Diversity and Within-Host Evolution of Leishmania donovani from Visceral Leishmaniasis Patients with and without HIV Coinfection in Northern Ethiopia.
Diversity and Within-Host Evolution of Leishmania donovani from Visceral Leishmaniasis Patients with and without HIV Coinfection in Northern Ethiopia.
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DOI：
10.1128/mbio.00971-21
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发表时间：
2021-06-29
期刊：
影响因子：
6.4
通讯作者：
Cotton JA
中科院分区：
文献类型：
--
作者：
Franssen SU;Takele Y;Adem E;Sanders MJ;Müller I;Kropf P;Cotton JA
内脏利什曼病（VL）是一种致命的疾病，是东非日益严重的公共卫生问题，埃塞俄比亚是VL负担最高的国家之一。在埃塞俄比亚，VL的最大焦点是由移民农业工人的高流行率驱动的，并与艾滋病毒的高合并感染率有关。这种合并感染使得VL更难以成功治疗，并且与高复发率相关，VL/HIV患者在死于这种感染之前经常经历多次VL复发。我们目前的全基因组数据从队列的VL和VL/HIV患者报告到一个单一的诊所在埃塞俄比亚的纵向研究杜氏利什曼原虫分离株。大量的临床数据使我们能够调查合并感染和复发对感染这些患者的寄生虫种群的影响。我们发现，相同的寄生虫种群负责VL和VL/HIV感染，在大多数情况下，疾病复发是由引起原发性VL的寄生虫种群复发引起的。复杂的多克隆感染存在于原发和复发病例中，但患者体内的寄生虫亚群在原发疾病表现和随后的复发之间失去了遗传多样性，这可能是由于治疗引起的群体瓶颈。这些数据表明，VL/HIV复发不是由遗传上不同的寄生虫感染或再感染引起的。VL的治疗不会导致无菌治愈，并且在VL/HIV中，感染寄生虫能够在临床成功治疗后重新建立，导致VL的反复复发。
Visceral leishmaniasis (VL) is a fatal disease and a growing public health problem in East Africa, where Ethiopia has one of the highest VL burdens. The largest focus of VL in Ethiopia is driven by high prevalence in migrant agricultural workers and associated with a high rate of coinfection with HIV. This coinfection makes VL more difficult to treat successfully and is associated with a high rate of relapse, with VL/HIV patients frequently experiencing many relapses of VL before succumbing to this infection. We present genome-wide data on Leishmania donovani isolates from a longitudinal study of cohorts of VL and VL/HIV patients reporting to a single clinic in Ethiopia. Extensive clinical data allow us to investigate the influence of coinfection and relapse on the populations of parasites infecting these patients. We find that the same parasite population is responsible for both VL and VL/HIV infections and that, in most cases, disease relapse is caused by recrudescence of the population of parasites that caused primary VL. Complex, multiclonal infections are present in both primary and relapse cases, but the infrapopulation of parasites within a patient loses genetic diversity between primary disease presentation and subsequent relapses, presumably due to a population bottleneck induced by treatment. These data suggest that VL/HIV relapses are not caused by genetically distinct parasite infections or by reinfection. Treatment of VL does not lead to sterile cure, and in VL/HIV, the infecting parasites are able to reestablish after clinically successful treatment, leading to repeated relapse of VL.