Version May 2024
INTRODUCTION — An overview of paralytic shellfish poisoning, neurotoxic shellfish poisoning, diarrheic shellfish poisoning, and pufferfish poisoning is provided here. Scombroid (histamine) poisoning, ciguatera fish poisoning and marine envenomations, such as coral abrasions and sea urchin injuries, are discussed separately. (See "Scombroid (histamine) poisoning" and "Ciguatera fish poisoning" and "Marine envenomations from corals, sea urchins, fish, or stingrays".)
BACKGROUND — As world travel and trade grow, physicians are increasingly likely to encounter patients poisoned by marine toxins. The world's oceans harbor hundreds of different types of marine toxins, and the epidemiology and clinical manifestations of these toxins vary widely. Several of these toxins are produced by dinoflagellates or phytoplankton during algae or marine diatom blooms. Shellfish and pufferfish poisoning arise from consumption of seafood that is contaminated by various toxins (table 1) [1-3]. In most instances the ingested seafood smells, appears, and tastes normal. Clinical features of the most common forms of shellfish or pufferfish poisoning typically develop within minutes to hours of ingestion. A food history that identifies ingestion of seafood commonly associated with the specific toxin, clinical features consistent with the specific poisoning, and detection of elevated levels of the toxin in the ingested seafood provides the diagnosis. Treatment is supportive.
PARALYTIC SHELLFISH POISONING
●Epidemiology – Paralytic shellfish poisoning (PSP) occurs after ingestion of shellfish contaminated with neurotoxins formed by algae, primarily saxitoxins [4]. It has been linked to algal blooms called "red tides," even though it can occur in the absence of red tides. PSP primarily occurs in temperate climates, although it has been described in shellfish from tropical waters [5]. Potential vectors for PSP include bivalve mollusks (eg, cockles, salt- and fresh-water mussels, or butter/little neck clams), gastropod mollusks (eg, whelk, moon snails, or abalone), crustaceans (eg, Dungeness crabs, shrimp, or lobsters), pufferfish (saxitoxin pufferfish poisoning), and zooplanktivorous fish (eg, Atlantic salmon, herring, and mackerel) [4,6]. Of these, outbreaks of human disease are most commonly associated with salt-water bivalve mollusks, especially mussels or clams.
PSP has been described worldwide [4]. In the United States, PSP primarily occurs in seafood harvested from the Northeast, Pacific Northwest, and Alaskan waters [7]. As an example, from 2010 to 2011, there was a marked increase in the number of PSP cases in southeast Alaska, all of which stemmed from the ingestion of non-commercially harvested shellfish (specifically, cockles, blue mussels, butter/little neck clams, and Dungeness crabs) [7]. A subsequent CDC report noted that non-commercially-harvested Alaskan shellfish can have high levels of PSP toxin at any time of year [7]. Clinicians were urged to report suspected cases to health officials and to collect and freeze patient urine and shellfish samples (if available) for testing. Some states, including California, Washington, Oregon, and Maine (but not Alaska), routinely monitor non-commercial shellfish for biotoxins [8-12]. In contrast, commercial shellfish are routinely monitored for PSP toxin in Alaska and are safe to consume [13].
●Pathophysiology – The toxins that cause PSP are formed by dinoflagellates of the genus Alexandrium and are collectively known as saxitoxins [4,14,15]. These toxins are taken up by seafood vectors, most commonly, bivalve mollusks such as mussels, clams, scallops, and oysters, as well as by crabs and snails, with no apparent ill effect. The PSP toxins are not destroyed by heat, marinating, or freezing. Contaminated seafood smells, tastes, and appears normal.
●Clinical manifestations and diagnosis – In humans, the PSP toxins block sodium ion channels and rapidly cause neurologic symptoms ranging from perioral tingling, ataxia, difficulty swallowing, dizziness, paresthesias, weakness to paralysis, brainstem dysfunction, and respiratory failure [4,7,14,16]. Onset of symptoms ranges from a few minutes to approximately four hours. In untreated patients, the case fatality rate is as high as 12 percent [1], and death may occur within 2 to 12 hours of seafood ingestion of contaminated seafood. With proper supportive care, most patients survive. Neurotoxic symptoms tend to improve gradually after 12 hours and resolve completely within a few days [4,14].
