Marine harmful algal bloom (HAB) toxins can cause a variety of illnesses in humans through shellfish ingestion. Marine HABs have occurred in the Gulf of Mexico and along the Atlantic and Pacific coasts of the United States. Two major groups of marine phytoplankton, diatoms and dinoflagellates, produce HAB toxins. Common marine HAB toxins found in shellfish include brevetoxins, azaspiracid, domoic acid, okadic acid, saxitoxin.[1]
Toxic outbreaks can cause a red-brown discoloration of the water. This proliferation of toxic dinoflagellates, known as red tide, is favored by warmer weather. This phenomenon has led to the general teaching in North America that shellfish are safe to eat only if harvested in a month containing the letter "r." Most states at risk for marine HABs have excellent monitoring programs in place to close harvesting when toxins are present in shellfish.
Red tide and its resultant massive kills of various birds and marine animals have become an enormous concern in Europe, prompting numerous international congresses to address the problem. In Canada, an outbreak of diarrhea following shellfish poisoning resulted in the formation of a voluntary algal bloom network.[2]
At least 5 distinct shellfish-poisoning syndromes have been identified, as follows[1] :
All 5 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. HAB toxins have also been found in gastropod mollusks (eg, abalone, whelks, moon snails), cephalopod mollusks (eg, octopi, squid, cuttlefish) and crustaceans (eg, Dungeness crabs, shrimp, lobsters).[3]
Poisoning results in gastrointestinal and neurologic illness of varying severity. Symptoms typically appear 30–60 minutes after ingesting toxic shellfish but can be delayed for several hours. Diagnosis is usually one of exclusion and is typically made clinically in patients who have recently eaten shellfish.[3] Care is primarily symptomatic and supportive.
For patient education resources, see Shellfish Poisoning, Gastrointestinal and Shellfish Poisoning, Paralysis.
The toxins responsible for most shellfish poisonings are water-soluble, are heat and acid-stable, and are not inactivated by ordinary cooking methods. The main toxins responsible for each of the shellfish syndromes are as follows:
The 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).
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 binds to intestinal epithelial cells and increases their permeability. This toxin is made by dinoflagellates of the species Dinophysis and Prorocentrum.
Domoic acid (DA) is structurally similar to the excitatory neurotransmitter glutamate. Domoic acid binds to and stimulates the kainic acid glutamate receptor,[4] which allows sodium influx and a small amount of potassium efflux—neuronal depolarization results. Domoic acid has been associated with necrosis of the glutamate-rich hippocampus and amygdala in autopsied cases. Domoic acid is produced by the diatom Nitzschia pungens.
Ingestion of raw or cooked mollusks that contain the toxin in sufficient quantities ensures the development of symptoms.
A wide range of shellfish may cause PSP, but most cases occur after eating mussels or clams. PSP occurs worldwide but is most common in temperate waters, especially off the Pacific and Atlantic Coasts of North America, including Alaska. Cases have also been reported from countries such as the Philippines, China, Chile, Scotland, Ireland, New Zealand, and Australia.[3]
NSP has been reported from the southeastern coast of the United States, the Gulf of Mexico, the Caribbean, and New Zealand.
Most cases of DSP result from eating toxic bivalve mollusks such as mussels and scallops. Occurrences have been reported in Europe, Asia, North America, South Africa, Australia, and New Zealand.[5]
ASP has been reported from Canada, Scotland, Ireland, France, Belgium, Spain, Portugal, New Zealand, Australia, and Chile. Toxic mussels, scallops, razor clams, and crustaceans were responsible in those outbreaks.[3] In the Pacific Northwest, Chesapeake Bay and along the coasts of western Europe and eastern Asia, peak annual levels of DA in shellfish can exceed the regulatory limit, resulting in intermittent restrictions on shellfish harvests.[6]
AZP was identified following cases of severe GI illness from the consumption of contaminated mussels from Ireland. It has since been found in the Netherlands, Belgium, Morocco, and eastern Canada.[1]
Education, surveillance, and strict regulation by public health officials appear to be decreasing the incidence of shellfish poisoning in the United States. Additionally, enzyme-linked immunosorbent assay (ELISA) screening techniques are making detection of these toxins simple and rapid.[7]
Cases of PSP have occurred along the northeast Atlantic coast, northwest Pacific coast, or Alaska.[8] Most cases have involved recreational shellfish collectors, not commercial vendors. The 2017 Annual Report of the American Association of Poison Control Centers' National Poison Data System (AAPCC-NPDS) documented 109 single exposures to paralytic shellfish poisoning; no deaths occurred.[9]
Sporadic outbreaks have been reported in Europe, Asia, Africa, and the Pacific Islands.
