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Introduction Influenza A(H3N2) clades 3C.2a and 3C.3a co-circulated in Europe in 2018/19. Immunological imprinting by first childhood influenza infection may induce future birth cohort differences in vaccine effectiveness (VE). Aim The I-MOVE multicentre primary care test-negative study assessed 2018/19 influenza A(H3N2) VE by age and genetic subgroups to explore VE by birth cohort. Methods We measured VE against influenza A(H3N2) and (sub)clades. We stratified VE by usual age groups (0–14, 15–64, ≥ 65-years). To assess the imprint-regulated effect of vaccine (I-REV) hypothesis, we further stratified the middle-aged group, notably including 32–54-year-olds (1964–86) sharing potential childhood imprinting to serine at haemagglutinin position 159. Results Influenza A(H3N2) VE among all ages was −1% (95% confidence interval (CI): −24 to 18) and 46% (95% CI: 8–68), −26% (95% CI: −66 to 4) and 20% (95% CI: −20 to 46) among 0–14, 15–64 and ≥ 65-year-olds, respectively. Among 15–64-year-olds, VE against clades 3C.2a1b and 3C.3a was 15% (95% CI: −34 to 50) and −74% (95% CI: −259 to 16), respectively. VE was −18% (95% CI: −140 to 41), −53% (95% CI: −131 to −2) and −12% (95% CI: −74 to 28) among 15–31-year-olds (1987–2003), 32–54-year-olds (1964–86) and 55–64-year-olds (1954–63), respectively. Discussion The lowest 2018/19 influenza A(H3N2) VE was against clade 3C.3a and among those born 1964–86, corresponding to the I-REV hypothesis. The low influenza A(H3N2) VE in 15–64-year-olds and the public health impact of the I-REV hypothesis warrant further study.

International audience; Importance: An increased risk of acute bacterial enteric infections has been reported among patients receiving proton pump inhibitor (PPI) therapy. The risk of acute gastroenteritis (AGE) of viral origin associated with continuous PPI exposure has been less studied.Objective: To investigate the association between continuous PPI therapy and AGE occurrence during winter epidemic periods when the circulation of enteric viruses is the highest.Design, setting, and participants: A matched cohort study was performed using a prospectively collected drug dispensing database from a large panel of community pharmacies in continental France. All patients recorded in the database during the 2015 to 2016 winter season, with documented age, sex, and use of an identifiable regular panel pharmacy, were eligible for the study. Each patient exposed to continuous PPI therapy was matched to 3 unexposed patients, according to year of birth, sex, and identifiable regular panel pharmacy. Analyses were performed between January 2017 and December 2018.Exposure: Continuous PPI use during the 2015 to 2016 AGE winter epidemic.Main outcomes and measures: The occurrence of at least 1 AGE episode during the 2015 to 2016 AGE winter epidemic was the main outcome. Episodes of AGE were identified using a previously validated algorithm based on drug dispensing data. Relative risks of AGE were estimated using a multivariable log-binomial model adjusted for age, sex, and treatments for chronic conditions.Results: There were 233 596 patients receiving PPI therapy (median [interquartile range] age, 71 [62-81] years; 55.8% female) and 626 887 matched patients not receiving PPI therapy (median [interquartile range] age, 70 [61-80] years; 56.3% female) included in the analyses. At least 1 AGE epidemic episode was identified in 3131 patients (1.3%) receiving PPI therapy and in 4327 patients (0.7%) not receiving PPI therapy. The adjusted relative risk of AGE for those receiving PPI therapy was 1.81 (95% CI, 1.72-1.90) for all ages considered, 1.66 (95% CI, 1.54-1.80) among those aged 45 to 64 years, 2.19 (95% CI, 1.98-2.42) among those aged 65 to 74 years, and 1.98 (95% CI, 1.82-2.15) among those aged 75 years and older.Conclusions and relevance: Continuous PPI therapy was associated with an increased risk of developing AGE during periods of highest circulation of enteric viruses. These findings support the hypothesis that PPI use is associated with an increased risk of enteric viral infections.