Anisakis and Pseudoterranova species (Anisakiasis)
Authors: Carlos Franco-Paredes, M.D., MPH, Helmut Albrecht, M.D.
GENERAL DESCRIPTION
Parasitology Life cycle
Anisakidosis or anisakiasis is caused by the accidental ingestion of contaminated seafood containing larval nematodes of the family Anisakidae. The nematode worms responsible for human infections are generally limited to three genera: Anisakis, Phocanema, and Contracaecum (1, 2, 8). The genus Phocanema has been renamed Pseudoterranova (7). Other anisakid nematodes that have rarely been reported as causes of visceral larva migrans are Thynnascaris and Terranova species. Advances in molecular testing have allowed for identification of novel anisakid species (9).
Adult worms are found in the stomach of marine mammals such as dolphins, seals, sea lions, and whales, but also aquatic birds and turtles (11). Eggs are passed in feces. They hatch as free-swimming larvae (L3) that are then eaten by crustaceans and mollusks, which are ingested by fish and cephalopods such as squid (3, 13). When infected fish or squid are ingested by marine mammals the life cycle is completed. Humans can act as accidental hosts when they eat undercooked infected fish or squid. While humans are not suitable hosts to complete the life cycle, infection with the third-stage larval forms causes two clinical syndromes: severe gastrointestinal manifestations such as nausea, vomiting, and abdominal pain; and allergic manifestations including immediate allergic reactions in the form of anaphylaxis or urticaria, dermatitis, and asthma. Exposure to these nematode parasites appears to be ion the rise due to increasing consumption of seafood worldwide (10, 11, 12).
Epidemiology
The first human case was described in the Netherlands in 1960 associated following ingestion of raw herring. Since then, Japan has become the major endemic focus (1, 5, 12).
The first human case was described in the Netherlands in 1960 associated following ingestion of raw herring. Since then, Japan has become the major endemic focus (1, 5, 17, 18 ). Although the incidence of anisakiasis in other countries is low, considerable numbers of cases have been reported from 19 countries, with a higher prevalence in the Netherlands, Germany, France, Korea, and the U. S (4, 12). The most common source of infection in the Netherlands is the green herring, whereas in Japan it is sashimi (raw fish) and sunomono (pickled fish). Pseudoterranova (Phocanema) species are commonly seen in the muscles of a wide variety of fish from waters in the U. S. (5). Clinically anisakidosis can be classified into five forms according to the location of the anisakine larvae; luminal, gastric, intestinal, intra-peritoneal, and extra-gastrointestinal (3, 16). The luminal and gastric forms are caused mainly by the Pseudoterranova species, while Anisakis species are mainly responsible for the intestinal form.
Clinical Manifestations
Gastrointestinal Manifestations
Anisakiasis is a cause of visceral larva migrans due to the incomplete maturation cycle that occurs in humans. Physical removal of the larvae may be required for symptoms to improve. Untreated anisakiasis may cause persistent inflammatory responses targeting remains of the larvae and can produce symptoms consistent with colitis, appendicitis, cholecystitis, or dyspepsia (12). The gastric form manifests usually within 12 hours after consumption of the infected seafood (i.e. raw fish or squid). The intra-peritoneal form is characterized by the penetration of the intestinal wall by the larva and migration to the mesenteries, lymph nodes, great omentum, liver pancreas, ovary and gallbladder, causing a visceral larva migrans-like syndrome with eosinophilia. Inflammation induced obstruction of biliary ducts can cause cholangitis and pancreatitis. Intussusception has been describes with intestinal disease in children. Anisakidosis is also an important cause of eosinophilic gastroenteritis (6, 7).
Allergic Manifestations
In some individuals infection of the gastrointestinal mucosa can lead to allergic sensitization to a range of proteins which can range from chronic urticarial, contact dermatitis, asthma and rhino-conjunctivitis to frank anaphylaxis in rare cases. Many of the affected individuals have a previous history of atopy. Recently it has been recognized that allergic reactions to Anisakis may occur in the absence of ingestion of Anisakis but due to inhalation or direct contact during the preparation of infected fish or seafood (occupational exposure) (10, 11).
Laboratory Diagnosis
Diagnosis should be considered in anyone with a history of ingestion of raw marine fish and suggestive abdominal symptoms. A definitive diagnosis can be established by endoscopy, radiographic studies or pathologic examination of tissue (14). Recently, it has been demonstrated that a positive Anisakis skin prick test (SPT) and/or measurement of Anisakis-specific IgE may aid in confirming the diagnosis. However, both tests are limited due to significant cross-reactivity to other helminths including Ascaris due to subclinical sensitization or prior exposures (3, 11, 13). Recent development of molecular tools such as DNA sequencing allow for rapid identification of species of nematodes associated with anisakiasis (9).
Pathogenesis
When the infected raw fish enters the host stomach, gastric enzymes release the parasite into the stomach or rarely, the small intestine. Tissue invasion is facilitated by release of hydrolytic enzymes from the parasite. In humans, the anasakid nematodes die within a few days provoking an eosinophilic granulomatous reaction (6, 7).
SUSCEPTIBILITY IN VITRO AND IN VIVO
There are no susceptibility data for this parasite.
ANTIPARASITIC THERAPY
There is no anthelmintic agent for the treatment of anisakiasis.
ADJUNCTIVE THERAPY
Treatment of anisakiasis may require the physical removal of the larvae. While symptoms improve spontaneously in most patients without specific therapy, recovery may be accelerated by endoscopic removal of worms. In the intestinal form, surgical removal, when required, is the only means of clearing the lesions. Symptoms will, however, improve spontaneously in most patients without specific therapy (2, 15). In a series of 12 patients with intestinal anisakiasis from Japan, all patients became asymptomatic by 2 to 3 weeks (8). Some investigators routinely recommend antacids following removal of worms to accelerate healing of the injured gastric mucosa (15)
ENDPOINTS FOR MONITORING THERAPY
The removal of the worm is curative.
VACCINES
There are no vaccines.
PREVENTION
Since infection of edible fish is common and the worm often difficult to detect (candling is only approximately 70% sensitive in the identification of nematodes in fish), the only means of prevention is the avoidance of inadequately prepared fish and shellfish. Anisakis larvae can survive for one day in soy sauce or Worcestershire sauce, six days in 10% formalin, > 50 days in vinegar and > 100 days in 1% HCl. Cooking to an internal temperature of 60 °C (140°F) for 10 minutes kills all nematodes and tapeworms. Hard salt curing before pickling is reportedly also effective. The FDA maintains that all fish and shellfish intended for raw consumption should be blast frozen to -35°C (-31°F) or below for 15 hours or routinely frozen to at least -20°C (-4°F) for at least seven days.
CONTROVERSIES
Most of the symptoms of visceral larva migrans appear to be driven by an allergic reaction to worm allergens. However, there are currently no data regarding the use of steroids in the management of this condition.,
Desensitization to Anisakis antigens has been used in selected individuals when patients present with severe allergic and recurrent manifestations (11, 12).
REFERENCES
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Tables
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