Two fixed-dose artemisinin combinations for drug-resistant falciparum and vivax malaria in Papua, Indonesia: an open-label randomised comparison

Lancet. 2007 Mar 3;369(9563):757-765. doi: 10.1016/S0140-6736(07)60160-3.

Abstract

Background: The burden of Plasmodium vivax infections has been underappreciated, especially in southeast Asia where chloroquine resistant strains have emerged. Our aim was to compare the safety and efficacy of dihydroartemisinin-piperaquine with that of artemether-lumefantrine in patients with uncomplicated malaria caused by multidrug-resistant P falciparum and P vivax.

Methods: 774 patients in southern Papua, Indonesia, with slide-confirmed malaria were randomly assigned to receive either artemether-lumefantrine or dihydroartemisinin-piperaquine and followed up for at least 42 days. The primary endpoint was the overall cumulative risk of parasitological failure at day 42 with a modified intention-to-treat analysis. This trial is registered with ClinicalTrials.gov, trial number 00157833.

Findings: Of the 754 evaluable patients enrolled, 466 had infections with P falciparum, 175 with P vivax, and 113 with a mixture of both species. The overall risk of failure at day 42 was 43% (95% CI 38-48) for artemether-lumefantrine and 19% (14-23) for dihydroartemisinin-piperaquine (hazard ratio=3.0, 95% CI 2.2-4.1, p<0.0001). After correcting for reinfections, the risk of recrudescence of P falciparum was 4.4% (2.6-6.2) with no difference between regimens. Recurrence of vivax occurred in 38% (33-44) of patients given artemether-lumefantrine compared with 10% (6.9-14.0) given dihydroartemisinin-piperaquine (p<0.0001). At the end of the study, patients receiving dihydroartemisinin-piperaquine were 2.0 times (1.2-3.6) less likely to be anaemic and 6.6 times (2.8-16) less likely to carry vivax gametocytes than were those given artemether-lumefantrine.

Interpretation: Both dihydroartemisinin-piperaquine and artemether-lumefantrine were safe and effective for the treatment of multidrug-resistant uncomplicated malaria. However, dihydroartemisinin-piperaquine provided greater post-treatment prophylaxis than did artemether-lumefantrine, reducing P falciparum reinfections and P vivax recurrences, the clinical public-health importance of which should not be ignored.

Trial registration: ClinicalTrials.gov NCT00157833.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Anemia / etiology
  • Antimalarials / administration & dosage*
  • Antimalarials / adverse effects
  • Artemether, Lumefantrine Drug Combination
  • Artemisinins / administration & dosage*
  • Artemisinins / adverse effects
  • Artemisinins / therapeutic use*
  • Child
  • Child, Preschool
  • Diarrhea / chemically induced
  • Drug Administration Schedule
  • Drug Combinations
  • Drug Resistance, Multiple / drug effects
  • Ethanolamines / therapeutic use*
  • Female
  • Fluorenes / therapeutic use*
  • Humans
  • Indonesia
  • Infant
  • Malaria, Falciparum / complications
  • Malaria, Falciparum / drug therapy*
  • Malaria, Vivax / complications
  • Malaria, Vivax / drug therapy*
  • Male
  • Middle Aged
  • Prospective Studies
  • Quinolines / administration & dosage*
  • Quinolines / adverse effects
  • Recurrence
  • Sesquiterpenes / administration & dosage*
  • Sesquiterpenes / adverse effects
  • Treatment Outcome
  • Urticaria / chemically induced
  • Vomiting / chemically induced

Substances

  • Antimalarials
  • Artemether, Lumefantrine Drug Combination
  • Artemisinins
  • Drug Combinations
  • Ethanolamines
  • Fluorenes
  • Quinolines
  • Sesquiterpenes
  • dihydroartemisinin
  • piperaquine

Associated data

  • ClinicalTrials.gov/NCT00157833