Using mechanistic models to highlight research priorities for tick-borne zoonotic diseases: improving our understanding of the ecology and maintenance of Kyasanur forest disease in India

•Abstract: The risk of spillover of zoonotic diseases to humans is changing in response to multiple environmental and societal drivers, particularly in tropical regions where the burden of neglected zoonotic diseases is highest and land use change and forest conversion is occurring most rapidly. Neglected zoonotic diseases can have significant impacts on poor and marginalised populations in low-resource settings but ultimately receive less attention and funding for research and interventions. As such, effective control measures and interventions are often hindered by a limited ecological evidence base, which results in a limited understanding of epidemiologically relevant hosts or vectors and the processes that contribute to the maintenance of pathogens and spillover to humans. Here, we develop a generalisable next generation matrix modelling framework to better understand the transmission processes and hosts that have the greatest contribution to the maintenance of tick-borne diseases with the aim of improving the ecological evidence base and framing future research priorities for tick-borne diseases. Using this model we explore the relative contribution of different host groups and transmission routes to the maintenance of a neglected zoonotic tick-borne disease, Kyasanur Forest Disease Virus (KFD), in multiple habitat types. The results highlight the potential importance of transovarial transmission and small mammals and birds in maintaining this disease. This contradicts previous hypotheses that primates play an important role influencing the distribution of infected ticks. There is also a suggestion that risk could vary across different habitat types but currently more research is needed to evaluate this relationship. In light of these results, we outline the key knowledge gaps for this system and future research priorities that could inform effective interventions and control measures. •Author summary: The risk of humans contracting zoonotic diseases (diseases passed from animals to humans) is being altered by changes in the environment. These changes are occurring rapidly in tropical areas, which are burdened with neglected diseases that often disproportionately affect poorer communities. These diseases generally receive little attention and are less well studied. This means we often have a limited understanding of the ecological processes that influence the risk of people catching zoonotic diseases, which can be crucial in designing effective interventions. In this study, we developed mathematical models to highlight the ecological processes that influence the maintenance of Kyasanur Forest Disease, a neglected zoonotic disease affecting people in India. Using this approach, we were able to determine the hosts and forms of transmission that are most likely to play important roles in maintaining this pathogen and understand how risk to humans might vary in different habitats. We were also able to highlight key knowledge gaps and future research priorities that would help to inform interventions. An additional benefit of this approach is that it can also be used for other tick-borne diseases to help understand how pathogens are maintained and to prioritise the research questions that need to be addressed in other disease systems