Efficacy and safety of triple combination therapy with artesunate-amodiaquine-methylene blue for falciparum malaria in children: a randomized controlled trial in Burkina Faso

J Infect Dis. 2015 Mar 1;211(5):689-97. doi: 10.1093/infdis/jiu540. Epub 2014 Sep 28.

Abstract

Background: Methylene blue (MB) has been shown to be safe and effective against falciparum malaria in Africa and to have pronounced gametocytocidal properties.

Methods: Three days of treatment with artesunate (AS)-amodiaquine (AQ) combined with MB was compared with AS-AQ treatment in a randomized controlled phase IIb study; the study included 221 children aged 6-59 months with uncomplicated falciparum malaria in Burkina Faso. The primary end point was gametocyte prevalence during follow-up, as determined by microscopy and real-time quantitative nucleic acid sequence-based amplification (QT-NASBA).

Results: The gametocyte prevalence of Plasmodium falciparum at baseline was 3.6% (microscopy) and 97% (QT-NASBA). It was significantly lower in the AS-AQ-MB than in the AS-AQ group on day 7 of follow-up (microscopy, 1.2% vs 8.9% [P < .05]; QT-NASBA, 36.7% vs 63.3% [P < .001]). Hemoglobin values were significantly lower in the AS-AQ-MB group than in the AS-AQ group at days 2 and 7 of follow-up. Vomiting of the study medication occurred significantly more frequently in the AS-AQ-MB group.

Conclusions: The combination of MB with an artemisinin-based combination therapy has been confirmed to be effective against the gametocytes of P. falciparum. MB-based combinations need to be compared with primaquine-based combinations, preferably using MB in an improved pediatric formulation. Clinical Trials Registration: NCT01407887.

Keywords: Africa; gametocytes; malaria; methylene blue.

Publication types

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

MeSH terms

  • Amodiaquine / adverse effects
  • Amodiaquine / therapeutic use*
  • Antimalarials / adverse effects
  • Antimalarials / therapeutic use*
  • Artemisinins / adverse effects
  • Artemisinins / therapeutic use*
  • Artesunate
  • Burkina Faso
  • Child, Preschool
  • Drug Therapy, Combination / methods
  • Drug-Related Side Effects and Adverse Reactions / epidemiology
  • Drug-Related Side Effects and Adverse Reactions / pathology
  • Female
  • Humans
  • Infant
  • Malaria, Falciparum / drug therapy*
  • Male
  • Methylene Blue / adverse effects
  • Methylene Blue / therapeutic use*
  • Microscopy
  • Plasmodium falciparum / isolation & purification
  • Polymerase Chain Reaction
  • Treatment Outcome

Substances

  • Antimalarials
  • Artemisinins
  • Amodiaquine
  • Artesunate
  • Methylene Blue

Associated data

  • ClinicalTrials.gov/NCT01407887