A working diagnosis of paralytic shellfish poisoning is made when there is a history of consumption of a known seafood vector of PSP followed by the onset of neurologic symptoms, including paralysis [7]. Frequently ingestion of a noncommercial harvest of shellfish or crabs is noted and a cluster of cases is identified. The diagnosis is confirmed by the detection of saxitoxin in the urine of affected patients or samples of the seafood. The local health department should be contacted to assist with laboratory confirmation.
●Differential diagnosis – Other foodborne illnesses, such as tetrodotoxin pufferfish poisoning, botulism, and ciguatera fish poisoning have clinical presentations that are similar to PSP. Careful food history accompanied by the detection of saxitoxins in the urine or contaminated seafood helps to distinguish PSP from these entities. (See 'Pufferfish poisoning (tetrodotoxin)' below and "Ciguatera fish poisoning", section on 'Diagnosis' and "Botulism", section on 'Clinical manifestations'.)
●Treatment and prevention – Treatment is primarily supportive, and mechanical ventilation is important for severely affected patients [4]. Prevention is dependent upon close monitoring of shellfish beds by health authorities, notification of the public when contaminated shellfish are found, and avoidance of shellfish beds that have been closed to harvesting [7].
NEUROTOXIC SHELLFISH POISONING
●Epidemiology – Neurotoxic shellfish poisoning (NSP) is also associated with "red tides." NSP tends to occur along the southeastern coast of the United States and in addition, the Gulf of Mexico, the Caribbean, and New Zealand [2,3]. Between 1998 and 2002, there were two outbreaks reported to the CDC in the United States that affected four persons, none of whom died [2].
●Pathophysiology – The NSP-related toxins are formed by the dinoflagellate species Karenia brevis (formerly Gymnodidium breve and Ptychodiscus brevis), which produces both hemolytic toxins and neurotoxins [3,14]. These toxins, called brevetoxins, are taken up by bivalve shellfish and are also aerosolized during algal blooms. Brevetoxins increase sodium ion channel permeability. They also inhibit cathepsins, lysosomal proteinases that are found in phagocytes such as macrophages [14].
●Clinical manifestations and diagnosis – NSP is diagnosed clinically based upon the history of exposure and typical physical findings in association with a red tide.
NSP has been associated with two clinical syndromes [3]:
•Ingestion – After eating contaminated shellfish, gastrointestinal distress (nausea, vomiting, diarrhea, and abdominal pain) and neurologic symptoms such as paresthesias of the face, mouth, and extremities, dizziness, ataxia, and muscle aches develop within 30 minutes to three hours. Patients may also experience temperature-related dysesthesias (sometimes described as hot/cold temperature reversal) [17]. In severe cases, paralysis, coma, and seizures have been described [18].
•Inhalation – The other syndrome, aerosolized red tide respiratory irritation (ARTRI), occurs when the toxins are inhaled from sea spray and consists of nasal and respiratory irritation, rhinorrhea, and bronchoconstriction [14]. People with chronic lung disease and asthma are especially susceptible [19].
●Management – For patients who have ingested neurotoxic shellfish, fluid repletion is important. Antiemetics (eg, ondansetron) may also be helpful. Although evidence is lacking regarding improved outcomes, activated charcoal administration to bind unabsorbed food is advocated by some experts because of the potential for serious adverse outcomes despite appropriate supportive care. In mild cases, toxic effects typically resolve fully within a few days.
Inhaled bronchodilators (eg, albuterol) are useful for treatment and possibly also for prevention of aerosolized red tide respiratory irritation [14,20].
NSP is generally not fatal in humans and most patients recover within 72 hours [21]. However, brevetoxins do exact a heavy toll on marine and bird life including large scale deaths of fish and manatees.
DIARRHEIC SHELLFISH POISONING
●Epidemiology – Diarrheic shellfish poisoning (DSP) occurs throughout the world. Major outbreaks, primarily associated with contaminated mussels, have occurred in Japan, China, Scandinavia, France, Belgium, Spain, Chile, Uruguay, Ireland, the United States, and Canada. [2,3,22-25].
●Pathophysiology – Several toxins have been associated with DSP, of which the best known is okadaic acid [22]. It is lipid soluble and acts as an inhibitor of certain types of phosphatases, thus increasing phosphorylation of proteins vital for regulation of mammalian cell metabolism [26].
●Evaluation and management – A case definition of DSP would include chills and gastrointestinal symptoms such as nausea, vomiting, diarrhea, and abdominal cramps shortly after eating bivalve mollusks, especially mussels and scallops [3]. The symptoms usually occur within two hours after shellfish consumption and resolve within two to three days. The presence of okadaic acid or one of the other DSP-associate toxins confirms the diagnosis. Treatment is supportive.
