Overview
Seafood-borne illness, or seafood poisoning, occurs as a result of human consumption of food harvested from the sea. This includes, but is not limited to, finfish and shellfish. Patients with seafood-borne illnesses may present a diagnostic challenge, as they may have variable signs and symptoms, different degrees of severity, as well as unclear timelines in relation to ingestion.
The scope of seafood-borne illness is vast, and, with increased travel and expanding seafood trade, the likelihood of a care provider seeing a seafood-borne illness is increasing. [1, 2, 3] The 2019 Annual Report of the American Association of Poison Control Centers' National Poison Data System documented 808 single exposures to ichthyosarcotoxins (ie, ciguatera, clupeotoxic fish, paralytic shellfish, scombroid fish, tetrodotoxin poisoning, and other types of seafood poisoning); no deaths occurred. [4]
The intent of this article is not to exhaustively cover all types of seafood-borne illness but, rather, to provide a general overview. Poisoning by viral and bacterial contamination of seafood, as well as marine envenomations, are not covered here. For more information on specific types, see the following:
For patient education resources, see Food Poisoning, Ciguatera Fish Poisoning, and Shellfish Poisoning.
Finfish Poisoning
Ciguatera Poisoning
Ciguatera poisoning is the most common nonbacterial fish-borne poisoning in the United States, with most of the cases being reported in Florida and Hawaii. [5] Ciguatera poisoning is endemic in warm waters, spans the globe, and is generally observed between latitudes within 35° of the equator. It is most commonly associated with larger reef-dwelling fish such as moray eels, barracuda, red snapper, and amberjack. Prevalence of ciguatera poisoning is likely underestimated due to lack of recognition of symptoms by clinicians. [6]
Ciguatera toxins (CTXs) are produced most often by the marine dinoflagellate Gambierdiscus toxicus, although other species responsible for CTX production have been identified. The toxin enters the food chain via fish, which are then consumed by humans, in whom the toxin causes symptoms.
Ciguatera toxin is a polyether ladder that binds to and opens voltage-dependent sodium channels. It is lipid soluble and concentrates in the flesh, adipose tissue, and organs of the larger fish. Contaminated fish smell and taste normal. The toxin is heat stable and thus may affect humans even if fish are properly prepared. Ciguatera toxin is secreted into breast milk and freely crosses the placenta. [7]
The onset of gastrointestinal (GI) and neurologic symptoms after the consumption of fish are the hallmarks of ciguatera poisoning. Symptoms are usually evident within 2-6 hours after ingestion and usually resolve within 24 hours, although a late-presenting and extended course is not uncommon. [8] GI symptoms generally consist of diaphoresis, abdominal cramps, nausea, vomiting, profuse watery diarrhea, and dysuria. GI symptoms are usually reported to occur prior to neurologic symptoms. Interestingly, however, the predominance of GI versus neurologic symptoms seems to vary according to regions, with GI-predominant illness seen in the Caribbean, while neurologic symptoms predominate in the Indo-Pacific region.
Neurologic symptoms tend to occur later (up to 72 h) and may persist for months. These are predominantly paresthesias, but myriad other, sometimes bizarre, neurologic symptoms may also be observed, including pruritus; the sensation of loose painful teeth; tingling in the lips, tongue, throat, and perioral tissues; metallic taste; reversal of temperature sensation; and the sensation of heat in the superficial tissues of the extremities with concomitant sensation of cold in the deeper tissues. [9] Further neurologic symptoms can include vertigo, ataxia, visual changes, and seizures.
In more severe poisonings, bradycardia with hypotension and cardiovascular collapse may occur. [10] Although ciguatera poisoning may rarely require intensive medical care, no fatalities in the United States have been documented. [4]
Ciguatera is diagnosed clinically. [9] Currently, no available biomarkers accurately confirm exposure in humans. The diagnosis is based on the history of consuming a reef fish (not shellfish) and the appropriate time course of symptoms, as well as the exclusion of other explanatory causes. It is also strongly suggested when multiple individuals who consumed the same fish present with similar signs and symptoms. Both an enzyme-linked immunosorbent assay (ELISA) and high-performance liquid chromatography (HPLC) test are available to confirm the presence of ciguatoxin in fish flesh but are not used in acute treatment.
