Projected impact of integrated malaria intervention packages on under-five Plasmodium falciparum prevalence and clinical incidence in Ghana's Guinea Savannah zone, 2023–2028: a modelling study

Background Malaria remains endemic in Ghana’s northern Savannah zone, which experiences highly seasonal transmission and disproportionate child burden. Within Ghana’s High-Burden-to-High-Impact framework, optimizing intervention mixes at the subnational level is critical for informing evidence-based, tailored intervention packages under resource constraints. This study simulated and compared the projected impacts of different scenarios of key malaria preventive and control tools on under-five Plasmodium falciparum Prevalence Rate and clinical incidence between 2023 and 2028. Methods We parameterised the Epidemiological MODeling software (EMOD v2.20) agent-based model of Plasmodium falciparum transmission and calibrated it to under-five parasite prevalence from the Ghana Demographic and Health Surveys and Multiple Indicator Cluster Surveys (2011–2022) using a beta-binomial likelihood. We projected under-five outcomes for 2023–2028 under business-as-usual (BAU) and 11 alternative scenarios that scaled insecticide-treated nets (ITN), indoor residual spraying (IRS), seasonal malaria chemoprevention (SMC), the RTS,S/AS01E vaccine and case management (CM), singly and in combination, in line with the National Malaria Elimination Programme strategy. Outcomes were annualised clinical incidence, annual-mean PfPR and survey-comparable PfPR (September–December mean, matching DHS/MIS fieldwork). Reductions relative to BAU were estimated by paired bootstrap across nine stochastic replicates, and the contribution of each tool by Shapley decomposition. Results Under BAU, under-five clinical incidence did not decline (1,284 episodes per 1,000 child-years in 2023; 1,372 in 2028) and annual-mean PfPR was 15.8% in 2028. Scenarios including scaled IRS produced the largest gains: in 2028, incidence was 49% (95% CI 39–59) lower than BAU with the full package (Scenario 14), 48% (38–58) with ITN + CM + IRS + SMC (Scenario 11) and 45% (36–53) with ITN + CM + IRS (Scenario 8), averting 3,810, 4,037 and 3,874 clinical episodes per 1,000 children over 2023–2028, respectively. Scaling ITN, SMC or RTS,S alone reduced incidence by 2–5%. IRS scale-up accounted for 84% and ITN scale-up for 17% of the full package’s benefit, with synergy between the two (p = 0.02). All scenarios with SMC at 95% reduced survey-comparable PfPR by 82–90%, but their incidence reductions ranged from 4% to 49% because the survey window overlaps the SMC campaign. No scenario reached the national target of halving incidence by 2028 (best 45%, 95% CI 36–55, relative to 2023). Conclusion Maintaining current coverage will not reduce under-five malaria in Ghana’s Guinea Savannah zone. Packages that intensify vector control IRS together with high ITN use and improved case management, alongside SMC and malaria vaccination as recommended by the NMEP and WHO could roughly halve clinical incidence, but even the full package may fall short of the 2028 national target in high-transmission years. Sustained multi-year investment, district-level tailoring and evaluation based on incidence, not survey-season prevalence alone, are needed.