title: Piperaquine Monotherapy of Drug-Susceptible Plasmodium falciparum Infection Results in Rapid Clearance of Parasitemia but Is Followed by the Appearance of Gametocytemia.
abstract: BACKGROUND
  Piperaquine, coformulated with dihydroartemisinin, is a component of a widely used artemisinin combination therapy. There is a paucity of data on its antimalarial activity as a single agent. Such data, if available, would inform selection of new coformulations.
  
  
  METHODS
  We undertook a study in healthy subjects, using the induced blood stage malaria (IBSM) model to test the antimalarial activity of single doses of piperaquine (960, 640, and 480 mg) in 3 cohorts. In a pilot study in the third cohort, gametocyte clearance following administration of 15 mg, or 45 mg or no primaquine was investigated.
  
  
  RESULTS
  Parasite clearance over the 48-hour period after piperaquine administration was more rapid in the 960 mg cohort, compared with the 640 mg cohort (parasite reduction ratio, 2951 [95% confidence interval {CI}, 1520-5728] vs 586 [95% CI, 351-978]; P < .001). All 24 subjects developed gametocytemia as determined by pfs25 transcripts. Clearance of pfs25 was significantly faster in those receiving primaquine than in those not receiving primaquine (P < .001).
  
  
  CONCLUSIONS
  Piperaquine possesses rapid parasite-clearing activity, but monotherapy is followed by the appearance of gametocytemia, which could facilitate the spread of malaria. This new information should be taken into account when developing future antimalarial coformulations.
  
  
  BACKGROUND
  ACTRN12613000565741.
authors.affiliation: QIMR Berghofer Medical Research Institute.
authors.forename: Cielo J
authors.initials: CJ
authors.lastname: Pasay
authors.affiliation: School of Chemistry and Molecular Biosciences Queensland Pediatric Infectious Diseases Laboratory.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Rockett
authors.affiliation: QIMR Berghofer Medical Research Institute.
authors.forename: Silvana
authors.initials: S
authors.lastname: Sekuloski
authors.affiliation: QIMR Berghofer Medical Research Institute School of Medicine, University of Queensland Q-Pharm Department of Infectious Diseases, Mater Health Services and Mater Research Institute.
authors.forename: Paul
authors.initials: P
authors.lastname: Griffin
authors.affiliation: QIMR Berghofer Medical Research Institute.
authors.forename: Louise
authors.initials: L
authors.lastname: Marquart
authors.affiliation: Australian Army Malaria Institute, Brisbane.
authors.forename: Christopher
authors.initials: C
authors.lastname: Peatey
authors.affiliation: Queensland Pediatric Infectious Diseases Laboratory.
authors.forename: Claire Y T
authors.initials: CY
authors.lastname: Wang
authors.affiliation: QIMR Berghofer Medical Research Institute.
authors.forename: Peter
authors.initials: P
authors.lastname: O'Rourke
authors.affiliation: Q-Pharm.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Elliott
authors.affiliation: Medicaments pour Tous, Rolle.
authors.forename: Mark
authors.initials: M
authors.lastname: Baker
authors.affiliation: Medicines for Malaria Venture, Geneva, Switzerland.
authors.forename: Jörg J
authors.initials: JJ
authors.lastname: Möhrle
authors.affiliation: QIMR Berghofer Medical Research Institute School of Medicine, University of Queensland Q-Pharm.
authors.forename: James S
authors.initials: JS
authors.lastname: McCarthy
mesh_terms: D000293:Adolescent; D000328:Adult; D000962:Antimalarials / Q000009:adverse effects* / Q000627:therapeutic use*; D001315:Australia; D015331:Cohort Studies; D005260:Female; D005718:Gametogenesis / Q000187:drug effects*; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D018512:Parasitemia / Q000188:drug therapy*; D010865:Pilot Projects; D010963:Plasmodium falciparum / Q000187:drug effects / Q000302:isolation & purification*; D011804:Quinolines / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D000962:Antimalarials; D011804:Quinolines
keywords: P. falciparum; gametocytemia; malaria; piperaquine clinical trial