title: Discovering New Transmission-Blocking Antimalarial Compounds: Challenges and Opportunities.
abstract: The ability to target human-mosquito parasite transmission challenges global malaria elimination. However, it is not obvious what a transmission-blocking drug will look like; should it target only parasite transmission stages; be combined with a partner drug killing the pathogenic asexual stages; or kill both the sexual and asexual blood stages, preferably displaying polypharmacology? The development of transmission-blocking antimalarials requires objective analyses of the current strategies. Here, pertinent issues and questions regarding the target candidate profile of a transmission-blocking compound, and its role in malaria elimination strategies, are highlighted and novel perspectives proposed. The essential role of a test cascade that integrates screening and validation strategies to identify next-generation transmission-blocking antimalarials is emphasised.
authors.affiliation: Department of Biochemistry, Centre for Sustainable Malaria Control, Faculty of Natural and Agricultural Sciences, University of Pretoria, Pretoria, South Africa. Electronic address: lbirkholtz@up.ac.za.
authors.forename: Lyn-Marie
authors.initials: LM
authors.lastname: Birkholtz
authors.affiliation: Department of Molecular Medicine and Haematology, Wits Research Institute for Malaria, Faculty of Health Sciences, University of the Witwatersrand, National Health Laboratory Service, Johannesburg, South Africa. Electronic address: theresa.coetzer@nhls.ac.za.
authors.forename: Theresa L
authors.initials: TL
authors.lastname: Coetzer
authors.affiliation: Department of Biochemistry, Centre for Sustainable Malaria Control, Faculty of Natural and Agricultural Sciences, University of Pretoria, Pretoria, South Africa; Biosciences, Council for Scientific and Industrial Research, Pretoria, South Africa. Electronic address: DMancama@csir.co.za.
authors.forename: Dalu
authors.initials: D
authors.lastname: Mancama
authors.affiliation: Medicines for Malaria Venture, Geneva, Switzerland. Electronic address: leroyd@mmv.org.
authors.forename: Didier
authors.initials: D
authors.lastname: Leroy
authors.affiliation: Dipartimento di Malattie Infettive, Parassitarie e Immunomediate, Istituto Superiore di Sanità, Rome, Italy. Electronic address: alano@iss.it.
authors.forename: Pietro
authors.initials: P
authors.lastname: Alano
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000627:therapeutic use*; D060740:Disease Eradication / Q000639:trends*; D004353:Drug Evaluation, Preclinical; D006801:Humans; D008018:Life Cycle Stages; D008288:Malaria / Q000188:drug therapy / Q000517:prevention & control* / Q000635:transmission
chemical_list: D000962:Antimalarials
keywords: drug discovery; elimination; gametocytes; malaria; transmission