Treatment of ciguatera poisoning is primarily supportive. The osmotic diuretic mannitol has become the mainstay of acute treatment in recent years, as it has been reported to dramatically diminish or prevent neurologic symptoms. [11, 12] However, at least one prospective, controlled study found no difference between mannitol and normal saline in the treatment of ciguatera poisoning. [13]
Amitriptyline has been reported to relieve pruritus and dysesthesias in patients with acute ciguatera toxicity, and to diminish the severity of residual symptoms. [14] Other symptomatic treatments may include gabapentin or pregabalin for neuropathic symptoms, fluoxetine for chronic fatigue, and nifedipine or acetaminophen for headache. [8]
Histamine Fish Poisoning
Histamine fish poisoning, also known as scombroid fish poisoning, results from the ingestion of improperly handled/stored finfish, such as tuna, bonito, and mackerel. [9] While it is the second most common finfish poisoning reported in the United States and in the world (behind ciguatera), what sets it apart from all other seafood poisonings is that it is 100% preventable if the fish are handled and stored (refrigerated) correctly. [15] Recent surveillance suggests the incidence of scombroid is decreasing. This is likely due to increased public awareness of the disease and public education on properly handling and storing fish.
The term “scombroid” gets its name from the Scombridae fish family, which includes mackerel and tuna—the original fish implicated. [16] While Scombridae are still a major cause of scombroid, the US Centers for Disease Control and Prevention (CDC) reports that non-Scombridae fish, such as amber jack, mahi mahi, and swordfish, are also common vectors. [17]
Regardless of which species, the commonality of all fish known to cause scombroid is the high levels of histidine in their muscle tissue. The pathophysiology of the syndrome is complex and not completely understood. It is accepted that the decarboxylation of histidine, naturally found in fish, into biogenic amines, such as histamine, is clearly a major part of the toxicity; however, the fact that a pure histamine ingestion, at any dose, does not reproduce the scombroid syndrome shows that other compounds, yet to be identified, exist in the scombrotoxin. [18, 19] The conversion of histidine to histamine occurs at temperatures greater than 15°C (temperatures well above proper refrigeration), and even proper cooking is not a remedy for improper storage, as histamine is heat stable.
A constellation of symptoms is seen in scombroid poisoning. These can include skin flushing, throbbing headache, peppery taste (while patients sometimes describe a peppery or bitter taste to the fish, often it tastes completely normal), oral numbness, abdominal cramps, nausea, diarrhea, palpitations, and anxiety. Symptoms usually occur within 10-60 minutes of ingesting fish; generally, they are self-limited. Physical signs may include a diffuse blanching erythema, tachycardia, wheezing, and hypotension or hypertension. More severe cardiovascular manifestations attributed to scombroid poisoning have been reported but are rare.
Scombroid is often is misdiagnosed because it resembles an allergic reaction [20] (thus a major reason for the belief that it is vastly underreported). The diagnosis is usually made on the basis of the history and physical examination. Laboratory tests are available to measure the concentration of histamine in fish; however, these are generally unnecessary.
In most healthy patients, scombroid is self-limiting; severe sequelae are rare but reported, mostly involving those with respiratory or cardiac comorbidities, though occasionally the young and healthy. Treatment is directed toward supportive care (eg, oxygen and fluids). H1-blockers and H2-blockers diminish the effects of histamine, and bronchodilators may be of benefit. Steroids are not effective. [21] Epinephrine is rarely necessary, as the full cascade of mediators of allergic reactions does not occur; thus, symptoms are usually less serious. Prevention involves proper refrigeration of fish at temperatures of less than 4.4º C (40ºF).
