Similar efficacy and tolerability of double-dose chloroquine and artemether-lumefantrine for treatment of Plasmodium falciparum infection in Guinea-Bissau: a randomized trial

J Infect Dis. 2011 Jan 1;203(1):109-16. doi: 10.1093/infdis/jiq001.

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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Amino Acid Substitution / genetics
  • Antimalarials / administration & dosage*
  • Antimalarials / adverse effects*
  • Antimalarials / pharmacokinetics
  • Artemether, Lumefantrine Drug Combination
  • Artemisinins / administration & dosage*
  • Artemisinins / adverse effects*
  • Artemisinins / pharmacokinetics
  • Blood Chemical Analysis
  • Child
  • Child, Preschool
  • Chloroquine / administration & dosage*
  • Chloroquine / adverse effects*
  • Chloroquine / pharmacokinetics
  • Chromatography, High Pressure Liquid
  • DNA, Protozoan / genetics
  • Drug Combinations
  • Ethanolamines / administration & dosage*
  • Ethanolamines / adverse effects*
  • Ethanolamines / pharmacokinetics
  • Female
  • Fluorenes / administration & dosage*
  • Fluorenes / adverse effects*
  • Fluorenes / pharmacokinetics
  • Guinea-Bissau
  • Humans
  • Infant
  • Malaria, Falciparum / drug therapy*
  • Male
  • Membrane Transport Proteins / genetics
  • Mutation, Missense
  • Plasmodium falciparum / drug effects
  • Plasmodium falciparum / genetics
  • Point Mutation
  • Polymerase Chain Reaction
  • Protozoan Proteins / genetics
  • Treatment Outcome

Substances

  • Antimalarials
  • Artemether, Lumefantrine Drug Combination
  • Artemisinins
  • DNA, Protozoan
  • Drug Combinations
  • Ethanolamines
  • Fluorenes
  • Membrane Transport Proteins
  • PfCRT protein, Plasmodium falciparum
  • Protozoan Proteins
  • Chloroquine

Associated data

  • ClinicalTrials.gov/NCT00426439