Building a platform to understand asymptomatic and symptomatic visceral leishmaniasis in Ethiopia

建立一个平台来了解埃塞俄比亚的无症状和有症状内脏利什曼病

• 批准号: MR/R021600/1
• 负责人: Pascale Kropf
• 金额: $ 19.29万
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FR021600%2F1
• 关键词: Building; platform; understand; asymptomatic; symptomatic

Visceral leishmaniasis (VL) is a parasitic disease caused by Leishmania (L.) donovani. It is one of the most neglected tropical diseases, affecting the poorest populations, for whom access to diagnosis and effective treatment is not readily accessible. In Ethiopia, over 3.2 million people live in areas where this disease is endemic and are therefore at risk of infection with L. donovani. While the majority of individuals infected with L. donovani show no symptoms and are therefore designated as asymptomatic; some develop a disease that, if left untreated, is almost always fatal. It is not understood why some individuals can control infection and stay asymptomatic whereas others develop progressive non-healing VL. Our aim is to identify distinct immunological and gene expression signatures that are associated with the control of parasite replication in asymptomatic individuals or uncontrolled parasite replication and dysfunctional immune responses in VL patients. To do this, we have identified a unique population of individuals in Northwest Ethiopia, in the Metema-Humera area: this is the most important endemic focus of VL in Ethiopia and accounts for 60% of the VL burden in the country. In this area, during the months of June to October, the intense seasonal agricultural activities attract >250,000 migrant workers, for weeding and harvest. The majority of these seasonal labourers come from leishmaniasis-free areas and travel for seasonal work to the Metema-Humera area where leishmaniasis is widespread. These migrant workers are at higher risk of being infected by Leishmania parasites as they live and work in areas where they are constantly being exposed to the sandflies that transmit Leishmania parasites. The environment and working conditions on these farms are extremely harsh and therefore, few studies have been made of these migrant workers, little is known about their lifestyle and their travelling and working habits. Therefore, here we propose a proof of concept study to demonstrate that we can:- Recruit sufficient numbers of migrant workers and follow them during and after the agricultural season.- Identify those who have been infected with L. donovani parasites by using different immunological, serological and molecular tests.- Collect blood and store it during our visits to the farm, transport it to our laboratory, 200km away from the farm, to send to the UK to quantify genome-wide host gene expression; as well as perform basic functional assay on this farm.- Generate preliminary epidemiological, immunological and gene expression data to identify immune signatures associated with either asymptomatic infection or VL disease. The results of this work will serve as a foundation to plan a larger study in the Metema-Humera area to identify immunological and gene expression signatures of each stage of the development of asymptomatic infection or VL. This will be essential for the development of new strategies to prevent and treat leishmaniasis.

内脏利什曼病（VL）是由利什曼原虫（L.）donovani。这是最被忽视的热带疾病之一，影响到最贫穷的人口，他们很难得到诊断和有效治疗。在埃塞俄比亚，超过320万人生活在这种疾病流行的地区，因此有感染L。donovani。而大多数感染L. donovani没有任何症状，因此被定为无症状;有些人患上了一种疾病，如果不治疗，几乎总是致命的。目前尚不清楚为什么有些人可以控制感染并保持无症状，而其他人则发展为进行性不愈合VL。我们的目的是确定不同的免疫学和基因表达的签名，与控制寄生虫复制无症状的个人或不受控制的寄生虫复制和VL患者的免疫反应功能障碍。为此，我们在埃塞俄比亚西北部的Metema-Humera地区确定了一个独特的个体群体：这是埃塞俄比亚最重要的VL地方病集中地，占该国VL负担的60%。在该地区，6月至10月期间，密集的季节性农业活动吸引了超过250 000名移民工人，从事除草和收获。这些季节性劳工大多数来自无利什曼病地区，前往利什曼病流行的Metema-Humera地区从事季节性工作。这些移民工人感染利什曼原虫的风险更高，因为他们生活和工作的地区经常暴露于传播利什曼原虫的白蛉。这些农场的环境和工作条件极其恶劣，因此，很少有人对这些移徙工人进行研究，对他们的生活方式以及他们的旅行和工作习惯知之甚少。因此，在这里，我们提出了一个概念研究的证明，以证明我们可以：-招募足够数量的农民工，并在农业季节期间和之后跟踪他们。识别那些已经感染L的人。Donovani寄生虫通过使用不同的免疫学，血清学和分子测试。在我们访问农场期间收集血液并储存，将其运送到我们的实验室，距离农场200公里，发送到英国量化全基因组宿主基因表达;以及在该农场进行基本功能测定。生成初步的流行病学、免疫学和基因表达数据，以确定与无症状感染或VL疾病相关的免疫特征。这项工作的结果将作为计划在Metema-Humera地区进行更大规模研究的基础，以确定无症状感染或VL发展的每个阶段的免疫学和基因表达特征。这对于制定预防和治疗利什曼病的新战略至关重要。

项目成果

Diversity and Within-Host Evolution of Leishmania donovani from Visceral Leishmaniasis Patients with and without HIV Coinfection in Northern Ethiopia.

• DOI: 10.1128/mbio.00971-21
• 发表时间: 2021-06-29
• 期刊: mBio
• 影响因子: 6.4
• 作者: Franssen SU;Takele Y;Adem E;Sanders MJ;Müller I;Kropf P;Cotton JA
• 通讯作者: Cotton JA

A Way Straight-Forward for Leishmania Genetics.

利什曼原虫遗传学的一种直接方法。

• DOI: 10.1016/j.pt.2020.07.005
• 发表时间: 2020
• 期刊: Trends in parasitology
• 影响因子: 9.6
• 作者: Cotton JA