{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T12:54:20Z","timestamp":1768568060136,"version":"3.49.0"},"posted":{"date-parts":[[2024,7,18]]},"group-title":"Infectious Diseases (except HIV\/AIDS)","reference-count":24,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,7,18]]},"abstract":"<jats:title>Summary<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>In Africa, the scale-up of malaria control interventions, including seasonal malaria chemoprevention (SMC), has dramatically reduced malaria burden, but progress toward malaria elimination has stalled. We evaluated mass drug administration (MDA) as a strategy to accelerate reductions in malaria incidence in Senegal.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>\n                    We conducted an open-label, cluster-randomised controlled trial in a low-to-moderate transmission setting of Tambacounda, Senegal. Eligible villages had a population size between 200\u2013800. All villages received pyrethroid-piperonyl butoxide bednets and proactive community case management of malaria at baseline. Sixty villages were randomised 1:1 to either three cycles of MDA with dihydroartemisinin-piperaquine+single-low dose primaquine administered to individuals aged \u22653 months, six-weeks apart starting the third week of June (intervention), or standard-of-care, which included three monthly cycles of SMC with sulfadoxine-pyrimethamine+amodiaquine administered to children aged 3\u2013120 months starting end of July (control). MDA and SMC were delivered door-to-door. The primary outcome was clinical malaria incidence in all ages assessed during the peak transmission season (July-December), the year after intervention. Here, we report safety, coverage, and impact outcomes during the intervention year. The trial is registered at ClinicalTrials.Gov (\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT04864444\">NCT04864444<\/jats:ext-link>\n                    ).\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Findings<\/jats:title>\n                  <jats:p>Between June 21, 2021 and October 3, 2021, 6505, 7125, and 7250 participants were administered MDA and 3202, 3174, and 3146 participants were administered SMC across cycles. Coverage of \u22651 dose of MDA drugs was 79%, 82%, and 83% across cycles. During the transmission season of the intervention year, MDA was associated with a 55% [95% CI: 28%\u2013 72%] lower incidence of malaria compared to control (MDA: 93 cases\/1000 population; control: 173 cases\/1000 population). No serious adverse events were reported in either arm.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Interpretation<\/jats:title>\n                  <jats:p>In low-to-moderate malaria transmission settings with scaled-up malaria control interventions, MDA with dihydroartemisinin-piperaquine+single-low dose primaquine is effective and well-tolerated for reducing malaria incidence. Further analyses will focus on the sustainability of this reduction.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Funding<\/jats:title>\n                  <jats:p>United States President\u2019s Malaria Initiative<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Research in context<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Evidence before this study<\/jats:title>\n                    <jats:p>\n                      The current World Health Organization (WHO) guidelines recommend that malaria programmes consider mass drug administration (MDA) for\n                      <jats:italic>Plasmodium falciparum<\/jats:italic>\n                      transmission reduction in low-to-very low transmission settings (broadly defined as parasite prevalence &lt;10% or annual malaria incidence of &lt;250 cases per population). In moderate-to-high transmission areas, MDA is recommended for rapid reduction of disease burden, but not for transmission reduction due to the lack of published studies demonstrating its short- or long-term benefits. Among the numerous studies that contributed to this recommendation, five evaluated the antimalarial combination, dihydroartemisinin-piperaquine + single low-dose primaquine. However, none of the studies were conducted in countries implementing seasonal malaria chemoprevention as part of their routine malaria control strategy.\n                    <\/jats:p>\n                    <jats:p>On January 23, 2024, we conducted a PubMed search using the following term: \u201cmass drug administration\u201d AND \u201cdihydroartemisinin-piperaquine\u201d. We found one additional cluster randomised controlled trial conducted in a moderate transmission setting of The Gambia (an SMC-implementing country), that evaluated mass drug administration with the antimalarial combination, dihydroartemisinin-piperaquine + ivermectin. This study demonstrated that MDA was associated with a 70% reduction in the odds of PCR-confirmed malaria two months after the last round of MDA. However, given the study demonstrated little evidence on entomological outcomes, authors concluded that much of the observed effect of MDA was likely attributable to the antimalarial efficacy of dihydroartemisinin-piperaquine.