title: Safety of the methylene blue plus chloroquine combination in the treatment of uncomplicated falciparum malaria in young children of Burkina Faso [ISRCTN27290841].
abstract: BACKGROUND
  Safe, effective and affordable drug combinations against falciparum malaria are urgently needed for the poor populations in malaria endemic countries. Methylene blue (MB) combined with chloroquine (CQ) has been considered as one promising new regimen.
  
  
  OBJECTIVE
  The primary objective of this study was to evaluate the safety of CQ-MB in African children with uncomplicated falciparum malaria. Secondary objectives were to assess the efficacy and the acceptance of CQ-MB in a rural population of West Africa.
  
  
  METHODS
  In this hospital-based randomized controlled trial, 226 children (6-59 months) with uncomplicated falciparum malaria were treated in Burkina Faso. The children were 4:1 randomized to CQ-MB (n = 181; 25 mg/kg CQ and 12 mg/kg MB over three days) or CQ (n = 45; 25 mg/kg over three days) respectively. The primary outcome was the incidence of severe haemolysis or other serious adverse events (SAEs). Efficacy outcomes were defined according to the WHO 2003 classification system. Patients were hospitalized for four days and followed up until day 14.
  
  
  RESULTS
  No differences in the incidence of SAEs and other adverse events were observed between children treated with CQ-MB (including 24 cases of G6PD deficiency) compared to children treated with CQ. There was no case of severe haemolysis and also no significant difference in mean haemoglobin between study groups. Treatment failure rates were 53.7% (95% CI [37.4%; 69.3%]) in the CQ group compared to 44.0% (95% CI [36.3%; 51.9%]) in the CQ-MB group.
  
  
  CONCLUSIONS
  MB is safe for the treatment of uncomplicated falciparum malaria, even in G6PD deficient African children. However, the efficacy of the CQ-MB combination has not been sufficient at the MB dose used in this study. Future studies need to assess the efficacy of MB at higher doses and in combination with appropriate partner drugs.
authors.affiliation: Department of Tropical Hygiene and Public Health, Ruprecht-Karls-University, INF 324, 69120 Heidelberg, Germany. peter.meissner@urz.uni-heidelberg.de
authors.forename: Peter E
authors.initials: PE
authors.lastname: Meissner
authors.forename: Germain
authors.initials: G
authors.lastname: Mandi
authors.forename: Steffen
authors.initials: S
authors.lastname: Witte
authors.forename: Boubacar
authors.initials: B
authors.lastname: Coulibaly
authors.forename: Ulrich
authors.initials: U
authors.lastname: Mansmann
authors.forename: Jens
authors.initials: J
authors.lastname: Rengelshausen
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Schiek
authors.forename: Albrecht
authors.initials: A
authors.lastname: Jahn
authors.forename: Mamadou
authors.initials: M
authors.lastname: Sanon
authors.forename: Théophile
authors.initials: T
authors.lastname: Tapsoba
authors.forename: Ingeborg
authors.initials: I
authors.lastname: Walter-Sack
authors.forename: Gerd
authors.initials: G
authors.lastname: Mikus
authors.forename: Jürgen
authors.initials: J
authors.lastname: Burhenne
authors.forename: Klaus-Dieter
authors.initials: KD
authors.lastname: Riedel
authors.forename: Heiner
authors.initials: H
authors.lastname: Schirmer
authors.forename: Bocar
authors.initials: B
authors.lastname: Kouyaté
authors.forename: Olaf
authors.initials: O
authors.lastname: Müller
mesh_terms: D002050:Burkina Faso; D002675:Child, Preschool; D002738:Chloroquine / Q000009:adverse effects* / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005953:Glycogen Storage Disease Type I; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000188:drug therapy*; D008751:Methylene Blue / Q000009:adverse effects* / Q000627:therapeutic use*
chemical_list: D002738:Chloroquine; D008751:Methylene Blue