Anisakiasis is a human parasitic infection of the gastrointestinal tract caused by the consumption of raw or undercooked seafood containing larvae of the nematode Anisakis simplex   . Fish, squid, and crustaceans often act as transport host in which larvae grow but do not mature into adults . When larger marine mammal such as seals, sea lions, dolphins and whales consume these smaller fish and crustaceans, the larvae develop into adult worms. In humans, larvae are unable to complete their development and cause infection. Symptoms of anisakiasis include violent abdominal pain, nausea, and vomiting. In some cases, antigens present in anisakis simplex can produce allergic reactions and hypersensitivity   . Most human infections have been reported from Japan, the Netherlands, and Spain   .
Agent (Classification and Taxonomy)
Anisakis is an intestinal nematode with a taxonomic classification as seen in Table 1. The species most commonly associated with human infections is Anisakis simplex. Infection with the closely related Anisakis physeteris has been reported in a few cases .
Table 1 (from Taxonomy browser
A. pegreffii, A. physeteris, A. schupakovi, A. simplex, A. typical, A. ziphidarum
History of Discovery
The first case of human infection by a member of the family Anisakidae was reported in the Netherlands by Van Thiel who described the presence of a marine nematode in a patient suffering from acute abdominal pain . The nematode was later identified as Anisakis spp. and the human infection was termed anisakiasis. Japanese authors have described the majority of cases, although cases have been reported in Korea, the Netherlands, Germany, Spain, Italy, and the United States among others  ,
Clinical Presentation in Humans
The majority of infections involve gastric or intestinal invasion. Tissue damage occurs because of the invasion of the gut wall, development of eosinophilic granuloma, and perforation . Invasive gastric anisakiasis is characterized by the abrupt onset of abdominal pain, nausea, sometimes vomiting or diarrhea with signs of peritoneal irritation and incomplete ileus of the small intestine . Invasion of the small intestine results in lower abdominal pain and signs of obstruction . Symptoms can occur from as little as an hour to two weeks after consumption of raw or undercooked seafood and can persist for months, rarely for years . If larvae pass into the bowel, a severe eosinophilic granulomatous response may occur one to two weeks after infection that mimic Crohn’s disease .
Acute allergic manifestations such as urticaria and anaphylaxis may occur with or without accompanying gastrointestinal symptoms. The frequency of allergic symptoms in connection with fish ingestion has lead to the concept of gastroallergic anisakiasis, an acute IgE-mediated generalized reaction . Occupational allergy including asthma, conjunctivitis, and contact dermatitis has been observed in fish processing workers .
A more benign form of infection, known as transient anisakiasis, occurs with no symptoms or mild throat irritation and the larva are occasionally coughed up. These transient infections often go undiagnosed 
Human infection is a result of ingestion of raw or undercooked fish containing third-stage Anisakis larvae   . A number of dishes including sushi, sashimi, smoked herring, ceviche and pickled anchovies are considered high-risk. The preparation of these foods does not involve sterilizing methods for anisakids.
Anisakis larvae can commonly occur in the flesh, internal organs, and/or muscle of cod, haddock, fluke, pacific salmon, herring, flounder, and monkfish  . Adult anisakids reside in the gastrointestinal tract of marine mammals such as seals, sea lions, dolphins, and whales, where they are embedded in the mucosa. Eggs, passed in the feces of marine mammals, hatch into larvae, which are then ingested by crustaceans, a food source for fish .
Being representative of intestinal nematodes, anisakids are free-living, non-segmented, cylindrical worms. Worms have both an oral and an anal opening as well as a complete digestive tract that includes an esophagus, a ventriculus, and an intestine. Additionally, third stage larva have the following characteristics: three bilobed lips, one dorsal and two ventrolateral; a boring tooth ventral to the mouth, and an excretory pore between the ventrolateral lips . Larva may reach a length of 50mm and a diameter of 1 to 2mm. Classification of the larva of anisakids is done on the basis of the structure of the digestive tract .
