Linking transmission dynamics and economic evaluation to assess schistosomiasis programme strategies across districts in Malawi

BackgroundPreventive chemotherapy targeting school-aged children has substantially reduced schistosomiasis morbidity, however, a key strategic tension remains between sustaining morbidity control and pursuing transmission elimination, particularly in settings characterised by heterogeneous transmission dynamics and persistent adult infection reservoirs. We developed a health system-integrated transmission and economic evaluation framework to identify optimal age-targeting and district-level prioritisation, providing a basis for determining when elimination-focused approaches offer advantages over morbidity reduction alone. MethodsThe Thanzi la Onse individual-based model was used to evaluate alternative age-targeted mass drug administration (MDA) strategies for Schistosoma haematobium and Schistosoma mansoni across all 32 districts of Malawi from 2024-2050. Strategies included treatment of school-aged children (MDA-SAC), pre-school and school-aged children (MDA-PSAC+SAC), and community-wide treatment (all ages). Health outcomes included person-years with any infection (PY), disability-adjusted life years (DALYs), probability of elimination (defined as reaching <2% prevalence of infection in all ages). The cost-effectiveness was evaluated using incremental cost-effectiveness ratios (ICERs), net health benefit (NHB), and by quantifying the maximum costs available for implementation, using a cost-effectiveness threshld for Malawi of 88 USD per DALY averted. FindingsIn the absence of MDA, the majority of the infection burden over 2024-2050 would be concentrated in adults aged 15 years and older (219.6 million person-years [PY], 95% CI 215.4-223.4), compared with 72.8 million PY (95% CI 71.5-74.3) among school-aged children (SAC) and 25.5 million PY (95% CI 25.1- 26.2) among preschool-aged children. Annual MDA-SAC would avert approximately 18.0 million DALYs (95% CI 17.6-18.4) between 2025 and 2050 and would be highly cost-effective nationally (ICER 4.76 USD/DALY, 95% CI 4.47-4.95). Across districts, ICERs were highly variable; 25 of 32 districts were cost-effective in [&ge;]90% of runs and 29 of 32 in [&ge;]50% of runs. Expanding treatment to include preschool-aged children (MDA PSAC+SAC) would produce modest additional gains (additional 44,500 DALYs averted) but with substantially higher costs (national ICER 606 USD/DALY, 95% CI 472-695), being dominated in 22 districts and cost-effective only in the high-burden Likoma district. Community-wide MDA would achieve elimination for both species in all districts by 2030 and avert a further 98,000 DALYs; nationally it would be cost-saving relative to PSAC+SAC although outcomes were heterogeneous, with this strategy being cost-saving in 11 high-prevalence districts (2023 prevalence range 13.7 - 41.5%) but dominated (in >80% of model runs) in 16 others. Threshold analyses of maximum implementation costs indicated substantial cost margins in high-burden districts, with cost-effectiveness maintained up to approximately 25-38 USD per treatment. InterpretationThe choice of schistosomiasis strategies should depend on whether programmes prioritise short-term morbidity reduction or long-term elimination, as well as the local disease burden and the prevailing cost of service delivery. Integrating district-level transmission dynamics with opportunity-cost-based economic evaluation reveals when broader coverage is justified and provides a framework for designing fiscally grounded elimination pathways in heterogeneous endemic settings.