title: A randomized, controlled study of a simple, once-daily regimen of dihydroartemisinin-piperaquine for the treatment of uncomplicated, multidrug-resistant falciparum malaria.
abstract: BACKGROUND
  Dihydroartemisinin-piperaquine (DP) is a fixed-combination antimalarial drug increasingly deployed in Southeast Asia. The current regimen involves 4 doses given over 3 days. Simplification of the dose regimen should facilitate treatment adherence and thereby increase effectiveness.
  
  
  METHODS
  In a randomized, controlled, 3-arm trial conducted along the northwestern border of Thailand, the standard 4-dose course of DP (DP4) was compared to an equivalent dose given as a once-daily regimen (DP3) and to the standard treatment of mefloquine-artesunate (MAS3).
  
  
  RESULTS
  A total of 499 patients were included in the study. Times to fever and parasite clearance were similar in all groups. The PCR genotyping-adjusted cure rates at day 63 after treatment initiation were 95.7% (95% confidence interval [95% CI], 92.2%-98.9%) for MAS3, 100% for DP4, and 99.4% (95% CI, 98.1%-100%) for DP3. The DP4 and DP3 cure rates were significantly higher than that for MAS3 (P=.008 and P=.03, respectively). All regimens were well tolerated. There were 3 deaths (1 in the MAS3 group and 2 in the DP3 group), all of which were considered to be unrelated to treatment. Rates of other adverse events were comparable between the groups, except for diarrhea, which was more common in the DP4 group (P=.05 vs. the MAS3 group).
  
  
  CONCLUSIONS
  A once-daily, 3-dose regimen of DP is a highly efficacious treatment for multidrug-resistant falciparum malaria. This simple, safe, and relatively inexpensive fixed combination could become the treatment of choice for falciparum malaria.
authors: Shoklo Malaria Research Unit, Mae Sot, Thailand.
authors: Elizabeth A
authors: EA
authors: Ashley
authors: Rose
authors: R
authors: McGready
authors: Robert
authors: R
authors: Hutagalung
authors: Lucy
authors: L
authors: Phaiphun
authors: Thra
authors: T
authors: Slight
authors: Stephane
authors: S
authors: Proux
authors: Kyaw Lay
authors: KL
authors: Thwai
authors: Marion
authors: M
authors: Barends
authors: Sornchai
authors: S
authors: Looareesuwan
authors: Nicholas J
authors: NJ
authors: White
authors: Francois
authors: F
authors: Nosten
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage*; D037621:Artemisinins / Q000008:administration & dosage*; D000077332:Artesunate; D002648:Child; D002675:Child, Preschool; D004338:Drug Combinations; D018432:Drug Resistance, Multiple; D005260:Female; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000188:drug therapy*; D008297:Male; D015767:Mefloquine / Q000008:administration & dosage; D008875:Middle Aged; D010963:Plasmodium falciparum / Q000187:drug effects; D011804:Quinolines / Q000008:administration & dosage*; D012717:Sesquiterpenes / Q000008:administration & dosage*; D010879:Piperazines
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D000077332:Artesunate; D004338:Drug Combinations; D015767:Mefloquine; D011804:Quinolines; D012717:Sesquiterpenes; C039060:artenimol; C034759:piperaquine; D010879:Piperazines