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

Abstract

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.

Vaccine Immunogenicity versus Gastrointestinal Microbiome Status: Implications for Poultry Production

“…One clear example of this is in chicken pox vaccination regimens in China. Lin et al [56] discovered that antibiotic exposure for at least seven days during the first two years of a child's life was positively correlated (p < 0.01) with chicken pox disease incidence, regardless of chicken pox vaccination status. Similar results were emulated in the murine model, where various types of antibiotic treatment and durations of exposure lead to decreased vaccine immunogenicity along with decreased gut microbiota diversity [57][58][59][60].…”

Factors Influencing Microbiota in Modulating Vaccine Immune Response: A Long Way to Go

“…The strong link of the GM with the immune response and, therefore, with vaccine immunogenicity has stimulated numerous speculations on what role GM modulation might have in this scenario [96,114]. Although the role in clinical practice still appears unclear, below, we discuss the main modulators of the GM that could be used in eliciting an effective vaccine response.…”

Host microbiome-pathogen interactions in pediatric infections

“…Our understanding of the role of the microbiome in shaping immune function is also advancing. Multiple recent studies identified associations between the microbiome and immune responses to childhood vaccines, suggesting that microbial adjuvants could be used to promote robust vaccine responses among children [54][55][56][57][58]. Finally, next-generation sequencing holds substantial promise for the diagnosis of infectious diseases, as illustrated by recent studies that used this technology to identify potential causative pathogens among critically ill children with LRTI [59,60].…”