Tetrodotoxin Toxicity
Poisoning with the neurotoxin tetrodotoxin (TTX) occurs after ingestion of various species of puffer fish, blue-ringed octopus, newts, gobies, frogs, starfish, and horseshoe crab eggs. While rare, TTX is the most common lethal seafood poisoning. [22] In the puffer fish, TTX concentration and distribution depend on the species, although generally the ovary, liver, and skin usually contain highest amount.
Puffer fish are most commonly found in the tropical waters of the Indo-Pacific region and poisoning occurs mainly in Southeast Asia. Japan accounts for the most poisonings worldwide (30-50/y), owing to its consumption of puffer fish, known as fugu, which is seen as a delicacy. While the literature does contain reports of puffer fish poisoning due to consumption of misidentified fish, [23] most occur due to unskilled preparation by unlicensed cooks. While the US Food and Drug Administration (FDA) does allow legal importation of puffer fish into the United States, through a single certified Japanese importer, [24] illegal importation continues in response to consumer demand and has resulted in multiple poisonings. [25] In 2019, the American Association of Poison Control Center National Poison Data System (AAPC-NPDS) reported 210 single exposures to TTX. [4]
TTX is one of the most potent nonprotein poisons found in nature. TTX physically blocks voltage-gated sodium channels, leading to failure of depolarization and propagation of the action potential in nerve cells. [26] The minimum lethal dose in humans for TTX is estimated to be 2 mg, [27] but this can vary based on age and existing comorbidities. The CDC has reported symptoms of TTX toxicity with consumption of as little as 0.25-1.5 oz of incorrectly prepared fugu.
Symptoms occur within 15 minutes of ingestion but may be observed as late as several hours later. More rapid onset of symptoms is associated with higher levels of toxin ingestion. Symptoms are principally neurologic and cardiovascular in nature and may include perioral tingling, a floating sensation, a feeling of overall warmth, weakness, incoordination, slurred speech, bradycardia, hypotension, and dyspnea. Decreased levels of consciousness, seizures, and death have occurred in as few as 17 minutes.
The following is the classic grading system for tetrodotoxin poisoning based on symptoms and signs [28, 29, 30] :
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Grade 1 - Perioral numbness and paraesthesia, with or without GI symptoms (mainly nausea)
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Grade 2 - Numbness of tongue, face, and other areas (distal); early motor paralysis and incoordination; slurred speech; normal reflexes
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Grade 3 - Generalized flaccid paralysis, respiratory failure (dyspnea), aphonia, and fixed/dilated pupils; patient still conscious
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Grade 4 - Severe respiratory failure and hypoxia; hypotension, bradycardia, and cardiac dysrhythmias; unconsciousness may occur
New literature has investigated the use of a magnetic bead (MB)-based colorimetric immunoassay for analysis of TTX in fish. [31]
No antidote is available for TTX poisoning, and good supportive care and serial neurologic reviews are the mainstays of treatment. Neostigmine (an anticholinesterase) has been used with little success and is described in case reports only. [29, 32] Atropine, pressors, and intravenous fluids can be used for cardiovascular instability, and ventilatory management may be needed for respiratory failure in more severe poisonings.
In all but the mildest cases, patients should be admitted until the peak effects have passed (life-threatening complications are highly unlikely after 24 h). [29] Remember that exposure to TTX generally leaves a patient awake and alert, even though they have findings consistent with paralysis, so do not overlook sedation.
Sardine poisoning (clupeotoxism)
Sardine poisoning, or clupeotoxism, is a rare and very poorly reported form of seafood poisoning caused by the ingestion of clupeiformes, which include sardines, herrings, and anchovies. [33, 34] The 2019 AAPCC-NPDS documented 2 single exposures. [4]
While clupeotoxism is sporadic and very rare, significant mortality is reported. The most distinctive and immediate symptom is a sharp metallic or bitter taste accompanied by nausea and tingling of tongue and lips. This is soon followed by GI symptoms that include vomiting, abdominal pain, and severe diarrhea, which may be accompanied by tachycardia, clammy skin, hypotension, and other signs of impending vascular collapse. Neurologic symptoms reported include nervousness, dilated pupils, severe headache, numbness, tingling, hypersalivation, dyspnea, progressive muscular paralysis, convulsions, coma, and death. The onset of symptoms is very rapid, usually within 15 minutes. Death may occur within hours. [33] No antidote is available, and treatment is supportive care only.
