Sushi Delight: Uncooked Seafood and Anisakidosis

Abstract & Commentary

By Maria D. Mileno, MD

Dr. Mileno is Associate Professor of Medicine, Alpert Medical School at Brown University, Providence, RI.

Dr. Mileno reports no financial relationships relevant to this field of study.

Synopsis: In 1960 Van Thiel identified the nematode responsible for ascarids most often vomited. More recently, anisakidosis has been increasingly identified as the cause of gastric, intestinal, and allergic syndromes in humans who have either occupational exposures to or who consume uncooked seafood.

Source: Hochberg NS, Hamer DH. Anisakidosis: Perils of the deep. Clin Infect Dis 2010;51(7):806-812.

Anisakis simplex and Pseudoterranova decipiens cause most human anisakidosis. The term anisakidosis refers to a dead-end human disease caused by ingestions of any such larvae. Most infections (> 90%) occur in adult Japanese men from coastal regions where people commonly consume raw or inadequately cooked saltwater fish or squid. Many case reports originate from coastal areas of Europe, especially the Netherlands, Germany, France, and Spain. About 60 cases have been described in the United States. Increasing regulatory controls of marine mammal exploitation, increased consumption of raw or lightly cooked food, and improved endoscopic diagnostics all account for a rising incidence of infections and increasing reports from New Zealand, Canada, Brazil, Chile, and Egypt.

All major oceans and seas harbor anisakid-infected marine life. A study of wholesale fish markets in Japan showed that 98% of mackerel and 94% of cod carried the parasite. High levels of infestation occurred among fish caught off the coast of Scotland, Italy, and France, and a fish market in Spain found anisakid infection in more than 39% of fish.

P. decipiens is largely transmitted by the Atlantic or Pacific cod, and Pacific halibut and red snapper. A substantial proportion of infected cod harvested in the U.S. coastal waters are infected.

In Japan, sushi chefs are experts in identifying and removing larval infestation; although sushi and sashimi are potentially high-risk meals there, the fish served in sushi bars tend to be less contaminated and free of anisakid nematodes. Risk of infection is greater with less expensive marine fish such as cod, herring, and mackerel and squid-fish that are more often consumed in local restaurants or at home.

Other high-risk dishes besides sushi include salted and smoked herring from the Netherlands; Scandinavian gravlax; Hawaiian lomi lomi or raw salmon; South American ceviche, Spanish pickled anchovies known as boquerones en vinagre, and raw sardines.

Marine mammals represent the primary hosts for Anisakis simplex and Pseudoterranova decipiens, while dolphins, porpoises, and whales host anisakids, and seals, walruses, and sea lions host P. decipiens. When marine mammals, acting as final hosts, ingest infected fish or squid, the parasite develops into the 4th-stage larvae and then into adults. Human consumption of raw or undercooked fish places humans as accidental hosts, and larvae most often embed in human gastric or intestinal mucosa and die.

Four major clinical syndromes in humans include gastric, intestinal, ectopic, and allergic disease. Gastric anisakidosis has a presentation of abrupt onset, 1-12 hours after ingestion of raw fish, with severe epigastric pain, nausea, vomiting, low-grade fever, and occasionally, rash. Acute symptoms resolve within a few days, but infected persons report persistent vague abdominal symptoms for weeks to months afterwards. If left untreated, chronic ulcer-like symptoms may continue for months.

Intestinal anisakidosis presents as intermittent or constant abdominal pain beginning 5-7 days after larval ingestion. It predominately involves the terminal ileum, although colon or jejunum are involved less commonly and can be complicated by ascites or peritoneal findings. Rare complications can include small bowel obstruction, ileal stenosis, intussusception, intestinal perforation, and pneumoperitoneum.

Ectopic presentations of anisakidosis include extra gastrointestinal or intraperitoneal infection. These are much less common, yet they can result from larval penetration of the stomach or intestine. If larvae migrate into the peritoneal cavity they may reach the pleural cavity, mesentery, liver, pancreas, ovary, and subcutaneous tissue, causing pneumoperitoneum from perforation of the GI tract. Mesenteric masses have also been described.

Allergic anisakidosis is associated with prominent responses. Manifestations ranging from urticaria and isolated angioedema to anaphylaxis, at times associated with GI symptoms, are documented in several reports from Spain. Symptoms occur approximately 5 hours after exposure.

In Japan, presentation with gastric infections occurs most commonly, whereas intestinal disease is more common in Europe. Pseudoterranova decipiens infection usually involves the stomach only and tends to be milder than disease due to Anisakis species. Infected persons may experience "tingling throat syndrome" from a worm crawling in the upper esophagus or oropharynx; the primary symptom is cough. Diagnosis can be made by history, with endoscopic or surgical removal of the larvae providing definite diagnosis.

Besides directly visualizing the worm embedded in gastric mucosa, endoscopy may reveal erythema, edema, severe erosive gastritis, a tumor-like nodule, or ulcerations. The larvae may be found up to approximately 6 days after consumption of seafood, although most degenerate and are either eliminated or pass through the mucosa resulting in ectopic disease. The only signs remaining may be thickened gastric folds and inflammation; chronic infection can result in abscess or granuloma formation in response to degenerating larvae.

Serologic evaluation can be useful in diagnosing intestinal, extra-intestinal, and allergic cases. ELISA, Latex agglutination, or other immunoassays are available, but many cross-react with other parasites including Ascaris, Toxocara canis, and unrelated beasts such as insects, including the German cockroach or even shrimp. A compatible history of allergic reactions after either consumption or exposure to fish with positive hypersensitivity testing and serology, as well as a lack of reaction to fish proteins on skin testing, can confirm a diagnosis of allergy to Anisakis.

Treatment is preferably early endoscopic extraction of gastric larvae, although surgical removal may be required. Intestinal infection may be treated conservatively, and limited evidence suggests that oral albendazole 400-800 mg daily for 6-21 days is effective.

Commentary

This thoughtful review is replete with references that support this discussion. Marinated and salted foods as well as "smoked" foods can be mistaken as safe methods of food preparation. Visual inspection of fish, extraction of visible parasites, and elimination of heavily parasitized fish all may reduce risk of human infection. The authors also speculate that eviscerating fish immediately after catch may decrease the number of larvae in the flesh of fish by preventing potential migration of larvae from the fish's intestinal tract into edible musculature. Heating kills larvae if temperatures greater than 60°C or 140°F are sustained for at least a minute.

For fish that will be consumed raw, the key to prevention is freezing. The FDA code recommends freezing to -20°C for 7 days or flash freezing to -35°C for more than 15 hours. The European code recommends freezing at less than -20°C for 4 days only. Travelers should be made aware that these standards are not uniformly enforced. Of note, A. simplex antigens are resistant to freezing or heating and so persons may develop allergic responses despite proper preparation. The key to elucidating the culprit causing the varied and complex intestinal symptoms of returned travelers would be to take a detailed food history.