PDF(Pubmed)
Abstract：
Standard diagnostics used in longitudinal antimalarial studies are unable to characterize the complexity of submicroscopic parasite dynamics, particularly in high transmission settings. We use molecular markers and amplicon sequencing to characterize post-treatment stage-specific malaria parasite dynamics during a 42 day randomized trial of 3- versus 5 day artemether-lumefantrine in 303 children with and without HIV (ClinicalTrials.gov number NCT03453840). The prevalence of parasite-derived 18S rRNA is >70% in children throughout follow-up, and the ring-stage marker SBP1 is detectable in over 15% of children on day 14 despite effective treatment. We find that the extended regimen significantly lowers the risk of recurrent ring-stage parasitemia compared to the standard 3 day regimen, and that higher day 7 lumefantrine concentrations decrease the probability of ring-stage parasites in the early post-treatment period. Longitudinal amplicon sequencing reveals remarkably dynamic patterns of multiclonal infections that include new and persistent clones in both the early post-treatment and later time periods. Our data indicate that post-treatment parasite dynamics are highly complex despite efficacious therapy, findings that will inform strategies to optimize regimens in the face of emerging partial artemisinin resistance in Africa.
摘要：
纵向抗疟研究中使用的标准诊断无法表征亚显微寄生虫动力学的复杂性，特别是在高传输设置。我们使用分子标记和扩增子测序来表征治疗后特定阶段的疟原虫动力学，在303名有和没有HIV的儿童中进行了3天与5天的蒿甲醚-lumefantrine的随机试验（ClinicalTrials.gov编号NCT03453840）。在整个随访期间，儿童中寄生虫来源的18SrRNA的患病率>70%，尽管治疗有效，但在第14天，超过15％的儿童中可检测到环阶段标记SBP1。我们发现，与标准的3天方案相比，延长方案显着降低了复发性环期寄生虫血症的风险。并且较高的第7天的lumefantrine浓度降低了治疗后早期出现环期寄生虫的可能性。纵向扩增子测序揭示了多克隆感染的显着动态模式，包括治疗后早期和后期的新克隆和持续克隆。我们的数据表明，尽管治疗有效，但治疗后的寄生虫动力学非常复杂，研究结果将为面对非洲出现的部分青蒿素耐药性优化方案提供参考。
