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

内脏利什曼病(VL)是由利什曼原虫引起的一种寄生虫病。多诺瓦尼。它是最被忽视的热带病之一，影响到最贫穷的人口，他们很难获得诊断和有效的治疗。在埃塞俄比亚，超过320万人生活在这种疾病流行的地区，因此面临感染多诺瓦尼乳杆菌的风险。虽然大多数感染了杜诺瓦尼乳杆菌的人没有表现出任何症状，因此被指定为无症状；但有些人会患上一种疾病，如果不治疗，几乎总是致命的。目前尚不清楚为什么一些人可以控制感染并保持无症状，而另一些人则发展为进行性不可愈合的VL。我们的目标是确定与控制无症状个体的寄生虫复制或VL患者的不受控制的寄生虫复制和功能失调的免疫反应相关的独特的免疫学和基因表达特征。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VL最重要的地方性疫源地，占该国VL负担的60%。在这一地区，在6月至10月的几个月里，紧张的季节性农业活动吸引了25万外来务工人员除草和收获。这些季节性劳动者大多来自无利什曼病地区，前往利什曼病流行的梅特马-胡梅拉地区从事季节性工作。这些外来务工人员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沙蝇。这些农场的环境和工作条件极其恶劣，因此，对这些农民工的研究很少，对他们的生活方式和旅行和工作习惯知之甚少。因此，我们在这里提出一项概念验证研究，以证明我们可以：-招募足够数量的外来工人，并在农季期间和之后跟踪他们。-通过使用不同的免疫学、血清学和分子测试来识别那些感染了多诺瓦尼寄生虫的人。-在我们访问农场期间收集血液并将其存储，将其运输到我们距离农场200公里的实验室，送往英国，以量化整个基因组范围的宿主基因表达；以及在该农场进行基本功能分析。-生成初步的流行病学、免疫学和基因表达数据，以识别与无症状感染或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。

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.