Diarrhetic shellfish poisoning has many clinical features in common with other types of foodborne illness, including poisoning from some types of mushroom and food contamination by a variety of bacterial organisms. A food history that indicates ingestion of bivalve mollusks from a region associated with DSP and isolation of okadaic acid or one of the other associated toxins from the contaminated food helps to distinguish it from other toxins or microbial contaminants. (See "Clinical manifestations and evaluation of mushroom poisoning", section on 'Acute gastroenteritis' and "Causes of acute infectious diarrhea and other foodborne illnesses in resource-abundant settings", section on 'Clinical clues to the microbial cause'.)
Management of diarrheic shellfish poisoning consists of fluid repletion and antiemetics (eg, ondansetron) for vomiting.
Okadaic acid is mutagenic in Chinese hamster lung cells and has been found to promote skin tumors in mice [22]. The human health implications of this are unknown although shellfish consumption as a risk factor for colorectal cancer has been proposed [27].
PUFFERFISH POISONING (TETRODOTOXIN)
●Epidemiology – Pufferfish poisoning is most commonly seen in Japan where the fish, called fugu, globefish, or blowfish, is considered a delicacy. Sporadic cases have also been reported in the United States [28,29].
●Pathophysiology – Pufferfish poisoning is caused by tetrodotoxin, a neurotoxin produced by microorganisms associated with the fish [30]. Tetrodotoxin is one of the deadliest natural toxins and is not destroyed by washing, cooking, or other food preparation. It concentrates in the liver and visceral organs along with the skin of the pufferfish and is also found in several species of frogs, salamanders, and octopus. Tetrodotoxin binds sodium channels, preventing sodium influx into nerve axons. It also acts on vascular smooth muscle and skeletal muscle [31].
Saxitoxin, the cause of PSP, can also be found in pufferfish. Cases of neurologic symptoms, including numbness and tingling of the lips and mouth, have been reported to arise rapidly after the consumption of pufferfish caught in the area of Titusville, Florida [32]. These symptoms generally resolve within hours to days, although one affected individual required intubation for 72 hours. Saxitoxin was confirmed by liquid chromatographic analysis. As a result of such cases, Florida banned the harvesting of pufferfish from certain bodies of water [33]. (See 'Paralytic shellfish poisoning' above.)
●Clinical manifestations and diagnosis – Symptoms of tetrodotoxin pufferfish poisoning occur rapidly after ingestion and include weakness, dizziness, paresthesias of the face and extremities, nausea, and loss of reflexes. With higher doses there is severe hypotension and, in some cases, generalized paralysis [31]. Death can occur due to respiratory failure and hypotension. It is not unusual for the patient to remain conscious while paralyzed.
●Management – Treatment of pufferfish poisoning consists of supportive care. Although evidence is lacking regarding improved outcomes, intestinal decontamination with gut lavage and activated charcoal if the patient presents within one hour of ingestion is advocated by many experts because of the seriousness of the poisoning and the potential for poor outcomes despite appropriate supportive care [34]. Case reports and series suggest that anticholinesterases such as edrophonium or neostigmine may be effective in partially reversing paralysis in some but not all patients [31,34,35].
OTHER MARINE TOXINS
Amnesic shellfish poisoning
●Epidemiology – Amnesic shellfish poisoning (ASP) was first recognized in 1987 following an outbreak involving 107 persons (four died) who became ill after consuming contaminated mussels cultivated off the coast of Prince Edward Island, Canada. It is caused by a heat stable toxin called domoic acid, which is produced by single-celled, algae-like organisms called diatoms of the species Pseudonitzschia [31]. Subsequently domoic acid contamination of mussels, scallops, razor clams, or crustaceans have been described in Spain, Portugal, Scotland, Ireland, France, New Zealand, Australia, Belgium, Peru, and Chile [3,36,37]. In California, domoic acid contamination of anchovies has resulted in erratic behavior and deaths of sea lions, pelicans, and cormorants.
●Pathophysiology – Domoic acid is structurally related to glutamate and acts as a powerful excitatory neurotransmitter that can cause the death of neurons in the amygdala and hippocampus. It is taken up by shellfish during harmful phytoplankton blooms.
