{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T16:42:58Z","timestamp":1792082578721,"version":"4.4.0"},"posted":{"date-parts":[[2025,5,18]]},"group-title":"Health Policy","reference-count":62,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,5,18]],"date-time":"2025-05-18T00:00:00Z","timestamp":1747526400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,5,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>\n                    The multiple emergences and continuing spread of partially artemisinin-resistant\n                    <jats:italic>Plasmodium falciparum<\/jats:italic>\n                    in Africa, where about 95% of malaria occurs, is a health challenge that requires urgent attention. The World Health Organization has developed a resistance response strategy that centers on enhancing surveillance, reducing drug pressure, and evaluating novel tools to slow resistance evolution which includes the deployment of multiple first-line therapies (MFT). Developing a specific resistance response is critical for Uganda, where four\n                    <jats:italic>pfkelch13<\/jats:italic>\n                    mutations are at local allele frequencies &gt;0.20.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>\n                    Using a previously validated Uganda-calibrated individual-based mathematical model of\n                    <jats:italic>P. falciparum<\/jats:italic>\n                    transmission and evolution, we evaluated 53 public-sector deployment strategies for artemisinin-based combination therapies (ACTs) aimed at reducing treatment failure and slowing the spread of\n                    <jats:italic>pfkelch13<\/jats:italic>\n                    alleles from 2025 to 2031. We assume that artemether-lumefantrine (AL) will continue to be used in the private sector.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>A change of first-line therapy from AL to artesunate-amodiaquine (ASAQ) is projected to reduce treatment failures by 34.7% to 38.3% (90% range of simulation outcomes) over six years, while a change to dihydroartemisinin-piperaquine (DHA-PPQ) is projected to reduce treatment failures over the same period by 10.0% to 12.9%. This pessimistic projection for DHA-PPQ deployment rests on a model assumption \u2013 supported by clinical data from SE Asia \u2013 that piperaquine resistance evolution will lead to high rates of treatment failure. Optimal MFT deployments and cycling approaches are projected to reduce treatment failure counts by \u223c36% when compared to status quo AL use, an outcome similar to country-wide ASAQ deployment. MFT and cycling approaches are predicted to work best when ASAQ is recommended for a majority of malaria cases and DHA-PPQ for a smaller proportion of cases. Deployment of the triple ACT artemether-lumefantrine-amodiaquine has the potential to reduce treatment failures by \u223c42% if enacted immediately.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Increased adoption of and coverage with ASAQ is projected to play a large role in reducing malaria treatment failure counts in Uganda over the next six years. With continued AL use in the private sector, ASAQ and DHA-PPQ deployment in the public sector creates a public-private MFT mix of antimalarial use. DHA-PPQ deployment should be accompanied by real-time molecular surveillance for piperaquine-resistant genotypes.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2025.05.15.25327701","type":"posted-content","created":{"date-parts":[[2025,5,18]],"date-time":"2025-05-18T22:15:11Z","timestamp":1747606511000},"source":"Crossref","is-referenced-by-count":4,"title":["Slowing the spread of treatment failure to artemisinin-based combination therapies in Uganda"],"prefix":"10.64898","author":[{"given":"Tran Dang","family":"Nguyen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J","family":"Zupko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9984-8030","authenticated-orcid":false,"given":"Melissa D","family":"Conrad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerald B","family":"Rukundo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carter C","family":"Farinha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor D","family":"Asua","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kien Trung","family":"Tran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah M","family":"Grace","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip J","family":"Rosenthal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bosco B","family":"Agaba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moses R","family":"Kamya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jimmy","family":"Opigo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maciej F","family":"Boni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025052102150663000_2025.05.15.25327701v1.1","unstructured":"World Health Organization. World Malaria Report 2024."