Summary

Anisakis spp. are parasitic nematodes of many marine species that are globally distributed and can infect humans via consumption of raw, undercooked, or processed food products. Anisakis infection causes ‘anisakiasis’, a clinical disease with nonspecific clinical manifestations including epigastric pain, nausea, vomiting, abdominal distention with intense pain, and occasionally hypersensitivity or anaphylaxis. Anisakiasis is a common form of food poisoning with tens of thousands of cases reported worldwide. Sensitized individuals can also develop Anisakis-induced asthma, rhinoconjunctivitis, dermatitis, and secondary gingivostomatitis following exposure to proteins of dead larvae. Approximately 26 allergens with a variety of biological functions have been characterized from Anisakis spp. to date, many of which persist and are highly resistant to heat and digestive enzymes. Major allergens include Ani s 1, Ani s 7, Ani s 12 and Ani s 14, while minor allergens are considered to be Ani s 4, Ani s 5, Ani s 6, Ani s 8, Ani s 9, Ani s 10, and Ani s 11. Ani s 2 (paramyosin) and Ani s 3 (tropomyosin) are considered pan-allergens with low specificity.

Route Of Exposure

Main

Ingestion of raw, undercooked, or processed (e.g. smoked, salted, brined, or canned) parasitized fish and cephalopod products that contain the Anisakis third-stage larvae (L3).

Clinical Relevance

Anisakis infection in humans causes ‘anisakiasis’, a clinical disease with nonspecific clinical manifestations including epigastric pain, nausea, vomiting, abdominal distention with intense pain, and occasionally hypersensitivity or anaphylaxis. Pathogenicity of anisakiasis results from direct tissue damage and/or an allergic response to the release of potent proteolytic enzymes and other metabolic products from the parasite. Anisakiasis is a common form of food poisoning. Tens of thousands of cases of anisakiasis reported from Europe, Asia, and other parts of the world can be grouped into four common symptomatic clinical manifestations: gastric, intestinal, ectopic (extra-intestinal), and allergic. Sensitization rates to Anisakis have increased worldwide with a significant impact on healthcare systems.

Allergic anisakiasis is characterized by angioedema, urticaria, hypersensitivity syndrome, or severe anaphylactic reaction, with immediate onset in IgE-mediated severe cases, or between 60‒120 minutes after digestion of infected food. Urticaria has been reported in 60‒70% of cases where there is a gastric presentation. Evidence suggests that humans previously sensitized to Anisakis can experience escalation of symptoms associated with allergic anisakiasis upon subsequent challenge, which can be serious or life-threatening. A recent systematic review reported the highest global rates of allergic anisakiasis in Portugal and Norway, with a prevalence rate of 18.45% to 22.50%, followed by Spain, Sweden, and Japan.

In most cases, initial sensitization and subsequent gastroallergic reactions are caused by exposure to live Anisakis larvae, however, sensitized individuals can also develop Anisakis-induced asthma, rhinoconjunctivitis, dermatitis, and secondary gingivostomatitis following exposure to proteins of dead larvae. Occupational exposure to parasitized fish can elicit allergic reactions including bronchial hyperreactivity and dermatitis.

Polymerase chain reaction (PCR) tests on intestinal biopsies from anisakiasis patients indicate a Th2 type immune response as T-cell receptor and Th2 cytokines IL-4 and IL-5 were detected, when IFN-gamma or IL-2 was not detected.Th2 cytokines are responsible for symptoms of gastroallergic anisakiasis as well as Anisakis allergy, which can manifest as asthma, rhinoconjunctivitis, urticaria, and atopic dermatitis, primarily driven by mediators released from mast cells. Gastroallergic anisakiasis can potentiate non-steroidal anti-inflammatory drug (NSAID)-induced upper gastrointestinal bleeding, and is associated with autoimmune disease, nontolerance of oral antigens, increasing susceptibility to secondary infections, and decreasing vaccine efficacy. Anisakis-induced granulomas have been mistaken for tumors and may persist for some time, leading to symptoms of chronic anisakiasis. Ectopic anisakiasis is less common but also has been associated with anaphylaxis in a case study of a person with scrotal localization,.

Diagnostics

Diagnosis of allergic anisakiasis is usually based on serology tests that are non-specific. The presence of specific IgE or a positive skin prick test alone does not indicate allergy, which can only be assessed by a clinical history, but sensitization. Of note, specific IgE detection by ImmunoCAP assay can overestimate the number of sensitized subjects.

Cross-Reactivity

Allergens from Anisakis spp. have been reported to cross-react with molecules from mites, crustaceans, insects, mollusks, and other nematode parasites. In a small study, a total of 44% of 25 Anisakis-allergic patients had specific IgE to Vespula spp. wasp venom and positivity to at least one of the Hymenoptera allergens was detected in 16% of individuals.