Efficacy of methylene blue monotherapy in semi-immune adults with uncomplicated falciparum malaria: a controlled trial in Burkina Faso

Abstract

Summaryobjective To assess the efficacy of methylene blue (MB) monotherapy in semi-immune adults with uncomplicated malaria in Burkina Faso.methods In an open-label controlled phase II study with 60 semi-immune adults with uncomplicated falciparum malaria in Nouna, north-western Burkina Faso, MB monotherapy (390 mg twice daily) was given sequentially to groups of 20 adults for 7 days (MB7), 5 days (MB5) and 3 days (MB3), respectively. The primary outcome was the rate of adequate clinical and parasitological response (ACPR) on day 28 of follow-up.results Of the study population, 27 ⁄ 58 (47%) and 5 ⁄ 51 (10%) patients still had parasites on days 2 and 3, respectively, of follow-up resulting in 9 ⁄ 58 (16%) early treatment failures. By day 14, no recrudescence was observed but in 4 ⁄ 19 (MB5) and 2 ⁄ 20 (MB3) individuals by day 28. The PCRcorrected rate of ACPR was 72%, 58% and 85% in groups 7, 5 and 3, respectively, by per protocol analysis. Self-limiting dysuria was the most frequent adverse event.conclusions MB acts slowly against the blood stages of P. falciparum. MB alone needs to be given for at least 7 days to be efficacious in the treatment of falciparum malaria but should be used in combination with a fast acting antimalarial.

Quantitative assessment of Plasmodium falciparum sexual development reveals potent transmission-blocking activity by methylene blue

“…One recent field trial from Burkina Faso observed excellent clinical efficacy of a MB-amodiaquine combination when tested in children with uncomplicated falciparum malaria (34). Another study reported moderate curative activity with MB monotherapy, illustrating the need for this slow-acting drug to be combined with fast-acting agents (35). Our results show that MB interferes with gametocyte development at all stages and can block transmission through the potent clearance of stage V gametocytes.…”

“…Characterized by a short plasma half-life and a high bioavailability (18 h and 72%, respectively) (30), this compound was the first synthetic compound ever used in clinical therapy, dating back to the 1891 report of its antimalarial properties by the renowned chemist Paul Ehrlich (31,32). Recently, there has been renewed interest in this affordable and already clinically registered compound, with a series of studies that have assessed the benefit of adding MB to antimalarial combinations (33)(34)(35). One recent field trial from Burkina Faso observed excellent clinical efficacy of a MB-amodiaquine combination when tested in children with uncomplicated falciparum malaria (34).…”

Baseline In Vitro Activities of the Antimalarials Pyronaridine and Methylene Blue against Plasmodium falciparum Isolates from Kenya

“…PRN has also been proven potent in vitro against P. falciparum isolates from Southeast Asia, a known area of multidrug resistance (23). Interestingly, PRN is also active against Plasmodium vivax in vitro (23), and recently, the in vivo efficacy of PRN-ART against P. vivax has been shown, making this combination a potential drug for the treatment of P. vivax infection as well (18).MB has proven efficacious in African countries, mainly in Burkina Faso (3,10,11,32), and has gametocytocidal properties; thus, it could be part of treatment combinations to reduce transmission of P. falciparum (6). Our data show that MB is active in vitro, in line with 2 previous studies using African parasites (1, 17).…”

“…MB has proven efficacious in African countries, mainly in Burkina Faso (3,10,11,32), and has gametocytocidal properties; thus, it could be part of treatment combinations to reduce transmission of P. falciparum (6). Our data show that MB is active in vitro, in line with 2 previous studies using African parasites (1,17).…”

Laser-guided magic bullets—A non-antibiotic answer to O’Neill

“…Managing the unusual side-effect is possible via effective counselling of the patient, relatives etc. This has been achieved in recent years during the conventional use of methylene blue in juvenile malaria in Burkina Faso [5]. …”