},{"key":"2025052102150663000_2025.05.15.25327701v1.2","unstructured":"World Health Organization. Artemisinin resistance and artemisinin-based combination therapy efficacy: status report. Geneva, Switzerland: World Health Organization; 2018. Report No.: WHO\/CDS\/GMP\/2018.18. Available: https:\/\/iris.who.int\/handle\/10665\/274362"},{"key":"2025052102150663000_2025.05.15.25327701v1.3","doi-asserted-by":"publisher","DOI":"10.2139\/ssrn.5020665"},{"key":"2025052102150663000_2025.05.15.25327701v1.4","doi-asserted-by":"publisher","DOI":"10.1101\/2025.01.07.25320158"},{"key":"2025052102150663000_2025.05.15.25327701v1.5","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-024-01008-2"},{"key":"2025052102150663000_2025.05.15.25327701v1.6","doi-asserted-by":"publisher","DOI":"10.1126\/science.adp5137"},{"key":"2025052102150663000_2025.05.15.25327701v1.7","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(24)00141-5"},{"key":"2025052102150663000_2025.05.15.25327701v1.8","doi-asserted-by":"publisher","DOI":"10.1038\/d41591-024-00028-y"},{"key":"2025052102150663000_2025.05.15.25327701v1.9","unstructured":"World Health Organization. Multiple first-line therapies as part of the response to antimalarial drug resistance: an implementation guide. Geneva, Switzerland; 2024 Nov. Available: https:\/\/who.int\/publications\/i\/item\/9789240103603"},{"key":"2025052102150663000_2025.05.15.25327701v1.10","unstructured":"World Health Organization. Strategy to respond to antimalarial drug resistance in Africa. 2022."},{"key":"2025052102150663000_2025.05.15.25327701v1.11","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-023-02551-w"},{"key":"2025052102150663000_2025.05.15.25327701v1.12","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1001984"},{"key":"2025052102150663000_2025.05.15.25327701v1.13","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1007125"},{"key":"2025052102150663000_2025.05.15.25327701v1.14","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD006404.pub4"},{"key":"2025052102150663000_2025.05.15.25327701v1.15","doi-asserted-by":"publisher","DOI":"10.1186\/s12936-023-04574-7"},{"key":"2025052102150663000_2025.05.15.25327701v1.16","doi-asserted-by":"publisher","DOI":"10.1186\/s12936-023-04618-y"},{"key":"2025052102150663000_2025.05.15.25327701v1.17","doi-asserted-by":"publisher","DOI":"10.1128\/aac.01525-23"},{"key":"2025052102150663000_2025.05.15.25327701v1.18","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2211803)"},{"key":"2025052102150663000_2025.05.15.25327701v1.19","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgph.0000111"},{"key":"2025052102150663000_2025.05.15.25327701v1.20","unstructured":"Humanitarian Data Exchange. Uganda - Subnational Administrative Boundaries - Humanitarian Data Exchange. [cited 5 Jan 2025]. Available: https:\/\/data.humdata.org\/dataset\/cod-ab-uga"},{"key":"2025052102150663000_2025.05.15.25327701v1.21","unstructured":"USAID. DHS Program, Spatial Data Repository - Boundaries. Feb 2024. Available: https:\/\/spatialdata.dhsprogram.com\/boundaries\/#countryId=UG&view=table"},{"key":"2025052102150663000_2025.05.15.25327701v1.22","doi-asserted-by":"publisher","DOI":"10.5258\/SOTON\/WP00660"},{"key":"2025052102150663000_2025.05.15.25327701v1.23","doi-asserted-by":"publisher","DOI":"10.1038\/nature25181"},{"key":"2025052102150663000_2025.05.15.25327701v1.24","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1004267"},{"key":"2025052102150663000_2025.05.15.25327701v1.25","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-26878-5"},{"key":"2025052102150663000_2025.05.15.25327701v1.26","unstructured":"ECMWF \/ Copernicus Climate Change Service. ERA5 Daily Aggregates - Latest Climate Reanalysis Produced by ECMWF \/ Copernicus Climate Change Service | Earth Engine Data Catalog. In: Google for Developers [Internet]. 2020 [cited 8 Jan 2025]. Available: https:\/\/developers.google.com\/earth-engine\/datasets\/catalog\/ECMWF_ERA5_DAILY"},{"key":"2025052102150663000_2025.05.15.25327701v1.27","unstructured":"Malaria Atlas Project. Malaria Atlas Project | Data. [cited 8 Jan 2025]. Available: https:\/\/data.malariaatlas.org\/trends?year=2020&metricGroup=Malaria&geographicLevel=admin0&metricSubcategory=Pf&metricType=rate&metricName=PR"},{"key":"2025052102150663000_2025.05.15.25327701v1.28","doi-asserted-by":"publisher","DOI":"10.13140\/RG.2.2.14091.20009"},{"key":"2025052102150663000_2025.05.15.25327701v1.29","unstructured":"Uganda Ministry of Health National Malaria Control Division. Uganda Malaria Indicator Survey 2018-2019. 