title: The effect of primaquine on gametocyte development and clearance in the treatment of uncomplicated falciparum malaria with dihydroartemisinin-piperaquine in South sumatra, Western indonesia: an open-label, randomized, controlled trial.
abstract: BACKGROUND
  Artemisinin-based combination therapy is very effective in clearing asexual stages of malaria and reduces gametocytemia, but may not affect mature gametocytes. Primaquine is the only commercially available drug that eliminates mature gametocytes.
  
  
  METHODS
  We conducted a 2-arm, open-label, randomized, controlled trial to evaluate the efficacy of single-dose primaquine (0.75 mg/kg) following treatment with dihydroartemisinin-piperaquine (DHP) on Plasmodium falciparum gametocytemia, in Indonesia. Patients aged ≥5 years with uncomplicated falciparum malaria, normal glucose-6-phosphate dehydrogenase enzyme levels, and hemoglobin levels ≥8 g/dL were assigned by computerized-generating sequence to a standard 3-day course of DHP alone (n = 178) or DHP combined with a single dose of primaquine on day 3 (n = 171). Patients were seen on days 1, 2, 3, and 7 and then weekly for 42 days to assess the presence of gametocytes and asexual parasites by microscopy. Survival analysis was stratified by the presence of gametocytes on day 3.
  
  
  RESULTS
  DHP prevented development of gametocytes in 277 patients without gametocytes on day 3. In the gametocytemic patients (n = 72), primaquine was associated with faster gametocyte clearance (hazard ratio = 2.42 [95% confidence interval, 1.39-4.19], P = .002) and reduced gametocyte densities (P = .018). The day 42 cure rate of asexual stages in the DHP + primaquine and DHP-only arms were: polymerase chain reaction (PCR) unadjusted, 98.7% vs 99.4%, respectively; PCR adjusted, 100% for both. Primaquine was well tolerated.
  
  
  CONCLUSIONS
  Addition of single-dose 0.75 mg/kg primaquine shortens the infectivity period of DHP-treated patients and should be considered in low-transmission regions that aim to control and ultimately eliminate falciparum malaria. Clinical Trials Registration. NCT01392014.
authors.affiliation: Department of Parasitology, Faculty of Medicine, University of Indonesia, 6 Salemba Raya, Jakarta 10430, Indonesia. sutanto.inge@yahoo.com
authors.forename: Inge
authors.initials: I
authors.lastname: Sutanto
authors.forename: Sri
authors.initials: S
authors.lastname: Suprijanto
authors.forename: Ayleen
authors.initials: A
authors.lastname: Kosasih
authors.forename: Muhamad S
authors.initials: MS
authors.lastname: Dahlan
authors.forename: Din
authors.initials: D
authors.lastname: Syafruddin
authors.forename: Rita
authors.initials: R
authors.lastname: Kusriastuti
authors.forename: William A
authors.initials: WA
authors.lastname: Hawley
authors.forename: Neil F
authors.initials: NF
authors.lastname: Lobo
authors.forename: Feiko O
authors.initials: FO
authors.lastname: Ter Kuile
mesh_terms: D000293:Adolescent; D000328:Adult; D000962:Antimalarials / Q000627:therapeutic use*; D037621:Artemisinins / Q000627:therapeutic use*; D002648:Child; D004359:Drug Therapy, Combination; D005260:Female; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D006801:Humans; D007214:Indonesia; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000469:parasitology / Q000517:prevention & control; D008297:Male; D018512:Parasitemia / Q000188:drug therapy; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000254:growth & development; D011804:Quinolines / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult; D010879:Piperazines
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D005954:Glucosephosphate Dehydrogenase; D011804:Quinolines; C039060:artenimol; C034759:piperaquine; D010879:Piperazines