●Clinical manifestations – After ingestion by humans, contaminated shellfish cause diarrhea and abdominal cramps, followed by headache, memory loss, and disorientation. In severe cases, domoic acid ingestion can lead to diminished reflexes, ophthalmoplegia, coma, and death [38]. Patients who survive may have severe anterograde short-term memory deficits [3,39]. Analysis of the initial outbreak suggested that more severe symptoms, including memory loss, was associated with an age >65 years [40].
●Management and prevention – Medical therapy consists of supportive care. Prompt treatment of seizures with benzodiazepines (eg, lorazepam) is proposed to help prevent neurologic damage, including memory loss [41]. Although evidence is lacking, some experts support administration of activated charcoal to bind any non-absorbed food given the potential for poor outcomes, including permanent short-term memory loss, despite appropriate supportive care.
After the Canadian outbreak, limits on domoic acid concentration in shellfish were rapidly adopted at 20 micrograms per gram of shellfish flesh. These limits based upon the lowest concentrations in mussels found to cause symptoms (200 micrograms per gram of shellfish flesh) reduced by a factor of 10 [40]. Wide adoption of the limits on harvested mussels by developed nations has been associated with no further outbreaks on the scale of the Canadian experience.
Harmful algal blooms — Harmful algal blooms can cause toxic effects and disease outbreaks in humans swimming, boating, or wading in freshwater lakes, estuaries, waterways, and, less commonly, along the sea coasts [42,43]. These blooms cause accumulation of biotoxins produced by cyanobacteria during periods of warm weather [44]. Illness has most commonly been reported in children. Identified toxins include saxitoxin, cylindrospermopsin, microcystin, and anatoxin. The water often has a visible scum and dead fish may be present. Animals such as birds and dogs that drink the water may also manifest symptoms. Microcystin has been detected in tap water of homes with lake water intake during a harmful algal bloom [45].
Skin contact, water ingestion, or inhalation of water vapor can all produce toxicity [44]. Clinical effects may present soon after exposure and include fever, headache, rash, eye irritation, vomiting, diarrhea, respiratory distress, wheezing, and neurologic symptoms (eg, paresthesias or confusion). Given the nonspecific nature of the presentation, the clinician must have a high degree of suspicion, especially in patients with unexplained neurologic findings, and ask about exposure to algae-infiltrated water in order to make the diagnosis.
Patients suspected of toxicity from harmful algal blooms should also be reported to the local department of public health to encourage investigation of the lake and prevent further exposures. The Centers for Disease Control and Prevention has established the One Health Harmful Algal Bloom System as a surveillance mechanism; state health departments can voluntarily report health effects observed with algal blooms [46].
There is concern that harmful algal blooms are increasing due to climate change and agricultural runoff, and the health effects of environmental cyanotoxins are an active area of research.
Florida red tide blooms — Florida red tide (FRT) blooms occur when the sea algae Karenia brevis grows in response to macro-nutrients from predominantly human-generated effluent along the Florida coast [47]. These organisms produce brevetoxins, a tasteless and odorless toxin that can trigger immune reactions and cause the death of sea animals such as manatees and fish [48]. During FRT blooms, there has been an increase in emergency department visits for asthma exacerbation, other respiratory symptoms, and gastrointestinal illness. Treatment is supportive. Strategies for preventing illness during FRT blooms include staying indoors with air-conditioning and windows closed, staying away from the coast, and not consuming local seafood [49,50].
Possible estuary-associated syndrome — Possible estuary-associated syndrome (PEAS) is believed to be a neurotoxin-mediated illness associated with exposure to waterways inhabited by dinoflagellates such as Pfiesteria. Pfiesteria has been found in the Tar-Pamlico and Neuse River estuaries of North Carolina and in the Pocomoke River on Maryland's Eastern Shore [21]. Pfiesteria is associated with ulcerative lesions on fish and fish kills.
Human laboratory workers and fishermen with PEAS have experienced respiratory and eye irritation, rashes, abdominal cramps and vomiting, and cognition and personality changes. Most of the neurocognitive symptoms appear to resolve within several months after exposure [41,51]. Ongoing studies are investigating long-term effects of PEAS and Pfiesteria exposure. Visual contrast sensitivity, a test of pattern-detection ability, is often markedly reduced in patients with acute and chronic PEAS, and may improve with treatment with cholestyramine [52].
