Viral sequencing to inform the global elimination of dog-mediated rabies - a systematic review

Abstract

Background: Rabies is a fatal zoonotic disease, present in almost 150 countries. The “Zero by 30” initiative aims to eliminate human deaths from dog-mediated rabies globally by 2030. This systematic review investigates how viral sequencing can contribute to achieving the “Zero by 30” goal by improving understanding of viral circulation and the impact of rabies control measures. Methods: A comprehensive search of bibliographic databases was conducted focusing on research on rabies from regions with endemic dog-mediated rabies published between 2000 and 2023, adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data were extracted and synthesised to provide recommendations for further research and application to support rabies control. Results: 220 studies were identified to have documented rabies virus (RABV) sequences from 94 countries, primarily using first-generation technology to produce partial genomes and with sequencing predominantly conducted overseas rather than in-country. Dogs were identified to be the primary RABV reservoir in these regions, although some studies identified more localised wildlife reservoirs. Clade classifications were commonly based on host association or geographical location, however, lack of standardised methods and nomenclature for classifying lineages limited comparison at higher resolution. Cross-species transmission, and both local and long-distance transmission were identified, although quantitative inference was limited. Sequence data was particularly useful for identifying transboundary spread and incursions, investigating host shifts, and tracing sources of human rabies, with endemicity typically characterised by the identification of multiple co-circulating viral lineages. Conclusion: There is an urgent need for standardised classification methods and phylogeny-based nomenclature for RABVs, and for improved sequencing capacity in regions with endemic dog-mediated rabies, including proficiency in bioinformatics and phylogenetics. Our findings emphasise the critical need to foster international cooperation and coordinate rabies control efforts to reduce transboundary spread, limit reintroductions and maintain progress towards the 2030 target.