Marine Toxins – Ciguatera and Friends

Gary Podolsky MD

Marine toxins are naturally occurring chemicals that can contaminate certain seafood. The seafood contaminated with these chemicals frequently looks, smells, and tastes normal. When humans eat such seafood, disease can result.

Types of Marine Toxins include : Scombrotoxic fish poisoning, Ciguatera poisoning, and Shellfish Associated Toxins (paralytic shellfish poisoning, neurotoxic shellfish poisoning, diarrheic shellfish, and amnesic shellfish poisoning).

Ciguatera poisoning or ciguatera is the most common fish poisoning and is caused by eating contaminated tropical reef fish. Ciguatoxins that cause ciguatera poisoning are actually produced by microscopic sea plants called dinoflagellates.

Scombrotoxic fish poisoning also known as scombroid or histamine fish poisoning is second most common and is caused by bacterial spoilage of certain finfish such as tuna, mackerel, bonito, and, rarely other fish.

Shellfish associated poisoning is caused by different dinoflagellates with different toxins from those that cause ciguatera poisoning.

Tetrodotoxin poisoning s in Fugu, Cone snails and spotted blue octopi concentrate a poison made by bacteria and are discussed in another lecture.

Figure 16 Harmful Algae Blooms in US Not all are discussed in our presentation

http://www.whoi.edu/redtide/HABdistribution/HABmap.html

HAB distribution

Red Tides and Harmful Algae Blooms

Harmful algae are microscopic, single-celled plants that live in the sea. Most species of algae or phytoplankton are not harmful and serve as the energy producers at the base of the food web, without which higher life on this planet would not exist

Occasionally, algae grow very fast or “bloom” accumulating into dense, visible patches near the surface of the water.

“Red Tide” is a common name for the phenomenon where certain phytoplankton species contain reddish pigments and “bloom” such that the water appears to be colored red. But “red tide” is a misnomer because these are not associated with tides; are usually not harmful; and those species that are harmful may never reach the densities required to discolor the water.

Harmful algae produce neurotoxins that are concentrated through the aquatic food web and affect and even kill higher forms of life such as zooplankton, shellfish, fish, birds, mammals, and even people that feed either directly or indirectly on them.

Figure 17 Aquatic Food web showing origin of toxins from Harmful Algae and distribution through ecosystem

http://www.whoi.edu/redtide/foodweb/HABfoodweb.html

Ciguatera or Ciguatera Fish Poisoning

Ciguatera poisoning or ciguatera is caused by eating contaminated subtropical or tropical marine finfish which have accumulated natural occurring toxins from their diet. These toxins originate from the dinoflagellates (algae) species Gambierdiscus toxicus that are common to ciguatera endemic regions in the lower latitudes. Gambierdiscus toxicus lives in association with other algae on dead corals.

These toxins become progressively concentrated as they move up the food chain from small fish to large fish that eat them, and reach particularly high concentrations in large predatory tropical reef fish. Barracuda are commonly associated with ciguatoxin poisoning, but grouper, sea bass, snapper, mullet, and a number of other fish that live in oceans between latitude 35° N and 35° S have also caused this disease.

 Common Ciguatera Fish

Marine finfish most commonly implicated in ciguatera fish poisoning include the groupers, barracudas, snappers, jacks, mackerel, and triggerfish. But other species of warm-water fishes harbour ciguatera toxins. The occurrence of toxic fish is sporadic, and not all fish of a given species or from a given locality will be toxic. Incidence may be under-reported because of the generally non-fatal nature and short duration of the disease.

Figure 18 Fish associated with Ciguatera, Source Pubic domain yahoo.com

Poisoning

Human ciguatera poisoning includes a combination of gastrointestinal, neurological, and cardiovascular symptoms. Ciguatoxin usually causes symptoms within a few minutes to 30 hours after eating contaminated fish, and occasionally it may take up to 6 hours.

Gastrointestinal Signs

Signs of poisoning occur within six hours after eating the toxic fish and include perioral numbness and tingling (paresthesia), which may spread to the extremities, nausea, vomiting, and diarrhea.

