Genomic Analyses Reveal the Common Occurrence and Complexity of Plasmodium vivax Relapses in Cambodia.
Genomic Analyses Reveal the Common Occurrence and Complexity of Plasmodium vivax Relapses in Cambodia.
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基因组分析揭示了柬埔寨疟原虫复发的常见发生和复杂性。
DOI：
10.1128/mbio.01888-17
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发表时间：
2018-01-23
期刊：
影响因子：
6.4
通讯作者：
Serre D
中科院分区：
文献类型：
--
作者：
Popovici J;Friedrich LR;Kim S;Bin S;Run V;Lek D;Cannon MV;Menard D;Serre D
间日疟原虫有一个独特的休眠阶段，可在最初感染几周或几个月后复发。这些休眠寄生虫是间日疟控制的主要挑战之一，因为它们构成了一个难以消除的宿主。由于实地研究受到再次感染和抗药性寄生虫可能复发的困扰，大多数对间日疟原虫复发的分析都集中在从疟疾流行地区返回的旅行者身上。然而，尚不清楚这些人是否准确地概括了居住在地方性流行地区的反复感染者的复发模式。在这里，我们介绍了柬埔寨一项严格控制的现场研究中登记的间日疟患者的分析。在接受抗疟疾药物治疗后，我们将20名患者重新安置到非传播区，并对他们进行了60天的跟踪，每隔一天进行一次采血。我们的分析显示，在监测期间，60%的患者复发。利用全基因组测序和高通量基因分型，我们发现柬埔寨的复发通常是多克隆的，复发的寄生虫与最初感染时存在的寄生虫存在不同程度的相关性。我们的分析还表明，克隆种群是动态变化的，在复发感染过程中出现了新的克隆。总体而言，我们的研究数据表明，有可能调查生活在疟疾流行地区的间日疟原虫复发的模式、动态和多样性，并揭示间日疟原虫复发比之前认为的更加普遍和复杂。(这项研究已在ClinicalTrials.gov注册，注册号：NCT02118090。)间日疟原虫可能仍在肝脏中休眠，并在最初感染后几周或几个月复发，极大地增加了疟疾控制和消除工作的难度。对这一休眠阶段的少数调查依赖于从疟疾流行地区返回的旅行者和军事人员。然而，目前尚不清楚这些接触有限数量感染的个人是否准确地代表了居住在地方性疾病流行地区的个人的复发模式，这些人反复感染间日疟原虫。我们的研究结合了严格控制的实地工作和全面的基因组分析，我们的报告提供了第一次机会来调查间日疟原虫直接与流行地区的个人复发的模式、动态和多样性。
Plasmodium vivax parasites have a unique dormant stage that can cause relapses weeks or months after the initial infection. These dormant parasites are among the main challenges of vivax malaria control as they constitute a reservoir that is difficult to eliminate. Since field studies are confounded by reinfections and possible recrudescence of drug-resistant parasites, most analyses of P. vivax relapses have focused on travelers returning from regions of malaria endemicity. However, it is not clear whether these individuals accurately recapitulate the relapse patterns of repeatedly infected individuals residing in areas of endemicity. Here, we present analyses of vivax malaria patients enrolled in a tightly controlled field study in Cambodia. After antimalarial drug treatment was administered, we relocated 20 individuals to a nontransmission area and followed them for 60 days, with blood collection performed every second day. Our analyses reveal that 60% of the patients relapsed during the monitoring period. Using whole-genome sequencing and high-throughput genotyping, we showed that relapses in Cambodia are often polyclonal and that the relapsing parasites harbor various degrees of relatedness to the parasites present in the initial infection. Our analyses also showed that clone populations differed dynamically, with new clones emerging during the course of the relapsing infections. Overall, our study data show that it is possible to investigate the patterns, dynamics, and diversity of P. vivax relapses of individuals living in a region of malaria endemicity and reveal that P. vivax relapses are much more pervasive and complex than previously considered. (This study has been registered at ClinicalTrials.gov under registration no. NCT02118090.) P. vivax parasites can remain dormant in the liver and relapse weeks or months after the initial infection, greatly complicating malaria control and elimination efforts. The few investigations of this dormant stage have relied on travelers and military personnel returning from areas of malaria endemicity. However, it is not clear whether these individuals, exposed to a limited number of infections, accurately represent the patterns of relapses of individuals living in areas of endemicity, who are repeatedly infected by P. vivax parasites. Our study combined tightly controlled fieldwork with comprehensive genomic analyses, and our report provides a first opportunity to investigate the patterns, dynamics, and diversity of P. vivax relapses directly with individuals living in areas of endemicity.