Highlight
This large pooled case-control study from the Multi-National Subpopulations Study to Evaluate Rotavirus Vaccines (MNSSTER-V) dataset shows that rotavirus vaccination provides 75.8% effectiveness against rotavirus-positive acute gastroenteritis mortality in children under five. Despite a smaller, non-significant reduction against all-cause acute gastroenteritis deaths, these findings highlight the critical importance of rotavirus vaccines in global child health. Continuous efforts to improve vaccine coverage could substantially reduce diarrhoeal deaths worldwide.
Study Background
Rotavirus remains a leading cause of severe diarrhoea and mortality in children under five years globally, accounting for approximately 25% of diarrhoeal deaths. While over 140 countries have integrated rotavirus vaccination into routine infant immunization schedules, disparities in vaccine uptake and effectiveness across diverse populations and settings remain a concern. Acute gastroenteritis caused by rotavirus leads to dehydration and potentially fatal complications in young children. High mortality in low- and middle-income countries underscores the urgent need for robust evidence on vaccine effectiveness against death, not just symptomatic disease.
Study Design and Methods
The MNSSTER-V project pooled individual-level data from 27,252 children under five years, recruited from 22 countries between 2007 and 2023. Data sources comprised test-negative case-control studies enrolling children presenting with acute gastroenteritis to hospitals or emergency departments. Inclusion criteria demanded rigorous case definitions (≥3 diarrhoeal episodes in 24 hours, non-bloody and non-chronic diarrhoea), stringent vaccine card quality verification, and availability of vaccine dates and vital outcomes (death or discharge). Mortality cases were documented for both rotavirus-positive and all-cause acute gastroenteritis.
Adjusted vaccine effectiveness (VE) against mortality was calculated using unconditional logistic regression, controlling for under-5 mortality strata at the national level and age of the child. Analyses focused on children aged at least three months who had received any routine vaccines, ensuring comparability for vaccination status. The primary endpoints were rotavirus-positive acute gastroenteritis deaths and all-cause acute gastroenteritis deaths occurring in-hospital.
Key Findings
Outcomes from 21,522 children across 16 countries with recorded in-hospital acute gastroenteritis deaths constituted the primary analysis set, documenting 183 all-cause acute gastroenteritis deaths and 25 rotavirus-positive deaths.
Among the subgroup of children aged ≥3 months who had received routine vaccines, at least one dose of rotavirus vaccine conferred robust protection against rotavirus-positive death with an adjusted VE of 75.8% (95% CI 28.4 to 91.8; n=13,630). This indicates that vaccinated children had approximately three-quarters lower odds of dying from rotavirus-positive gastroenteritis than unvaccinated peers.
Against all-cause acute gastroenteritis mortality, the adjusted VE was lower and not statistically significant at 20.8% (95% CI -47.0 to 57.3; n=20,005). This suggests that while rotavirus vaccination specifically curtails rotavirus-related deaths effectively, its effect on deaths from all acute gastroenteritis etiologies is less pronounced, likely due to other pathogens contributing to mortality.
Expert Commentary
These findings bolster the biological plausibility that rotavirus vaccines directly reduce mortality by preventing severe rotavirus infection, a major contributor to childhood diarrhoeal death. The high VE against rotavirus-positive mortality parallels previous evidence for vaccine effectiveness in preventing hospitalization and severe disease. The less definitive impact on all-cause acute gastroenteritis mortality underscores the multifactorial nature of diarrhoeal deaths and suggests complementary interventions may be needed to address morbidity and mortality caused by other pathogens (e.g., bacterial and other viral agents).
Limitations include reliance on in-hospital mortality data, which may underestimate community deaths and potential variability in diagnostic testing sensitivity. Differences in health infrastructure and vaccine coverage across the 22 countries may influence the generalizability of results. Nevertheless, the extensive multinational scope and methodological standardization strengthen confidence in these findings.
Conclusion
Rotavirus vaccines substantially reduce mortality from rotavirus-confirmed acute gastroenteritis in children under five and remain a cornerstone in combating diarrhoeal disease burden globally. These results support ongoing global immunization efforts, highlighting the need to enhance rotavirus vaccine delivery and coverage, particularly in high-mortality settings. Integration with broader child health strategies, including water sanitation and management of other diarrhoeal pathogens, is essential to further reduce acute gastroenteritis-related child mortality.
Future research should continue monitoring vaccine performance in diverse settings and explore strategies to address gaps in all-cause diarrhoeal death reduction.
Funding and Disclosure
This study was conducted without external funding. Author disclosures were not provided in the source abstract.
References
1. Moran MC, Burnett E, Groome MJ, Michael F, Breiman RF, Robinson AL, Iniguez V, Mujuru HA, Goldfarb DM, Lungayo CL, Mandomando I, Bonkoungou IJO, Anwari P, Contreras-Roldán I, Enweronu-Laryea C, N’Zue K, Nalunkuma C, Trang NV, Gheorghita S, Sahakyan G, Nazurdinov A, Latipov R, Uwimana J, Rey-Benito G, Weldegebriel G, Mwenda JM, Parashar UD, Tate JE; Multi-National Subpopulations Study to Evaluate Rotavirus Vaccines (MNSSTER-V) project working group. Rotavirus vaccine effectiveness against rotavirus and acute gastroenteritis mortality: an analysis of pooled case-control studies from the MNSSTER-V dataset. Lancet Child Adolesc Health. 2026 Aug 12:S2352-4642(26)00158-6. doi: 10.1016/S2352-4642(26)00158-6. Epub ahead of print. PMID: 42586106.