Neurological signs include intensified paresthesia, arthralgia, myalgia, headache, temperature sensory reversal and acute sensitivity to temperature extremes, vertigo, and muscular weakness to the point of prostration.

Cardiovascular signs include arrhythmia, bradycardia or tachycardia, and reduced blood pressure. Ciguatera poisoning is self-limiting, and signs of poisoning often subside within several days from onset but, in severe cases the neurological symptoms are known to persist from weeks to months. In a few isolated cases neurological symptoms have persisted for several years, and in other cases recovered patients have experienced recurrence of neurological symptoms months to years after recovery. Such relapses are most often associated with changes in dietary habits or with consumption of alcohol. There is a low incidence of death resulting from respiratory and cardiovascular failure.

Mannitol and Ciguatera

Mannitol was serendipitously discovered a possible antidote when Ciguatera broke out. Two victims were suspected to have cerebral edema and were administered mannitol. Mannitol produced a rapid improvement in consciousness and has been empirically shown to decrease gastrointestinal as well as neurological symptoms. by an unknown mechanism. Used on ciguatera victims there were no adverse effects reported. Mannitol may be tried in cases of extreme poisoning.

Tests

Clinical tests for ciguatera are not presently available. Diagnosis is made entirely on dietary history and symptoms.

An enzyme immunoassay (EIA) designed to detect toxic fish in field situations is under evaluation by the Association of Official Analytical Chemists (AOAC) and may provide some measure of protection to the public in the future.

All people are believed to be susceptible to ciguatera toxins.

Populations in tropical/subtropical regions are most likely to be affected because of the frequency of exposure to toxic fishes.

Areas at risk:

Any event, either natural or man-made, that significantly disturbs coral reefs and the associated eco-systems, there is an increased short- and long-term risk for ciguatera. Decay of live corals that provide opportunities for proliferation of seaweeds, on which benthic toxic microalgae responsible for ciguatera grow.

Fish Selection and Preparation

The ciguatoxin is very heat-stable. Normal household cooking ( e.g. boiling, steaming, frying) will not reduce or eliminate the toxin.

Guidelines to Prevent Poisonings

Detailed analysis of epidemiological records on ciguatoxin poisonings in Cuba has led to dose/response data being defined as functions of the size of fish consumed and have allowed limit weights (critical limits) to be set for five of the most important species and potential toxicity to be set for another 15 species (regardless of their weight). This is effective in Cuba and similar programs to improve understanding of seasons/ species involved and other factors will help anticipate and limit ciguatera outbreaks in other areas.

By talking to local fishermen we can learn which areas to avoid and which fishes may be dangerous to eat. Between 300 to 400 species of fish have been implicated in ciguatera fish poisoning. If no information is available, it is wise not to eat any large reef fishes. That fish could have lived through several blooms of ciguatera and concentrated the toxin.

Hawaii now uses a “stick test” immunoassay to detect ciguatoxin in fish. The test is sensitive, specific, inexpensive, and easy to use in the field. In Hawaii, if an outbreak-related fish tests positive for ciguatoxin, the reef area of catch is posted to discourage further fishing in that area. In Miami, Florida, because barracuda have been frequently associated with ciguatera poisoning, a city ordinance bans the sale of barracuda.

Further reading:

Assessment and Management of Seafood Safety and Quality , By H.H. Huss , L. Ababouch , L. Gram, Food and Agriculture Organization (FAO) of the United Nations, Rome, 2003
http://www.fao.org/documents/show_cdr.asp?

