Combining seasonal malaria chemoprevention with novel therapeutics for malaria prevention: a mathematical modelling study.

Vaccines, monoclonal antibodies, and long-acting injectables are being developed to prevent Plasmodium falciparum malaria. These therapeutics may target multiple stages of the parasite life cycle; evidence is needed to articulate their benefits with chemoprevention and prioritise candidates for clinical development. We used an individual-based malaria transmission model to estimate the health impact of combining new therapeutics with seasonal malaria chemoprevention (SMC). Our modelling framework used emulator-based methods with models of pre-liver and blood stage therapeutic dynamics. We evaluated the benefit of combining therapeutics with SMC in children under five by estimating reductions in the cumulative incidence of uncomplicated and severe malaria, relative to SMC or the new therapeutic alone, during and five years after deployment. Results showed that new therapeutics may require extended pre-liver stage duration or multi-stage activity to combine with SMC. For three SMC cycles in a high transmission setting, a pre-liver stage therapeutic with partial initial efficacy (>50%) required a protection half-life >230 days to reduce cumulative severe cases by >23% during interventions, and >5% five years after deployment stopped. Longer protection was needed when combined with four or five SMC cycles. And, combining SMC with a multi-stage therapeutic increased public health impact both during and after deployment. These results indicate that combining SMC with malaria therapeutics active against multiple stages of the parasite life cycle can improve the effectiveness of SMC, and highlight the need for clinical development to prioritise multi-stage therapeutics for improved malaria prevention in children.