Making genomic surveillance deliver: A lineage classification and nomenclature system to inform rabies elimination

The availability of pathogen sequence data and use of genomic surveillance is rapidly increasing. Genomic tools and classification systems need updating to reflect this. Here, rabies virus is used as an example to showcase the potential value of updated genomic tools to enhance surveillance to better understand epidemiological dynamics and improve disease control. Previous studies have described the evolutionary history of rabies virus, however the resulting taxonomy lacks the definition necessary to identify incursions, lineage turnover and transmission routes at high resolution. Here we propose a lineage classification system based on the dynamic nomenclature used for SARS-CoV-2, defining a lineage by phylogenetic methods for tracking virus spread and comparing sequences across geographic areas. We demonstrate this system through application to the globally distributed Cosmopolitan Glade of rabies virus, defining 96 total lineages within the Glade, beyond the 22 previously reported. We further show how integration of this tool with a new rabies virus sequence data resource (RABV-GLUE) enables rapid application, for example, highlighting lineage dynamics relevant to control and elimination programmes, such as identifying importations and their sources, as well as areas of persistence and routes of virus movement, including transboundary incursions. This system and the tools developed should be useful for coordinating and targeting control programmes and monitoring progress as countries work towards eliminating dog-mediated rabies, as well as having potential for broader application to the surveillance of other viruses. Author summary The importance of the ability to track the diversity and spread of viruses in a universal way that can be clearly communicated has been highlighted during the SARS-CoV-2 pandemic. This, accompanied with the increase in the availability and use of pathogen sequence data, means the development of new genomic tools and classification systems can strengthen outbreak response and disease control. Here, we present an easy-to-use objective and transferable classification tool for tracking viruses at high resolution. We use rabies virus, the cause of a neglected zoonotic disease that kills around 59,000 people each year, as an example use case of this tool. Applying our tool to a global Glade of rabies virus, we find an increase in resolution from 22 subclades to 96 lineages; this fourfold increase in the definition at which we can classify the virus, may allow us to identify areas of persistence and transmission that were not previously apparent and further resolve patterns of virus spread. Insights from the application of this tool should prove valuable in targeting dog vaccination campaigns and improving surveillance as countries work towards the elimination of dog-mediated rabies.

Automated summary

The availability of pathogen sequence data and the use of genomic surveillance are increasing rapidly. In this study, the researchers propose an updated genomic tool and classification system for better understanding the dynamics of rabies virus and improving disease control. By implementing this tool, they were able to define 96 total lineages within the globally distributed Cosmopolitan Glade of rabies virus, which is a significant increase from the previously reported 22 lineages. The integration of this tool with a new rabies virus sequence data resource enables rapid application and provides insights into the control and elimination of dog-mediated rabies.