Indirect Effects of Universal Infant Rotavirus Vaccination: A Narrative Systematic Review.

Rotavirus is a major cause of acute gastroenteritis (AGE) in children <5 years. While rotavirus vaccines are effective in reducing AGE, limited data on their indirect effects exist. The aim of our narrative systematic review was to summarise the indirect effects of rotavirus vaccines on unvaccinated children and adults (PROSPERO: CRD42023418015). Peer-reviewed articles and conference abstracts were searched through Medline, Embase and PubMed on 8 December 2024. Observational studies of national/regional vaccine introduction were included. We included five outcomes: rotavirus-AGE inpatient admissions, rotavirus-AGE outpatient attendances, all-cause AGE inpatient admissions, all-cause AGE outpatient attendances, and stool rotavirus positivity. Outcome measures reported as percent reduction or individual incidence rates for the pre- and post-introduction periods were transformed to incidence rate ratios (IRRs). Median IRRs and interquartile ranges (IQRs) were calculated for each outcome by age group (<5, 5-19, and >18 years). From an initial 757 articles, 44 studies including 9,327,974 participants were included. In unvaccinated children <5 years, there were reductions in rotavirus-AGE admissions (median IRR: 0.62, IQR: 0.40-0.82), rotavirus-AGE outpatient attendances (0.74, 0.16-0.98), all-cause AGE admissions (0.70, 0.56-0.86), and stool rotavirus positivity (0.42, 0.31-0.57), but not all-cause AGE outpatient attendances (0.92, 0.78-1.17). Few studies reported these outcomes for children and adolescents aged 5-19 years and adults >18 years. Indirect effects appeared to be greater in higher income and lower under-five mortality settings. Understanding these indirect benefits is crucial for evaluating the broader impact and cost-effectiveness of rotavirus immunisation programs.