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

利用环境监测和宏基因组了解病原体在人类-野生动物-牲畜界面传播的流行病学

• 批准号: 2888376
• 金额: --
• 依托单位: University of Aberdeen
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2888376
• 关键词: Understanding; epidemiology; pathogen; transmission; across

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.

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原因。这些疾病的流行病学通常很复杂，水源等环境在多个宿主物种之间发生传播的界面中发挥着至关重要的作用。越来越多的证据表明，多宿主、环境传播病原体的多样性被低估，而且不同物种或菌株之间的毒力和环境传播的重要性可能不同，甚至在同一病原体属内也是如此。因此，表征环境中这些病原体的多样性对于改进诊断分析、确定哪些菌株导致人类和牲畜疾病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非常具有挑战性且耗时，这使得传统的微生物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（例如环境样本）或目标 DNA 水平较低的样本（例如临床样本）中分离和测序目标 DNA 的能力。这些方法无需培养即可从现场样本中表征病原体多样性，对于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。钩端螺旋体属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，并导致牲畜生产力大幅下降，其中最大的疾病负担落在了发展中国家最贫困的社区身上。人类和牲畜主要通过接触受感染维持宿主尿液污染的环境（例如水源）而受到感染。在非洲，最近的研究在小型哺乳动物和牲畜中发现了多种钩端螺旋体菌株，其中许多菌株在任何参考培养物保藏中都没有出现。尽管这些发现表明潜在致病性钩端螺旋体属的多样性。非洲的估计被低估了，对非洲广泛的潜在储存宿主进行采样在逻辑上是不可行的。该项目以南非、马达加斯加、坦桑尼亚和苏格兰现有和正在进行的项目为基础，将使用来自潜在污染环境的样本、来自同时野生动物储存宿主采样的数据以及来自人类和牲畜的临床样本，以表征潜在致病性钩端螺旋体的多样性环境中的菌株，ii) 确定导致人类和牲畜疾病的菌株，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) 探索如何利用结果为旨在缓解疾病的策略提供信息人类和牲畜的疾病风险。