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Added value of this study<\/jats:title>\n                    <jats:p>Our study adds to the current evidence base demonstrating the benefits of MDA with dihydroartemisinin-piperaquine + single-dose primaquine on malaria burden reduction and may have impacts on short-term transmission. Combined with The Gambia trial results, our study provides new evidence demonstrating that MDA with dihydroartemisinin-piperaquine can have short-term benefits on transmission in low and moderate transmission settings where malaria transmission is highly seasonal.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Implications of all the available evidence<\/jats:title>\n                    <jats:p>As countries in sub-Sahelian and Sahelian Africa progressively scale-up their malaria control interventions, they will reach a plateau where no further gains can be made. In low and moderate transmission settings, MDA is a well-tolerated and effective intervention for rapidly reducing malaria burden and may have an impact on transmission in the short-term.<\/jats:p>\n                  <\/jats:sec>\n                <\/jats:sec>","DOI":"10.1101\/2024.07.17.24310593","type":"posted-content","created":{"date-parts":[[2024,7,18]],"date-time":"2024-07-18T18:15:11Z","timestamp":1721326511000},"source":"Crossref","is-referenced-by-count":2,"title":["Mass drug administration to reduce malaria incidence in a low-to-moderate endemic setting: short-term impact results from a cluster randomised controlled trial in Senegal"],"prefix":"10.64898","author":[{"given":"El-hadji","family":"Ba Konko Cir\u00e9","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michelle E.","family":"Roh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abdoulaye","family":"Diallo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tidiane","family":"Gadiaga","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amadou","family":"Seck","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sylla","family":"Thiam","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seynabou","family":"Gaye","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ibrahima","family":"Diallo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aminata Colle","family":"Lo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elhadji","family":"Diouf","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Omar Gallo","family":"Ba","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alioune Badara","family":"Gueye","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ari","family":"Fogelson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xue","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul","family":"Milligan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tabitha","family":"Kibuka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Moustapha","family":"Hama","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erin","family":"Eckert","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julie","family":"Thwing","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adam","family":"Bennett","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roly","family":"Gosling","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jimee","family":"Hwang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Doudou","family":"Sene","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fatou","family":"Ba","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bayal","family":"Ciss\u00e9","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katharine","family":"Sturm-Ramirez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michelle S.","family":"Hsiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean Louis","family":"Ndiaye","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2024072123301110000_2024.07.17.24310593v1.1","unstructured":"World Health Organization. WHO guidelines for malaria, 3 June 2022: World Health Organization, 2022."},{"key":"2024072123301110000_2024.07.17.24310593v1.2","unstructured":"SMC Alliance. 53 million children living in 18 countries covered with Seasonal Malaria Chemoprevention in 2023. April 5, 2024 2024. https:\/\/www.smc-alliance.org\/53-million-children-living-in-18-countries-covered-with-seasonal-malaria-chemoprevention-in-2023 (accessed July 17, 2024."},{"key":"2024072123301110000_2024.07.17.24310593v1.3","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1003727"},{"key":"2024072123301110000_2024.07.17.24310593v1.4","unstructured":"World Health Organization. World Malaria Report 2022. Geneva, Switzerland: World Health Organization; 2022."