title: Efficacy and day 7 plasma piperaquine concentrations in African children treated for uncomplicated malaria with dihydroartemisinin-piperaquine.
abstract: BACKGROUND
  One promising new Artemisinin-based combination therapies (ACTs) is dihydroartemisinin-piperaquine (DHA-PQ). However, the pharmacokinetics of piperaquine and the relationship between drug levels and clinical efficacy are incompletely characterized, particularly in children.
  
  
  METHODS
  We performed a single-arm open-label trial in Bobo-Dioulasso, Burkina Faso. A total of 379 participants aged 6 months or more with uncomplicated falciparum malaria were enrolled. Each participant received daily dose of DHA-PQ for three days and followed for 42 days. Parasitological efficacy was analyzed, considering rates of recrudescence and overall recurrence. PK was an exploratory endpoint and a priori, no sample size had been determined. Day 7 capillary and venous plasma concentrations of piperaquine were measured in children aged 2-10 years.
  
  
  RESULTS
  Of the 379 participants, 365 (96.3%) completed 42 days of follow-up. The median daily dose of PQ was 18.5 mg/kg [6.5-24]. Treatment with DHA-PQ was well tolerated with fever and parasitemia resolution within 48 hours in nearly all children. Recurrent malaria within 42 days of follow-up occurred in 31.3% (10/34) of children less than 2 years old, 16.0% (16/106) of those aged 2-5 years, 9.4% (15/160) of those aged 5-10 years, and none (0/68) of those over 10 years old. After genotyping, 3 of 41 recurrent episodes were recrudescence. An exploratory analysis shows that children with successful treatment outcomes had significantly higher median plasma concentrations of PQ compared to those with recurrent malaria within 42 days after therapy, considering either capillary samples (68 ng/ml [50-85] compared to 48 ng/ml [36-55], p<0.001) or venous samples (42 ng/ml [29-59] compared to 25 ng/ml [19-44], p<0.001).
  
  
  CONCLUSIONS
  DHA-PQ was effective for uncomplicated P. falciparum malaria treatment and offers an alternative to other ACTs. Recurrent malaria was mainly due to new infections after treatment and was correlated with low day 7 PQ concentration in the youngest patients.
  
  
  BACKGROUND
  Controlled-Trials.com ISRCTN59761234.
authors.affiliation: Direction Régionale de l'Ouest, Institut de Recherche en Sciences de la Santé, Bobo-Dioulasso, Burkina Faso.
authors.forename: Issaka
authors.initials: I
authors.lastname: Zongo
authors.affiliation: Direction Régionale de l'Ouest, Institut de Recherche en Sciences de la Santé, Bobo-Dioulasso, Burkina Faso.
authors.forename: Fabrice A
authors.initials: FA
authors.lastname: Somé
authors.affiliation: Non Transmissible disease department, Centre Muraz Bobo-Dioulasso, Bobo-Dioulasso, Burkina Faso.
authors.forename: Serge A M
authors.initials: SA
authors.lastname: Somda
authors.affiliation: Department of Medicine, Yale University School of Public Health, New Haven, Connecticut, United States of America.
authors.forename: Sunil
authors.initials: S
authors.lastname: Parikh
authors.affiliation: Direction Régionale de l'Ouest, Institut de Recherche en Sciences de la Santé, Bobo-Dioulasso, Burkina Faso.
authors.forename: Noel
authors.initials: N
authors.lastname: Rouamba
authors.affiliation: Department of Medicine, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Rosenthal
authors.affiliation: Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom.
authors.forename: Joel
authors.initials: J
authors.lastname: Tarning
authors.affiliation: Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom.
authors.forename: Niklas
authors.initials: N
authors.lastname: Lindegardh
authors.affiliation: Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand; Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom.
authors.forename: François
authors.initials: F
authors.lastname: Nosten
authors.affiliation: Direction Régionale de l'Ouest, Institut de Recherche en Sciences de la Santé, Bobo-Dioulasso, Burkina Faso; Non Transmissible disease department, Centre Muraz Bobo-Dioulasso, Bobo-Dioulasso, Burkina Faso.
authors.forename: Jean Bosco
authors.initials: JB
authors.lastname: Ouédraogo
mesh_terms: D000962:Antimalarials / Q000008:administration & dosage* / Q000493:pharmacokinetics; D037621:Artemisinins / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002050:Burkina Faso; D002648:Child; D002675:Child, Preschool; D004334:Drug Administration Schedule; D004338:Drug Combinations; D005260:Female; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000469:parasitology; D008297:Male; D011804:Quinolines / Q000008:administration & dosage* / Q000493:pharmacokinetics; D017211:Treatment Failure; D010879:Piperazines
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D004338:Drug Combinations; D011804:Quinolines; C031327:artemisinin; C034759:piperaquine; D010879:Piperazines