Abstract / Summary
Abstract Background Persistent malaria infections contribute to the malaria burden and may hinder progress towards elimination in sub-Saharan Africa. We evaluated the effectiveness of a high-coverage, community-wide mass drug administration (MDA) intervention incorporating dihydroartemisinin–piperaquine (DHAP) in reducing malaria prevalence and improving haemoglobin and anaemia outcomes in a moderate-to-high transmission setting in Ghana. Methods We conducted an open-label, two-arm cluster-randomised controlled trial involving 18 communities (9 intervention and 9 control clusters) in the Pokrom sub-district of Ghana between November 2023 and November 2024. Intervention communities received five rounds of community-wide DHAP-based MDA delivered through trained community health volunteers, with household-level support for treatment delivery and adherence, while control communities continued routine malaria prevention and case management. Cross-sectional household surveys were conducted at baseline (n = 1,784) and endline (n = 1,878). The primary outcome was RDT-detected malaria infection prevalence at endline. Secondary outcomes included haemoglobin concentration and anaemia prevalence among children aged ≤ 15 years. Analyses followed the intention-to-treat principle using mixed-effects Poisson regression with robust standard errors to account for community-level clustering and were adjusted for prespecified baseline covariates. Results Baseline demographic and epidemiological characteristics were broadly comparable between study arms. At endline, RDT-detected malaria infection prevalence was substantially lower in intervention than in control communities (1.5% [15/976] vs 26.2% [236/902]), corresponding to a 94% relative reduction (adjusted prevalence ratio [aPR] 0.07, 95% CI 0.02–0.11; p < 0.001). In children aged ≤ 15 years, the adjusted analysis estimated a 2.25 g/dL higher mean haemoglobin concentration in intervention than control communities (95% CI 1.26–3.24; p < 0.001), based on a linear mixed-effects model adjusted for age and sex and accounting for community-level clustering. At endline, anaemia prevalence was 9.1% in intervention communities compared with 51.3% in control communities (aPR 0.15, 95% CI 0.09–0.28). No cases of severe anaemia were detected in intervention communities at endline, and no serious adverse events related to MDA were reported. Conclusions A high-coverage, community-wide MDA intervention incorporating repeated DHAP administration, CHV-led delivery, and household engagement was associated with a substantial reduction in RDT-detected malaria infection prevalence and improvements in haemoglobin and anaemia outcomes among children aged ≤ 15 years. These findings support community-wide MDA as a complementary strategy for reducing malaria prevalence in endemic settings. Further surveillance is needed to determine the durability of these effects after cessation of the scheduled MDA rounds and across subsequent transmission seasons. Trial Registration : ClinicalTrials.gov (retrospective registration). Date of Registration: 15/01/2026. Registration Number: NCT07389057, Website: https://clinicaltrials.gov/study/NCT07389057