title: Antimalarial resistance and DHFR/DHPS genotypes of Plasmodium falciparum three years after introduction of sulfadoxine-pyrimethamine and amodiaquine in rural Tanzania.
abstract: We assessed the efficacy of sulfadoxine-pyrimethamine (SP) and amodiaquine (AQ) and DHFR/DHPS genotypes of Plasmodium falciparum in rural Tanzania, 3 years after their introduction as first- and second-line treatments for uncomplicated malaria, respectively. Under five children with uncomplicated malaria were given standard treatments of either SP (n=66) or AQ (n=30) and treatment outcomes after 14 and 28 days were determined. Total treatment failure of 18 and 42.5% was observed for SP on days 14 and 28, respectively. For AQ, total treatment failure of 27 and 53% was found on day 14 and 28, respectively. On day 14, significantly lower SP total treatment failures were observed in 2004 compared with results from a study conducted in 1999 in the same location. No relationship was detected between clinical outcome and DHFR/DHPS genotypes, but the point mutation prevalence in parasites was higher than in 1999. Pre-treatment blood levels of SP were detected in a quarter of the study children: less than expected. We report unacceptably high levels of total treatment failures, both for first- and second-line treatments for uncomplicated malaria in Tanzania 3 years after their introduction, supporting the decision to replace them with artemisinin-based combination therapy.
authors: Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska Institutet at Karolinska University Hospital Huddinge, Stockholm, Sweden. jaran.eriksen@ki.se <jaran.eriksen@ki.se>
authors: J
authors: J
authors: Eriksen
authors: S
authors: S
authors: Mwankusye
authors: S
authors: S
authors: Mduma
authors: M I
authors: MI
authors: Veiga
authors: A
authors: A
authors: Kitua
authors: G
authors: G
authors: Tomson
authors: M G
authors: MG
authors: Petzold
authors: G
authors: G
authors: Swedberg
authors: L L
authors: LL
authors: Gustafsson
authors: M
authors: M
authors: Warsame
mesh_terms: D000655:Amodiaquine / Q000627:therapeutic use*; D000818:Animals; D000962:Antimalarials / Q000627:therapeutic use*; D002675:Child, Preschool; D004094:Dihydropteroate Synthase / Q000235:genetics; D004338:Drug Combinations; D004351:Drug Resistance; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000469:parasitology; D008297:Male; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics; D017354:Point Mutation; D011739:Pyrimethamine / Q000097:blood / Q000627:therapeutic use*; D012423:Rural Health; D013413:Sulfadoxine / Q000097:blood / Q000627:therapeutic use*; D013636:Tanzania; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics; D017211:Treatment Failure
chemical_list: D000962:Antimalarials; D004338:Drug Combinations; D000655:Amodiaquine; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D013762:Tetrahydrofolate Dehydrogenase; D004094:Dihydropteroate Synthase; D011739:Pyrimethamine