Global estimates of rotavirus vaccine efficacy and effectiveness: a rapid review and meta-regression analysis.

Background: Rotavirus is the leading cause of diarrhoea worldwide, particularly affecting young children. While national rotavirus immunization programs have reduced rotavirus morbidity and mortality, vaccine performance varies considerably between high-income and low-income settings.

Methods: We updated a previous systematic review of studies reporting rotavirus vaccine efficacy and vaccine effectiveness against severe rotavirus-associated gastroenteritis (RVGE) by performing a rapid review from July 1, 2020 through October 16, 2024. We included randomized controlled trials reporting vaccine efficacy against severe RVGE and case-control and cohort studies reporting vaccine effectiveness against hospitalization with RVGE in children <5 years old for current internationally licensed vaccines. We developed a meta-regression model for vaccine efficacy and effectiveness using widely available country-specific predictors of rotavirus vaccine performance and simultaneously estimated the relationship between vaccine efficacy and effectiveness. We used the model to predict vaccine efficacy and effectiveness for all countries and assessed its predictive accuracy using a modified leave-one-country-out validation approach.

Findings: Predicted vaccine efficacy ranged from 69.6% to 94.3% across countries in the Americas, European, and Western Pacific Regions, with a decreased efficacy ranging from 18.6% to 85.3% in the African, South-East Asian, and Eastern Mediterranean regions. Estimates of vaccine effectiveness were generally lower than vaccine efficacy when efficacy was greater than 60%, but effectiveness was predicted to be higher when vaccine efficacy was low. A strong correlation ( = 0.63) was found between the observed and predicted vaccine efficacy and effectiveness, with 98.2% of observed efficacy and effectiveness estimates falling within the 95% prediction intervals.

Interpretation: Our approach enhances the understanding of global variation in rotavirus vaccine performance and can be used to inform predictions of the potential impact of rotavirus vaccines for countries that have yet to introduce them. Higher-quality data on predictor variables and broader regional representation in vaccine trials are required for more robust vaccine performance estimates.

Funding: National Institutes of Health/National Institute of Allergy and Infectious Diseases (R01AI112970) and the Bill & Melinda Gates Foundation (INV-17940).