Dormant Plasmodium Falciparum Parasites In Human Infections Following Artesunate Therapy

JOURNAL OF INFECTIOUS DISEASES(2021)

引用 15|浏览26
暂无评分
摘要
Background. Artemisinin monotherapy of Plasmodium falciparum infection is frequently ineffective due to recrudescence. Artemisinin-induced dormancy, shown in vitro and in animal models, provides a plausible explanation. To date, direct evidence of artemisinin-induced dormancy in humans is lacking.Methods. Blood samples were collected from Plasmodium falciparum 3D7- or K13-infected participants before and 48-72 hours after single-dose artesunate (AS) treatment. Parasite morphology, molecular signature of dormancy, capability and dynamics of seeding in vitro cultures, and genetic mutations in the K13 gene were investigated.Results. Dormant parasites were observed in post-AS blood samples of 3D7- and K13-infected participants. 'I he molecular signature of dormancy, an up-regulation of acetyl CoA carboxylase, was detected in 3D7 and K13 samples post-AS, but not in pre-AS samples. Posttreatment samples successfully seeded in vitro cultures, with a significant delay in time to reach 2% parasitemia compared to pretreatment samples.Conclusions. This study provides strong evidence for the presence of artemisinin-induced dormant parasites in P. falciparum infections. These parasites are a likely reservoir for recrudescent infection following artemisinin monotherapy and artemisinin combination therapy (ACT). Combination regimens that target dormant parasites or remain at therapeutic levels for a sufficient time to kill recovering parasites will likely improve efficacy of ACTs.
更多
查看译文
关键词
Plasmodium falciparum, parasitemia, artemisinin, artesunate, artemisinin-induced dormancy, dormant parasites, K13 gene, acetyl CoA carboxylase, pLDH
AI 理解论文
溯源树
样例
生成溯源树,研究论文发展脉络
Chat Paper
正在生成论文摘要