{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T17:42:44Z","timestamp":1791308564612,"version":"4.3.1"},"reference-count":32,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2010,1,1]],"date-time":"2010-01-01T00:00:00Z","timestamp":1262304000000},"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":[[2010,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Antifolate drugs have an important role in the treatment of malaria. Polymorphisms in the genes encoding the dihydrofolate reductase and dihydropteroate synthetase enzymes cause resistance to the antifol and sulfa drugs, respectively. Rwanda has the highest levels of antimalarial drug resistance in Africa. We correlated the efficacy of chlorproguanil-dapsone plus artesunate (CPG-DDS+A) and amodiaquine plus sulfadoxine-pyrimethamine (AQ+SP) in children with uncomplicated malaria caused by\n                    <jats:italic>Plasmodium falciparum<\/jats:italic>\n                    parasites with\n                    <jats:italic>p<\/jats:italic>\n                    <jats:italic>fdhfr<\/jats:italic>\n                    and\n                    <jats:italic>p<\/jats:italic>\n                    <jats:italic>fdhps<\/jats:italic>\n                    mutations, which are known to confer reduced drug susceptibility, in two areas of Rwanda. In the eastern province, where the cure rates were low, over 75% of isolates had three or more\n                    <jats:italic>p<\/jats:italic>\n                    <jats:italic>fdhfr<\/jats:italic>\n                    mutations and two or three\n                    <jats:italic>p<\/jats:italic>\n                    <jats:italic>fdhps<\/jats:italic>\n                    mutations and 11% had the\n                    <jats:italic>p<\/jats:italic>\n                    <jats:italic>fdhfr<\/jats:italic>\n                    164-Leu polymorphism. In the western province, where the cure rates were significantly higher (\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.001), the prevalence of multiple resistance mutations was lower and the\n                    <jats:italic>p<\/jats:italic>\n                    <jats:italic>fdhfr<\/jats:italic>\n                    I164L polymorphism was not found. The risk of treatment failure following the administration of AQ+SP more than doubled for each additional\n                    <jats:italic>p<\/jats:italic>\n                    <jats:italic>fdhfr<\/jats:italic>\n                    resistance mutation (odds ratio [OR] = 2.4; 95% confidence interval [CI] = 1.01 to 5.55;\n                    <jats:italic>P<\/jats:italic>\n                    = 0.048) and each\n                    <jats:italic>p<\/jats:italic>\n                    <jats:italic>fdhps<\/jats:italic>\n                    mutation (OR = 2.1; 95% CI = 1.21 to 3.54;\n                    <jats:italic>P<\/jats:italic>\n                    = 0.008). The risk of failure following CPG-DDS+A treatment was 2.2 times higher (95% CI = 1.34 to 3.7) for each additional\n                    <jats:italic>p<\/jats:italic>\n                    <jats:italic>fdhfr<\/jats:italic>\n                    mutation, whereas there was no association with mutations in the\n                    <jats:italic>p<\/jats:italic>\n                    <jats:italic>fdhps<\/jats:italic>\n                    gene (\n                    <jats:italic>P<\/jats:italic>\n                    = 0.13). The\n                    <jats:italic>p<\/jats:italic>\n                    <jats:italic>fdhfr<\/jats:italic>\n                    164-Leu polymorphism is prevalent in eastern Rwanda. Antimalarial treatments with currently available antifol-sulfa combinations are no longer effective in Rwanda because of high-level resistance.\n                  <\/jats:p>","DOI":"10.1128\/aac.00498-09","type":"journal-article","created":{"date-parts":[[2009,10,19]],"date-time":"2009-10-19T21:29:39Z","timestamp":1255987779000},"page":"477-483","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":48,"title":["Molecular Correlates of High-Level Antifolate Resistance in Rwandan Children with\n                    <i>Plasmodium falciparum<\/i>\n                    Malaria"],"prefix":"10.1128","volume":"54","author":[{"given":"Corine","family":"Karema","sequence":"first","affiliation":[{"name":"National Malaria Control Program, Kigali, Rwanda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mallika","family":"Imwong","sequence":"additional","affiliation":[{"name":"Centre for Tropical Medicine, Nuffield Department of Medicine, Oxford University, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caterina I.","family":"Fanello","sequence":"additional","affiliation":[{"name":"Centre for Tropical Medicine, Nuffield Department of Medicine, Oxford University, United Kingdom"},{"name":"Mahidol-Oxford Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kasia","family":"Stepniewska","sequence":"additional","affiliation":[{"name":"Centre for Tropical Medicine, Nuffield Department of Medicine, Oxford University, United Kingdom"},{"name":"Mahidol-Oxford Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aline","family":"Uwimana","sequence":"additional","affiliation":[{"name":"National Malaria Control Program, Kigali, Rwanda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Supatchara","family":"Nakeesathit","sequence":"additional","affiliation":[{"name":"Mahidol-Oxford Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arjen","family":"Dondorp","sequence":"additional","affiliation":[{"name":"Centre for Tropical Medicine, Nuffield Department of Medicine, Oxford University, United Kingdom"},{"name":"Mahidol-Oxford Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas P.","family":"Day","sequence":"additional","affiliation":[{"name":"Centre for Tropical Medicine, Nuffield Department of Medicine, Oxford University, United Kingdom"},{"name":"Mahidol-Oxford Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas J.","family":"White","sequence":"additional","affiliation":[{"name":"Centre for Tropical Medicine, Nuffield Department of Medicine, Oxford University, United Kingdom"},{"name":"Mahidol-Oxford Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, 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