Summary: Infection of humans with the nematode worm parasite Anisakis simplex was first described in the 1960s in association with the consumption of raw or undercooked fish During the 1990s it was realized that even the ingestion of dead worms in food fish can cause severe hypersensitivity reactions, that these may be more prevalent than infection itself, and that this outcome could be associated with food preparations previously considered safe Not only may allergic symptoms arise from infection by the parasites (“gastroallergic anisakiasis”), but true anaphylactic reactions can also occur following exposure to allergens from dead worms by food-borne, airborne, or skin contact routes This review discusses A simplex pathogenesis in humans, covering immune hypersensitivity reactions both in the context of a living infection and in terms of exposure to its allergens by other routes Over the last 20 years, several studies have concentrated on A simplex antigen characterization and innate as well as adaptive immune response to this parasite Molecular characterization of Anisakis allergens and isolation of their encoding cDNAs is now an active field of research that should provide improved diagnostic tools in addition to tools with which to enhance our understanding of pathogenesis and controversial aspects of A simplex allergy We also discuss the potential relevance of parasite products such as allergens, proteinases, and proteinase inhibitors and the activation of basophils, eosinophils, and mast cells in the induction of A simplex-related immune hypersensitivity states induced by exposure to the parasite, dead or alive

Anisakis simplex: from Obscure Infectious Worm to Inducer of Immune Hypersensitivity

Background Several case reports show allergy and anaphylactic reactions to the fish parasite Anisakis in the domestic and occupational setting. Further research is needed on the prevalence and mechanisms of disease. Objective To determine the prevalence of Anisakis sensitization and related symptoms among workers in 2 fish-processing factories, and to use gene-deficient mice to determine the working mechanisms of Anisakis allergy. Methods A modified version of the European Community Respiratory Health Survey was used to interview 578 South African fish-processing workers. Sensitization to Anisakis , seafood, and common aeroallergens was determined by skin prick test. Lung function was measured by spirometry and methacholine challenge. Serum eicosapentaenoic acid levels were used as an index of seafood consumption. Sensitized wild-type, IL-4, or IL-4 receptor α–deficient mice were challenged orally with Anisakis extract. Allergic reactions, lung pathology, antibodies, cytokines, mast cell proteases, and histamine were evaluated. Results The prevalence of sensitization to Anisakis was higher than the prevalence of sensitization to fish (8% vs 6%). Anisakis -specific IgE reactivity was associated with bronchial hyperreactivity and dermatitis, and significantly increased with fish consumption. In mice, Anisakis infective larvae (L 3 ) induced a striking T H 2/type 2 response. Food-allergic–type reactions induced by oral challenge with Anisakis extract were absent in IL-4 receptor α knockout mice. Conclusion Anisakis sensitization in fish-processing workers is associated with allergic symptoms and correlates with high levels of fish consumption. Anisakis proteins induce allergic reactions in sensitized mice by IL-4/IL-13–mediated mechanisms. Clinical implications Anisakis allergy should be considered in fish-processing workers with allergic symptoms.

Exposure to the fish parasite Anisakis causes allergic airway hyperreactivity and dermatitis

This review addresses the biodiversity, biology, distribution, ecology, epidemiology, and consumer health significance of the so far known species of Anisakis, both in their natural hosts and in human accidental host populations, worldwide. These key aspects of the Anisakis species' biology are highlighted, since we consider them as main driving forces behind which most of the research in this field has been carried out over the past decade. From a public health perspective, the human disease caused by Anisakis species (anisakiasis) appears to be considerably underreported and underestimated in many countries or regions around the globe. Indeed, when considering the importance of marine fish species as part of the everyday diet in many coastal communities around the globe, there still exist significant knowledge gaps as to local epidemiological and ecological drivers of the transmission of Anisakis spp. to humans. We further identify some key knowledge gaps related to Anisakis species epidemiology in both natural and accidental hosts, to be filled in light of new 'omic' technologies yet to be fully developed. Moreover, we suggest that future Anisakis research takes a 'holistic' approach by integrating genetic, ecological, immunobiological, and environmental factors, thus allowing proper assessment of the epidemiology of Anisakis spp. in their natural hosts, in human populations, and in the marine ecosystem, in both space and time.

Molecular Epidemiology of Anisakis and Anisakiasis: An Ecological and Evolutionary Road Map.

Anisakiasis is an emerging zoonosis caused by the fish parasitic nematode Anisakis. Spain appears to have the highest reported incidence in Europe and marinated anchovies are recognised as the main food vehicle. Using data on fishery landings, fish infection rates and consumption habits of the Spanish population from questionnaires, we developed a quantitative risk assessment (QRA) model for the anchovy value chain. Spaniards were estimated to consume on average 0.66 Anisakis per untreated (non-frozen) raw or marinated anchovy meal. A dose-response relationship was generated and the probability of anisakiasis was calculated to be 9.56 × 10−5 per meal, and the number of annual anisakiasis cases requiring medical attention was predicted between 7,700 and 8,320. Monte Carlo simulations estimated post-mortem migration of Anisakis from viscera to flesh increases the disease burden by >1000% whilst an education campaign to freeze anchovy before consumption may reduce cases by 80%. However, most of the questionnaire respondents who ate untreated meals knew how to prevent Anisakis infection. The QRA suggests that previously reported figures of 500 anisakiasis per year in Europe is a considerable underestimate. The QRA tool can be used by policy makers and informs industry, health professionals and consumers about this underdiagnosed zoonosis.

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Assessing the risk of an emerging zoonosis of worldwide concern: anisakiasis.

Purpose of reviewWhereas gastric anisakiasis has been known for several decades, the implications of Anisakis simplex-related allergic disorders had not been thoroughly studied until the late 1990s. This article reviews recent knowledge of allergic disorders ascribed to A. simplex contact or parasit

Anisakis simplex: sensitization and clinical allergy.

We analysed patients with allergic or digestive symptoms after seafood ingestion in order to assess a correct diet in Anisakis simplex sensitised individuals. A total of 120 patients who suffered allergic and/or digestive symptoms after marine food ingestion were studied. We performed skin prick tests for A. simplex and seafood, total serum and specific serum immunoglobulin E to A. simplex in the acute stage and 1 month later. A gastroscopy was carried out to find larvae in those patients with persistent abdominal pain. A challenge with non-infective larvae was performed to assess a correct diet. Some 96 patients were sensitised to A. simplex. Gastroscopy was performed in 47 and we detected larvae in 24. We compared symptoms, skin tests, total and specific IgE and the latency of appearance of symptoms in patients positive for Anisakis larvae, patients without larvae at gastroscopy and patients without digestive symptoms. There was no difference among the groups. We challenged 22 patients with frozen A. simplex larvae. After allowing deep-frozen seafood in the diet for more than 2 years, no patient suffered a reaction. At this time, we allowed all our patients well-frozen seafood without any allergic reaction occurring. Allergic symptoms are the most frequent manifestation of A. simplex parasitism. We could not find any patient allergic to the thermostable proteins of parasite.

M Concepción López-Serrano

Papers

Anisakis simplex only provokes allergic symptoms when the worm parasitises the gastrointestinal tract.