Palytoxin poisoning — Palytoxin derives from the microalgae, Ostreopsis ovate and O. siamensis, corals, and sea anemones. Palytoxin was originally described in Hawaii but more recently has caused health problems among home aquarium enthusiasts [53] and after an algal bloom in Italy [54]. It binds to and disables the sodium/potassium ATPase pump. Human exposure to palytoxin has been described following ingestion of crabs, fish, and shellfish that have fed on palytoxin-containing algae or coral [55], inhalational exposure from corals in fish tanks or sea air [53,56-59], and dermal or eye exposure after touching corals that elaborate the toxin [59-62].
Inhalational exposure from soft corals in aquariums or sea air can produce conjunctivitis, chest pain, fever, shortness of breath, and bronchospasm [55,63]. Rarely, adult respiratory distress syndrome and acute respiratory failure may occur. Treatment is supportive with administration of antihistamines, inhaled bronchodilators, and systemic corticosteroids.
Although rare, ingestion of contaminated seafood (algae- and reef-feeding fish, crustaceans, and shellfish) can produce neurologic symptoms of paresthesias, weakness, severe uncontrollable muscle cramping (potentially leading to rhabdomyolysis), and hot-cold reversal [55]. Additional findings may include diaphoresis, vomiting, diarrhea, and severe abdominal cramping. Poisoning may occur in outbreaks with mortality rates as high as 10 percent [55].
Others — Hundreds of other marine toxins exist. In all cases, it is important for the clinician to work closely with local public health authorities. Clinicians should also remember that while marine toxin-induced diseases are not uncommon, food poisoning from infectious agents is far more prevalent and should always be included in the differential diagnosis of a patient with seafood-related illness. (See "Causes of acute infectious diarrhea and other foodborne illnesses in resource-abundant settings".)
ADDITIONAL RESOURCES
Regional poison control centers — Regional poison control centers in the United States are available at all times for consultation on patients with known or suspected poisoning, and who may be critically ill, require admission, or have clinical pictures that are unclear (1-800-222-1222). In addition, some hospitals have medical toxicologists available for bedside consultation. Whenever available, these are invaluable resources to help in the diagnosis and management of ingestions or overdoses. Contact information for poison centers around the world is provided separately. (See "Society guideline links: Regional poison control centers".)
SUMMARY AND RECOMMENDATIONS
●Shellfish and pufferfish poisoning – Shellfish and pufferfish poisoning arise from consumption of seafood that is contaminated by various toxins. In most instances the ingested seafood smells, appears, and tastes normal. Clinical features of the most common forms of shellfish or pufferfish poisoning typically develop within minutes to hours of ingestion. A food history that identifies ingestion of seafood commonly associated with the specific toxin, clinical features consistent with the specific poisoning, and detection of elevated levels of the toxin in the ingested seafood provides the diagnosis. (See 'Background' above.)
An overview of the clinical presentation, diagnosis, and treatment of common shellfish and pufferfish syndromes are provided in the table (table 1) and described above:
•Paralytic shellfish poisoning (see 'Paralytic shellfish poisoning' above)
•Neurotoxic shellfish poisoning (see 'Neurotoxic shellfish poisoning' above)
•Diarrheic shellfish poisoning (see 'Diarrheic shellfish poisoning' above)
•Amnestic shellfish poisoning (see 'Amnesic shellfish poisoning' above)
•Pufferfish poisoning (see 'Pufferfish poisoning (tetrodotoxin)' above)
●Harmful algae blooms – Algae blooms in salt water (neurotoxic shellfish poisoning [red tide]) and estuaries (possible estuary-associated syndrome) can lead to inhalational exposure to water-borne toxins and result in eye irritation, respiratory symptoms, vomiting, diarrhea, and nonspecific neurologic symptoms such as confusion or behavior changes. The presence of causative toxins in the water often results in fish kills; other exposed animals, such as dogs and birds, may also be affected. (See 'Harmful algal blooms' above and 'Possible estuary-associated syndrome' above.)
●Palytoxin poisoning – Inhalation exposure to algae blooms in home aquariums and in Italy have been associated with fever, conjunctivitis, respiratory distress, wheezing, and rarely, adult respiratory distress syndrome caused by palytoxin. (See 'Palytoxin poisoning' above.)
●Reporting – In all cases, it is important for the clinician to work closely with local public health authorities. Clinicians should also remember that while marine toxin-induced diseases are not uncommon, food poisoning from infectious agents is far more prevalent and should always be included in the differential diagnosis of a patient with seafood-related illness. (See "Causes of acute infectious diarrhea and other foodborne illnesses in resource-abundant settings".)
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