Early-Life Antibiotic Exposure Associated With Varicella Occurrence and Breakthrough Infections: Evidence From Nationwide Pre-Vaccination and Post-Vaccination Cohorts

Frontiers in Immunology

Chun-Ying Wu¹  Teng-Li Lin³  Yi-Ling Chang³  Yi-Hsuan Fan⁴  Yi-Ju Chen⁷  Hsiu J. Ho⁸  Li-Lin Liang⁹ 

[1] 0National Institute of Cancer Research and Institute of Population Health Science, National Health Research Institutes, Miaoli, Taiwan;Department of Dermatology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan;Department of Dermatology, Taichung Veterans General Hospital, Taichung, Taiwan;Department of Pediatrics, Chung Shan Medical University Hospital, Taichung, Taiwan;Department of Public Health, China Medical University, Taichung, Taiwan;Division of Translational Research, Taipei Veterans General Hospital, Taipei, Taiwan;Faculty of Medicine and Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan;Institute of Biomedical Informatics and Research Center for Epidemic Prevention, National Yang Ming Chiao Tung University, Taipei, Taiwan;Institute of Public Health, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan;School of Life Sciences, National Chung-Hsing University, Taichung, Taiwan;

关键词: varicella;    breakthrough infection;    vaccine;    antibiotic;    microbiota;    dysbiosis;   

DOI  :  10.3389/fimmu.2022.848835

来源: DOAJ

【 摘 要 】

BackgroundAntibiotic-driven dysbiosis may impair immune function and reduce vaccine-induced antibody titers.ObjectivesThis study aims to investigate the impacts of early-life antibiotic exposure on subsequent varicella and breakthrough infections.MethodsThis is a nationwide matched cohort study. From Taiwan’s National Health Insurance Research Database, we initially enrolled 187,921 children born from 1997 to 2010. Since 2003, the Taiwan government has implemented a one-dose universal varicella vaccination program for children aged 1 year. We identified 82,716 children born during the period 1997 to 2003 (pre-vaccination era) and 48,254 children born from July 1, 2004, to 2009 (vaccination era). In the pre-vaccination era, 4,246 children exposed to antibiotics for at least 7 days within the first 2 years of life (Unvaccinated A-cohort) were compared with reference children not exposed to antibiotics (Unvaccinated R-cohort), with 1:1 matching for gender, propensity score, and non-antibiotic microbiota-altering medications. Using the same process, 9,531 children in the Vaccinated A-cohort and Vaccinated R-cohort were enrolled from the vaccination era and compared. The primary outcome was varicella. In each era, demographic characteristics were compared, and cumulative incidences of varicella were calculated. Cox proportional hazards model was used to examine associations.ResultsIn the pre-vaccination era, the 5-year cumulative incidence of varicella in the Unvaccinated A-cohort (23.45%, 95% CI 22.20% to 24.70%) was significantly higher than in the Unvaccinated R-cohort (16.72%, 95% CI 15.62% to 17.82%) (p<.001). In the vaccination era, a significantly higher 5-year cumulative incidence of varicella was observed in the Vaccinated A-cohort (1.63%, 95% 1.32% to 1.93%) than in the Vaccinated R-cohort (1.19%, 95% CI 0.90% to 0.45%) (p=0.006). On multivariate analyses, early-life antibiotic exposure was an independent risk factor for varicella occurrence in the pre-vaccination (adjusted hazard ratio [aHR] 1.92, 95% CI 1.74 to 2.12) and vaccination eras (aHR 1.66, 95% CI 1.24 to 2.23). The use of penicillins, cephalosporins, macrolides, or sulfonamides in infancy was all positively associated with childhood varicella regardless of vaccine administration.ConclusionsAntibiotic exposure in early life is associated with varicella occurrence and breakthrough infections.

【 授权许可】

Unknown