Discovering New Transmission-Blocking Antimalarial Compounds: Challenges and opportunities

被引:37
作者
Birkholtz, Lyn-Marie [1 ]
Coetzer, Theresa L. [2 ]
Mancama, Dalu [1 ,3 ]
Leroy, Didier [4 ]
Alano, Pietro [5 ]
机构
[1] Univ Pretoria, Fac Nat & Agr Sci, Ctr Sustainable Malaria Control, Dept Biochem, Pretoria, South Africa
[2] Univ Witwatersrand, Natl Hlth Lab Serv, Fac Hlth Sci, Wits Res Inst Malaria,Dept Mol Med & Haematol, Johannesburg, South Africa
[3] CSIR, Biosci, Pretoria, South Africa
[4] Med Malaria Venture, Geneva, Switzerland
[5] Ist Super Sanita, Dipartimento Malattie Infett Parassitarie & Immun, Rome, Italy
基金
英国医学研究理事会;
关键词
HIGH-THROUGHPUT ASSAY; PLASMODIUM-FALCIPARUM TRANSMISSION; MEMBRANE-FEEDING ASSAY; SEXUAL DEVELOPMENT; SMALL MOLECULES; CELL BIOLOGY; MALARIA; GAMETOCYTES; IDENTIFICATION; PARASITES;
D O I
10.1016/j.pt.2016.04.017
中图分类号
R38 [医学寄生虫学]; Q [生物科学];
学科分类号
07 ; 0710 ; 09 ; 100103 ;
摘要
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.
引用
收藏
页码:669 / 681
页数:13
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