Human Illness Associated With Harmful Algal Blooms

Ciguatera Fish Poisoning

Worldwide, ciguatera fish poisoning is the most clinical syndrome associated with marine biotoxins, with estimates that global case numbers range from 50,000 to 500,000 per year. It is a major public health problem in the Caribbean and South Pacific regions, particularly in areas with tropical reefs. Illness is caused by ciguatoxins that are passed up the marine food chain, with large predatory reef fish (e.g., barracuda, jacks, snappers, moray eels) posing the greatest risk for toxicity. A 2013 study in the US Virgin Islands found that 12% of lionfish (a highly invasive species being found with increasing frequency on tropical reefs in Florida and the Caribbean) had potentially toxic levels of ciguatoxin, suggesting that recommendations to “eat more lionfish” to save reefs may be ill-advised.

Toxins are produced by dinoflagellates within at least eight species in the genera Gambierdiscus and Fukuyoa, with toxicity varying by species. Increases in numbers of these toxic dinoflagellates have been associated with disruption of normal reef ecology and reef communities, including disruption by storms, human activity, and climate change. Multiple ciguatoxin conjoiners have been identified, with ciguatoxins from the Pacific having slight structural differences from ciguatoxins found in the Caribbean. The toxin acts by stimulation of mucosal ion transport in the gastrointestinal tract and interaction with voltage-gated sodium channels along the peripheral nerves; in animal studies, it has been shown to cross the blood-brain barrier.

Among patients with ciguatera fish poisoning, gastrointestinal symptoms—nausea, vomiting, and diarrhea—are usually the presenting symptoms, occurring within 6 to 24 hours of eating a toxic fish. Patients typically present to emergency departments in the early hours of the morning after unknowingly eating a toxic fish for dinner. Within 12 to 48 hours of onset of illness, most patients also begin to experience neurologic symptoms, including headache; pain and weakness in the legs; and dysesthesias such as tingling sensations in the extremities and around the mouth, cold allodynia (cold objects feeling burning hot), burning sensation in the mouth, and aching pain around the teeth. These neurologic symptoms may persist for weeks to months and may be linked with clinical depression. In a small percentage of cases, this can lead to a chronic/recurring syndrome that has many of the manifestations of chronic fatigue syndrome.

In severe cases, patients may be acutely bradycardic and hypotensive; in the Pacific, respiratory difficulties have also been reported. Restlessness and confusion may occur, and seizures and coma have rarely been reported. Deaths are exceedingly rare and are generally associated with high toxin exposure (consumption of viscera of a highly toxic fish), often in the setting of underlying cardiac or respiratory illness. The diagnosis of ciguatera fish poisoning is clinical, based on the combination of gastrointestinal and characteristic neurologic symptoms occurring after eating a reef fish that carries a risk for toxicity. Other individuals who have eaten the same fish may also be ill, although not everyone who eats a toxic fish will manifest symptoms. Individuals who have had prior episodes of ciguatera fish poisoning are more likely to be symptomatic, and there is a suggestion that alcohol consumption increases symptom risk. There are no confirmatory laboratory tests for illness. Identification of toxin in fish is possible but technically difficult. In the United States, testing is available only through the US Food and Drug Administration laboratories as part of an outbreak investigation.

Treatment is symptomatic and includes maintenance of adequate hydration, use of atropine for bradycardia/hypotension, and administration of analgesics and antidepressants as appropriate. For severe cases in the Pacific, monitoring of respiratory status is indicated. Some literature suggests that intravenous mannitol alleviates acute symptoms, and use of mannitol is common in emergency departments in endemic areas; however, no benefit with use of mannitol was seen in one double-blind randomized clinical trial. At an anecdotal level, case reports suggest that neurologic manifestations, including pain syndromes, can be reduced by drugs such as amitriptyline, nifedipine, gabapentin, or pregabalin.

Prevention is difficult because the toxin is not inactivated by cooking, and toxic fish have a normal appearance and taste. For native populations in endemic areas, prevention requires avoidance of high-risk fish from reef areas known to be toxic. Families concerned about the toxicity of a specific fish often report the use of crude bioassays, including feeding of suspect fish to the family cat.

In endemic areas in the Pacific and Caribbean, ciguatera fish poisoning can have major economic and nutritional impact, as local populations are often reluctant to eat locally caught fish because of the risk for illness. Reflecting these concerns, tourist hotels and restaurants in endemic areas such as the Caribbean tend to import all of their seafood from nonendemic regions. Cases are common in local populations in Puerto Rico and the US Virgin Islands, where the annual incidence in one study was estimated at 1200 cases per 100,000 population. Cases seen in South Florida and Hawaii are generally associated with recreational fishing in reef areas. In Florida, data from a population survey are consistent with an incidence of between 5 and 6 cases per 100,000 population per year; rates are highest in Hispanic populations (relative risk, 3.4), possibly due to differences in patterns of fish consumption, including increased consumption of high-risk fish such as barracuda.

Paralytic Shellfish Poisoning

Based on reported cases, paralytic shellfish poisoning is one of the most common causes of marine biotoxin–associated illness in the continental United States and Alaska. Illness has traditionally been associated with eating clams and mussels that contain saxitoxins produced by Alexandrium spp. and related dinoflagellates, although a variety of other vehicles have been reported. Saxitoxins exert their effect by binding directly to the voltage-dependent sodium channels in nerve and muscle cell membranes, interrupting nerve signal transmission and leading to paralysis.

In contrast to ciguatera poisoning, gastrointestinal symptoms are less prominent than neurologic manifestations. Circumoral paresthesias and paresthesias of the extremities usually appear within 1 hour of ingesting toxic shellfish, and they may be accompanied by ataxia, dysphagia, and changes in mental status. Hypertension may occur and corresponds to the extent of the ingested dose; in the most severe cases, patients may proceed to respiratory paralysis, usually within the first 24 hours of illness. Assays are available for identification of saxitoxins in serum and urine samples from affected patients, albeit at an experimental level. Treatment is symptomatic; respiratory support may be necessary in the most severe cases.

Prevention is achieved through regular monitoring of shellfish populations for saxitoxin by public health authorities, with sampling data available on state health department web pages (e.g., the biotoxin web page of the Washington State Department of Health, www.doh.wa.gov/CommunityandEnvironment/Shellfish.aspx ). Blooms of toxic Alexandrium spp. occur primarily between April and October along cold water marine coasts. In North America, this includes Alaska, the Pacific Northwest, and the St. Lawrence Seaway region of Canada. Toxic shellfish have also been found in cold water regions of southern Chile, England, Japan, and the North Sea. Most shellfish remain toxic for several weeks after a bloom subsides, although some shellfish species including butter clams may retain toxicity for more than a year.