How to perform a semi-quantitative risk assessment: Ciguatera Fish Poisoning. From: Application of Risk assessment in the Fish Industry, by J. Sumner, T. Ross and L. Ababouch , Food and Agriculture £organization (FAO) of the United Nation, Rome, 2004. http://www.fao.org/documents/show_cdr.asp?url_file=/docrep/007/y4722e/y4722e07.htm

Ciguatera Fish Poisoning, A Review in a Risk assessment Framework . by L. Lehane , National Office of Animal and Plant Health, Canberra, 1999.

http://www.affa.gov.au/corporate_docs/publications/pdf/animalplanthealth/chief_vet/ciguatera.pdf

World Health Organization- Impact of Tsunami on Ciguatera

http://w3.whosea.org/EN/Section23/Section1108/Section1835/Section1864_8508.htm

Ciguatera fish poisoning�Florida, 1991. MMWR June 4, 1993; 42(21): 417-8

Ciguatera fish poisoning�Texas, 1997. MMWR August 28, 1998; 47(33): 692-4

Epidemiological notes and reports ciguatera fish poisoning�Vermont. MMWR April 25, 1986; 35(16): 263-4

Health Canada’s Travel Medicine Program’s Ciguatera Fish Poisoning Site

Epidemiological notes and reports ciguatera fish poisoning�Bahamas, Miami. MMWR July 23, 1982; 31(28): 391-2

CDC National Center for Infectious Diseases’ Marine Toxins Site

Ciguatera Fact Sheet

Canadian Food Inspection Agency http://www.inspection.gc.ca/english/corpaffr/foodfacts/ciguate.shtml

Red Tide http://www.redtide.whoi.edu/hab/illness/ciguatera_fish_poisoning.html

Tahiti.net http://www.tahitinet.com/presense/ciguatera.html

Morbidity and Mortality Weekly Report Centers for Disease Control and Prevention http://vm.cfsan.fda.gov/~mow/cigua.html

CDC http://www.cdc.gov/ncidod/diseases/submenus/sub_marine.htm

Divers Alert Network http://www.diversalertnetwork.org/medical/travel/seafood.asp

Successful Treatment of Ciguatera Fish Poisoning With Intravenous Mannitol Neal A. Palafox et al. JAMA, May 13, 1988 – Vol 259, No. 18

Various Shellfish-Associated Toxins

Figure 19 Filter feeders: Mussels, Clams, Scallops and Oyster

Shellfish poisoning is caused by a group of toxins elaborated by planktonic algae (dinoflagellates in most cases) upon which the shellfish eat. The toxins are bioaccumulated and sometimes metabolised by the shellfish. All shellfish (filter-feeding molluscs) are potentially toxic since the method in which they feed will concentrate the toxins in their environment.

Four diseases associated with shellfish poisoning are discussed.

Paralytic shellfish poisonings (PSP is caused by 20 toxins all derivatives of saxitoxin. PSP is generally associated with mussels, clams, cockles, and scallops.

In PSP, the effects are predominantly neurological and include tingling, burning, numbness, drowsiness, incoherent speech, and respiratory paralysis.

Less well defined are symptoms associated with DSP, NSP, and ASP.

Of these toxicoses, the most is PSP. The potency of the PSP toxins has had a high mortality rate.

Symptoms

Symptoms of the disease develop fairly rapidly, within 0.5 to 2 hours after ingestion of the shellfish, depending on the amount of toxin aten. With severe cases respiratory paralysis is common, and death may follow if respiratory support is not provided. When respiratory support within 12 hours of exposure, recovery is complete, with no lasting side effects. But the weak hypotensive effect of the toxin has caused, death from cardiovascular collapse despite good respiratory support.

Paralytic shellfish poisoning (PSP) is caused by consuming of shellfish or broth from cooked shellfish that contain concentrated saxitoxin, an alkaloid neurotoxin, or related compounds.

In Guatemala, where an outbreak of 187 cases with 26 deaths, recorded in 1987, resulted from ingestion of a clam soup. The outbreak led to the establishment of a control program over shellfish harvested in Guatemala.

