{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T03:55:13Z","timestamp":1791258913956,"version":"4.1.0"},"reference-count":74,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2015,6,1]],"date-time":"2015-06-01T00:00:00Z","timestamp":1433116800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2015,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Changing treatment practices may be selecting for changes in the drug sensitivity of malaria parasites. We characterized\n                    <jats:italic>ex vivo<\/jats:italic>\n                    drug sensitivity and parasite polymorphisms associated with sensitivity in 459\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Plasmodium falciparum<\/jats:named-content>\n                    samples obtained from subjects enrolled in two clinical trials in Tororo, Uganda, from 2010 to 2013. Sensitivities to chloroquine and monodesethylamodiaquine varied widely; sensitivities to quinine, dihydroartemisinin, lumefantrine, and piperaquine were generally good. Associations between\n                    <jats:italic>ex vivo<\/jats:italic>\n                    drug sensitivity and parasite polymorphisms included decreased chloroquine and monodesethylamodiaquine sensitivity and increased lumefantrine and piperaquine sensitivity with\n                    <jats:italic>pfcrt<\/jats:italic>\n                    76T, as well as increased lumefantrine sensitivity with\n                    <jats:italic>pfmdr1<\/jats:italic>\n                    86Y, Y184, and 1246Y. Over time,\n                    <jats:italic>ex vivo<\/jats:italic>\n                    sensitivity decreased for lumefantrine and piperaquine and increased for chloroquine, the prevalences of\n                    <jats:italic>pfcrt<\/jats:italic>\n                    K76 and\n                    <jats:italic>pfmdr1<\/jats:italic>\n                    N86 and D1246 increased, and the prevalences of\n                    <jats:italic>pfdhfr<\/jats:italic>\n                    and\n                    <jats:italic>pfdhps<\/jats:italic>\n                    polymorphisms associated with antifolate resistance were unchanged. In recurrent infections, recent prior treatment with artemether-lumefantrine was associated with decreased\n                    <jats:italic>ex vivo<\/jats:italic>\n                    lumefantrine sensitivity and increased prevalence of\n                    <jats:italic>pfcrt<\/jats:italic>\n                    K76 and\n                    <jats:italic>pfmdr1<\/jats:italic>\n                    N86, 184F, and D1246. In children assigned chemoprevention with monthly dihydroartemisinin-piperaquine with documented circulating piperaquine, breakthrough infections had increased the prevalence of\n                    <jats:italic>pfmdr1<\/jats:italic>\n                    86Y and 1246Y compared to untreated controls. The noted impacts of therapy and chemoprevention on parasite polymorphisms remained significant in multivariate analysis correcting for calendar time. Overall, changes in parasite sensitivity were consistent with altered selective pressures due to changing treatment practices in Uganda. These changes may threaten the antimalarial treatment and preventive efficacies of artemether-lumefantrine and dihydroartemisinin-piperaquine, respectively.\n                  <\/jats:p>","DOI":"10.1128\/aac.05141-14","type":"journal-article","created":{"date-parts":[[2015,3,9]],"date-time":"2015-03-09T22:03:07Z","timestamp":1425938587000},"page":"3018-3030","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":58,"title":["Impact of Antimalarial Treatment and Chemoprevention on the Drug Sensitivity of Malaria Parasites Isolated from Ugandan Children"],"prefix":"10.1128","volume":"59","author":[{"given":"Patrick","family":"Tumwebaze","sequence":"first","affiliation":[{"name":"Infectious Diseases Research Collaboration, Kampala, Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa D.","family":"Conrad","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of 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Diseases Research Collaboration, Kampala, Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Kapisi","sequence":"additional","affiliation":[{"name":"Infectious Diseases Research Collaboration, Kampala, Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Legac","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California, San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiri","family":"Gut","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California, San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland A.","family":"Cooper","sequence":"additional","affiliation":[{"name":"Department of Natural Sciences and Mathematics, Dominican University of California, San Rafael, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moses R.","family":"Kamya","sequence":"additional","affiliation":[{"name":"School of Medicine, Makerere University College of Health Sciences, Kampala, Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane V.","family":"Havlir","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California, San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grant","family":"Dorsey","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California, San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryan","family":"Greenhouse","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California, San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel 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