A simple and predictive phenotypic High Content Imaging assay for Plasmodium falciparum mature gametocytes to identify malaria transmission blocking compounds

• DOI: 10.1038/srep16414
• Publication Date: 2015-11-10T10:12:44Z
• Authors: Leonardo Lucantoni; Francesco Silvest...; Michele Signore; Giulia Siciliano; Maarten Eldering; Koen J. Dechering; Vicky M. Avery; Pietro Alano
• Keywords: Acridine orange

Plasmodium falciparum gametocytes, specifically the mature stages, are only malaria parasite stage in humans transmissible to mosquito vector. Anti-malarial drugs capable of killing these forms considered essential for eradication and tools allowing screening large compound libraries with high predictive power needed identify new candidates. As gametocytes not a replicative it is difficult apply same drug methods used asexual stages. Here we propose an assay, based on content imaging, combining "classic" gametocyte viability readout counts functional readout, activation discrimination typical gamete spherical morphology. This simple rapid assay has been miniaturized 384-well format using acridine orange staining wild type P. 3D7A sexual forms, was validated by reference antimalarial MMV Malaria Box. The demonstrated excellent robustness ability quality hits likelihood confirmation transmission reducing activity subsequent membrane feeding assays.