Tourists and PSP poisonings: A disproportionate number of cases occur in tourists or others who are not native to areas where the toxic shellfish are harvested. This may be due to disregard for either official quarantines or traditions of safe consumption, both of which tend to protect the local population

Fig 5. Death of Humpback whale due to saxitoxin in mackerel it had consumed. Cape Cod

http://www.whoi.edu/redtide/foodweb/marinemammals.html#deadwhale

Diarrheic shellfish poisoning (DSP) is presumably caused by a group of high molecular weight polyethers, including okadaic acid, the dinophysis toxins, the pectenotoxins, and yessotoxin. DSP is associated with mussels, oysters, and scallops. DSP is primarily observed as a generally mild gastrointestinal disorder, i.e., nausea, vomiting, diarrhea, and abdominal pain accompanied by chills, headache, and fever. Onset of the disease, depending on the dose of toxin ingested, is from 30 minutes to 2 to 3 hours, with symptoms lasting 2 to 3 days. Recovery is complete with no after effects; the disease is generally not life threatening.

 

The occurrence of DSP in Europe is sporadic, continuous and presumably widespread (anecdotal). DSP poisoning has not been confirmed in U.S. seafood, but the organisms that produce DSP are present in U.S. waters. An outbreak of DSP was recently confirmed in Eastern Canada. Outbreaks of NSP are sporadic and continuous along the Gulf coast of Florida and were recently reported in North Carolina and Texas.

Neurotoxic shellfish poisoning (NSP) is the result of exposure to a group of polyethers called brevetoxins. NSP has both gastrointestinal and neurological symptoms including tingling and numbness of lips, tongue, and throat, muscular aches, dizziness, reversal of the sensations of hot and cold, diarrhea, and vomiting. NSP is associated with shellfish harvested along the Florida coast and the Gulf of Mexico.

Onset of this disease occurs after a few minutes to a few hours; duration is fairly short, from a few hours to several days. Recovery is complete with few after effects; and no fatalities have been reported.

Amnesic shellfish poisoning (ASP) is caused by the unusual amino acid, domoic acid, as the contaminant of shellfish. ASP is characterized by gastrointestinal disorders (vomiting, diarrhea, abdominal pain) and neurological problems (confusion, memory loss, disorientation, seizure, coma) ASP is associated with mussels. This poisoning is characterized by gastrointestinal symptoms within 24 hours; neurological symptoms occur within 48 hours. The toxicosis is serious in elderly patients, and includes symptoms reminiscent of Alzheimer’s disease. All fatalities have involved elderly patients.

ASP first came to the attention of public health authorities in 1987 when 156 cases of acute intoxication occurred as a result of ingestion of cultured blue mussels (Mytilus edulis) harvested off Prince Edward Island, in eastern Canada; 22 individuals were hospitalized and three elderly patients eventually died.

Shellfish Poisoning Awareness, Surveillance and Prevention

Ingestion shellfish contaminated with toxins results in a wide variety of symptoms, depending on the toxin(s) present, their concentrations and the amount of contaminated shellfish consumed.

Diagnosis of shellfish poisoning is based entirely on observed symptoms and recent dietary history. Clusters of cases help alert cases.

Scientists are unable to measure the true incidence of the disease. Cases are misdiagnosed and infrequently reported.

Screening Shellfish

In recent years considerable effort has been applied to development of chemical assays to replace old bioassays using mice that were not reliable.

High performance liquid chromatography (HPLC) procedure has been developed to identify individual PSP toxins (detection limit for saxitoxin = 20 fg/100 g of meats; 0.2 ppm), an excellent HPLC procedure (detection limit for okadaic acid = 400 ng/g; 0.4 ppm), a commercially available immunoassay (detection limit for okadaic acid = 1 fg/100 g of meats; 0.01 ppm) for DSP and a totally satisfactory HPLC procedure for ASP (detection limit for domoic acid = 750 ng/g; 0.75 ppm).

What else can be done?

Undoubtedly Shellfish poisonings are unusual and unexpected.

Travelers and people eating imported shellfish should be aware of the possibility of outbreaks and follow local guidelines from consuming shellfish abroad.

Scombroid (histamine poisoning)

This food poisoning is associated with ingestion of fish and fish products (canned fish), which include tuna, mackerel and sardines. This disease is named for a family of fish called scombridae, and usually occurs after eating the dark-fleshed fish within this family, which include tuna, mahi mahi, and blue fish. The Centers for Disease Control and Prevention (CDC) has identified the largest vector of scombroid to be nonscombroid fish, such as mahi-mahi and amberjack. Other nonscombroid includes sardine, yellowtail, herring, bluefish and whitefish. Other products also have caused the toxic effects. The primary cheese involved in intoxications has been Swiss cheese.

