Incidence rates of malaria, meningitis, and mortality in children younger than 5 years: a prospective cohort study in Ghana and Kenya before the roll-out of the RTS,S/AS01_E malaria vaccine from 2016 to 2022.

Abstract

The RTS,S/AS01_E malaria vaccine was introduced in selected communities of Ghana, Kenya, and Malawi in 2019 under a WHO-coordinated pilot programme. The scarcity of background disease incidence rates might hamper the assessment of vaccine safety and effectiveness. We aimed to determine the incidence rates of malaria, meningitis, and death, and health outcomes leading to hospital admission in children younger than 5 years enrolled before RTS,S/AS01_E implementation. Interim results from EPI-MAL-002 up to Oct 5, 2018, were reported previously. Here, we report results from the final analysis of the pre-vaccine introduction study. This disease surveillance study combined two approaches: (1) prospective cohort event monitoring (home visits scheduled to mimic a future four-dose RTS,S/AS01_E vaccination schedule [ie, a simulated vaccination schedule], with additional visits after the simulated schedule and continuous disease monitoring of outpatient visits and hospital admission) in children enrolled in two age groups (6-12 weeks [6-12W] and 5-17 months [5-17M]), and (2) hospital-based disease surveillance for children not enrolled in the prospective cohort, in three sites in Ghana and Kenya. Key outcomes were rates of meningitis, malaria, adverse events of special interest, other adverse events leading to hospital admission, all-cause mortality, and malaria-attributable mortality. The final analysis included 23 427 children: 9032 in the 6-12W age group, 9694 in the 5-17M age group, and 4701 in hospital-based disease surveillance. In the 5-17M age group (corresponding to the WHO-recommended age for RTS,S/AS01_E vaccination), the incidence rates of meningitis and cerebral malaria within an at-risk period of 1 year after the simulated vaccination schedule were both equal to 28 (95% CI 9-65) per 100 000 person-years. There were 11 (0·1%) children with an adverse event of special interest during hospital admission. In the 5-17M age group, the all-cause mortality rate was 643 (95% CI 531-771) per 100 000 person-years. Observed incidence of meningitis and cerebral malaria were in the previously published range, whereas childhood mortality was lower, suggesting that the recent efforts to reduce mortality in children younger than 5 years have been impactful. Data from this study have public health use and will form the baseline evidence for ongoing evaluation of the benefit-risk of RTS,S/AS01_E. GSK and PATH.