title: Randomized trial of artesunate-amodiaquine, atovaquone-proguanil, and artesunate-atovaquone-proguanil for the treatment of uncomplicated falciparum malaria in children.
abstract: BACKGROUND
  Artemisinin-based combination therapies (ACTs) are recommended for the treatment of acute uncomplicated falciparum malaria in many malaria-endemic countries. Despite the emergence of artemisinin resistance, few alternative non-ACTs, including atovaquone-proguanil, are currently available.
  
  
  METHODS
  Plasmodium falciparum-infected Cameroonian children ≤5 years old (n = 338) were randomly assigned to artesunate-amodiaquine, atovaquone-proguanil, or artesunate-atovaquone-proguanil treatment groups and followed for 28 days, according to the standard World Health Organization protocol. In vitro response to atovaquone and cytochrome b sequence of clinical isolates were determined.
  
  
  RESULTS
  Eight late failures and 16 failures (8 late and 8 early failures) were observed after artesunate-amodiaquine and atovaquone-proguanil therapies, respectively. Most late failures were due to reinfections. Artesunate-atovaquone-proguanil was not associated with any failure. After correction by genotyping, per-protocol analysis showed no difference in the efficacy of 3 drugs. However, the proportion of atovaquone-proguanil-treated patients with positive smears on day 3 was much higher (36.0%; P < .05) than that of the artesunate-amodiaquine (2.9%) and artesunate-atovaquone-proguanil (1.0%) groups. In vitro response and cytochrome b sequence did not indicate atovaquone resistance.
  
  
  CONCLUSIONS
  Atovaquone-proguanil was characterized by a slow blood schizontocidal action and resulted in early treatment failure in a few patients. Artesunate-atovaquone-proguanil was a highly effective alternative treatment.
  
  
  BACKGROUND
  UMIN000003813.
authors.affiliation: Unité Mixte de Recherche 216 Mère et Enfant Face aux Infections Tropicales, Institut de Recherche pour le Développement (IRD), Unité de formation et de recherche de Pharmacie, Paris Laboratoire de Recherche sur le Paludisme, Organisation de Coordination pour la lutte contre les Endémies en Afrique Centrale, Yaoundé, Cameroon.
authors.forename: Rachida
authors.initials: R
authors.lastname: Tahar
authors.affiliation: Unité Mixte de Recherche 216 Mère et Enfant Face aux Infections Tropicales, Institut de Recherche pour le Développement (IRD), Unité de formation et de recherche de Pharmacie, Paris.
authors.forename: Talleh
authors.initials: T
authors.lastname: Almelli
authors.affiliation: Unité Mixte de Recherche 216 Mère et Enfant Face aux Infections Tropicales, Institut de Recherche pour le Développement (IRD), Unité de formation et de recherche de Pharmacie, Paris.
authors.forename: Camille
authors.initials: C
authors.lastname: Debue
authors.affiliation: Laboratoire de Recherche sur le Paludisme, Organisation de Coordination pour la lutte contre les Endémies en Afrique Centrale, Yaoundé, Cameroon.
authors.forename: Vincent
authors.initials: V
authors.lastname: Foumane Ngane
authors.affiliation: Unité de Recherche Neurobiologie et Développement, Unité Propre de Recherche 3294, Centre National de la Recherche Scientifique, Université Paris-Sud XI, Orsay Laboratoire de Pharmacodynamie Biochimique, Unité de Formation et de Recherche Biosciences, Université de Cocody Département de Biochimie, Institut Pasteur de Côte d'Ivoire, Abidjan, Côte d'Ivoire.
authors.forename: Joseph
authors.initials: J
authors.lastname: Djaman Allico
authors.affiliation: Laboratoire de Recherche sur le Paludisme, Organisation de Coordination pour la lutte contre les Endémies en Afrique Centrale, Yaoundé, Cameroon.
authors.forename: Solange
authors.initials: S
authors.lastname: Whegang Youdom
authors.affiliation: Unité de Recherche 198, Unité de Recherche des Maladies Infectieuses et Tropicales Emergentes, IRD, Faculté de Médecine La Timone, Aix-Marseille Université, Marseille, France Laboratoire de Recherche sur le Paludisme, Organisation de Coordination pour la lutte contre les Endémies en Afrique Centrale, Yaoundé, Cameroon.
authors.forename: Leonardo K
authors.initials: LK
authors.lastname: Basco
mesh_terms: D000655:Amodiaquine / Q000627:therapeutic use*; D000962:Antimalarials / Q000627:therapeutic use*; D037621:Artemisinins / Q000627:therapeutic use*; D053626:Atovaquone / Q000627:therapeutic use*; D002163:Cameroon; D002675:Child, Preschool; D045303:Cytochromes b / Q000235:genetics; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000188:drug therapy*; D008297:Male; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects / Q000201:enzymology; D002727:Proguanil / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D004338:Drug Combinations; C515299:amodiaquine, artesunate drug combination; C109496:atovaquone, proguanil drug combination; D000655:Amodiaquine; D045303:Cytochromes b; D002727:Proguanil; D053626:Atovaquone
keywords: Plasmodium falciparum; artemisinin; cytochrome b; drug resistance; molecular epidemiology