Hallucinogenic fish poisoning
Hallucinogenic fish poisoning, or ichthyoallyeinotoxism, is rare form of seafood poisoning that can occur with the ingestion of a number of fish species (many of which are implicated in ciguatera poisoning, adding to the difficulty of diagnosis). It is mainly found in reef fish from the Mediterranean Sea and the Indian and Pacific Oceans. The exact toxin is unknown, although indole compounds formed by macroalgae have been implicated. [35, 36]
Clinical symptoms of ichthyoallyeinotoxism occur within a few minutes to 2 hours after ingestion of toxic fish. The first symptoms usually seen are a loss of balance and coordination and generalized malaise. [35] GI symptoms are generally mild and include nausea, abdominal pain, and diarrhea. Within a few hours, specific signs of poisoning occur including delirium, visual and/or auditory hallucinations (often involving animals), depression, feeling of impending death with reactive tachycardia and hyperventilation, and disturbed behavior. If they are able to sleep, patients classically report terrifying nightmares. [36] While hallucinogenic fish poisoning does share many similarities with ciguatera, it has pronounced central nervous system involvement, whereas ciguatera features peripheral nervous system involvement.
No specific treatment or antidote is available. Appropriate management of transient behavioral disturbances (eg, using benzodiazepine or neuroleptics) is important to prevent self-inflicted or other injury. Symptomatic treatment for GI manifestations can enhance patient comfort. Symptoms generally resolve within 24-36 hours, but weakness may persist for several days. [35]
Shellfish Poisoning
The bulk of shellfish “poisonings” are likely infectious in nature, with hepatitis A, Norwalk virus, and Vibrio species all being implicated and with Norwalk virus likely accounting for the bulk of GI cases. That being said, marine harmful algal bloom (HAB) toxins can cause a variety of illnesses in humans through shellfish ingestion. Two major groups of marine phytoplankton, diatoms and dinoflagellates, produce HAB toxins. [37] Most dinoflagellate toxins are neurotoxins, often acting on voltage-sensitive ion channels to cause their effects.
Common marine HAB toxins found in shellfish include brevetoxins, azaspiracid, domoic acid, okadic acid, saxitoxin. These toxins cause paralytic, neurologic, diarrheal, amnestic and azaspiracid shellfish poisonings. 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). [8]
Contaminated (toxic) shellfish may be found in temperate and tropical waters, typically during or after a harmful phytoplankton bloom such as the Florida red tide caused by Karenia brevis. [38] Red tide gets its name from the phenomenon by which pigmented phytoplankton reproduce to such a high concentration that it turns the water red or dark brown. However, it should be noted that most production of toxic algae is not accompanied by the red coloration of seawater. Most states at risk for marine HABs have excellent monitoring programs in place to close harvesting when toxins are present in shellfish. The incidence of shellfish poisoning has been declining, most likely because of this careful monitoring, beach closures, and improved public awareness. [37]
Paralytic shellfish poisoning
Paralytic shellfish poisoning (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. PSP is not only the most common form of shellfish poisoning, but it is also the deadliest, with a mortality rate of 6% worldwide (higher in developing countries). [29, 39, 40]
The causative agent is saxitoxin, which is produced by dinoflagellates (microalgae) ingested by filter-feeding bivalve shellfish (eg, oysters, mussels, clams) that concentrate the toxin and are subsequently consumed by predators, including humans. Saxitoxin is one of the most potent neurotoxins known. It is estimated that 0.5–1 mg can be fatal to humans. [41, 42] It acts similarly to TTX in that it blocks voltage-sensitive sodium channels, which, in turn, disrupts nerve conduction and results in motor and sensory neurologic abnormalities.
