Genomic Epidemiology to underpin One Health surveillance for rabies

Genomic surveillance, i.e. using a pathogen's genetic blueprint to track it's spread in response to control measures, has become a key tool in contemporary disease management. This approach can now be deployed almost anywhere and conducted in near real-time to inform rapid and targeted interventions. Yet genomic surveillance is typically applied to emerging diseases with pandemic potential (e.g. SARS-COV-2) in high-income countries. I propose repurposing genomic surveillance for endemic zoonoses, diseases that spread from animals to people, such as rabies, that inflict a major preventable disease burden in many low- and middle-income countries. Such an approach would simultaneously improve surveillance for emerging infectious diseases through locally relevant capacity strengthening and provide the means to develop cutting-edge methodologies and capacities in "pandemic peacetime", whilst generating visible, tangible impacts on public health.
My proposal focuses on developing and optimising an accessible toolkit for generating and interpreting rabies virus genetic sequence data, supporting the global strategy to achieve zero human rabies deaths from rabies spread by domestic dogs by 2030. Genomic surveillance can play a key role in resolving complex transmission dynamics, detecting introductions and identifying their sources. This epidemiological understanding is important for both designing and evaluating national rabies elimination programmes, as they are increasingly rolled out. The proposed work encapsulates novel laboratory techniques to generate sequences in resource poor settings, and contemporary methods for analyzing these data to track rabies spread and persistence, both locally within communities and longer-range movement across countries and regions. I will deploy this toolbox through my extensive international collaborations across Africa, Asia and Latin America to address specific questions to support rabies elimination programmes in practice, building local capacity and expertise for routine in-country genomic surveillance.

Rabies is a zoonotic disease at the human-animal-ecosystem interface ('One Health') that kills thousands of people every year in low- and middle-income countries yet has recently been prioritised for elimination by 2030. Elimination efforts stand to benefit enormously from insights provided by genomic data, by monitoring lineage dynamics, using them to evaluate the success of interventions, and for the rapid detection of sources of incursions. Yet, as highlighted by the SARS-CoV-2 pandemic there are major global disparities in sequencing capacity that limit its use in low resource settings, which is where rabies circulates. This research will focus on developing and optimising Rabies Accessible GEnomics (RAGE), an accessible toolkit to sequence, analyse and interpret rabies virus genomes that can be applied to deliver actionable epidemiological insights that can directly inform rabies virus elimination programmes. These tools will constitute methodological advances in sequencing methods, including testing SMART-N9, a new metagenomic sequencing approach for viral pathogens; the development of deployable bioinformatic pipelines and easy-to-use software to aid non-bioinformatic users in the analysis of genomes. These methods will be used to track rabies lineage dynamics and comprehend the mechanisms driving lineage spread and persistence, the impact of dog vaccination programs and the sources and frequency of incursions that underpin viral circulation. I will deploy this toolbox through my extensive international collaborations across Africa, Asia and Latin America to address specific questions to support rabies elimination programmes in practice, building local capacity and expertise for routine in-country genomic surveillance.