title: Efficacy of artesunate-amodiaquine and artemether-lumefantrine fixed-dose combinations for the treatment of uncomplicated Plasmodium falciparum malaria among children aged six to 59 months in Nimba County, Liberia: an open-label randomized non-inferiority trial.
abstract: BACKGROUND
  Prospective efficacy monitoring of anti-malarial treatments is imperative for timely detection of resistance development. The in vivo efficacy of artesunate-amodiaquine (ASAQ) fixed-dose combination (FDC) was compared to that of artemether-lumefantrine (AL) among children aged six to 59 months in Nimba County, Liberia, where Plasmodium falciparum malaria is endemic and efficacy data are scarce.
  
  
  METHODS
  An open-label, randomized controlled non-inferiority trial compared the genotyping adjusted day 42 cure rates of ASAQ FDC (ASAQ Winthrop®) to AL (Coartem®) in 300 children aged six to 59 months with uncomplicated falciparum malaria. Inclusion was between December 2008 and May 2009. Randomization (1:1) was to a three-day observed oral regimen (ASAQ: once a day; AL: twice a day, given with fatty food). Day 7 desethylamodiaquine and lumefantrine blood-concentrations were also measured.
  
  
  RESULTS
  The day 42 genotyping-adjusted cure rate estimates were 97.3% [95% CI: 91.6-99.1] for ASAQ and 94.2% [88.1-97.2] for AL (Kaplan-Meier survival estimates). The difference in day 42 cure rates was -3.1% [upper limit 95% CI: 1.2%]. These results were confirmed by observed proportion of patients cured at day 42 on the per-protocol population. Parasite clearance was 100% (ASAQ) and 99.3% (AL) on day 3. The probability to remain free of re-infection was 0.55 [95% CI: 0.46-0.63] (ASAQ) and 0.66 [0.57-0.73] (AL) (p = 0.017).
  
  
  CONCLUSIONS
  Both ASAQ and AL were highly efficacious and ASAQ was non-inferior to AL. The proportion of patients with re-infection was high in both arms in this highly endemic setting. In 2010, ASAQ FDC was adopted as the first-line national treatment in Liberia. Continuous efficacy monitoring is recommended.
  
  
  BACKGROUND
  The protocols were registered with Current Controlled Trials, under the identifier numbers ISRCTN51688713, ISRCTN40020296.
authors.affiliation: Epicentre, 75011 Paris, France. birgit.schramm@epicentre.msf.org
authors.forename: Birgit
authors.initials: B
authors.lastname: Schramm
authors.forename: Parastou
authors.initials: P
authors.lastname: Valeh
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Baudin
authors.forename: Charles S
authors.initials: CS
authors.lastname: Mazinda
authors.forename: Richard
authors.initials: R
authors.lastname: Smith
authors.forename: Loretxu
authors.initials: L
authors.lastname: Pinoges
authors.forename: Mehul
authors.initials: M
authors.lastname: Dhorda
authors.forename: Yap
authors.initials: Y
authors.lastname: Boum
authors.forename: Timothy
authors.initials: T
authors.lastname: Sundaygar
authors.forename: Yah M
authors.initials: YM
authors.lastname: Zolia
authors.forename: Joel J
authors.initials: JJ
authors.lastname: Jones
authors.forename: Eric
authors.initials: E
authors.lastname: Comte
authors.forename: Pascal
authors.initials: P
authors.lastname: Houzé
authors.forename: Vincent
authors.initials: V
authors.lastname: Jullien
authors.forename: Gwenaelle
authors.initials: G
authors.lastname: Carn
authors.forename: Jean-René
authors.initials: JR
authors.lastname: Kiechel
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Ashley
authors.forename: Philippe J
authors.initials: PJ
authors.lastname: Guérin
mesh_terms: D000655:Amodiaquine / Q000627:therapeutic use*; D000962:Antimalarials / Q000627:therapeutic use*; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins / Q000627:therapeutic use*; D002675:Child, Preschool; D004338:Drug Combinations; D004983:Ethanolamines / Q000627:therapeutic use*; D005260:Female; D005449:Fluorenes / Q000627:therapeutic use*; D006801:Humans; D007223:Infant; D007988:Liberia; D016778:Malaria, Falciparum / Q000188:drug therapy*; D008297:Male; D016896:Treatment Outcome
chemical_list: D000962:Antimalarials; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins; D004338:Drug Combinations; D004983:Ethanolamines; D005449:Fluorenes; C515299:amodiaquine, artesunate drug combination; D000655:Amodiaquine