Children appear to be more sensitive than adults to the saxitoxins of PSP. To date, all the reported deaths from ASP have been in elderly persons who had more severe neurologic symptoms.
The 2017 Annual Report of the American Association of Poison Control Centers' NPDS reported 17 minor outcomes, 20 moderate outcomes, 3 major outcomes, and no deaths among 109 patients with paralytic shellfish poisoning single exposures.[9] Although any person eating fish or shellfish containing HAB toxins may become ill, persons with some chronic diseases, such as liver disease, could potentially have more severe illnesses.[3]
Fatality rates from PSP, the most severe of the 4 shellfish poisoning syndromes, ranges from 1-12% in isolated outbreaks. In cases of severe PSP, muscle paralysis and respiratory failure can lead to death in 2–25 hours. The risk of death from PSP is reduced if healthcare professionals have access to advanced life support capabilities.[1]
Depending upon the dose of DA and adult age, ASP may result in mild discomforts, such as gastrointestinal symptoms, but with progressively larger doses, memory loss, seizures, coma, or death occur.[10]
The first reported human domoic acid poisoning event occurred in 1987 and affected more than 100 people after eating mussels harvested off Prince Edward Island, Canada. Gastroenteritis followed by headache and short-term memory loss occurred. In a few cases, severe cognitive dysfunction to the point of interfering with the patient's ability to perform normal daily activities was noted. Seizures, coma, hemiparesis, and ophthalmoplegia were noted in the most severe cases. The mortality rate of ASP was 3%.[4]
Research strongly indicates that infants and fetuses are much more susceptible to the toxic effects of DA than are adults. DA can move across the placenta and concentrate in amniotic fluid, which can be swallowed during late gestation. DA also transfers to infants via breastmilk. It has been hypothesized that early exposure to DA may render the developing fetus at risk for schizophrenia and autism. Studies in rodents and California sea lions exposed to DA reported effects including seizures, diminished social regulation, and repetitive behaviors bearing a striking resemblance to the clinical features of these disorders in humans.[6, 10, 11]
To date, no deaths have been reported for NSP or DSP. There are no reports of long-term effects, but no long-term follow-up studies of those affected by HABs have been conducted.[1]
All 5 shellfish poisoning syndromes can produce symptoms lasting from a few minutes to several hours after ingestion of contaminated shellfish.
Symptoms usually begin within 2 hours of eating contaminated shellfish, but can start anywhere from 15 minutes to 10 hours after the meal.[1, 3] The onset generally is noted with paresthesias of the lips, tongue, and gums. After onset, symptoms rapidly progress to involve the distal extremities. Other symptoms include a sensation of floating, headache, ataxia, muscle weakness, paralysis, and cranial nerve dysfunction.
Gastrointestinal symptoms are less common and may include nausea, vomiting, diarrhea, and abdominal pain. Fatalities are usually within the first 12 hours of symptom onset and are caused by unsupported respiratory failure. PSP usually lasts 3 days, but muscle weakness may persist for weeks.
The illness encountered with NSP is milder than that with PSP. Symptom onset ranges from 15 minutes to 18 hours postingestion, and the duration of toxicity ranges from 1-72 hours (usually < 24 h) postingestion.
Presenting symptoms include gastroenteritis; rectal burning; paresthesias of the face, trunk, and limbs; myalgias; ataxia; vertigo; and reversal of hot/cold sensation. Other less common features include tremor, dysphagia, bradycardia, decreased reflexes, and mydriasis.
