title: Dihydroartemisinin-piperaquine versus chloroquine to treat vivax malaria in Afghanistan: an open randomized, non-inferiority, trial.
abstract: BACKGROUND
  Afghanistan's national guidelines recommend chloroquine for the treatment of Plasmodium vivax infection, the parasite responsible for the majority of its malaria burden. Chloroquine resistance in P. vivax is emerging in Asia. Therapeutic responses across Afghanistan have not been evaluated in detail.
  
  
  METHODS
  Between July 2007 and February 2009, an open-label, randomized controlled trial of chloroquine and dihydroartemisinin-piperaquine in patients aged three months and over with slide-confirmed P. vivax mono-infections was conducted. Consistent with current national guidelines, primaquine was not administered. Subjects were followed up daily during the acute phase of illness (days 0-3) and weekly until day 56. The primary endpoint was the overall cumulative parasitological failure rate at day 56 after the start of treatment, with the hypothesis being that dihydroartemisinin-piperaquine was non-inferior compared to chloroquine (Delta = 5% difference in proportion of failures).
  
  
  RESULTS
  Of 2,182 individuals with positive blood films for P. vivax, 536 were enrolled in the trial. The day 28 cure rate was 100% in both treatment groups. Parasite clearance was more rapid with dihydroartemisinin-piperaquine than chloroquine. At day 56, there were more recurrent infections in the chloroquine arm (8.9%, 95% CI 6.0-13.1%) than the dihydroartemisinin-piperaquine arm (2.8%, 95% CI 1.4-5.8%), a difference in cumulative recurrence rate of 6.1% (2-sided 90%CI +2.6 to +9.7%). The log-rank test comparing the survival curves confirmed the superiority of dihydroartemisinin-piperaquine over chloroquine (p = 0.003). Multivariate analysis showed that a lower initial haemoglobin concentration was also independently associated with recurrence. Both regimens were well tolerated and no serious adverse events were reported.
  
  
  CONCLUSIONS
  Chloroquine remains an efficacious treatment for the treatment of vivax malaria in Afghanistan. In a setting where radical therapy cannot be administered, dihydroartemisinin-piperaquine provides additional benefit in terms of post-treatment prophylaxis, reducing the incidence of recurrence from 4-8 weeks after treatment.
authors.affiliation: Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
authors.forename: Ghulam Rahim
authors.initials: GR
authors.lastname: Awab
authors.forename: Sasithon
authors.initials: S
authors.lastname: Pukrittayakamee
authors.forename: Mallika
authors.initials: M
authors.lastname: Imwong
authors.forename: Arjen M
authors.initials: AM
authors.lastname: Dondorp
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Woodrow
authors.forename: Sue Jean
authors.initials: SJ
authors.lastname: Lee
authors.forename: Nicholas P J
authors.initials: NP
authors.lastname: Day
authors.forename: Pratap
authors.initials: P
authors.lastname: Singhasivanon
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: White
authors.forename: Faizullah
authors.initials: F
authors.lastname: Kaker
mesh_terms: D000293:Adolescent; D000346:Afghanistan; D000962:Antimalarials / Q000627:therapeutic use*; D037621:Artemisinins / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D002738:Chloroquine / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D016780:Malaria, Vivax / Q000188:drug therapy* / Q000469:parasitology; D008297:Male; D015999:Multivariate Analysis; D010966:Plasmodium vivax / Q000187:drug effects* / Q000302:isolation & purification; D011446:Prospective Studies; D011804:Quinolines / Q000627:therapeutic use*; D012008:Recurrence; D016896:Treatment Outcome; D010879:Piperazines
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D002738:Chloroquine; D011804:Quinolines; C039060:artenimol; C034759:piperaquine; D010879:Piperazines
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