Abstract
In 2022, the World Health Organization extended their guidelines for perennial malaria chemoprevention (PMC) from infants to children up to 24 months old. However, evidence for PMC's public health impact is primarily limited to children under 15 months. Further research is needed to assess the public health impact and cost-effectiveness of PMC, and the added benefit of further age-expansion. We integrated an individual-based model of malaria with pharmacological models of drug action to address these questions for PMC and a proposed age-expanded schedule (referred as PMC+, for children 03-36 months). Across malaria prevalence settings of 5-70% and different drug sensitivity assumptions, we predicted PMC and PMC+'s median efficacy (interquartile range) of 18.6% (12.2-25.0%) and 21.9% (14.3-29.5%) against clinical disease and 9.0% (2.0-16.0%) and 10.8% (3.2-18.4%) against severe malaria, respectively, in children under three years. PMC's total impact outweighed the risk of delayed malaria in children up to age five and remained cost-effective across currently recommended transmission intensities (over 10% prevalence) when delivered through the existing Expanded Program on Immunization channels. Further empirical evidence of likely added benefit, operational feasibility and sustainability of age-expanded PMC will be essential to complement our model-based findings.