title: Antimalarial efficacy of sulfadoxine-pyrimethamine, amodiaquine and a combination of chloroquine plus sulfadoxine-pyrimethamine in Bundi Bugyo, western Uganda.
abstract: We report below an in vivo antimalarial efficacy study conducted in 2002 in Bundi Bugyo, a district of western Uganda housing a large displaced population. We tested sulfadoxine-pyrimethamine (SP), amodiaquine (AQ) and the combination chloroquine plus SP (CQ + SP). A total of 268 children with uncomplicated Plasmodium falciparum malaria were followed-up for 28 days according to WHO recommendations, with PCR genotyping to distinguish late recrudescences from re-infections. PCR-adjusted failure proportions at day 28 were 37.0% (34/92, 95% CI 27.1-47.7) in the SP group, 20.6% (14/68, 95% CI 11.7-32.1) in the AQ group and 22.8% (18/79, 95% CI 14.1-33.6) in the CQ + SP group. Early failures were particularly frequent in the SP group (15.2%). Clearance of gametocytes was slower in the SP and CQ + SP groups than in the AQ group. This study suggests that, in Bundi Bugyo, CQ + SP (Uganda's first-line regimen) will need to be replaced by a more efficacious regimen. Across Uganda, the deployment of SP containing combinations may not be a feasible long-term strategy. For Bundi Bugyo, we recommend a combination of artesunate and AQ. Our study also confirms previous findings that resistance is considerably underestimated by 14-day follow-ups. Antimalarial policy decisions should therefore be based on 28-day studies, with PCR adjustment to distinguish re-infections.
authors.affiliation: Epicentre, Paris, France. fchecci@epicentre.msf.org
authors.forename: Francesco
authors.initials: F
authors.lastname: Checchi
authors.forename: Patrice
authors.initials: P
authors.lastname: Piola
authors.forename: Cara
authors.initials: C
authors.lastname: Kosack
authors.forename: Elisa
authors.initials: E
authors.lastname: Ardizzoni
authors.forename: Derryck
authors.initials: D
authors.lastname: Klarkowski
authors.forename: Eric
authors.initials: E
authors.lastname: Kwezi
authors.forename: Gerardo
authors.initials: G
authors.lastname: Priotto
authors.forename: Suna
authors.initials: S
authors.lastname: Balkan
authors.forename: Nathan
authors.initials: N
authors.lastname: Bakyaita
authors.forename: Alan
authors.initials: A
authors.lastname: Brockman
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Guthmann
mesh_terms: D000655:Amodiaquine / Q000627:therapeutic use; D000962:Antimalarials / Q000627:therapeutic use*; D002675:Child, Preschool; D002738:Chloroquine / Q000627:therapeutic use; D003906:Developing Countries; D004338:Drug Combinations; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000469:parasitology; D008297:Male; D011739:Pyrimethamine / Q000627:therapeutic use; D013413:Sulfadoxine / Q000627:therapeutic use; D017211:Treatment Failure; 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