Rapid and Specific Action of Methylene Blue against Plasmodium Transmission Stages

Autor:	Nathanaël Saison, Jean-François Franetich, Yudi T. Pinilla, Anton Hoffmann, Stravensky T. Boussougou-Sambe, Barclaye Ngossanga, Maurel Tefit, Kutub Ashraf, Nadia Amanzougaghene, Shahin Tajeri, Ayola A. Adegnika, Dominique Mazier, Steffen Borrmann
Jazyk:	angličtina
Rok vydání:	2022
Předmět:	Plasmodium berghei Plasmodium falciparum Plasmodium yoelii Anopheles gambiae Anopheles stephensi methylene blue Gabon transmission in vivo and ex vivo experiments Pharmaceutical Science 600 Technik Medizin angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit
Zdroj:	Pharmaceutics; Volume 14; Issue 12; Pages: 2794
ISSN:	1999-4923
DOI:	10.3390/pharmaceutics14122794
Popis:	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.
Databáze:	OpenAIRE
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