activity of clinically relevant antimalarial drugs on plasmodium falciparum mature gametocytes in an atp bioluminescence “transmission blocking” assay活动的临床相关的抗疟药恶性疟原虫配子体成熟的atp生物发光分析输电阻塞.pdfVIP

Activity of Clinically Relevant Antimalarial Drugs on Plasmodium falciparum Mature Gametocytes in an ATP Bioluminescence ‘‘Transmission Blocking’’ Assay ¨ ` 1 . 1. 1 1 1¤ 2 Joel Lelievre * , Maria Jesus Almela , Sonia Lozano , Celia Miguel , Virginia Franco , Didier Leroy , Esperanza Herreros1* 1 GlaxoSmithKline RD, Tres Cantos Medicine Development Campus, Malaria Discovery Performance Unit, Madrid, Spain, 2 Medicines for Malaria Venture, Geneva, Switzerland Abstract Background: Current anti-malarial drugs have been selected on the basis of their activity against the symptom-causing asexual blood stage of the parasite. Which of these drugs also target gametocytes, in the sexual stage responsible for disease transmission, remains unknown. Blocking transmission is one of the main strategies in the eradication agenda and requires the identification of new molecules that are active against gametocytes. However, to date, the main limitation for measuring the effect of molecules against mature gametocytes on a large scale is the lack of a standardized and reliable method. Here we provide an efficient method to produce and purify mature gametocytes in vitro. Based on this new procedure, we developed a robust, affordable, and sensitive ATP bioluminescence-based assay. We then assessed the activity of 17 gold-standard anti-malarial drugs on Plasmodium late stage gametocytes. Methods and Findings: Difficulties in producing large amounts of gametocytes have limited progress in the development of malaria transmission blo