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.