title: Comparative efficacy of aminoquinoline-antifolate combinations for the treatment of uncomplicated falciparum malaria in Kampala, Uganda.
abstract: Resistance to chloroquine (CQ) requires its replacement as first-line therapy for uncomplicated malaria in much of Africa. Combination therapy may improve efficacy and delay the selection of resistant malaria parasites. Combinations of sulfadoxine-pyrimethamine (SP) with 4-aminoquinolines offer affordable and available alternatives to CQ. We conducted a randomized, single-blinded trial to compare the efficacy of SP monotherapy with combinations of SP and either CQ or amodiaquine (AQ) for the treatment of uncomplicated falciparum malaria in patients over 6 months of age in Kampala, Uganda. Of the 448 patients enrolled, 428 (95%) completed follow-up. Clinical treatment failure after 14 days occurred in 21/140 (15.0%, 95% CI 9.5-22.0%) SP-treated, 11/152 (7.2%, 95% CI 3.7-12.6%) SP/CQ-treated, and 0/136 (0%, 95% CI 0-2.7%) SP/AQ-treated patients. Combination therapies were safe and offered superior efficacy to SP monotherapy. SP/AQ was the most efficacious. This low-cost combination regimen may provide an optimal alternative to CQ for the treatment of uncomplicated malaria in Uganda.
authors.affiliation: Makerere University Medical School, Kampala, Uganda.
authors.forename: Anne F
authors.initials: AF
authors.lastname: Gasasira
authors.forename: Grant
authors.initials: G
authors.lastname: Dorsey
authors.forename: Bridget
authors.initials: B
authors.lastname: Nzarubara
authors.forename: Sarah G
authors.initials: SG
authors.lastname: Staedke
authors.forename: Annette
authors.initials: A
authors.lastname: Nassali
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Rosenthal
authors.forename: Moses R
authors.initials: MR
authors.lastname: Kamya
mesh_terms: D000293:Adolescent; D000328:Adult; D000655:Amodiaquine / Q000008:administration & dosage / Q000627:therapeutic use*; D000962:Antimalarials / Q000008:administration & dosage / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D002738:Chloroquine / Q000008:administration & dosage / Q000627:therapeutic use*; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011739:Pyrimethamine / Q000008:administration & dosage / Q000627:therapeutic use*; D016037:Single-Blind Method; D013413:Sulfadoxine / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome; D014454:Uganda
chemical_list: D000962:Antimalarials; D004338:Drug Combinations; D000655:Amodiaquine; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D002738:Chloroquine; D011739:Pyrimethamine