title: Multicentric assessment of the efficacy and tolerability of dihydroartemisinin-piperaquine compared to artemether-lumefantrine in the treatment of uncomplicated Plasmodium falciparum malaria in sub-Saharan Africa.
abstract: BACKGROUND
  The choice of appropriate artemisinin-based combination therapy depends on several factors (cost, efficacy, safety, reinfection rate and simplicity of administration). To assess whether the combination dihydroartemisinin-piperaquine (DP) could be an alternative to artemether-lumefantrine (AL), the efficacy and the tolerability of the two products for the treatment of uncomplicated falciparum malaria in sub-Saharan Africa have been compared.
  
  
  METHODS
  A multicentric open randomized controlled clinical trial of three-day treatment of DP against AL for the treatment of two parallel groups of patients aged two years and above and suffering from uncomplicated falciparum malaria was carried out in Cameroon, Côte d'Ivoire and Senegal. Within each group, patients were randomly assigned supervised treatment. DP was given once a day for three days and AL twice a day for three days. Follow-up visits were performed on day 1 to 4 and on day 7, 14, 21, 28 to evaluate clinical and parasitological results. The primary endpoint was the recovery rate by day 28.
  
  
  RESULTS
  Of 384 patients enrolled, 197 were assigned DP and 187 AL. The recovery rates adjusted by genotyping, 99.5% in the DP group and 98.9% in the AL group, were not statistically different (p=0.538). No Early Therapeutic Failure (ETF) was observed. At day 28, two patients in the DP group and five in AL group had recurrent parasitaemia with Plasmodium falciparum. In the DP group, after PCR genotyping, one of the two recurrences was classified as a new infection and the other as recrudescence. In AL group, two recurrences were classified after correction by PCR as recrudescence. All cases of recrudescence were classified as Late Parasitological Failure (LPF). In each group, a rapid recovery from fever and parasitaemia was noticed. More than 90% of patients did no longer present fever or parasitaemia 48 hours after treatment. Both drugs were well tolerated. Indeed, no serious adverse events were reported during the follow-up period. Most of the adverse events which developed were moderate and did not result in the treatment being stopped in either treatment group.
  
  
  CONCLUSIONS
  Dihydroartemisinin-piperaquine was as effective and well-tolerated as artemether-lumefantrine in the treatment of uncomplicated falciparum malaria. In addition, dihydroartemisinin-piperaquine, a single daily dose, could be an advantage over artemether-lumefantrine in Africa because of better treatment observance.
authors.affiliation: Department of Parasitology and Mycology, Faculty of Pharmaceutical and Biological Sciences, Abidjan, Côte d'Ivoire. yavowilliam@yahoo.fr
authors.forename: William
authors.initials: W
authors.lastname: Yavo
authors.forename: Babacar
authors.initials: B
authors.lastname: Faye
authors.forename: Thomas
authors.initials: T
authors.lastname: Kuete
authors.forename: Vincent
authors.initials: V
authors.lastname: Djohan
authors.forename: Serge A
authors.initials: SA
authors.lastname: Oga
authors.forename: Richard R
authors.initials: RR
authors.lastname: Kassi
authors.forename: Mariama
authors.initials: M
authors.lastname: Diatta
authors.forename: Moor V
authors.initials: MV
authors.lastname: Ama
authors.forename: Roger
authors.initials: R
authors.lastname: Tine
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Ndiaye
authors.forename: Jean-Bedel
authors.initials: JB
authors.lastname: Evi
authors.forename: Albert
authors.initials: A
authors.lastname: Same-Ekobo
authors.forename: Oumar
authors.initials: O
authors.lastname: Faye
authors.forename: Moussa
authors.initials: M
authors.lastname: Koné
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000962:Antimalarials / Q000008:administration & dosage* / Q000009:adverse effects; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins / Q000008:administration & dosage* / Q000009:adverse effects; D002163:Cameroon; D002648:Child; D002675:Child, Preschool; D007560:Cote d'Ivoire; D004338:Drug Combinations; D004983:Ethanolamines / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D005449:Fluorenes / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011804:Quinolines / Q000008:administration & dosage* / Q000009:adverse effects; D012675:Senegal; D016896:Treatment Outcome; D055815:Young Adult; D010879:Piperazines
chemical_list: D000962:Antimalarials; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins; D004338:Drug Combinations; D004983:Ethanolamines; D005449:Fluorenes; D011804:Quinolines; C039060:artenimol; C034759:piperaquine; D010879:Piperazines