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

## TL;DR

This study uses mathematical modeling to explore how new malaria prevention tools can be combined with seasonal malaria chemoprevention to improve protection in children.

## Contribution

The study introduces a modeling framework to evaluate the public health impact of combining multi-stage therapeutics with seasonal malaria chemoprevention.

## Key findings

- Therapeutics targeting early stages of infection need long-lasting protection to improve outcomes when combined with SMC.
- Combining SMC with multi-stage therapeutics increases public health impact during and after deployment.
- Multi-stage therapeutics offer greater protection against severe malaria compared to single-stage approaches.

## Abstract

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.

Preventive interventions, such as seasonal malaria chemoprevention (SMC), have reduced the burden of malaria in children living in regions with seasonal malaria transmission. Our study asks how best to combine new malaria prevention products, such as vaccines, monoclonal antibodies, and long-acting injectable drugs, with existing tools like SMC. Understanding which product characteristics make these combinations most useful is important to be able to guide their development and deployment. In this study, we used mathematical modelling to explore how different types of malaria therapeutics might be combined with SMC to improve health outcomes in children. We found that therapeutics targeting early stages of infection need to provide long-lasting protection to offer added value alongside SMC. However, combining SMC with new tools almost always led to better outcomes than using the new tools alone, highlighting the importance of continuing to provide SMC. We also found that therapeutics that act against multiple stages of the malaria parasite could offer greater protection against severe disease. These findings can help inform priorities for product developers, funders, and policymakers working to reduce the burden of malaria through smarter use of new and existing tools.