title: Artesunate-clindamycin versus quinine-clindamycin in the treatment of Plasmodium falciparum malaria: a randomized controlled trial.
abstract: BACKGROUND
  Artemisinin-based drug combinations are the mainstay in the fight against drug-resistant malaria in Africa. Currently available antimalarial drug combinations that include artemisinins are pharmacokinetically unmatched and are therefore potentially increasing the risk of selection of resistant mutants in areas in which the rate of transmission of malaria is high. We tested the potential value of artemisinin-based combination therapy with a short elimination half-life for the treatment of uncomplicated Plasmodium falciparum malaria in sub-Saharan Africa.
  
  
  METHODS
  We conducted an open-label, randomized, controlled clinical trial to evaluate the efficacy and tolerability of oral artesunate-clindamycin therapy given twice daily for 3 days (artesunate, 2 mg/kg, and clindamycin, 7 mg/kg, per dose), compared with a standard quinine-clindamycin regimen given twice daily for 3 days (quinine, 15 mg/kg, and clindamycin, 7 mg/kg, per dose), for the treatment of uncomplicated falciparum malaria in 100 Gabonese children aged 3-12 years. The primary end point of the study was the polymerase chain reaction-corrected cure rate for the per-protocol population.
  
  
  RESULTS
  The activity of artesunate-clindamycin was comparable to that of quinine-clindamycin in the per-protocol analysis of cure rates at day 28 of follow-up (87% versus 94%). No serious adverse events were reported, and tolerability was good and was similar in both groups. Times to clearance of fever and clearance of parasites were significantly shorter in the artesunate-clindamycin group.
  
  
  CONCLUSIONS
  Artesunate-clindamycin and other matching artemisinin-based combinations with a short plasma half-life merit further attention for use in regions in which the rate of transmission of malaria is high.
authors.affiliation: Albert Schweitzer Hospital, Lambaréné, Gabon, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Ramharter
authors.forename: Sunny
authors.initials: S
authors.lastname: Oyakhirome
authors.forename: Peter
authors.initials: P
authors.lastname: Klein Klouwenberg
authors.forename: Ayola A
authors.initials: AA
authors.lastname: Adégnika
authors.forename: Sélidji T
authors.initials: ST
authors.lastname: Agnandji
authors.forename: Michel A
authors.initials: MA
authors.lastname: Missinou
authors.forename: Pierre-Blaise
authors.initials: PB
authors.lastname: Matsiégui
authors.forename: Benjamin
authors.initials: B
authors.lastname: Mordmüller
authors.forename: Steffen
authors.initials: S
authors.lastname: Borrmann
authors.forename: Jürgen F
authors.initials: JF
authors.lastname: Kun
authors.forename: Bertrand
authors.initials: B
authors.lastname: Lell
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Krishna
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Graninger
authors.forename: Saadou
authors.initials: S
authors.lastname: Issifou
authors.forename: Peter G
authors.initials: PG
authors.lastname: Kremsner
mesh_terms: D000962:Antimalarials / Q000009:adverse effects / Q000627:therapeutic use*; D037621:Artemisinins / Q000009:adverse effects / Q000627:therapeutic use*; D000077332:Artesunate; D002648:Child; D002675:Child, Preschool; D002981:Clindamycin / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D005681:Gabon; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy*; D008297:Male; D011803:Quinine / Q000009:adverse effects / Q000627:therapeutic use*; D012717:Sesquiterpenes / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D012717:Sesquiterpenes; D002981:Clindamycin; D000077332:Artesunate; D011803:Quinine