title: Sulfadoxine-pyrimethamine plus chloroquine or amodiaquine for uncomplicated falciparum malaria: a randomized, multisite trial to guide national policy in Uganda.
abstract: The use of combinations of inexpensive drugs for the treatment of malaria in Africa has been proposed as an interim policy while awaiting the widespread availability of more effective regimens. We compared sulfadoxine-pyrimethamine plus chloroquine or amodiaquine in three districts in Uganda. Patients aged 6 months or greater with uncomplicated falciparum malaria were enrolled and randomized to therapy. Safety, tolerability, and efficacy outcomes, adjusted by genotyping, were assessed over 28 days. Of 1,105 patients enrolled, 1,057 (96%) completed follow-up. For children less than 5 years old, the risk of clinical treatment failure adjusted by genotyping at the three sites ranged from 34% to 67% with chloroquine plus sulfadoxine-pyrimethamine and from 13% to 35% with amodiaquine plus sulfadoxine-pyrimethamine (risk differences 21-32%, P < 0.0001 at all sites). Serious adverse events were uncommon with both regimens. The risk of treatment failure with chloroquine plus sulfadoxine-pyrimethamine, the current standard in Uganda, was unacceptably high. Amodiaquine plus sulfadoxine-pyrimethamine was significantly more efficacious; however, existing levels of resistance raises concern about the useful therapeutic life-span of this regimen.
authors.affiliation: Ministry of Health, Kampala, Uganda. nbakyaita@yahoo.com
authors.forename: Nathan
authors.initials: N
authors.lastname: Bakyaita
authors.forename: Grant
authors.initials: G
authors.lastname: Dorsey
authors.forename: Adoke
authors.initials: A
authors.lastname: Yeka
authors.forename: Kristin
authors.initials: K
authors.lastname: Banek
authors.forename: Sarah G
authors.initials: SG
authors.lastname: Staedke
authors.forename: Moses R
authors.initials: MR
authors.lastname: Kamya
authors.forename: Ambrose
authors.initials: A
authors.lastname: Talisuna
authors.forename: Fred
authors.initials: F
authors.lastname: Kironde
authors.forename: Sam
authors.initials: S
authors.lastname: Nsobya
authors.forename: Albert
authors.initials: A
authors.lastname: Kilian
authors.forename: Arthur
authors.initials: A
authors.lastname: Reingold
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Rosenthal
authors.forename: Fred
authors.initials: F
authors.lastname: Wabwire-Mangen
mesh_terms: D000655:Amodiaquine / Q000008:administration & dosage* / Q000009:adverse effects; D000962:Antimalarials / Q000008:administration & dosage* / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D002738:Chloroquine / Q000008:administration & dosage* / Q000009:adverse effects; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D006291:Health Policy; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000453:epidemiology; D011739:Pyrimethamine / Q000008:administration & dosage* / Q000009:adverse effects; D013413:Sulfadoxine / Q000008:administration & dosage* / Q000009:adverse effects; D014454:Uganda
chemical_list: D000962:Antimalarials; D004338:Drug Combinations; D000655:Amodiaquine; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D002738:Chloroquine; D011739:Pyrimethamine