},{"key":"2024072123301110000_2024.07.17.24310593v1.5","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.14-0254"},{"key":"2024072123301110000_2024.07.17.24310593v1.6","doi-asserted-by":"crossref","unstructured":"Shah MP , Hwang J , Choi L , Lindblade KA , Kachur SP , Desai M . Mass drug administration for malaria. The Cochrane Database of Systematic Reviews 2021; 2021(9).","DOI":"10.1002\/14651858.CD008846.pub3"},{"key":"2024072123301110000_2024.07.17.24310593v1.7","unstructured":"World Health Organization. Mass drug administration for falciparum malaria: a practical field manual. 2017."},{"issue":"8","key":"2024072123301110000_2024.07.17.24310593v1.8","doi-asserted-by":"crossref","first-page":"e1003214","DOI":"10.1371\/journal.pmed.1003214","article-title":"Evaluation of seasonal malaria chemoprevention in two areas of intense seasonal malaria transmission: secondary analysis of a household-randomised, placebo-controlled trial in Hound\u00e9 District, Burkina Faso and Bougouni District, Mali","volume":"17","year":"2020","journal-title":"PLoS Med"},{"key":"2024072123301110000_2024.07.17.24310593v1.9","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0162563"},{"key":"2024072123301110000_2024.07.17.24310593v1.10","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(16)30378-4"},{"key":"2024072123301110000_2024.07.17.24310593v1.11","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.04923-14"},{"key":"2024072123301110000_2024.07.17.24310593v1.12","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(18)30044-6"},{"key":"2024072123301110000_2024.07.17.24310593v1.13","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jit077"},{"key":"2024072123301110000_2024.07.17.24310593v1.14","unstructured":"World Health Organization. Policy brief on single-dose primaquine as a gametocytocide in Plasmodium falciparum malaria: World Health Organization, 2015."},{"issue":"7","key":"2024072123301110000_2024.07.17.24310593v1.15","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1093\/infdis\/jiaa498","article-title":"Efficacy of single-dose primaquine with artemisinin combination therapy on Plasmodium falciparum gametocytes and transmission: an individual patient meta-analysis","volume":"225","year":"2022","journal-title":"J Infect Dis"},{"key":"2024072123301110000_2024.07.17.24310593v1.16","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiw416"},{"key":"2024072123301110000_2024.07.17.24310593v1.17","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1004057"},{"key":"2024072123301110000_2024.07.17.24310593v1.18","doi-asserted-by":"publisher","DOI":"10.1186\/s12936-016-1291-9"},{"key":"2024072123301110000_2024.07.17.24310593v1.19","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.42.12.5636-5643.2004"},{"issue":"4","key":"2024072123301110000_2024.07.17.24310593v1.20","first-page":"207","article-title":"Technique d\u2019analyse des courbes de fusion haute r\u00e9solution (FHR) ou High Resolution Melting analysis (HRM) en infectiologie","volume":"26","year":"2011","journal-title":"Immuno-Anal Biol Spe"},{"key":"2024072123301110000_2024.07.17.24310593v1.21","unstructured":"Schneider ZD , Shah MP , Boily MC , et al. Mass Drug Administration to Reduce Malaria Transmission: A Systematic Review and Meta-Analysis. Am J Trop Med 2023: tpmd220766-tpmd."},{"key":"2024072123301110000_2024.07.17.24310593v1.22","unstructured":"Malaria Policy Advisory Committee. Meeting report of the Evidence Review Group on mass drug administration, mass screening and treatment and focal screening and treatment for malaria (20\u201322 April 2015). Geneva, Switzerland, 2015."},{"issue":"4","key":"2024072123301110000_2024.07.17.24310593v1.23","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/S1473-3099(21)00557-0","article-title":"Mass drug administration of ivermectin and dihydroartemisinin\u2013piperaquine against malaria in settings with high coverage of standard control interventions: a cluster-randomised controlled trial in The Gambia","volume":"22","year":"2022","journal-title":"Lancet Infect Dis"},{"issue":"4","key":"2024072123301110000_2024.07.17.24310593v1.24","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1093\/infdis\/jiac169","article-title":"Asymptomatic school-aged children are important drivers of malaria transmission in a high endemicity setting in Uganda","volume":"226","year":"2022","journal-title":"J Infect Dis"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2024.07.17.24310593","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T20:07:00Z","timestamp":1768507620000},"score":1,"resource":{"primary":{"URL":"http:\/\/medrxiv.org\/lookup\/doi\/10.1101\/2024.07.17.24310593"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,18]]},"references-count":24,"URL":"https:\/\/doi.org\/10.1101\/2024.07.17.24310593","relation":{},"subject":[],"published":{"date-parts":[[2024,7,18]]},"subtype":"preprint"}}