title: A randomized trial on effectiveness of artemether-lumefantrine versus artesunate plus amodiaquine for unsupervised treatment of uncomplicated Plasmodium falciparum malaria in Ghanaian children.
abstract: BACKGROUND
  Numerous trials have demonstrated high efficacy and safety of artemisinin-based combination therapy (ACT) under supervised treatment. In contrast, effectiveness studies comparing different types of ACT applied unsupervised are scarce. The aim of this study was to compare effectiveness, tolerability and acceptance of artesunate plus amodiaquine (ASAQ) against that of artemether-lumefantrine (AL) in Ghanaian children with uncomplicated Plasmodium falciparum malaria.
  
  
  METHODS
  A randomized open-label trial was conducted at two district hospitals in the Ashanti region, Ghana, an area of intense malaria transmission. A total of 246 children under five years of age were randomly assigned to either ASAQ (Arsucam) or AL (Coartem). Study participants received their first weight-adjusted dose under supervision. After the parent/guardian was advised of times and mode of administration the respective three-day treatment course was completed unobserved at home. Follow-up visits were performed on days 3, 7, 14 and 28 to evaluate clinical and parasitological outcomes, adverse events, and haematological recovery. Length polymorphisms of variable regions of msp1 and msp2 were determined to differentiate recrudescences from reinfections. Acceptance levels of both treatment regimens were assessed by means of standardized interviews.
  
  
  RESULTS
  Adequate clinical and parasitological responses after AL and ASAQ treatment were similar (88.3% and 91.7%, respectively). Interestingly, more late clinical failures until day 28 occurred in AL-treated children than in those who received ASAQ (17.5% and 7.3%, respectively; Hazard Ratio 2.41, 95% CI 1.00-5.79, p < 0.05).Haematological recovery and drug tolerability were not found to be significantly different in both study arms. The acceptance of treatment with ASAQ was higher than that with AL (rank-scores 10.6 and 10.3, respectively; p < 0.05).
  
  
  CONCLUSIONS
  Unobserved AL and ASAQ treatment showed high adequate clinical and parasitological responses, though AL was inferior in preventing late clinical failures.
authors.affiliation: Infectious Disease Epidemiology, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany. kobbe@bni-hamburg.de
authors.forename: Robin
authors.initials: R
authors.lastname: Kobbe
authors.forename: Philipp
authors.initials: P
authors.lastname: Klein
authors.forename: Samuel
authors.initials: S
authors.lastname: Adjei
authors.forename: Solomon
authors.initials: S
authors.lastname: Amemasor
authors.forename: William Nana
authors.initials: WN
authors.lastname: Thompson
authors.forename: Hanna
authors.initials: H
authors.lastname: Heidemann
authors.forename: Maja V
authors.initials: MV
authors.lastname: Nielsen
authors.forename: Julia
authors.initials: J
authors.lastname: Vohwinkel
authors.forename: Benedikt
authors.initials: B
authors.lastname: Hogan
authors.forename: Benno
authors.initials: B
authors.lastname: Kreuels
authors.forename: Martina
authors.initials: M
authors.lastname: Bührlen
authors.forename: Wibke
authors.initials: W
authors.lastname: Loag
authors.forename: Daniel
authors.initials: D
authors.lastname: Ansong
authors.forename: Jürgen
authors.initials: J
authors.lastname: May
mesh_terms: D000655:Amodiaquine / Q000009:adverse effects / Q000627:therapeutic use*; D000818:Animals; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins / Q000009:adverse effects / Q000627:therapeutic use*; D002675:Child, Preschool; D004338:Drug Combinations; D004983:Ethanolamines / Q000009:adverse effects / Q000627:therapeutic use*; D005449:Fluorenes / Q000009:adverse effects / Q000627:therapeutic use*; D005869:Ghana; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000188:drug therapy*; D010342:Patient Acceptance of Health Care / Q000706:statistics & numerical data; D010963:Plasmodium falciparum / Q000145:classification / Q000187:drug effects / Q000235:genetics; D016896:Treatment Outcome
chemical_list: D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins; D004338:Drug Combinations; D004983:Ethanolamines; D005449:Fluorenes; C515299:amodiaquine, artesunate drug combination; D000655:Amodiaquine