerate. Domoic acid has also been shown to cause renal damage at doses much lower than those required to cause neurologic symptoms. Okadaic acid is a powerful protein phosphatase inhibitor; this inhibition results in loss of control over sodium secretion and solute permeability in the cell. Brevetoxins bind to voltage-sensitive sodium channels of neurons and muscle cells, lowering the activation potential of neurons and causing them to fire repetitively. [14] 

Toxicokinetics

Saxitoxin is most commonly absorbed by oral ingestion when eating shellfish containing the toxin. However, it can also exert its toxic effect when injected or inhaled. Symptoms of PSP are dose-dependent and can appear in as few as ten minutes after ingestion. The LD50 of saxitoxin, when ingested by humans, is 5.7 micrograms per kilogram. When delivered by injection, the LD50 of saxitoxin is 0.6 micrograms per kilogram. Symptoms of ASP begin from 15 minutes to 38 hours after ingestion, and the mortality rate is two percent. The exact LD50 of domoic acid in humans is not known, but humans have been shown to develop symptoms at a dose of 0.5 mg/kg. Symptoms of DSP begin from 30 minutes to 12 hours after consumption of toxic shellfish, and as little as forty micrograms of okadaic acid can cause gastrointestinal symptoms in humans. However, no fatalities have been reported. Ingestion and inhalation can absorb brevetoxins; dermal uptake may also occur but has not been well studied. Symptoms begin 15 minutes to 18 hours after exposure. Neurotoxic shellfish poisoning is not fatal, however many hospitalizations have been reported.

History and Physical

A history of recent shellfish ingestion may be present. In coastal areas, the presence of harmful algal blooms may increase the risk of episodes of shellfish toxicity. Saxitoxin causes a flaccid paralysis. Thus, difficulty breathing may be present, and death by respiratory failure may occur. Ataxia, vertigo, dysphagia, dysarthria, blindness, paresthesias, and burning sensations of the face and extremities may also be present; paralysis usually resolves within 12 hours. However, muscle weakness may persist for weeks. Domoic acid can cause memory loss as well as coma, seizures, hemodynamic instability, and cardiac dysrhythmias. Approximately 10% of patients will have long-term antegrade memory deficits and paresthesias. Symptoms of diarrhetic shellfish poisoning include nausea, vomiting, diarrhea, and abdominal pain. However, these symptoms may also be seen in the other shellfish poisoning syndromes. Brevetoxins can cause gastrointestinal symptoms as well as paresthesias, myalgias, vertigo, ataxia, reversal of hot and cold temperature sensation, headache, bradycardia, and mydriasis. Aerosolization of brevetoxins in sea spray can cause severe bronchoconstriction, mucosal irritation, and cough. [15] [14] [16] [17]

Evaluation

High-pressure liquid chromatography (HPLC) and enzyme-linked immunosorbent assays (ELISA) can be used to detect saxitoxin, domoic acid, okadaic acid, and brevetoxins. Diagnosis of shellfish poisonings is based on history and clinical presentation. [18] [19] [20] [21] [22] 

Treatment / Management

Treatment of PSP is supportive. If the ingestion of shellfish occurred recently, gastric lavage might be performed, and activated charcoal may be given. Studies in rats and guinea pigs have shown that 4-aminopyridine can reverse the flaccid paralysis and respiratory failure caused by saxitoxin, however, no studies have been performed in humans. Treatment of ASP is also supportive; respiratory support and correction of hemodynamic instability and cardiac dysrhythmias may be necessary. Treatment of DSP includes replacement of electrolyte and fluid loss. Depending on the method of exposure and presenting symptoms, treatment of NSP may include removing the patient from exposure to brevetoxins, airway management, bronchodilators, fluid replacement, and general supportive care. 

Pearls and Other Issues

Saxitoxin was issued to pilots of U-2 spy planes as an injector hidden in a silver dollar; this was depicted in the film Bridge of Spies. The United States military also researched saxitoxin as a chemical weapon before President Nixon’s ban on biological warfare in 1969. Saxitoxin was assigned the chemical weapon designation TZ. An outbreak of ASP in Prince Edward Island, Canada, in 1987 resulted in 19 hospitalizations and four deaths; consumption of blue mussels containing domoic acid was determined to be the cause. In 1977, mussels and scallops harvested in the Miyagi prefecture of Japan caused outbreaks of DSP in Tokyo and Yokohama.

Enhancing Healthcare Team Outcomes

Interprofessional communication will be important to the management of shellfish toxicity. Upon identifying shellfish toxicity as the cause of a patient's symptoms, healthcare providers should contact their public health colleagues to discuss the diagnosis as well as a detailed patient history. Identifying how and where the patient contracted shellfish toxicity will be vital to preventing disease in others. Likewise, after an outbreak has been identified, public health officials should communicate with healthcare providers about likely sources of toxicity so that providers are aware of the sympoms and can ask patients about their potential exposure to the toxin. For large outbreaks, care coordination among multiple physicians, nurses, and hospitals may be necessary. (Level V)


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Shellfish Toxicity - Questions

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Which of the following toxins causes paralytic shellfish poisoning?



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What is the mechanism of action of saxitoxin that causes paralytic shellfish poisoning?



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What are the four different syndromes of shellfish poisoning?



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A patient develops sudden onset of respiratory failure and flaccid paralysis shortly after eating oysters Rockefeller at a seafood restaurant. He is intubated by emergency medical services before arrival at the emergency department. When considering paralytic shellfish poisoning in the differential diagnosis, which of the following is true?



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A patient presents with complaints of headaches, muscle aches, dizziness, and unsteady gait that began about six hours ago. His vital signs are pulse 40 bpm, blood pressure 130/80 mmHg, respiratory rate 15/minute, pulse oximetry 99% on room air, and temperature 98.4 F. During his history, he reports he dined at a seafood restaurant last night. On physical exam, you notice pronounced dilation of his pupils, and when you place your stethoscope on his chest, he winces and pulls away claiming that the stethoscope felt hot. Which shellfish toxin might cause these symptoms?



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Shellfish Toxicity - References

References

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