2020. Available: https:\/\/dhsprogram.com\/pubs\/pdf\/MIS34\/MIS34.pdf"},{"key":"2025052102150663000_2025.05.15.25327701v1.30","unstructured":"World Health Organization. World Malaria Report 2024. [cited 21 Mar 2025]. Available: https:\/\/www.who.int\/teams\/global-malaria-programme\/reports\/world-malaria-report-2024"},{"key":"2025052102150663000_2025.05.15.25327701v1.31","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2101746"},{"key":"2025052102150663000_2025.05.15.25327701v1.32","doi-asserted-by":"publisher","DOI":"10.3201\/eid2404.170141"},{"key":"2025052102150663000_2025.05.15.25327701v1.33","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01818-18"},{"key":"2025052102150663000_2025.05.15.25327701v1.34","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-33873-x"},{"key":"2025052102150663000_2025.05.15.25327701v1.35","doi-asserted-by":"publisher","DOI":"10.1145\/3620665.3640366"},{"key":"2025052102150663000_2025.05.15.25327701v1.36","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-27486-z"},{"key":"2025052102150663000_2025.05.15.25327701v1.37","doi-asserted-by":"publisher","DOI":"10.1145\/3292500.3330701"},{"key":"2025052102150663000_2025.05.15.25327701v1.38","doi-asserted-by":"publisher","DOI":"10.1101\/2021.04.08.437876"},{"key":"2025052102150663000_2025.05.15.25327701v1.39","doi-asserted-by":"publisher","DOI":"10.1111\/j.1752-4571.2008.00067.x"},{"key":"2025052102150663000_2025.05.15.25327701v1.40","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiaa687"},{"key":"2025052102150663000_2025.05.15.25327701v1.41","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(16)30415-7"},{"key":"2025052102150663000_2025.05.15.25327701v1.42","unstructured":"Uganda Ministry of Health. Strategy to Respond to Antimalarial Drug Resistance in Uganda. Kampala, Uganda: [private]; 2025."},{"key":"2025052102150663000_2025.05.15.25327701v1.43","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0804628105"},{"key":"2025052102150663000_2025.05.15.25327701v1.44","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-39914-3"},{"key":"2025052102150663000_2025.05.15.25327701v1.45","doi-asserted-by":"publisher","DOI":"10.1101\/2024.12.18.628924"},{"key":"2025052102150663000_2025.05.15.25327701v1.46","doi-asserted-by":"publisher","DOI":"10.1016\/S2214-109X(16)30236-4"},{"key":"2025052102150663000_2025.05.15.25327701v1.47","doi-asserted-by":"publisher","DOI":"10.1186\/s12936-021-04021-5"},{"key":"2025052102150663000_2025.05.15.25327701v1.48","doi-asserted-by":"publisher","DOI":"10.1186\/s12936-024-05158-9"},{"key":"2025052102150663000_2025.05.15.25327701v1.49","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD006404.pub4"},{"key":"2025052102150663000_2025.05.15.25327701v1.50","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(19)30391-3"},{"key":"2025052102150663000_2025.05.15.25327701v1.51","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adi2364"},{"key":"2025052102150663000_2025.05.15.25327701v1.52","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1010278"},{"key":"2025052102150663000_2025.05.15.25327701v1.53","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-05652-0"},{"key":"2025052102150663000_2025.05.15.25327701v1.54","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(19)30543-2"},{"key":"2025052102150663000_2025.05.15.25327701v1.55","doi-asserted-by":"publisher","DOI":"10.3390\/tropicalmed8040195"},{"key":"2025052102150663000_2025.05.15.25327701v1.56","doi-asserted-by":"publisher","DOI":"10.1186\/s12936-022-04225-3"},{"key":"2025052102150663000_2025.05.15.25327701v1.57","doi-asserted-by":"publisher","DOI":"10.2139\/ssrn.4756459"},{"key":"2025052102150663000_2025.05.15.25327701v1.58","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(24)00746-1"},{"key":"2025052102150663000_2025.05.15.25327701v1.59","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiae288"},{"key":"2025052102150663000_2025.05.15.25327701v1.60","doi-asserted-by":"publisher","DOI":"10.1101\/2024.12.31.24319821"},{"key":"2025052102150663000_2025.05.15.25327701v1.61","doi-asserted-by":"publisher","DOI":"10.1101\/2025.02.28.25323072"},{"key":"2025052102150663000_2025.05.15.25327701v1.62","doi-asserted-by":"publisher","DOI":"10.25561\/118190"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2025.05.15.25327701","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T20:36:17Z","timestamp":1768509377000},"score":1,"resource":{"primary":{"URL":"http:\/\/medrxiv.org\/lookup\/doi\/10.1101\/2025.05.15.25327701"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,18]]},"references-count":62,"URL":"https:\/\/doi.org\/10.1101\/2025.05.15.25327701","relation":{},"subject":[],"published":{"date-parts":[[2025,5,18]]},"subtype":"preprint"}}