Tafenoquine-Atovaquone Combination Achieves Radical Cure and Confers Sterile Immunity in Experimental Models of Human Babesiosis.
Tafenoquine-Atovaquone Combination Achieves Radical Cure and Confers Sterile Immunity in Experimental Models of Human Babesiosis.
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他非诺喹-阿托伐醌组合在人类巴贝虫病实验模型中实现了根治并赋予了无菌免疫力。
DOI：
10.1093/infdis/jiad315
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发表时间：
2024
期刊：
影响因子：
--
通讯作者：
Mamoun,ChoukriBen
中科院分区：
文献类型：
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作者：
Vydyam,Pratap;Pal,AnasuyaC;Renard,Isaline;Chand,Meenal;Kumari,Vandana;Gennaro,JosephC;Mamoun,ChoukriBen
人类巴贝斯虫病是一种由红细胞内巴贝斯虫引起的潜在致命的蜱传疾病。对推荐疗法的耐药性的出现突出了对新的和更有效的治疗方法的需求。在这里，我们证明了8-氨基喹啉抗疟药他非诺喹在体外抑制不同巴贝斯虫种的生长，对小鼠中的微小巴贝斯虫和邓肯巴贝斯虫非常有效，并保护动物免受阿托伐醌敏感和耐药巴贝斯虫B引起的致死性感染。邓肯菌株。我们进一步表明，他非诺喹和阿托伐醌的组合在两种人类巴贝虫病模型中均实现了治愈而无复发。有趣的是，消除B。药物治疗后动物中的邓肯氏感染也赋予对随后攻击的免疫力。总之，这些数据证明了他非诺喹加阿托伐醌联合治疗人类巴贝虫病的上级疗效优于目前的治疗方法，并强调了其在提供保护性免疫力以对抗巴贝虫寄生虫清除方面的潜力。
Human babesiosis is a potentially fatal tick-borne disease caused by intraerythrocyticBabesiaparasites. The emergence of resistance to recommended therapies highlights the need for new and more effective treatments. Here we demonstrate that the 8-aminoquinoline antimalarial drug tafenoquine inhibits the growth of differentBabesiaspecies in vitro, is highly effective againstBabesia microtiandBabesia duncaniin mice and protects animals from lethal infection caused by atovaquone-sensitive and -resistantB. duncanistrains. We further show that a combination of tafenoquine and atovaquone achieves cure with no recrudescence in both models of human babesiosis. Interestingly, elimination ofB. duncaniinfection in animals following drug treatment also confers immunity to subsequent challenge. Altogether, the data demonstrate superior efficacy of tafenoquine plus atovaquone combination over current therapies for the treatment of human babesiosis and highlight its potential in providing protective immunity againstBabesiafollowing parasite clearance.