Marine Toxins: 5 Poisons Under the Sea

Article

The etiology, poisoning, and treatment of various marine toxins.

Marine toxins originate from microorganisms native to aquatic ecosystems. These molecules eventually find their way into the human gastrointestinal tract through concentrating and bioaccumulating in species such as mollusks, crustaceans, and various fish. Ingestion of marine toxins can generate foodborne illnesses and a constellation of neurologic and gastrointestinal manifestations accompanied by other symptoms.

Below are 5 of these compounds that are lurking under the sea:

CIGUATOXIN

Ciguatera illness is caused by ciguatoxins, which are compounds that bioaccumulate in shallow, coastal water-dwelling fish. This amplification occurs as a consequence of the marine food web where fish like barracuda, red snapper, and moray eel feed on smaller fish that utilize ciguatoxin-producing dinoflagellates as a food source.1 Though ciguatoxins concentrate in fish organs, these compounds can’t be detected by the sight, taste, or smell of the affected fish. As ciguatoxins are heat-stable polyethers, this toxic component can’t be 'cooked' away. 1,2 In fact, the methods of transportation, preparation, nor cooking of the fish affect the presence or concentrations of these toxins.1

Diagnosis for ciguatera poisoning is based on the patient’s clinical picture and an account of recent marine fish consumption that has been previously associated with ciaguatera fish poisoning.3 Ciguatoxins act as potent activators of sodium channels and result in neurotoxicities.2 The classic, distinctive dysesthesia is a burning pain upon cold exposure.2,4 The complete clinical picture may include neurologic symptoms (parasthesia, dysesthesia, arthralgia, pruritus, asthenia, sensation of loose teeth), gastrointestinal symptoms (vomiting, diarrhea, stomach pain), and cardiovascular symptoms (arrhythmia, hypotension, bradycardia).5 Patients may take from days to weeks to recover, but there are case reports of symptoms lingering for years.

Though this foodborne illness is seldom fatal, supportive care may be paramount as death may occur in patients who experience severe dehydration or respiratory failure.5 The most studied therapeutic intervention for ciguatera fish poisoning is use of intravenous mannitol. The benefit this treatment provides is thought to be through osmotic reduction of neuronal edema and scavenging of free radicals that would otherwise exert effects on ion channels.4,5 A main consideration for this therapy is the volume-depleting effects of mannitol, requiring the drug’s reservation until the patient is rehydrated.

According to the CDC, as many as 3% of travelers to high-risk areas (the Caribbean Sea, Indian Ocean, and Pacific Ocean) get ciguatera.1 Patients presenting in the Caribbean predominate with gastrointestinal symptoms, whereas poisoning in the latter two regions is characterized by neurologic symptoms.

SAXITOXIN

Paralytic shellfish poisoning (PSP) is a foodborne illness brought on by saxitoxin, a chemical compound produced by cyanobacteria of freshwater and by dinoflagellates of marine water. As with ciguatoxin, saxitoxin reaches the human gastrointestinal tract through concentration in species that are higher up in the food chain. In this case, the vectors are generally mollusks and crustaceans that filter the water around them. It is for this reason that shellfish harvested during toxic algal blooms are not safe for consumption.6

Saxitoxin interacts with sodium, potassium, and calcium channels, though its primary molecular target is voltage-gated sodium channels, where one molecule of toxin blocks one sodium channel.7 Symptoms are quick to onset and begin within one to two hours of toxin ingestion. Gastrointestinal symptoms are common and can be accompanied by neurologic manifestations that include paresthesias of the face, weakness, tingling, and paralysis. Though patients don’t always need medical help, some cases have required respiratory support.6

Similar to ciguatera, diagnosis of PSP is clinical and based on consumption of food associated with its respective neurotoxin. While many patients recover without any intervention, treatment is mainly supportive.

BREVETOXIN

Also a result of toxic algal blooms and mollusk consumption, neurotoxic shellfish poisoning (NSP) is thought of as a 'milder' case of the paralytic shellfish poisoning described above. Its cause is brevetoxin, a group of more than 10 lipid soluble polyether compounds. These bind to voltage-gated sodium channels and have the ability to cross the blood-brain barrier and lead to severe numbness, ataxia, and even requirement for respiratory support. Though mainly produced by the dinoflagellate Karenia brevis, brevetoxin has also been found in a bloom of Chattonella cf. verruculosa.8

As with the other marine toxins, brevetoxin has no antidote for human use. However, Karenia brevis does produce a natural antagonist named brevenal. This compound is currently studied in animals for inhaled brevetoxin poisoning, as aerosolized toxin can find its way from the algal blooms to mammalian airways.9 Similar to the management of the other toxins, treatment for NSP is largely supportive. One possible therapeutic addition comes as a result of brevetoxin’s structural similarity to ciguatoxin, which may suggest the use of mannitol in this case, as well.8

TETRODOTOXIN

Tetrodotoxin (TTX) is perhaps the most well known of the marine toxins. Its notoriety arises from the popularity of pufferfish. This Japanese delicacy, among other terrestrial and marine organisms, harbors the toxin in its organs and can be deadly if improperly prepared. Unlike the previous etiologies, the culpable microorganism for this toxin’s production can vary and the molecule has been isolated from several bacteria. The organisms found in pufferfish specifically are of the Vibrio and Aeromonas genera.

