title: Safety and efficacy of dihydroartemisinin-piperaquine versus artemether-lumefantrine in the treatment of uncomplicated Plasmodium falciparum malaria in Zambian children.
abstract: BACKGROUND
  Malaria in Zambia remains a public health and developmental challenge, affecting mostly children under five and pregnant women. In 2002, the first-line treatment for uncomplicated malaria was changed to artemether-lumefantrine (AL) that has proved to be highly efficacious against multidrug resistant Plasmodium falciparum.
  
  
  OBJECTIVE
  The study objective was to determine whether dihydroartemisinin-piperaquine (DHA/PQP) had similar efficacy, safety and tolerability as AL for the treatment of children with uncomplicated P. falciparum malaria in Ndola, Zambia.
  
  
  METHODS
  Between 2005 and 2006, 304 children (6-59 months old) with uncomplicated P. falciparum were enrolled, randomized to AL (101) or DHA/PQP (203) and followed up for 42 days. Outcome of treatment was defined according to the standard WHO classification, i.e. early treatment failure (ETF), late clinical failure (LCF, late parasitological failure (LPF) and adequate clinical and parasitological response (ACPR). Recurrent infections were genotyped to distinguish between recrudescence and new infection.
  
  
  RESULTS
  No ETF was observed. At day 28, PCR-uncorrected ACPR was 92% in the DHA/PQP and 74% in the AL arm (OR: 4.05; 95%CI: 1.89-8.74; p < 0.001). Most failure were new infections and PCR-corrected ACPR was similar in the two study arms (OR: 0.69; 95%CI: 0.22-2.26; p = 0.33). Similar results were observed for day 42, i.e. higher PCR-uncorrected ACPR for DHA/PQP, mainly due to the difference observed up to day 28, while the PCR-corrected ACPR was similar: DHA/PQP: 93% (179/192), AL: 93% (84/90), (OR: 0.92; 95%CI: 0.30-2.64; p = 0.85). Except for cough, more frequent in the DHA/PQP arm (p = 0.04), there were no differences between treatment arms in the occurrence of adverse events. Two serious adverse events were probably associated to AL treatment.
  
  
  CONCLUSIONS
  DHA/PQP was as efficacious, safe and well tolerated in treatment of uncomplicated malaria as AL, though in the latter group more new infections during the follow up were observed. DHA/PQP seems a potential candidate to be used as an alternative first-line or rescue treatment in Zambia.
  
  
  BACKGROUND
  ISRCTN16263443, at http://www.controlled-trials.com/isrctn.
authors.affiliation: Department of Clinical Sciences, Tropical Disease Research Center, P,O Box 71769, Ndola Zambia. michaelnambozi@yahoo.com
authors.forename: Michael
authors.initials: M
authors.lastname: Nambozi
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Van Geertruyden
authors.forename: Sebastian
authors.initials: S
authors.lastname: Hachizovu
authors.forename: Mike
authors.initials: M
authors.lastname: Chaponda
authors.forename: Doreen
authors.initials: D
authors.lastname: Mukwamataba
authors.forename: Modest
authors.initials: M
authors.lastname: Mulenga
authors.forename: David
authors.initials: D
authors.lastname: Ubben
authors.forename: Umberto
authors.initials: U
authors.lastname: D'Alessandro
mesh_terms: D000962:Antimalarials / Q000008:administration & dosage / Q000009:adverse effects; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins / Q000008:administration & dosage* / Q000009:adverse effects*; D002675:Child, Preschool; D004338:Drug Combinations; D004983:Ethanolamines / Q000008:administration & dosage* / Q000009:adverse effects*; D005449:Fluorenes / Q000008:administration & dosage* / Q000009:adverse effects*; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000188:drug therapy*; D010963:Plasmodium falciparum / Q000302:isolation & purification; D011804:Quinolines / Q000008:administration & dosage* / Q000009:adverse effects*; D016896:Treatment Outcome; D015024:Zambia; D010879:Piperazines
chemical_list: D000962:Antimalarials; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins; D004338:Drug Combinations; D004983:Ethanolamines; D005449:Fluorenes; D011804:Quinolines; C039060:artenimol; C034759:piperaquine; D010879:Piperazines