Understanding the epidemiology of pathogen transmission across the human-wildlife-livestock interface using environmental surveillance and metagenomic

环境传播的病原体是世界上一些最重要的人畜共患病和牲畜疾病的罪魁祸首。这些疾病的流行病学往往很复杂，水源等环境发挥着关键作用，可以通过这些接口在多个宿主物种之间进行传播。越来越多的证据表明，环境传播的多宿主病原体的多样性被低估了，而且毒力和环境传播的重要性在物种或菌株之间可能不同，甚至在同一病原体属内也是如此。因此，确定环境中这些病原体的多样性对于改进诊断分析、确定哪些菌株对人类和牲畜疾病负责以及预测和减轻疾病风险至关重要。许多环境传播的病原体的培养具有极大的挑战性和耗时，使得传统的微生物学方法难以表征病原体多样性。然而，全基因组和标记基因元基因组方法和便携式DNA测序技术的快速进步正在彻底改变我们从复杂样本矩阵(如环境样本)或低水平目标DNA样本(如临床样本)中分离和测序目标DNA的能力。这些方法能够在不需要培养的情况下从现场样本中确定病原体多样性的特征，在发展中国家特别有用，因为那里可能缺乏培养病原体所需的专门设施和能力。钩端螺旋体是世界上最常见的环境传播病原体之一，每年造成约60000人死亡和严重的牲畜生产力损失，最大的疾病负担落在发展中世界最贫穷的社区。人和牲畜主要是通过接触环境而感染的，例如水源，被受感染的维护宿主的尿液污染。在非洲，最近的研究在小型哺乳动物和家畜中发现了各种各样的钩端螺旋体菌株，其中许多没有出现在任何参考培养库中。尽管这些发现表明潜在致病钩端螺旋体的多样性。在非洲被低估，在非洲对广泛的潜在宿主进行抽样在后勤上是不可行的。在南非、马达加斯加、坦桑尼亚和苏格兰现有和正在进行的项目的基础上，该项目将使用来自潜在污染环境的样本、来自野生动物水库宿主并行样本的数据和来自人畜的临床样本，以i)描述环境中潜在致病钩端螺旋体菌株的多样性，ii)确定导致人畜疾病的菌株，iii)调整现有的检测方法，以改进钩端螺旋体病的诊断，以及iv)探索如何将结果用于为旨在降低人畜疾病风险的战略提供参考。

Environmentally transmitted pathogens are responsible for some of the most important zoonoses and livestock diseases in the world. The epidemiology of these diseases is often complex, with environments, such as water sources, playing a crucial role as interfaces across which transmission can occur between multiple host species. There is increasing evidence that the diversity of multi-host, environmentally transmitted pathogens is underestimated, and that virulence and the importance of environmental transmission may differ between species or strains, even within the same pathogen genera. Therefore, characterising the diversity of these pathogens in the environment is crucial to improving diagnostic assays, identifying which strains are responsible for human and livestock disease and predicting and mitigating disease risk. Many environmentally transmitted pathogens are exceptionally challenging and time consuming to culture, making traditional microbiological approaches to characterising pathogen diversity difficult. However, rapid advances in whole genome and marker gene metagenomic approaches and portable DNA sequencing technologies are revolutionising our ability to isolate and sequence target DNA from complex sample matrices, such as environmental samples, or samples with low levels of target DNA, such as clinical samples. These approaches, which enable characterisation of pathogen diversity from field samples without requiring culture, are particularly useful in the developing world where the specialised facilities and capacity required for culturing pathogens may be lacking. Leptospira spp. are some of the world's most common environmentally transmitted pathogens, responsible for an estimated 60000 human deaths a year and significant livestock productivity loss, with the greatest burden of disease falling on the poorest communities in the developing world. Humans and livestock are predominantly infected through contact with environments, such as water sources, contaminated with urine from infected maintenance hosts. In Africa, recent studies have identified a wide diversity of Leptospira strains, many of which are not represented in any reference culture collections, in small mammals and livestock. Although these findings suggest that the diversity of potentially pathogenic Leptospira spp. in Africa is underestimated, sampling the broad range of potential reservoir hosts in Africa would be logistically unfeasible. Building on existing and ongoing projects in South Africa, Madagascar, Tanzania and Scotland, this project will use samples from potentially contaminated environments, data from concurrent wildlife reservoir host sampling and clinical samples from humans and livestock to i) characterise the diversity of potentially pathogenic Leptospira strains in the environment, ii) identify the strains responsible for human and livestock disease, iii) tailor existing assays to improve the diagnosis of leptospirosis and iv) explore how results could be used to inform strategies aimed at mitigating disease risk for humans and livestock.