TTX is an extremely potent sodium channel blocker; even small amounts ingested can have powerful effects on nerve conduction. This results in 'intoxication' symptoms that are scored from grade 1 to 4. These can range from mild isolated facial paresthesias and abdominal pain to severe respiratory paralysis and cardiac arrhythmias.10

Current research involving TTX includes several clinical trials that look to the neurotoxin’s capacity for aiding pain relief, heroin cravings, and heroin withdrawal syndrome.

HISTAMINE

A red herring in the recognition of fish food poisoning is scombroid syndrome. This illness is commonly mistaken for fish allergy, but instead results from improper storage and transportation of fish belonging to the Scombroidiae family.11 Scombroids include tuna, mackerel, and anchovies. If not properly preserved upon getting caught, their deterioration creates an environment suitable for gram-negative bacterial growth. The bacteria include Morganella morganii, Escherichia coli, Klebsiella, and Pseudomonas aeruginosa. These microorganisms are then able to utilize histidine decarboxylase and convert histidine to histamine.12

As the fish is consumed, the ingested histamine begins to exert its effects. The ensuing signs and symptoms can include erythema, urticaria, hypotension, tachycardia, cramps, and even bronchoconstriction, presenting a clinical scenario reminiscent of an allergic reaction. Treatment includes both H1- and H2-blocking histamines alongside fluids, corticosteroids, and epinephrine, depending on the presentation of the patient.12

Though not a marine toxin by definition, histamine’s role in scombroid syndrome merits the molecule a spot alongside toxins. Histamine is not eradicated through cooking. Sometimes the compound may alter the taste of the fish, though this is not always true. Thus, prevention of this syndrome is reliant on appropriate cooling and transportation.

References

  • Fish Poisoning in Travelers: Ciguatera and Scombroid. Traveler’s Health. Centers for Disease Control and Prevention. 2014 Jan 30. https://wwwnc.cdc.gov/travel/page/fish-poisoning-ciguatera-scombroid. Accessed March 12, 2018.
  • Pearn J. Neurology of ciguatera. J Neurol Neurosurg Psychiatry. 2001 Jan;70(1):4-8.
  • Friedman MA, Fernandez M, Backer LC, et al. An Updated Review of Ciguatera Fish Poisoning: Clinical, Epidemiological, Environmental, and Public Health Management. Mar Drugs. 2017 Mar 14;15(3). pii: E72. doi: 10.3390/md15030072.
  • Mullins ME, Hoffman RS. Is mannitol the treatment of choice for patients with ciguatera fish poisoning? Clin Toxicol (Phila). 2017 Nov;55(9):947-955. doi: 10.1080/15563650.2017.1327664. Epub 2017 May 23.
  • Friedman MA, Fleming LE, Fernandez M, et al. Ciguatera Fish Poisoning: Treatment, Prevention and Management. Mar Drugs. 2008 Sep; 6(3): 456—479. Published online 2008 Aug 21. doi: 10.3390/md20080022
  • Hurley W, Wolterstorff C, MacDonald R, Schultz D. Paralytic shellfish poisoning: a case series. West J Emerg Med. 2014 Jul;15(4):378-81. doi: 10.5811/westjem.2014.4.16279.
  • Cusick KD, Sayler GS. An overview on the marine neurotoxin, saxitoxin: genetics, molecular targets, methods of detection and ecological functions. Mar Drugs. 2013 Mar 27;11(4):991-1018. doi: 10.3390/md11040991.
  • Watkins SM, Reich A, Fleming LE, Hammond R. Neurotoxic shellfish poisoning. Mar Drugs. 2008 Sep; 6(3): 431—455. Published online 2008 Jul 12. doi: 10.3390/md20080021
  • Abraham WM, Bourdelais AJ, Ahmed A, Serebriakov I, Baden DG. Effects of Inhaled Brevetoxins in Allergic Airways: Toxin—Allergen Interactions and Pharmacologic Intervention. Environ Health Perspect. 2005 May; 113(5): 632—637. Published online 2005 Feb 10. doi: 10.1289/ehp.7498
  • Lago J, Rodriguez LP, Blanco L, Vieites JM, Cabado AG. Tetrodotoxin, an Extremely Potent Marine Neurotoxin: Distribution, Toxicity, Origin and Therapeutical Uses. Mar Drugs. 2015 Oct; 13(10): 6384—6406. Published online 2015 Oct 19. doi: 10.3390/md13106384
  • Ridolo E, Martignago I, Senna G, Ricci G. Scombroid syndrome: it seems to be fish allergy but... it isn't. Curr Opin Allergy Clin Immunol. 2016 Oct;16(5):516-21. doi: 10.1097/ACI.0000000000000297.
  • Tortorella V, Masciari P, Pezzi M, et al. Histamine Poisoning from Ingestion of Fish or Scombroid Syndrome. Case Rep Emerg Med. 2014; 2014: 482531. Published online 2014 Dec 7. doi: 10.1155/2014/482531.

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