title: Methylene blue for malaria in Africa: results from a dose-finding study in combination with chloroquine.
abstract: The development of safe, effective and affordable drug combinations against malaria in Africa is a public health priority. Methylene blue (MB) has a similar mode of action as chloroquine (CQ) and has moreover been shown to selectively inhibit the Plasmodium falciparum glutathione reductase. In 2004, an uncontrolled dose-finding study on the combination MB-CQ was performed in 435 young children with uncomplicated falciparum malaria in Burkina Faso (CQ monotherapy had a > 50% clinical failure rate in this area in 2003). Three serious adverse events (SAE) occurred of which one was probably attributable to the study medication. In the per protocol safety analysis, there were no dose specific effects. The overall clinical and parasitological failure rates by day 14 were 10% [95% CI (7.5%, 14.0%)] and 24% [95% CI (19.4%, 28.3%)], respectively. MB appears to have efficacy against malaria, but the combination of CQ-MB is clearly not effective in the treatment of malaria in Africa.
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: Boubacar
authors.initials: B
authors.lastname: Coulibaly
authors.forename: Steffen
authors.initials: S
authors.lastname: Witte
authors.forename: Théophile
authors.initials: T
authors.lastname: Tapsoba
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: 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: R Heiner
authors.initials: RH
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 / Q000453:epidemiology; D002675:Child, Preschool; D002738:Chloroquine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000453:epidemiology; D008297:Male; D008751:Methylene Blue / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D011897:Random Allocation; D017211:Treatment Failure
chemical_list: D002738:Chloroquine; D008751:Methylene Blue