• allergy;
  • Anisakis simplex;
  • Anisakis simplex allergy ;
  • challenge;
  • gastroallergic anisakiasis;
  • seafood


  1. Top of page
  2. Abstract
  3. Material and methods
  4. Results
  5. Discussion
  6. References

Background: Anisakis simplex can cause allergic reactions in sensitized patients. Some of these reactions are related to acute parasitism, as is shown in gastroallergic anisakiasis (anisakiasis with digestive and predominantly allergic symptoms). At present, a nonseafood diet is recommended for all patients with any kind of A. simplex allergy. We wished to confirm the clinical suspicion that patients with allergic symptoms after ingestion of raw or undercooked seafood who are sensitized to A. simplex, and diagnosed with gastroallergic anisakiasis, can tolerate the ingestion of seafood when the parasites are dead and noninfective.

Methods: We included patients diagnosed with gastroallergic anisakiasis (positive skin prick test or/and serum specific IgE to A. simplex, with one or more parasites found by gastroscopy in the stomach). Patients included in the study gave written, informed consent. Specimens of A. simplex about 2 cm long were selected, placed in capsules, and frozen at −20°C for more than 48 h to make them noninfective. We administered 11 specimens to every patient at the hospital. If they tolerated the larvae, they were told to eat well-frozen seafood (−20°C at least 48 h). After 6 months, the patients were re-evaluated.

Results: Five patients accepted the challenge with noninfective A. simplex larvae. All tolerated the noninfective larvae. After eating deep-frozen seafood for 6 months, no patient suffered a reaction.

Conclusions: In gastroallergic anisakiasis, the antigens of the live parasite probably cause the allergic symptoms. Patients with this disease can tolerate deep-frozen seafood, in which the parasites are dead.

Anisakis simplex is a nematode of the Anisakidae family, Ascaridoidea superfamily, Ascaridida order, that in its adult stage parasitizes sea mammals. The common intermediary host species are codfish, hake, sardine, anchovy, salmon, red mullet, tuna, mackerel, horse mackerel, and squid ( 1). In these intermediary hosts, the larvae enter the third stage. The ingestion of third-stage Anisakidae larvae in raw or undercooked seafood may cause the human disease known as anisakiasis or anisakidosis (2[3-9]10). After ingestion, A. simplex larvae can attach themselves to gastric mucosa (acute anisakiasis), or penetrate the host stomach or intestinal wall (chronic anisakiasis). In the latter form, the invasion causes abscesses or eosinophilic granulomas. This form is rare, and can mimic appendicitis, gastroduodenal ulcer, eosinophilic colitis, inflammatory bowel disease, and intestinal obstruction (2[3-5]6). Some rare cases of anisakiasis affecting the lung, spleen, pancreas, and liver have been reported ( 4). Because of the national eating habits, anisakiasis is common in Japan (2, 4[5-8]9). In Europe, several cases have been reported over the years (3, 10[11-17]18).

The larvae of A. simplex cannot survive a temperature higher than 60°C for 10 min, or lower than −20°C for 48 h ( 19). However, the ingestion of safely cooked sea fish, without viable larvae, has been reported to cause allergy (20[21-23]24). In such cases, the allergy to the parasite is avoided by a seafood-free diet.

It is believed that allergic reaction plays a role in the pathogenesis of anisakiasis (7[8]9). We have described a form of anisakiasis with severe allergic symptoms ( 17). This gastroallergic form includes allergic and gastric symptoms after contact with live parasites, which disappear after removal of the worms by gastroscopy. However, purely gastrointestinal anisakiasis has marked digestive symptoms without allergic symptoms.

Until now, allergists recommended a seafood-free diet for both kinds of patients, i.e., those with A. simplex allergy and those with gastroallergic anisakiasis; however, many of the patients with gastroallergic anisakiasis went on eating seafood, mainly well cooked or frozen, without problems.

After considering this fact and our patients with gastroallergic anisakiasis who suffered allergic reactions only after ingesting live parasites, we decided to determine the correct diet for these patients by performing food challenge with the seafood involved in their reactions and with noninfective larvae of A. simplex.

Material and methods

  1. Top of page
  2. Abstract
  3. Material and methods
  4. Results
  5. Discussion
  6. References


We selected patients diagnosed with gastroallergic anisakiasis (allergic symptoms, such as urticaria, bronchospasm, angioedema, or anaphylaxis; and digestive symptoms, such as epigastric pain and, in some cases, nausea, vomiting and diarrhea) less than 24 h after the ingestion of raw or undercooked seafood, with detection of one or more A. simplex larvae in gastric mucosa by fiberoptic gastroscopy ( Fig. 1). All patients were sensitized to A. simplex. Skin testing was performed with A. simplex extract (I.P.I. Pharmaceutical, Madrid, Spain) sea fishes, cephalopods, and other seafood involved in the reaction. Serum specific IgE was determined against the implicated seafood and A. simplex by the CAP System (Pharmacia Diagnostics, Uppsala, Sweden). All patients showed positive SPT and serum specific IgE to A. simplex and were negative to any seafood ( Table 1).


