RT Journal Article T1 Synergism between prior anisakis simplex infections and intake of NSAIDs, on the risk of upper digestive bleeding: A case-control study A1 Martínez Ubeira, Florencio César A1 Anadón Ruiz, Ana María A1 Salgado Barreira, Ángel A1 Ortega, Sara A1 Aguirre, Carmelo A1 López Goikoetxea, María José A1 Ibáñez, Luisa A1 Figueiras Guzmán, Adolfo K1 Anisakis simplex K1 NSAIDs K1 Allergens K1 Gastrointestinal infections K1 Parasitic diseases K1 Hemorrhage K1 Larvae K1 Lesions AB Background: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 effects AB Author 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 SummaryAnisakiasis 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 periods PB PLOS SN 1935-2735 YR 2011 FD 2011 LK http://hdl.handle.net/10347/21910 UL http://hdl.handle.net/10347/21910 LA eng NO Ubeira 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.0001214 NO This study was supported by grants PI021512, PI021364, PI020661, PI021572 (Health Research Fund /Fondo de Investigación Sanitaria), SAF2002-04057 (Ministry of Health and Consumer Affairs, Spain), PGIDIT03PXIC20806PN (Galician Regional Authority, Spain) and 02/1572 (Basque Regional Authority, Spain) DS Minerva RD 25 abr 2026