Martínez Ubeira, Florencio CésarAnadón Ruiz, Ana MaríaSalgado Barreira, ÁngelOrtega, SaraAguirre, CarmeloLópez Goikoetxea, María JoséIbáñez, LuisaFigueiras Guzmán, Adolfo2020-04-302020-04-302011Ubeira FM, Anadón AM, Salgado A, Carvajal A, Ortega S, Aguirre C, et al. (2011) Synergism between Prior Anisakis simplex Infections and Intake of NSAIDs, on the Risk of Upper Digestive Bleeding: A Case-Control Study. PLoS Negl Trop Dis 5(6): e1214. https://doi.org/10.1371/journal.pntd.00012141935-2735http://hdl.handle.net/10347/21910Background: The aim of this study was to investigate the relationship between prior Anisakis infections and upper gastrointestinal bleeding (UGIB), and its interaction with non-steroidal anti-inflammatory drug (NSAID) intake. Methods/Principal Findings: We conducted a hospital-based case-control study covering 215 UGIB cases and 650 controls. Odds ratios (ORs) with their confidence intervals (95% CIs) were calculated, as well as the ratio of the combined effects to the sum of the separate effects of Anisakis allergic sensitization and NSAIDs intake. Prior Anisakis infections were revealed by the presence of anti-Anisakis IgE antibodies specific to the recombinant Ani s 1 and Ani s 7 allergens used as the targets in indirect ELISA. Prior Anisakis infections (OR 1.74 [95% CI: 1.10 to 2.75]) and the intake of NSAIDs (OR 6.63 [95% CI: 4.21 to 10.43]) increased the risk of bleeding. Simultaneous NSAIDs intake and Anisakis allergic sensitization increased the risk of UGIB 14-fold (OR = 14.46 [95% CI: 6.08 to 34.40]). This interaction was additive, with a synergistic index of 3.01 (95% CI: 1.18–7.71). Conclusions: Prior Anisakis infection is an independent risk factor for UGIB, and the joint effect with NSAIDs is 3 times higher than the sum of their individual effectsAuthor Summary: Anisakiasis is a worldwide re-emerging disease produced by the consumption of raw, lightly cooked, smoked or marinated fish containing live Anisakis larvae. In acute anisakiasis, mucosal lesions generated by the larvae may provoke upper gastrointestinal bleeding (UGIB). However, the effect of past unnoticed Anisakis infections as a risk factor for UGIB, and a possible synergism with other risk factors such as NSAIDs intake, have never been investigated. In this case-control study we observed that: i) prior Anisakis infections and NSAIDs intake are two independent risk factors for UGIB, and ii) that both risk factors act synergistically to the extent that their joint effect is 3 times higher than the sum of their individual effects. We concluded that, in countries where Anisakis infections are frequent, it would be wise to determine parasite-specific IgE antibodies and to conduct a closer follow-up of patients who consume raw or lightly cooked fish and who are prescribed NSAIDs for long periodsAuthor Summary Anisakiasis is a worldwide re-emerging disease produced by the consumption of raw, lightly cooked, smoked or marinated fish containing live Anisakis larvae. In acute anisakiasis, mucosal lesions generated by the larvae may provoke upper gastrointestinal bleeding (UGIB). However, the effect of past unnoticed Anisakis infections as a risk factor for UGIB, and a possible synergism with other risk factors such as NSAIDs intake, have never been investigated. In this case-control study we observed that: i) prior Anisakis infections and NSAIDs intake are two independent risk factors for UGIB, and ii) that both risk factors act synergistically to the extent that their joint effect is 3 times higher than the sum of their individual effects. We concluded that, in countries where Anisakis infections are frequent, it would be wise to determine parasite-specific IgE antibodies and to conduct a closer follow-up of patients who consume raw or lightly cooked fish and who are prescribed NSAIDs for long periodsengCopyright: © 2011 Ubeira et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedhttps://creativecommons.org/licenses/by/2.0/Anisakis simplexNSAIDsAllergensGastrointestinal infectionsParasitic diseasesHemorrhageLarvaeLesionsjournal article10.1371/journal.pntd.0001214open access