title: Efficacy and effectiveness of dihydroartemisinin-piperaquine versus artesunate-mefloquine in falciparum malaria: an open-label randomised comparison.
abstract: Artemisinin-based combinations are judged the best treatments for multidrug-resistant Plasmodium falciparum malaria. Artesunate-mefloquine is widely recommended in southeast Asia, but its high cost and tolerability profile remain obstacles to widespread deployment. To assess whether dihydroartemisinin-piperaquine is a suitable alternative to artesunate-mefloquine, we compared the safety, tolerability, efficacy, and effectiveness of the two regimens for the treatment of uncomplicated falciparum in western Myanmar (Burma).
  
  
  
  We did an open randomised comparison of 3-day regimens of artesunate-mefloquine (12/25 mg/kg) versus dihydroartemisinin-piperaquine (6.3/50 mg/kg) for the treatment of children aged 1 year or older and in adults with uncomplicated falciparum malaria in Rakhine State, western Myanmar. Within each group, patients were randomly assigned supervised or non-supervised treatment. The primary endpoint was the PCR-confirmed parasitological failure rate by day 42. Failure rates at day 42 were estimated by Kaplan-Meier survival analysis. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN27914471.
  
  
  
  Of 652 patients enrolled, 327 were assigned dihydroartemisinin-piperaquine (156 supervised and 171 not supervised), and 325 artesunate-mefloquine (162 and 163, respectively). 16 patients were lost to follow-up, and one patient died 22 days after receiving dihydroartemisinin-piperaquine. Recrudescent parasitaemias were confirmed in only two patients; the day 42 failure rate was 0.6% (95% CI 0.2-2.5) for dihydroartemisinin-piperaquine and 0 (0-1.2) for artesunate-mefloquine. Whole-blood piperaquine concentrations at day 7 were similar for patients with observed and non-observed dihydroartemisinin-piperaquine treatment. Gametocytaemia developed more frequently in patients who had received dihydroartemisinin-piperaquine than in those on artesunate-mefloquine: day 7, 18 (10%) of 188 versus five (2%) of 218; relative risk 4.2 (1.6-11.0) p=0.011.
  
  
  
  Dihydroartemisinin-piperaquine is a highly efficacious and inexpensive treatment of multidrug-resistant falciparum malaria and is well tolerated by all age groups. The effectiveness of the unsupervised treatment, as in the usual context of use, equalled its supervised efficacy, indicating good adherence without supervision. Dihydroartemisinin-piperaquine is a good alternative to artesunate-mefloquine.
authors.affiliation: Médecins Sans Frontières (Holland), Yangon, Myanmar.
authors.forename: Frank
authors.initials: F
authors.lastname: Smithuis
authors.forename: Moe Kyaw
authors.initials: MK
authors.lastname: Kyaw
authors.forename: Ohn
authors.initials: O
authors.lastname: Phe
authors.forename: Khin Zarli
authors.initials: KZ
authors.lastname: Aye
authors.forename: Linn
authors.initials: L
authors.lastname: Htet
authors.forename: Marion
authors.initials: M
authors.lastname: Barends
authors.forename: Niklas
authors.initials: N
authors.lastname: Lindegardh
authors.forename: Thida
authors.initials: T
authors.lastname: Singtoroj
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Ashley
authors.forename: Saw
authors.initials: S
authors.lastname: Lwin
authors.forename: Kasia
authors.initials: K
authors.lastname: Stepniewska
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: White
mesh_terms: D000293:Adolescent; D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage / Q000627:therapeutic use*; D037621:Artemisinins / Q000008:administration & dosage / Q000627:therapeutic use*; D000077332:Artesunate; D002648:Child; D002675:Child, Preschool; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000188:drug therapy*; D008297:Male; D015767:Mefloquine / Q000008:administration & dosage / Q000627:therapeutic use; D002052:Myanmar; D010963:Plasmodium falciparum / Q000187:drug effects; D011804:Quinolines / Q000008:administration & dosage / Q000627:therapeutic use; D012008:Recurrence; D012717:Sesquiterpenes / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome; D010879:Piperazines
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D000077332:Artesunate; D015767:Mefloquine; D011804:Quinolines; D012717:Sesquiterpenes; C039060:artenimol; C031327:artemisinin; C034759:piperaquine; D010879:Piperazines