Strong gametocytocidal effect of methylene blue-based combination therapy against falciparum malaria: a randomised controlled trial.
BACKGROUND
With the availability of new preventive and curative interventions, global malaria control has been strengthened significantly in recent years. Drugs effective in reducing malaria gametocytaemia might contribute to local elimination and possible long-term eradication. We here report on the effects of methylene blue (MB)-based malaria combination therapy on gametocytaemia during a randomised-controlled trial in Burkina Faso.


METHODS
An open-label randomised controlled phase II study in 180 children aged 6-10 years with uncomplicated falciparum malaria was conducted in Nouna, north-western Burkina Faso. Children were randomised to MB-artesunate (AS), MB-amodiaquine (AQ), and AS-AQ (local standard of care). Overall follow-up was for 28 days, follow-up for gametocytaemia was for 14 days.


RESULTS
The treatment groups were similar in baseline characteristics and there was only one loss to follow-up. Compared to AS-AQ, both MB-containing regimens were associated with significantly reduced gametocyte carrier rates during follow-up days 3, 7, and 14. This effect was seen both in patients with and without P. falciparum gametocytaemia at baseline.


CONCLUSIONS
MB reveals pronounced gametocytocidal activity which appears to act against both existing and developing P. falciparum gametocytes. MB-based combination therapy thus has the potential to reduce transmission of P. falciparum malaria in endemic regions, which has important implications for future elimination and eradication strategies.


BACKGROUND
(ClinicalTrials.gov) NCT00354380.
Coulibaly
Boubacar
B
Centre de Recherche en Santé de Nouna, Nouna, Burkina Faso.
Zoungrana
Augustin
A
Mockenhaupt
Frank P
FP
Schirmer
R Heiner
RH
Klose
Christina
C
Mansmann
Ulrich
U
Meissner
Peter E
PE
Müller
Olaf
O
D000655:Amodiaquine / Q000008:administration & dosage; D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage*; D037621:Artemisinins / Q000008:administration & dosage; D000077332:Artesunate; D002050:Burkina Faso; D002648:Child; D004359:Drug Therapy, Combination; D005854:Germ Cells / Q000187:drug effects*; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy*; D008751:Methylene Blue / Q000008:administration & dosage* / Q000627:therapeutic use; D010963:Plasmodium falciparum / Q000187:drug effects; D016896:Treatment Outcome
D000962:Antimalarials; D037621:Artemisinins; D000655:Amodiaquine; D000077332:Artesunate; D008751:Methylene Blue