title: Similar efficacy and tolerability of double-dose chloroquine and artemether-lumefantrine for treatment of Plasmodium falciparum infection in Guinea-Bissau: a randomized trial.
abstract: BACKGROUND
  In 2008, Guinea-Bissau introduced artemether-lumefantrine for treatment of uncomplicated malaria. Previously, 3 times the standard dose of chloroquine, that was probably efficacious against Plasmodium falciparum with the resistance-associated chloroquine-resistance transporter (pfcrt) 76T allele, was routinely used. The present study compared the efficacy and tolerability of a double standard dose of chloroquine with the efficacy and tolerability of artemether-lumefantrine.
  
  
  METHODS
  In a randomized open-label clinical trial, artemether-lumefantrine or chloroquine (50 mg/kg) were given as 6 divided doses over 3 days to children aged 6 months--15 years who had uncomplicated P. falciparum monoinfection. Drug concentrations were measured on day 7. P. falciparum multidrug resistance gene N86Y and pfcrt K76T alleles were identified.
  
  
  RESULTS
  The polymerase chain reaction-adjusted day 28 and 42 treatment efficacies were 162 (97%) of 168 and 155 (97%) of 161, respectively, for artemether-lumefantrine and 150 (95%) of 158 and 138 (94%) of 148, respectively, for chloroquine. When parasites with resistance-associated pfcrt 76T were treated, the day 28 efficacy of chloroquine was 87%. No severe drug-related adverse events were detected. Symptom resolution was similar with both treatments.
  
  
  CONCLUSIONS
  Both treatments achieved the World Health Organization-recommended efficacy for antimalarials that will be adopted as policy. High-dose chloroquine treatment regimes should be further evaluated with the aim of assessing chloroquine as a potential partner drug to artemisinin derivatives. Clinical trials registration. NCT00426439.
authors.affiliation: Projecto de Saúde de Bandim, Indepth Network, Bissau, Guinea-Bissau.
authors.forename: Johan
authors.initials: J
authors.lastname: Ursing
authors.forename: Poul-Erik
authors.initials: PE
authors.lastname: Kofoed
authors.forename: Amabelia
authors.initials: A
authors.lastname: Rodrigues
authors.forename: Daniel
authors.initials: D
authors.lastname: Blessborn
authors.forename: Rikke
authors.initials: R
authors.lastname: Thoft-Nielsen
authors.forename: Anders
authors.initials: A
authors.lastname: Björkman
authors.forename: Lars
authors.initials: L
authors.lastname: Rombo
mesh_terms: D000293:Adolescent; D019943:Amino Acid Substitution / Q000235:genetics; D000962:Antimalarials / Q000008:administration & dosage* / Q000009:adverse effects* / Q000493:pharmacokinetics; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins / Q000008:administration & dosage* / Q000009:adverse effects* / Q000493:pharmacokinetics; D001774:Blood Chemical Analysis; D002648:Child; D002675:Child, Preschool; D002738:Chloroquine / Q000008:administration & dosage* / Q000009:adverse effects* / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid; D016054:DNA, Protozoan / Q000235:genetics; D004338:Drug Combinations; D004983:Ethanolamines / Q000008:administration & dosage* / Q000009:adverse effects* / Q000493:pharmacokinetics; D005260:Female; D005449:Fluorenes / Q000008:administration & dosage* / Q000009:adverse effects* / Q000493:pharmacokinetics; D006169:Guinea-Bissau; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000188:drug therapy*; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics; D020125:Mutation, Missense; D010963:Plasmodium falciparum / Q000187:drug effects / Q000235:genetics; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D015800:Protozoan Proteins / Q000235:genetics; D016896:Treatment Outcome
chemical_list: D000962:Antimalarials; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins; D016054:DNA, Protozoan; D004338:Drug Combinations; D004983:Ethanolamines; D005449:Fluorenes; D026901:Membrane Transport Proteins; C416369:PfCRT protein, Plasmodium falciparum; D015800:Protozoan Proteins; D002738:Chloroquine