Safety of the methylene blue plus chloroquine combination in the treatment of uncomplicated falciparum malaria in young children of Burkina Faso [ISRCTN27290841]

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. Objectives: 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.
Conclusion: 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.