Scanning electron micrograph of mouthpartsSource: http://en.wikipedia.org/wiki/File:So4b-08.jpg
Larva in the fish
Life Cycle 
Marine mammals excrete unembryonated eggs produced by female larvae. Eggs become embryonated in water, forming first stage larva, which molt to become second stage larvae. Larvae hatch from the eggs and become free-swimming. Free-swimming larvae are ingested by crustacean, where they develop into infective third stage larvae. If infected crustaceans are eaten by fish, the larvae can penetrate into the body cavity and/or muscles of that host. Fish and squid act as a paratenic host in which larvae can grow but do not become adults. When infected fish are eaten by marine animals, third stage larvae molt to become adults. Humans are unintentional hosts; the parasites cannot mature or reproduce in humans.
A presumptive diagnosis can be made by examining a patient’s food habits and exposure to raw or uncooked seafood. A definitive diagnosis is made by obtaining and visualizing worms through gastroscopy, at surgery, or in patient’s vomit  A histopathological study of gastric or intestinal tissue may also be useful in determining the presence of worms . Due to its vague symptoms, anisakiasis is commonly misdiagnosed as appendicitis or Crohn’s disease  However, greater awareness and development of better diagnostic tools has led to increased reporting of anisakiasis in many parts of the world including the United States .
Sensitivization and allergy are determined by skin-prick test and detection of specific antibodies against anisakis. Hypersensitivity is indicated by a rapid rise in levels of IgE in the first several days following consumption of infected fish. . Serodiagnostic tests available for Anisakis reactivity include latex-based agglutination procedures, Ouchterlony tests and immunoelectrophoresis, immunofluorescence, indirect haemagglutination, complement fixation, immunoblotting and ELISA  
Management and Therapy
Because humans are the dead-end host of anisakis, no treatment is needed in most cases. Gastroscopy and surgery serve to confirm diagnosis and to provide treatment. Treatment with albendazole, 400 mg twice daily for 21 days, has been used successfully in patients . For patients with allergy, modification of diet to exclude fish can be used to manage symptoms 
Anisakiasis has been reported worldwide, with higher incidence in areas where raw fish are eaten such as Japan, the Netherlands, France, Spain, Germany, and California. Approximately 14,000 cases have been reported since 2000 [GIDEON]. Given the widespread consumption of raw fish in the form of sushi and sashimi, Japan is the country with the highest prevalence of gastric anisakiasis. Many infections have also been reported in the Netherlands from the consumption of pickled herring. Over 150 cases involving allergic reaction to anisakis have been reported and investigated in Spain   . Less than ten cases occur annually in the United States . Development of better diagnostic tools and greater awareness has led to more frequent reporting of anisakiasis.
Consumers of raw seafood are at risk for gastric and allergic anisakiasis. Fishermen or fish-processing workers are at risk for developing allergy to anisakis .
Public Health and Prevention Strategies
Raising consumer and producer awareness about the existence of anisakid worms in fish is a critical and effective prevention strategy. Anisakiasis can be easily prevented by adequate cooking at temperatures greater than sixty degrees or freezing. The FDA recommends that all shellfish and fish intended for raw consumption be blast frozen to -35°C or below for fifteen hours or be regularly frozen to -20°C or below for seven days . Salting and marinating will not necessarily kill the parasites 
Anisakis worms represent a biological hazard for the fishing industry [11[. Larva can persist in fish that has not been frozen immediately after being caught . Current European community regulations on dish and seafood require visual examination of fish, extraction of visible parasites, and removal of heavily parasitized fish from the market . The mandate to freeze herring in the Netherlands, has virtually eliminated human anisakiasis 
- “Anisakis.” Wikipedia, the free encyclopedia. http://en.wikipedia.org/wiki/Anisakis
- DPDx: Laboratory Identification of Parasites of Public Health Concern: Anisakiasis http://www.dpd.cdc.gov/dpdx/html/Anisakiasis.htm
- “Infectious Disease: Anisakiasis: General” GIDEON. 20 Feb. 2010 http://web.gideononline.com/web/epidemiology/
- “Taxonomy browser (Anisakis)” NCBI. http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi
 “Anisakis simplex and Related”. Bad Bug Book: Foodborne Pathogens Microorganisms and Natural Toxins Handbook. Food and Drug Administration. http://www.fda.gov/Food/FoodSafety/FoodborneIllness/FoodborneIllnessFoodbornePathogensNaturalToxins/BadBugBook/ucm070768.htm
 Audicana, M. T., and M. W. Kennedy. "Anisakis Simplex: From Obscure Infectious Worm to Inducer of Immune Hypersensitivity." Clinical microbiology reviews 21.2 (2008): 360,79, table of contents. Print.
