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

Abstract

Background/Objective: 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). Methods: 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). Results: 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. Conclusions: Understanding these indirect benefits is crucial for evaluating the broader impact and cost-effectiveness of rotavirus immunisation programs.

Keywords: herd immunity; immunisation; indirect effect; rotavirus; vaccine.

Figure 1

Flow diagram of included studies. “Wrong comparator” refers to studies that made the wrong comparison for the purposes of this review, such as calculating a ratio between unvaccinated versus vaccinated participants, rather than comparing the pre- versus post-vaccine introduction periods.

Figure 2

Distribution of the indirect effects of universal infant rotavirus vaccine introduction in (A) unvaccinated children <5 years, (B) children and adolescents 5–19 years, and (C) adults >18 years. Outcome measures shown are incidence rate ratios (IRR) of laboratory-confirmed rotavirus-specific acute gastroenteritis (RV-AGE) inpatient admissions, laboratory-confirmed RV-AGE outpatient attendances, all-cause AGE inpatient admissions, all-cause AGE outpatient attendances, and laboratory-confirmed RV positivity in stool samples, between the post- vs. pre-vaccine introduction periods. The boxes indicate the medians (centre line) and interquartile ranges (top and bottom lines) for each category. The number of individual estimates and median (interquartile range) for each outcome measure are shown. Total number of studies reporting the outcome: RV-AGE inpatient admissions (n = 20), RV-AGE outpatient attendances (n = 5), all-cause AGE inpatient admissions (n = 11), all-cause AGE outpatient attendances (n = 3), stool RV positivity (n = 9).