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BackgroundMass drug administration (MDA) is a powerful tool for malaria control, but the medicines to use, dosing, number of rounds, and potential selection of drug resistance remain open questions.MethodsTwo monthly rounds of artemisinin-piperaquine (AP), each comprising 2 daily doses, were administered across the 7 districts of Grande Comore Island. In 3 districts, low-dose primaquine (PMQLD) was also given on the first day of each monthly round. Plasmodium falciparum malaria rates, mortality, parasitemias, adverse events, and genetic markers of potential drug resistance were evaluated.ResultsAverage population coverages of 80%–82% were achieved with AP in 4 districts (registered population 258 986) and AP + PMQLD in 3 districts (83 696). The effectiveness of MDA was 96.27% (95% confidence interval [CI], 95.27%–97.06%; P < .00001) in the 4 AP districts and 97.46% (95% CI, 94.54%–98.82%; P < .00001) in the 3 AP + PMQLD districts. In comparative statistical modeling, the effectiveness of the 2 monthly rounds on Grande Comore Island was nearly as high as that of 3 monthly rounds of AP or AP + PMQLD in our earlier study on Anjouan Island. Surveys of pre-MDA and post-MDA samples showed no significant changes in PfK13 polymorphism rates, and no PfCRT mutations previously linked to piperaquine resistance in Southeast Asia were identified.ConclusionsMDA with 2 monthly rounds of 2 daily doses of AP was highly effective on Grande Comore Island. The feasibility and lower expense of this 2-month versus 3-month regimen of AP may offer advantages for MDA programs in appropriate settings.

After decades of efforts, malaria is still a the major public health problem in many countries, especially in sub-Saharan Africa. Mass drug administration (MDA) has been one of the interventions used to control malaria. China, the largest and most populous country in the world, has recently achieved malaria elimination with MDA with its strategy. Therefore, knowing the history of the use of MDA, and its advantages and challenges are crucial to better implement MDA as a component of malaria control and elimination strategy. This narrative review focused on the use of MDA from the past to present, the experiences of successful and failed MDA intervention to control malaria in Africa, Asia, and South Pacific region, the challenges faced, as well as China's with an emphasis on China's experience in malaria control and elimination. A direct search using key words and phrases was conducted using the web search engines Google and Google Scholar, peer-reviewed journal websites and PubMed database to mainly screen articles on MDA studies with positive and negative results. The World Health Organization guidelines and other MDA-related reports. We also summarized our historical field experiences on MDA in malaria control to provide informed perspective on the challenges of MDA. Following the spirit of innovation, a comprehensive strategy with MDA at its core and each additional measure compensating one another's shortage based on different malaria transmission settings and stratification could be the highlight of future malaria control and elimination strategy to help achieve the vision of a malaria-free world.