title: Efficacy and safety of triple combination therapy with artesunate-amodiaquine-methylene blue for falciparum malaria in children: a randomized controlled trial in Burkina Faso.
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.
authors.affiliation: Centre de Recherche en Santé de Nouna, Nouna.
authors.forename: Boubacar
authors.initials: B
authors.lastname: Coulibaly
authors.affiliation: Division of Infectious Diseases and Tropical Medicine, Medical Center Department of Bacteriology, Max von Pettenkofer-Institute, Ludwig Maximilian University of Munich German Center for Infection Research, Partner Site Munich.
authors.forename: Michael
authors.initials: M
authors.lastname: Pritsch
authors.affiliation: Centre de Recherche en Santé de Nouna, Nouna.
authors.forename: Mamadou
authors.initials: M
authors.lastname: Bountogo
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Medical School, Ulm University.
authors.forename: Peter E
authors.initials: PE
authors.lastname: Meissner
authors.affiliation: Centre de Recherche en Santé de Nouna, Nouna.
authors.forename: Eric
authors.initials: E
authors.lastname: Nebié
authors.affiliation: Institute of Medical Biometry and Informatics.
authors.forename: Christina
authors.initials: C
authors.lastname: Klose
authors.affiliation: Institute of Medical Biometry and Informatics.
authors.forename: Meinhard
authors.initials: M
authors.lastname: Kieser
authors.affiliation: Division of Infectious Diseases and Tropical Medicine, Medical Center.
authors.forename: Nicole
authors.initials: N
authors.lastname: Berens-Riha
authors.affiliation: Division of Infectious Diseases and Tropical Medicine, Medical Center Department of Bacteriology, Max von Pettenkofer-Institute, Ludwig Maximilian University of Munich German Center for Infection Research, Partner Site Munich.
authors.forename: Andreas
authors.initials: A
authors.lastname: Wieser
authors.affiliation: Centre de Recherche et de la Formation au Paludisme, Ouagadougou, Burkina Faso.
authors.forename: Sodiomon B
authors.initials: SB
authors.lastname: Sirima
authors.affiliation: Institute of Pharmaceutics and Biopharmaceutics, Heinrich Heine University Düsseldorf.
authors.forename: Jörg
authors.initials: J
authors.lastname: Breitkreutz
authors.affiliation: Biochemistry Centre, Ruprecht-Karls-University, Heidelberg.
authors.forename: R Heiner
authors.initials: RH
authors.lastname: Schirmer
authors.affiliation: Centre de Recherche en Santé de Nouna, Nouna.
authors.forename: Ali
authors.initials: A
authors.lastname: Sié
authors.affiliation: Institute of Tropical Medicine and International Health, Charité-Universitätsmedizin Berlin, Germany.
authors.forename: Frank P
authors.initials: FP
authors.lastname: Mockenhaupt
authors.affiliation: Department of Immunology & Infection, London School of Tropical Medicine and Hygiene, United Kingdom.
authors.forename: Chris
authors.initials: C
authors.lastname: Drakeley
authors.affiliation: Department of Immunology & Infection, London School of Tropical Medicine and Hygiene, United Kingdom Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Teun
authors.initials: T
authors.lastname: Bousema
authors.affiliation: Institute of Public Health, Medical School.
authors.forename: Olaf
authors.initials: O
authors.lastname: Müller
mesh_terms: D000655:Amodiaquine / Q000009:adverse effects / Q000627:therapeutic use*; D000962:Antimalarials / Q000009:adverse effects / Q000627:therapeutic use*; D037621:Artemisinins / Q000009:adverse effects / Q000627:therapeutic use*; D000077332:Artesunate; D002050:Burkina Faso; D002675:Child, Preschool; D004359:Drug Therapy, Combination / Q000379:methods; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000473:pathology; D005260:Female; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000188:drug therapy*; D008297:Male; D008751:Methylene Blue / Q000009:adverse effects / Q000627:therapeutic use*; D008853:Microscopy; D010963:Plasmodium falciparum / Q000302:isolation & purification; D016133:Polymerase Chain Reaction; D016896:Treatment Outcome
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D000655:Amodiaquine; D000077332:Artesunate; D008751:Methylene Blue
keywords: Africa; gametocytes; malaria; methylene blue