Effect of population-wide repeated dihydroartemisinin–piperaquine mass drug administration in Ghana: a cluster-randomised trial

Abstract Background Persistent asymptomatic malaria infections remain a major obstacle to malaria elimination in sub-Saharan Africa by sustaining transmission and contributing to malaria-associated anaemia despite widespread implementation of vector control and case management interventions. We evaluated the effectiveness of repeated community-wide mass drug administration (MDA) with dihydroartemisinin–piperaquine (DHAP) in reducing malaria parasite prevalence and improving haemoglobin 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 (nine intervention and nine 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, while control communities received standard malaria prevention and case management. Cross-sectional household surveys were conducted at baseline (n = 1,785) and endline (n = 1,878). The primary outcome was cluster-level prevalence of rapid diagnostic test (RDT)-confirmed malaria infection at endline. Secondary outcomes included haemoglobin concentration, anaemia prevalence, and reinfection risk. Analyses followed the intention-to-treat principle using mixed-effects Poisson regression models with robust standard errors to account for clustering and were adjusted for baseline malaria status, age, sex, and insecticide-treated net use. Results Baseline demographic and epidemiological characteristics were comparable between study arms. At endline, RDT-confirmed malaria prevalence was substantially lower in intervention than in control communities (1.5% [15/976] vs 28.0% [236/902]), representing a 94% relative reduction (adjusted prevalence ratio [aPR] 0.07, 95% confidence interval [CI] 0.02–0.10; p < 0.001). Protective effects were observed in both children and adults (p < 0.001). Reinfection risk was significantly lower in intervention communities (PR 0.052, 95% CI 0.046–0.061; p < 0.001). Mean haemoglobin concentration increased by 0.74 g/dL (95% CI 0.51–1.00), with the greatest improvement among participants in the lowest baseline haemoglobin quartile. Anaemia prevalence declined substantially, and no cases of severe anaemia were detected in intervention communities at endline. No serious adverse events related to MDA were reported. Conclusions Repeated, high-coverage DHAP-based mass drug administration substantially reduced malaria parasite prevalence, lowered reinfection risk, and improved haemoglobin and anaemia outcomes in a moderate-to-high transmission setting. These findings support the integration of structured, high-coverage MDA into comprehensive malaria elimination programmes in settings where asymptomatic infections continue to sustain transmission.