Chapter 334. Anasakiasis and Angiostrongyliasis

Anisakiasis is caused by several related larval nematodes, especially those of the genera Anisakis, Phoconema, and Contracaecum, that are ingested when eating raw or insufficiently cooked marine fish, as in sushi or sashimi.1 Adult nematodes are found mainly in the gastrointestinal tract of cetaceans (dolphins, porpoises, and whales), and nematode eggs shed in the feces of these definitive hosts are ingested by small crustaceans, where they develop into third-stage larvae.2 Fish and cephalopod mollusks become infected by eating crustaceans infected by larval forms, which invade the tissues of the fish. Definitive hosts and humans usually become infected by eating fish containing these larval stages. Most cases are associated with mackerel, but other fish, such as cod, whiting, haddock, herring, and salmon, may be infected.

There has been a dramatic increase in the incidence of anisakiasis since 1980, probably due to a (1) improvement in endoscopic procedures needed to make the definitive diagnosis; (2) increasing global demand for seafood and a growing preference for raw or lightly cooked food, especially in Western countries; and (3) the impact of regulatory controls on harvesting of marine mammals, leading to increased populations of potential definitive hosts. Human infection is most common in Japan, where consumption of raw fish is common and approximately 2000 anisakiasis cases are reported annually (accounting for 90% of all reported cases worldwide). However, incidence is also increasing in the United States (with about 50 annual cases) and in Europe (with about 500 annual cases).

Clinical Manifestations, Diagnosis, and Treatment

Several clinical manifestations are seen depending on whether the worm localizes in the stomach or small intestine.3 In the former, acute gastritis with severe epigastric pain, nausea, and vomiting may occur, often within the first 12 hours of ingestion. More severe symptoms with fever, chills, and urticaria may develop with repeated exposure because of Arthus-type allergic reactions. The relationship between anisakiasis and strong allergic reactions, ranging from isolated swellings to urticaria and life-threatening anaphylaxis, has become clearer in recent years. Most cases of allergic manifestations have been reported from Spain, where cases reported have demonstrated elevated IgE responses against A simplex. There is also speculation that initial sensitization may occur from exposure to dead parasites, as well as after exposure to live parasitic larvae.

Intestinal anisakiasis may not become symptomatic until up to a week after initial infection. Usually, the worms are regurgitated or expelled by coughing or defecating, which terminates the episode. Invasion of the gastric or intestinal wall may be associated with a severe eosinophilic granulomatous reaction that may become chronic, causing gastric or right lower quadrant pain, eosinophilia, and fecal occult blood. Occasionally, the stomach or intestine may be perforated by the invading worm, causing an acute surgical abdomen. Gastric anisakiasis is often misdiagnosed as peptic ulcer, and intestinal infection may mimic appendicitis or peritonitis.

Diagnosis can be difficult. Serodiagnosis generally is not available, although several experimental tests have been developed and an antigen-capture ELISA with a reported sensitivity and specificity near 100% has been described.4 Proper cooking of fish to at least 60°C (140°F) or freezing to 10°C (14°F) for a week will kill the worms. No chemotherapeutic agent has clearly been found to treat anisakiasis successfully, although albendazole has been reported to be successful in case reports. Surgical or endoscopic removal are the standard methods of treatment.

Angiostrongyliasis is caused by Angiostrongylus cantonensis, a nematode of rodents that occasionally infects humans. This parasite, also known as the rat lungworm, is the principal cause of eosinophilic meningitis. The organism is widely distributed but most commonly found in the Pacific islands and Southeast Asia; recent cases have also been reported from Cuba and Egypt. The first case reported in North America was in 1995, occurred in a child who had eaten a raw snail.5

Humans are infected after eating raw snails, slugs, and crustaceans that serve as intermediate hosts for the infective larva. Outbreaks in Taiwan and Japan have been associated with drinking vegetable juice or eating salads and raw vegetables, presumably due to contamination with mollusk slime. The ingested larva enters the circulation and migrates by the meningeal vessels to cause a marked eosinophilic meningitis with focal neurologic signs and symptoms, including paresthesias and cranial nerve deficits. Ocular complications, such as visual disturbances or diplopia associated with headaches, and neurologic sequelae are reported. The CSF leukocyte count is often between 150 and 2000 cells per microliter, and eosinophilic pleocytosis exceeds 10% in more than 95% of patients. Peripheral and cerebrospinal fluid (CSF) eosinophilia can be as high as 90%. Unlike other helminthic infections of the central nervous system, computed tomographic or magnetic resonance imaging of the brain does not demonstrate focal lesions. Larvae are rarely detected in the CSF, but Western blot assays for antibodies to the 31-kd antigen of A cantonensis in serum specimens are relatively specific (there is some cross-reactivity with Trichinella spiralis) and have been useful for diagnosis. Assays for antibodies in the CSF are reported, but experience is limited.

Angiostrongyliasis is generally a self-limited disease, but infrequent deaths occur. Therapy with various anthelminthics, such as thiabendazole and albendazole (either alone or in combination with corticosteroids), has been attempted, but the benefit of treatment is unclear and some reports suggest that treatment with anthelminthics alone can be detrimental, possibly due to inflammatory reactions to dead worms. Most patients do not receive specific therapy and recover spontaneously in 3 to 6 weeks. The Food and Drug Administration considers use of these drugs investigational for this indication.

Angiostrongylus costaricensis is a related parasite with a similar life cycle; it is found in South and Central America as well as in the United States. It does not produce eosinophilic meningitis, but results primarily in gastrointestinal pathology at the site of larval penetration, including eosinophilic infiltrates with deep ulcerations and fistulae. Infection may present with a palpable mass in the right lower quadrant, and symptoms often are misdiagnosed as acute appendicitis. Peripheral eosinophilia can exceed 60%. Young children are infected more often than adults. Treatment with albendazole has been recommended, but experience is limited.