Effectiveness of monovalent rotavirus vaccine among young children in Pakistan: a test-negative case-control evaluation

Background: Pakistan ranks among top 4 countries with greatest number of rotavirus deaths among young children. To reduce the burden of severe rotavirus disease, Pakistan introduced monovalent oral rotavirus vaccine, Rotarix (RV1), into its routine immunization program in one area in early 2017 and reached all areas by April 2018, using a 2-dose schedule at ages 6 and 10 weeks. Methods: During April 2018 through March 2023, we performed active surveillance for acute rotavirus gastroenteritis resulting in intravenous hydration at 9 hospitals in 3 provinces among children eligible to have received rotavirus vaccine. Cases were enrolled children whose stool sample tested positive for rotavirus by enzyme immunoassay and controls were those testing negative. Unconditional logistic regression was used to estimate the effectiveness of 2 doses of RV1 vs 0 doses in reducing likelihood of hospital care for rotavirus disease. Results: Overall, 6454 children aged 22 weeks−59 months were eligible for enrollment and a stool sample was tested by EIA in 4833 (75%). Among children with an EIA result, rotavirus vaccination information was available on 78% (3774/4833). Based on 517 rotavirus cases and 1310 controls, the effectiveness of 2 RV1 doses vs 0 doses among children aged 22 weeks–11 months was 33% (95% CI 12–49); the effectiveness was 45% (95% CI 21–62) among those better nourished by weight-for-age z-score (WAZ ≥−2). Among children aged 1 year, the effectiveness was 24% (95% CI −20 – 52). A wide array of genotypes were detected and nearly 40% of cases with genotype results had >1 G and/or >1 P genotype identified. Vaccine effectiveness point estimates were lowest for those with genotype P[4] detected vs those with P[8] or P[6] detected. Conclusion: 2 RV1 doses appear to provide fair protection in this very high burden setting. Additional vaccination strategies should continue to be pursued for children in this and similar locations.