title: Safety and efficacy of methylene blue combined with artesunate or amodiaquine for uncomplicated falciparum malaria: a randomized controlled trial from Burkina Faso.
abstract: BACKGROUND
  Besides existing artemisinin-based combination therapies, alternative safe, effective and affordable drug combinations against falciparum malaria are needed. Methylene blue (MB) was the first synthetic antimalarial drug ever used, and recent studies have been promising with regard to its revival in malaria therapy. The objective of this study was to assess the safety and efficacy of two MB-based malaria combination therapies, MB-artesunate (AS) and MB-amodiaquine (AQ), compared to the local standard of care, AS-AQ, in Burkina Faso.
  
  
  RESULTS
  Open-label randomised controlled phase II study in 180 children aged 6-10 years with uncomplicated falciparum malaria in Nouna, north-western Burkina Faso. Follow-up was for 28 days and analysis by intention-to-treat. The treatment groups were similar in baseline characteristics and there was only one loss to follow-up. No drug-related serious adverse events and no deaths occurred. MB-containing regimens were associated with mild vomiting and dysuria. No early treatment failures were observed. Parasite clearance time differed significantly among groups and was the shortest with MB-AS. By day 14, the rates of adequate clinical and parasitological response after PCR-based correction for recrudescence were 87% for MB-AS, 100% for MB-AQ (p = 0.004), and 100% for AS-AQ (p = 0.003). By day 28, the respective figure was lowest for MB-AS (62%), intermediate for the standard treatment AS-AQ (82%; p = 0.015), and highest for MB-AQ (95%; p<0.001; p = 0.03).
  
  
  CONCLUSIONS
  MB-AQ is a promising alternative drug combination against malaria in Africa. Moreover, MB has the potential to further accelerate the rapid parasite clearance of artemisinin-based combination therapies. More than a century after the antimalarial properties of MB had been described, its role in malaria control deserves closer attention.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00354380.
authors.affiliation: Centre de Recherche en Santé de Nouna, Nouna, Burkina Faso.
authors.forename: Augustin
authors.initials: A
authors.lastname: Zoungrana
authors.forename: Boubacar
authors.initials: B
authors.lastname: Coulibaly
authors.forename: Ali
authors.initials: A
authors.lastname: Sié
authors.forename: Ingeborg
authors.initials: I
authors.lastname: Walter-Sack
authors.forename: Frank P
authors.initials: FP
authors.lastname: Mockenhaupt
authors.forename: Bocar
authors.initials: B
authors.lastname: Kouyaté
authors.forename: R Heiner
authors.initials: RH
authors.lastname: Schirmer
authors.forename: Christina
authors.initials: C
authors.lastname: Klose
authors.forename: Ulrich
authors.initials: U
authors.lastname: Mansmann
authors.forename: Peter
authors.initials: P
authors.lastname: Meissner
authors.forename: Olaf
authors.initials: O
authors.lastname: Müller
mesh_terms: D000655:Amodiaquine / Q000008:administration & dosage*; D037621:Artemisinins / Q000008:administration & dosage*; D000077332:Artesunate; D002050:Burkina Faso; D004359:Drug Therapy, Combination; D064420:Drug-Related Side Effects and Adverse Reactions; D053159:Dysuria / Q000139:chemically induced; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy*; D008751:Methylene Blue / Q000008:administration & dosage*; D012717:Sesquiterpenes / Q000008:administration & dosage*; D016896:Treatment Outcome; D014839:Vomiting / Q000139:chemically induced
chemical_list: D037621:Artemisinins; D012717:Sesquiterpenes; D000655:Amodiaquine; D000077332:Artesunate; D008751:Methylene Blue