期刊
PHARMACEUTICS
卷 14, 期 12, 页码 -出版社
MDPI
DOI: 10.3390/pharmaceutics14122794
关键词
Plasmodium falciparum; Plasmodium berghei; Plasmodium yoelii; Anopheles gambiae; Anopheles stephensi; methylene blue; Gabon; transmission; in vivo and ex vivo experiments
资金
- German Center for Infection Research (DZIF) [TI 07.003]
- University of Tuebingen
The study found that methylene blue has activity against malaria parasite transmission, interfering with the spread of the parasites in both mosquitoes and humans. Methylene blue can block the infection of the parasites in mosquito midgut and human liver.
Methylene blue (MB) is the oldest synthetic anti-infective. Its high potency against asexual and sexual stages of malaria parasites is well documented. This study aimed to investigate possible additional activities of MB in interfering with parasite transmission and determine target stages in Anopheles vectors and humans. MB's transmission-blocking activity was first evaluated by an ex vivo direct membrane feeding assay (DMFA) using Plasmodium falciparum field isolates. To investigate anti-mosquito stage activity, Plasmodium berghei-infected Anopheles stephensi mosquitoes were fed a second blood meal on mice that had been treated with methylene blue, 3, 6- and 15-days after the initial infectious blood meal. Anti-sporozoite and liver stage activities were evaluated in vitro and in vivo via sporozoite invasion and liver stage development assays, respectively. MB exhibited a robust inhibition of P. falciparum transmission in An. gambiae, even when added shortly before the DMFA but only a moderate effect against P. berghei oocyst development. Exposure of mature P. berghei and P. falciparum sporozoites to MB blocked hepatocyte invasion, yet P. berghei liver stage development was unaffected by MB. Our results indicate previously underappreciated rapid specific activities of methylene blue against Plasmodium transmission stages, preventing the establishment of both mosquito midgut and liver infections as the first essential steps in both hosts.
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