PSP usually occurs in outbreaks and is observed most commonly in recreational shellfish diggers. [43] Symptoms occur within 15 minutes to 3 hours and include paresthesias of the mouth, face, and limbs with nausea, vomiting, and diarrhea. A floating sensation often is described. Dysphonia, ataxia, weakness, and paralysis of skeletal muscles (leading to respiratory failure) can occur within 2-12 hours in severe poisoning and may persist for as long as 72 hours to a week. Death from PSP occurs secondary to paralysis of the muscles of respiration. [9]
The mainstay of treatment for PSP is supportive care similar to that for puffer fish poisoning (TTX poisoning). Mechanical ventillation is indicated in the case of insufficient respiratory function. [9]
Neurotoxic shellfish poisoning
Neurotoxic shellfish poisoning (NSP) has been reported from the southeastern coast of the United States, the Gulf of Mexico, the Caribbean, and New Zealand. NSP is caused by brevetoxins, which are produced by dinoflagellates (micro algae) ingested by filter-feeding bivalve shellfish (eg, oysters, mussels, clams) that concentrate the toxin and are subsequently consumed by predators, including humans. Respiratory complaints and eye irritation have been reported due to aerosolized exposure from waves as they break near the beach. [42]
Like many marine toxins, the brevetoxins are tasteless, odorless, and heat stable. They are similar to ciguatoxins in that they are sodium channel openers that cause neuroexcitatory effects. This syndrome presents much like ciguatera poisoning but without a paralytic component, and it may last from several hours to a few days. Although brevetoxins can accumulate in muscles and viscera of finfish, there are no documented cases of NSP after finfish consumption in humans, thus NSP and CFP can be differentiated with a complete history of seafood consumption. [44]
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). 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.
Treatment is supportive care.
Diarrheal shellfish poisoning
Most cases of diarrheal shellfish poisoning (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. [45]
DSP is a mild poisoning. The main causative agent appears to be okadaic acid (although others are implicated), which is produced by dinoflagellates (microalgae) ingested by filter-feeding bivalve shellfish (eg, oysters, mussels, clams) that concentrate the toxin and are subsequently consumed. Symptoms are generally mild and consist of nausea, vomiting, diarrhea, and abdominal pain. Time to onset is within 30 minutes to a few hours, with complete recovery within 3 days. Treatment is symptomatic and supportive. No cases of death from DSP have been reported.
Amnestic shellfish poisoning (domoic acid poisoning)
Amnestic shellfish poisoning (ASP) is a potentially serious poisoning that 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. [8] Diatoms produce domoic acid (DA), which enters the food chain via contaminated mollusks. DA is a glutamate agonist, and, while symptoms of ASP include nausea, vomiting, diarrhea, what sets it apart from other shellfish poisonings is its profound effects on the CNS. [29]
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. [46]
The first reported human outbreak of ASP occurred in 1987 in Canada's eastern province of Prince Edward Island and affected more than 100 people. Approximately 50% of patients experienced severe headache; some suffered confusion, seizures, and coma. Twenty-five percent of patients had short-term memory loss, which, for many, was permanent. Of those afflicted, 4 patients died. [47] Treatment is supportive care, with neurological follow-up recommended.
Azaspiracid shellfish poisoning
Azaspiracid shellfish poisoning (AZP) is one of the more recently discovered seafood poisonings. It was identified following cases of severe GI illness from the consumption of contaminated mussels from Ireland, and contamination was subsequently confirmed throughout the western coastline of Europe The implicated toxins, azaspiracids, accumulate in bivalve mollusks that feed on toxic microalgae. Toxicological studies have indicated that azaspiracids can induce widespread organ damage in mice and that they are probably more dangerous than previously known classes of shellfish toxins. [48, 49]
