{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T13:04:09Z","timestamp":1768568649038,"version":"3.49.0"},"posted":{"date-parts":[[2025,10,20]]},"group-title":"Infectious Diseases (except HIV\/AIDS)","reference-count":36,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T00:00:00Z","timestamp":1760918400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,10,20]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>\n                    Intermittent preventive treatment with monthly sulfadoxine-pyrimethamine (IPTp-SP) is recommended during pregnancy in malaria-endemic countries. However, widespread resistance of\n                    <jats:italic>Plasmodium falciparum<\/jats:italic>\n                    to SP has compromised its efficacy, and the alternative dihydroartemisinin-piperaquine (DP) is under study. Potential selection of drug resistance is of interest.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We sequenced 1377 samples collected from pregnant women enrolled in a trial comparing monthly SP, DP, and DP+SP for IPTp in Busia, Uganda and with asymptomatic parasitemia at the time of IPTp administration. We characterized known markers of drug resistance and assessed the 28-day cumulative risk of recurrent parasitemia, with genotyping to distinguish recrudescence from new infections.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    Among 771 samples collected on the day IPTp was initiated, the prevalences of five resistance mutations in\n                    <jats:italic>P. falciparum<\/jats:italic>\n                    dihydrofolate reductase (PfDHFR) and dihydropteroate synthase (PfDHPS) were nearly 100%, and the PfDHFR I164L and PfDHPS A581G mutations, associated with high-level resistance, had combined prevalence of 26.5%. The cumulative risks of recurrent parasitemia (SP 57.8%, DP 4.1%, DP+SP 3.9%), symptomatic malaria (SP 9.3%, DP 1.1%, DP+SP 0.3%), and recrudescent parasitemia (SP 40.1%, DP 2.0%, DP+SP 0.8%) were all significantly greater in the SP arm, with risks greatest in primigravidae. In the IPT-SP arm, the combined prevalence of the PfDHFR I164L and PfDHPS A581G mutations increased significantly from 24.9% at initiation of IPTp to 35.2% after receipt of IPTp-SP. Infection with mutant parasites was associated with non-significant increases in risks of recrudescence.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>IPTp-SP had poor preventive efficacy and selected for increased drug resistance, questioning the value of this intervention.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2025.10.18.25338277","type":"posted-content","created":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T18:15:12Z","timestamp":1760984112000},"source":"Crossref","is-referenced-by-count":0,"title":["Recurrent\n                  <i>Plasmodium falciparum<\/i>\n                  parasitemia and drug resistance mutations during intermittent preventive treatment of malaria in pregnancy in Uganda"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0224-4044","authenticated-orcid":false,"given":"Jimmy","family":"Kizza","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2002-8911","authenticated-orcid":false,"given":"Thomas","family":"Katairo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9941-1309","authenticated-orcid":false,"given":"Abel","family":"Kakuru","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bienvenu","family":"Nsengimaana","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Trevor","family":"Esilu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Innocent","family":"Wiringilimaana","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francis D","family":"Semakuba","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Inna","family":"Gerlovina","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9639-2894","authenticated-orcid":false,"given":"Nicholas","family":"Hathaway","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica","family":"Briggs","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6469-6516","authenticated-orcid":false,"given":"Stephen","family":"Tukwasibwe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven M.","family":"Kiwuwa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9106-4234","authenticated-orcid":false,"given":"Moses R.","family":"Kamya","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7818-3845","authenticated-orcid":false,"given":"Joaniter I.","family":"Nankabirwa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0740-0317","authenticated-orcid":false,"given":"Grant","family":"Dorsey","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7953-7622","authenticated-orcid":false,"given":"Philip J.","family":"Rosenthal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2025102305250551000_2025.10.18.25338277v1.1","unstructured":"World Health Organization. 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