Methylene blue for malaria in Africa: results from a dose-finding study in combination with chloroquine.
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.
Meissner
Peter E
PE
Department of Tropical Hygiene and Public Health, Ruprecht-Karls-University, INF 324, 69120 Heidelberg, Germany. peter.meissner@urz.uni-heidelberg.de
Mandi
Germain
G
Coulibaly
Boubacar
B
Witte
Steffen
S
Tapsoba
Théophile
T
Mansmann
Ulrich
U
Rengelshausen
Jens
J
Schiek
Wolfgang
W
Jahn
Albrecht
A
Walter-Sack
Ingeborg
I
Mikus
Gerd
G
Burhenne
Jürgen
J
Riedel
Klaus-Dieter
KD
Schirmer
R Heiner
RH
Kouyaté
Bocar
B
Müller
Olaf
O
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
D002738:Chloroquine; D008751:Methylene Blue