If any fish contains large amounts of a chemical, histidine, and these fish are not kept on ice or frozen after being caught, this histidine will break down and be converted into histamine, which causes the symptoms of the poisoning.

The histamine is produced via bacterial decarboxylation of histidine and is normally present at levels less than 0.1 mg per 100 g of fish. In contrast, samples of fish that produce poisoning contain histamine levels of at least 20-50 mg per 100 g of fish.

Higher temperatures favour the formation of histamine. The key to prevent Scrombroid is continuous temperature control i.e. refrigeration close to 0 o C from the time fish are caught until they are cooked. This is important for fishermen, street hawkers, dealers, retailers and food-handlers at home alike. In the case of canned fish products, this should be consumed as soon as possible once the can is opened .

The most common causes of poisonings are eating spoiled fish, consuming caught fish that had been cooled and refrigerated inadequately, or consumption of frozen fish that has been allowed to sit at room air temperature for a prolonged time after thawing. Eating a portion of fish closer to the outside of a previously frozen mass of fish also causes more toxicity.

Diners at the same meal may get different symptoms depending on: Individual differences in sensitivity to histamine, size of their portion consumed, whether their portion was from the same fish, and how cold the fish was before cooking (i.e., more thawing may have taken place at the surface, and a fish portion from this area may contain more histamine). Patients on isoniazide are more susceptible to Scombroid. Scombroid poisoning cannot be detected by appearance or taste although a peppery taste is often noted this is not reliable.

Histamine is not destroyed by normal cooking temperatures, so cooked fish can be affected. Histamine is a mediator of allergic reactions, so the symptoms produced resemble those in severe allergic responses.

The onset of symptoms is usually 10-30 minutes after eating of the implicated fish, which is said to have a characteristic peppery bitter taste and generally are self-limited. The symptoms are non-specific and may include skin flushing, throbbing headache, oral burning, abdominal cramps, nausea, diarrhea, palpitations, a sense of unease, and, rarely prostration or loss of vision.

Physical signs may include a diffuse blanching erythema, tachycardia, wheezing, and hypotension or hypertension. People with asthma are more vulnerable to respiratory symptoms.

Treatment: If the patient only has minimal symptoms, reassurance and observation may be the only treatment necessary. For severe symptoms, t reatment is supportive with fluids, oxygen; and (H1 and H2 receptor) anti-histamines. Epinephrine or other adrenergic agents are rarely necessary because the entire cascade of mediators released by a true allergic reaction is not found in scombroid poisoning. Blockade of histamine, the sole pharmacological mediator of scombrotoxism symptoms, is the only treatment necessary. Adrenergic agents may be considered in the rare case of secondary bronchospasm or refractory hypotension associated with this type of poisoning. Consider use of activated charcoal only if poisoning is very early and a large amount of fish was ingested. Differential diagnosis could include: a naphylaxis or angioedema , Bee Stings , Sunburn, Toxic Shock Syndrome , Toxicity from shellfish or ciguatera, any acute allergic reaction, carcinoid syndrome, Chinese restaurant syndrome (monosodium glutamate reaction), niacin like reaction, atypical migraine or cluster headache; and keriorrhoea, an oily diarrhea related to ingestion of marine wax esters.

The diagnosis is usually made clinically although histamine levels can be shown to be elevated in blood and urine. Also the fish can be tested for elevated histamine levels. Remember public health issues. Notify the local board of health if the diagnosis is confirmed, especially if the source was public. The US FDA requires fish to have a histamine level of less than 50 mg/kg; a level of 200 mg/kg is considered hazardous

What should one do to avoid scombroid poisoning?

Remember potential scombrotoxic fish should not be allowed to initially spoil. These species should receive special care in handling, washing, and proper icing, refrigeration or immediate freezing to prevent bacterial growth and spoilage. Any suspected fish should be kept frozen, handled gently and sent to a diagnostic lab. The recreational catch lying on a warm dock or beach or fishing boat is prone to histamine production.

