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

Boubacar Coulibaly, Michael Pritsch, Mamadou Bountogo, Peter E Meissner, Eric Nebié, Christina Klose, Meinhard Kieser, Nicole Berens-Riha, Andreas Wieser, Sodiomon B Sirima, Jörg Breitkreutz, R Heiner Schirmer, Ali Sié, Frank P Mockenhaupt, Chris Drakeley, Teun Bousema, Olaf Müller

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
JournalJournal of Infectious Diseases
Issue number5
Pages (from-to)689-97
Number of pages9
Publication statusPublished - 2015


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

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