This syndrome presents much like ciguatera poisoning but without a paralytic component, and it may last from several hours to a few days. The brevetoxins, unlike the other shellfish toxins, can become aerosolized by the surf and produce an allergic response characterized by rhinorrhea, conjunctivitis, bronchospasm, and cough in sensitive individuals along the shore.
DSP produces stomach and intestinal symptoms that usually begin 30 minutes to a few hours after eating contaminated shellfish and include the following[1] :
In most cases, gastrointestinal symptoms such as diarrhea, vomiting, and abdominal pain develop within 24 hours of eating toxic shellfish, followed by headache, memory loss, and cognitive impairment. In severe cases there may be hypotension, arrhythmias, ophthalmoplegia, coma, and death. Survivors may have severe anterograde, short-term memory deficits.[3]
Azaspiracid Shellfish Poisoning (AZP) is the most recently discovered human illness related to shellfish contaminated with a HAB toxin. AZP is believed to be caused by a dinoflagellate that produces toxins that have been found in Ireland, the Netherlands, Belgium, Morocco, and eastern Canada.[1]
Eating contaminated shellfish can result in symptoms including the following[1] :
Findings vary according to the syndrome involved but volume depletion from gastrointestinal symptoms is common to all syndromes. Gastrointestinal symptoms occur less often in PSP than in the other syndromes. Paresthesias of the face and extremities are noted only in PSP and NSP. ASP is the only shellfish syndrome with cognitive dysfunction as an early finding.
Direct human serum assays for shellfish toxins are not yet available to clinicians. Research in this area is ongoing, and a reliable assay for several of these specific toxins should be available soon.
Saxitoxin can be assayed by using a mouse bioassay, enzyme-linked immunosorbent assay (ELISA), and high-performance liquid chromatography (HPLC). Brevetoxin can be assayed by using a mouse bioassay, ELISA, and antibody radioimmunoassay (RIA). Liquid chromatography, mass spectrometry, and ELISA techniques have been developed for domoic acid.[12]
A mass spectrometry assay was used to quantify saxitoxin and neosaxitoxin in human urine samples, with results suggesting that few false-positive outcomes would occur when attempting to identify people exposed to these toxins.[13]
Therapy for all shellfish poisonings is supportive and symptom-driven. Support and maintenance of the airway are of crucial importance in paralytic shellfish poisoning.
Gastrointestinal decontamination with activated charcoal is recommended for patients who 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.
If gastric lavage is performed, the use of isotonic sodium bicarbonate solution as a lavage irrigant has been suggested because many of the shellfish toxins have reduced potency in an alkaline environment.
Okadaic acid undergoes enterohepatic recycling that could be interrupted by delayed or repeat charcoal administration.
The greatest danger is respiratory paralysis. Close monitoring for at least 24 hours and aggressive airway management at any sign of respiratory compromise should prevent severe morbidity and mortality.
Neostigmine and edrophonium have been used to improve muscle weakness following tetrodotoxin intoxication, which is similar to saxitoxin intoxication. Nonetheless, no clinical trials have evaluated the use of these drugs for saxitoxin exposures.
Routine surveillance of shellfish beds for known toxins should prevent most forms of shellfish poisoning. Consumption of shellfish harvested outside of regulated areas or during times known to be associated with red tide is dangerous and should be avoided. Check with local health officials before collecting shellfish, and look for advisories about harmful algal blooms or water conditions that may be posted at fishing supply stores, by beach managers, or local health authorities. Harmful algal bloom (HAB) advisories are posted online by many states.[1]
Shellfish sold as bait should never be consumed. Bait products do not need to meet the same food safety regulations as seafood for human consumption.[1]
Clinical Context: Emergency treatment in poisoning. Network of pores present in activated charcoal adsorbs 100-1000 mg of drug per gram of charcoal. Does not dissolve in water. For maximum effect, administer within 30 min of ingesting poison.
Cathartic not to be used in children < 2 y.
GI decontaminants are empirically used to minimize systemic absorption of the toxin. They may only be beneficial if administered within 1-2 h of ingestion.