Safety and efficacy of methylene blue combined with artesunate or amodiaquine for uncomplicated falciparum malaria

Besides existing artemisinin-based combination therapies,
alternative safe, effective and affordable drug combinations
against falciparum malaria are needed. Methylene blue (MB) was the
first synthetic antimalarial drug ever used, and recent studies
have been promising with regard to its revival in malaria therapy.
The objective of this study was to assess the safety and efficacy
of two MB-based malaria combination therapies, MB-artesunate (AS)
and MB-amodiaquine (AQ), compared to the local standard of care,
AS-AQ, in Burkina Faso. Open-label randomised controlled phase II
study in 180 children aged 6-10 years with uncomplicated falciparum
malaria in Nouna, north-western Burkina Faso. Follow-up was for 28
days and analysis by intention-to-treat. The treatment groups were
similar in baseline characteristics and there was only one loss to
follow-up. No drug-related serious adverse events and no deaths
occurred. MB-containing regimens were associated with mild vomiting
and dysuria. No early treatment failures were observed. Parasite
clearance time differed significantly among groups and was the
shortest with MB-AS. By day 14, the rates of adequate clinical and
parasitological response after PCR-based correction for
recrudescence were 87% for MB-AS, 100% for MB-AQ (p = 0.004), and
100% for AS-AQ (p = 0.003). By day 28, the respective figure was
lowest for MB-AS (62%), intermediate for the standard treatment
AS-AQ (82%; p = 0.015), and highest for MB-AQ (95%; p