Killing the hypnozoite - drug discovery approaches to prevent relapse in Plasmodium vivax

被引:77
作者
Campo, Brice [1 ]
Vandal, Omar [2 ]
Wesche, David L. [2 ,3 ]
Burrows, Jeremy N. [1 ]
机构
[1] Med Malaria Venture, Geneva, Switzerland
[2] Bill & Melinda Gates Fdn, Seattle, WA USA
[3] Great Lakes Drug Dev Certara, Princeton, NJ USA
关键词
Plasmodium vivax; Radical cure; Hypnozoite; Strategy; Drug discovery assays; IN-VITRO CULTURE; LIVER STAGE; MALARIA PARASITES; EXOERYTHROCYTIC PARASITES; ANTIMALARIAL ACTIVITY; FALCIPARUM-MALARIA; HUMAN HEPATOCYTES; RADICAL CURE; MOUSE MODELS; PRIMAQUINE;
D O I
10.1179/2047773215Y.0000000013
中图分类号
R1 [预防医学、卫生学];
学科分类号
1004 ; 120402 ;
摘要
The eradication of malaria will only be possible if effective, well-tolerated medicines kill hypnozoites in vivax and ovale malaria, and thus prevent relapses in patients. Despite progress in the 8-aminoquinoline series, with tafenoquine in Phase III showing clear benefits over primaquine, the drug discovery challenge to identify hypnozoiticidal or hypnozoite-activating compounds has been hampered by the dearth of biological tools and assays, which in turn has been limited by the immense scientific and logistical challenges associated with accessing relevant human tissue and sporozoites. This review summarises the existing drug discovery series and approaches concerning the goal to block relapse.
引用
收藏
页码:107 / 122
页数:16
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