•  References: •  Predy G, Honish L, Hohn W, Jones S: Was it something she ate? Case report and discussion of scombroid poisoning. CMAJ 2003 Mar 4; 168(5): 587-8 http://www.cmaj.ca/cgi/content/full/168/5/587 •  FDA Advisory note: http://vm.cfsan.fda.gov/~lrd/sea-scm.html •  Health Canada http://www.inspection.gc.ca/english/corpaffr/foodfacts/histame.shtml •  Scuba-doc.com http://www.scuba-doc.com/scomlnks.htm •  CDC http://www.cdc.gov/epo/mmwr/preview/mmwrhtml/00000723.htm

Marine toxin Summary

How can these diseases be diagnosed?

Diagnosis of marine toxin poisoning is generally based on symptoms and a history of recently eating a particular kind of seafood. Laboratory testing for the specific toxin in patient samples is generally not necessary because this requires special techniques and equipment available in only specialized laboratories. If suspect, leftover fish or shellfish are available, they can be tested for the presence of the toxin more easily. Identification of the specific toxin is not usually necessary for treating patients because there is no specific treatment.

How can these diseases be treated?

Other than supportive care there are few specific treatments for ciguatera poisoning, paralytic shellfish poisoning, neurotoxic shellfish poisoning, or amnesic shellfish poisoning.

Antihistamines and epinephrine, however, may sometimes be useful in treating the symptoms of scombrotoxic fish poisoning.

Intravenous mannitol has been suggested for the treatment of severe ciguatera poisoning.

Are there long-term consequences to these diseases?

Ciguatera poisoning has resulted in some neurologic problems persisting for weeks, and in rare cases, even years. Symptoms have sometimes returned after eating contaminated fish a second time. Amnesic shellfish poisoning has resulted in long-term problems with short-term memory. Long-term consequences have not been associated with paralytic shellfish poisoning, neurotoxic shellfish poisoning, and scombrotoxic fish poisoning.

How common are these diseases?

Every year, approximately 30 cases of poisoning by marine toxins are reported in the United States. Because healthcare providers are not required to report these illnesses and because many milder cases are not diagnosed or reported, the actual number of poisonings may be much greater. Toxic seafood poisonings are more common in the summer than winter because dinoflagelates grow well in warmer seasons. It is estimated from cases with available data that one person dies every 4 years from toxic seafood poisonings.

What can an individual do to prevent poisoning by marine toxins?

General guidelines for safe seafood consumption:

  • Although any person eating fish or shellfish containing toxin or disease-causing bacteria may become ill, persons with weakened immune systems or liver problems should not eat raw seafood because of their higher risk of Vibrio infection. (See our seperate talk on vibrio infections)
  • Keep seafood on ice or refrigerated at less than 38° Fahrenheit to prevent spoilage.

Specific advise for avoiding marine toxin poisoning:

  • Keep fresh tuna, mackerel, grouper, and mahi mahi refrigerated to prevent development of histamine. Don’t believe that cooking spoiled or toxic seafood will keep you safe. Cooking does not destroy these toxins.
  • Do not eat barracuda, especially, those from the Caribbean
  • Do not eat finfish or shellfish sold as bait. Bait products do not need to meet the same food safety regulations as seafood for human consumption.
  • Check with local health officials before collecting shellfish, and look for Health Department advisories about algal blooms, dinoflagellate growth or “redtide” conditions that may be posted at fishing supply stores.

Ciguatera can involve over 200 spp of fish so eating fish under safe conditions is more important than relying on species of fish.

Scombroid fish include tuna as well as non-scombroid spp.

Shellfish as filter feeders may accumulate dangerous dinoflagellates although this is very rare. Rare shellfish also can transmit vibrio infections particularly to people with chronic medical problems.

Tetrodotoxin poisoning from Fugu is easy to avoid. Blue ringed octopus and cone shell envenomations although rare are medical emergencies

 

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