title: The addition of artesunate to chloroquine for treatment of Plasmodium falciparum malaria in Gambian children delays, but does not prevent treatment failure.
abstract: In a randomized controlled trial, chloroquine monotherapy was compared with the combination of artesunate and chloroquine for treating uncomplicated Plasmodium falciparum malaria in 536 Gambian children. Chloroquine-treated children exhibited a 28-day clinical failure rate of 15% (95% confidence interval [CI] = 9.2-22%) compared with 11% (7.8-15%) among children receiving the combination (P = 0.08, by Wilcoxon test). Seventy-three percent of chloroquine-treated children exhibited parasitemia during follow-up compared with 49% of children receiving the combination (relative risk = 1.5, 95% CI = 1.3-1.7; chi2 = 21.18, P < 0.001). A significant reduction in clinical and parasitologic treatment failure in the combination group occurred in the first two weeks following treatment, but this was eroded over weeks three and four of follow-up. The impact of combination therapy on the transmission of chloroquine-resistant parasites is discussed. Chloroquine plus artesunate is not sufficiently efficacious to justify its introduction as a replacement for chloroquine monotherapy in The Gambia.
authors.affiliation: Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom. colin.sutherland@lshtm.ac.uk
authors.forename: Colin J
authors.initials: CJ
authors.lastname: Sutherland
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Drakeley
authors.forename: Uche
authors.initials: U
authors.lastname: Obisike
authors.forename: Rosalind
authors.initials: R
authors.lastname: Coleman
authors.forename: Musa
authors.initials: M
authors.lastname: Jawara
authors.forename: Geoffrey A T
authors.initials: GA
authors.lastname: Targett
authors.forename: Paul
authors.initials: P
authors.lastname: Milligan
authors.forename: Margaret
authors.initials: M
authors.lastname: Pinder
authors.forename: Gijs
authors.initials: G
authors.lastname: Walraven
mesh_terms: D000367:Age Factors; D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage* / Q000627:therapeutic use*; D037621:Artemisinins / Q000008:administration & dosage* / Q000627:therapeutic use*; D000077332:Artesunate; D002648:Child; D002675:Child, Preschool; D002738:Chloroquine / Q000008:administration & dosage* / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D005714:Gambia; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000469:parasitology; D008297:Male; D010963:Plasmodium falciparum / Q000502:physiology; D012717:Sesquiterpenes / Q000008:administration & dosage* / Q000627:therapeutic use*; D017211:Treatment Failure
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D012717:Sesquiterpenes; D000077332:Artesunate; D002738:Chloroquine