Evaluation of Rotavirus Vaccine Effectiveness by Severity of Rotavirus Disease: Findings From the MNSSTER-V Project.

BACKGROUND: Since the introduction of rotavirus vaccines, acute gastroenteritis (AGE) hospitalizations due to rotavirus have decreased globally; however, vaccine effectiveness (VE) differs by country, age and disease severity. We evaluated rotavirus VE by disease severity in different age groups and under-5 childhood mortality (U5M) strata.

METHODS: The Vesikari score is a common measure of AGE disease severity. A modified Vesikari Score (mVS) was calculated for 18,426 children with medically attended AGE across 16 countries from the Multi-National Subpopulations Study To Evaluate Rotavirus Vaccines dataset. Using a test-negative case-control design (cases had rotavirus-positive AGE and controls had rotavirus-negative AGE), we calculated complete rotavirus series VE against different severity categories among children 6-59 months old, stratified by age and country U5M level, respectively.

RESULTS: VE increased with increasing disease severity: 38% (95% confidence interval [CI]:17-53) for mild/moderate disease versus 58% (95% CI: 50-64) for severe/very severe disease, and this pattern persisted with stratification by age and U5M. Among children with severe/very severe disease, VE was higher in infants aged 6-11 months (62%, 95% CI: 51-70) compared with children aged 24-59 months (11%, 95% CI: -78 to 56), and lower among children in the highest U5M strata (44%, 95% CI: 26-58) compared to children in the high U5M strata (60%, 95% CI: 47-69).

CONCLUSIONS: Rotavirus vaccines provide the greatest protection against very severe rotavirus disease. VE remains lower in countries with higher U5M levels, even among children with very severe rotavirus disease, highlighting the need for improved vaccine performance in countries with high disease burden.