 Audicana, María Teresa, et al. "Anisakis Simplex: Dangerous — Dead and Alive?" Trends in parasitology 18.1 (2002): 20-5. Print.
 Butt, A. A., K. E. Aldridge, and C. V. Sanders. "Infections Related to the Ingestion of Seafood. Part II: Parasitic Infections and Food Safety." The Lancet infectious diseases 4.5 (2004): 294-300. Print.
 Caramello, P., et al. "Intestinal Localization of Anisakiasis Manifested as Acute Abdomen." Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases 9.7 (2003): 734-7. Print.
 ---. "Infections Related to the Ingestion of Seafood. Part II: Parasitic Infections and Food Safety." The Lancet infectious diseases 4.5 (2004): 294-300. Print.
 Cho, S. W., and H. N. Lee. "Immune Reactions and Allergy in Experimental Anisakiasis." The Korean journal of parasitology 44.4 (2006): 271-83. Print.
 Daschner, A., and C. Y. Pascual. "Anisakis Simplex: Sensitization and Clinical Allergy." Current opinion in allergy and clinical immunology 5.3 (2005): 281-5. Print.
[9[ Dorny, P., et al. "Emerging Food-Borne Parasites." Veterinary parasitology 163.3 (2009): 196-206. Print.
 Gill, C. J., and D. H. Hamer. "An Uninvited Dinner Guest." Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 41.12 (2005): 1764, 1810-1. Print.
[11[ Hastein, T., et al. "Food Safety Hazards that Occur during the Production Stage: Challenges for Fish Farming and the Fishing Industry." Revue scientifique et technique (International Office of Epizootics) 25.2 (2006): 607-25. Print.
 John, David T., and William A. Petri. Markell and Voge's Medical Parasitology. St. Louis: Saunders, 2006. 267-270.
 Kleter, G. A., et al. "Identification of Potentially Emerging Food Safety Issues by Analysis of Reports Published by the European Community's Rapid Alert System for Food and Feed (RASFF) during a Four-Year Period." Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association 47.5 (2009): 932-50. Print.
 Laffon-Leal, S. M., V. M. Vidal-Martinez, and G. Arjona-Torres. "'Cebiche'--a Potential Source of Human Anisakiasis in Mexico?" Journal of helminthology 74.2 (2000): 151-4. Print.
 Lopez-Serrano, M. C., et al. "Gastroallergic Anisakiasis: Findings in 22 Patients." Journal of gastroenterology and hepatology 15.5 (2000): 503-6. Print.
 Montalto, M., et al. "Anisakis Infestation: A Case of Acute Abdomen Mimicking Crohn's Disease and Eosinophilic Gastroenteritis." Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver 37.1 (2005): 62-4. Print.
 Nieuwenhuizen, N., et al. "Exposure to the Fish Parasite Anisakis Causes Allergic Airway Hyperreactivity and Dermatitis." The Journal of allergy and clinical immunology 117.5 (2006): 1098-105. Print.
 Sakanari, J. A., and J. H. McKerrow. "Anisakiasis." Clinical microbiology reviews 2.3 (1989): 278-84. Print.
 Ventura, M. T., et al. "Immediate and Cell-Mediated Reactions in Parasitic Infections by Anisakis Simplex." Journal of investigational allergology & clinical immunology : official organ of the International Association of Asthmology (INTERASMA) and Sociedad Latinoamericana de Alergia e Inmunologia 18.4 (2008): 253-9. Print.
Weir, E. "Sushi, Nemotodes and Allergies." CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne 172.3 (2005): 329. Print.