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

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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.