Figure 1. Third-stage larval A.simplex attached to gastric mucosa.

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Table 1.  Characteristics of challenged patients
NameAge (years) SexSeafoodSPTIgE-AsGastroscopyAs challenge Seafood challenge VIsit at 6 months
  1. As: Anisakis simplex; SPT: skin prick test. Anchovy was taken raw in vinegar sauce. Hake was taken undercooked.

MDH58FAnchovy+100 ku/lAs larvaNegativeNegativeNo problems
FYM59MHake+86.9 ku/lAs larvaNegativeNegativeNo problems
SHR46MHake+12.2 ku/lAs larvaeNegativeNegativeNo problems
EFS27FAnchovy+2.16 ku/lAs larvaNegativeNegativeNo problems
ARM19FAnchovy+2.84 ku/lAs larvaNegativeNegativeNo problems

Five patients gave written, informed consent to carry out the challenge.


We performed two types of food challenge. The first challenge was performed with 11 noninfective A. simplex larvae which had been frozen at −20°C for 48 h, and the second challenge with the seafood involved in their reactions, after freezing at −20°C for 48 h. The challenges were performed single-blind vs placebo (Table 1).

We obtained the larvae from anchovy, hake, and blue whiting. We selected worms about 2 cm long. They were identified as A. simplex larvae by the microbiology service of our hospital, who listed the following characteristics for identification: three bilibed lips, one dorsal and two ventrolateral; a boring tooth projecting anteroventrally, ventral to the mouth; a simple digestive tube; distinctive Y-shaped lateral chords; and no lateral alae extending from the cuticle. Then we separated the larvae, and introduced them into capsules, where they were frozen for 48 h at −20°C. The patients swallowed capsules with one, four, and six larvae, with a 1-h interval, and they remained at the hospital for 6 h after the last administration. If no symptom appeared, they were told that they could eat deep-frozen seafood until the next visit. If there was no allergic reaction, the challenged patients were seen again after 6 months.


  1. Top of page
  2. Abstract
  3. Material and methods
  4. Results
  5. Discussion
  6. References

Five patients were included in the study. Their characteristics are shown in Table 1. All of them tolerated both challenges without any allergic or gastric symptom. After 6 months, no reaction had been reported, and all of them had eaten seafood at least once a week, according to our recommendation; that is, deep-frozen. Skin prick testing and serum specific IgE were still positive in all patients after 6 months.


  1. Top of page
  2. Abstract
  3. Material and methods
  4. Results
  5. Discussion
  6. References

Gastroallergic anisakiasis is a form of acute anisakiasis, with allergic and gastric symptoms, that has usually been misdiagnosed. In large series of patients, Japanese authors ascribed marked importance to the local allergic reaction in gastric mucosa (5[6-8]9), but the only therapy for acute anisakiasis is endoscopic removal of the larvae. The treatment of chronic anisakiasis (gastric or intestinal) is surgery. No drugs have been able to destroy the larvae.

In A. simplex allergy, most allergists recommend a nonseafood diet, because it is impossible to know whether a piece of fish contains the parasite or not. The thermostability of some A. simplex allergens has previously been confirmed, and this explains the allergic manifestations after ingestion of cooked or frozen seafood (20[21-23]24).

In gastroallergic anisakiasis, allergic symptoms after the attachments of live worms are manifestations of allergy to antigens of the live parasite. Gastroscopy and clinical findings showed that these patients become sensitized to the Anisakis allergens in response to being parasitized (8, 9, 17).

The challenge with A. simplex or infected seafood to assess the true clinical implication of a positive skin prick test or serum specific IgE has been considered unethical. However, since the sea fish of all fishing grounds are infested by nematodes ( 25), many people ingest larvae every day. In Spain, the incidence of infected fish is 37.7% of samples in the Madrid markets ( 26). Hake is the most parasitized North Sea fish, with an infection rate of 45% in the north of Spain ( 25), and an intensity (parasites per fish) of 12–63 in studies from Spain and Italy (19, 25, 27).

On the other hand, we had patients diagnosed with gastroallergic anisakiasis who did not follow a correct diet, but allergic episodes appeared again only after they ate raw or undercooked food. In addition, although heated or deep-frozen seafood can cause allergic reactions due to the sensitization to thermostable antigens of A. simplex, in gastroallergic anisakiasis, the patients are probably sensitized to other A. simplex antigens, such as the secretor antigens. All these facts were investigated in the present work by performing a challenge with noninfective deep-frozen parasites. A food challenge with noninfective A. simplex is an ethical solution in those patients who have been diagnosed with gastroallergic anisakiasis.

The results of these challenges and the evolution of the challenged patients after 6 months support our thesis. No patient suffered any reaction to noninfective larvae. Those patients with gastroallergic anisakiasis had allergic reactions only after ingestion of the live parasite, a fact which is very important for a correct dietary assessment.

Further in vitro investigations are needed to determine the immunologic basis of these clinical findings.


  1. Top of page
  2. Abstract
  3. Material and methods
  4. Results
  5. Discussion
  6. References
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