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，水源等环境作为多种宿主物种之间可能发生传播的界面起着至关重要的作用。越来越多的证据表明，多宿主、环境传播的病原体的多样性被低估了，即使在同一病原体属内，不同物种或菌株之间的毒力和环境传播的重要性也可能不同。因此，描述环境中这些病原体的多样性对于改进诊断分析、确定导致人类和牲畜疾病的菌株以及预测和减轻疾病风险至关重要。许多环境传播病原体的培养非常具有挑战性和耗时，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宏基因组方法以及便携式DNA测序技术的快速发展正在彻底改变我们从复杂样本基质（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实地样本中确定病原体多样性的特征，在可能缺乏培养病原体所需的专门设施和能力的发展中国家特别有用。钩端螺旋体是世界上最常见的环境传播病原体之一，估计每年造成6万人死亡，牲畜生产力遭受重大损失，发展中世界最贫困社区承受的疾病负担最重。人类和牲畜主要通过接触被受感染维持宿主尿液污染的水源等环境而受到感染。在非洲，最近的研究已经在小型哺乳动物和牲畜中发现了多种多样的钩端螺旋体菌株，其中许多在任何参考培养标本中都没有出现。尽管这些发现表明非洲潜在致病性钩端螺旋体的多样性被低估了，但在非洲对广泛的潜在宿主进行取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、同时进行的野生动物宿主采样的数据以及人类和牲畜的临床样本，以i)表征环境中潜在致病性钩端螺旋体菌株的多样性，ii)确定导致人类和牲畜疾病的菌株。Iii)调整现有的分析方法，以改进钩端螺旋体病的诊断；iv)探索如何利用结果为旨在减轻人类和牲畜疾病风险的战略提供信息。

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.