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free areas or areas with low-incidence, where introductions pose risks [89,149] . Likewise, identification of novel
variants and genetic diversity prompted suggestions for oral vaccines and baits tailored to hosts, e.g., for
ferret badgers [118,143] . There were no instances of vaccine-derived cases/outbreaks in the review, but genomic
surveillance would be a crucial tool to identify and monitor such occurrences.

Widespread coexistence of diverse lineages and insights into their evolutionary history, transmission
dynamics and dispersal rates from more complex phylogeographic analysis, highlighted the urgency of
addressing transboundary transmission, which requires coordinated effort [65,80,140] . Vaccination campaigns
focusing solely on urban localised dog populations have demonstrated short-lived success due to rabies
circulation across land borders. Examples include Chad and Central African Republic [13,14] , India and
[163]
[58]
Bhutan , and Peru and Brazil bordering Bolivia . The same was true between islands, for example
Pemba, off Tanzania , and within and between archipelagic countries in Southeast Asia [78,108,138] and also
[155]
was identified at the borders of states in India . Therefore, recommendations included scaling up dog
[164]
vaccination beyond urban centres to encompass surrounding rural areas, along with coordinating
transboundary dog vaccination to minimise spread into cities or between neighbouring countries or
administrative units such as states or provinces [13,14] .

DISCUSSION
In this review, we focused on how genetic data informs understanding of rabies dynamics and its control.
Findings from 220 studies demonstrate sequencing as a potentially powerful tool for contributing to “Zero
by 30”. However, information from sequences is often not fully or consistently synthesised into specific,
actionable recommendations. When used effectively, sequencing has been instrumental in tracing
incursions into rabies-free areas and highlighting extensive transboundary transmission that necessitates
coordination of control nationally and regionally [78,138,149] . Although RABV diversity differs across these
regions with endemic dog-mediated rabies, spillovers and transboundary movement was repeatedly
reported, emphasising the importance of coordinated transboundary vaccination efforts and surveillance.
As countries approach the “endgame”, i.e., the final stages of an elimination programme where disease is
still circulating but at much reduced levels, genetic data is expected to become increasingly useful, providing
greater insights for monitoring emerging issues such as spillover and adaptation to alternative hosts and
potential re-emergence in dogs.

A major challenge is how classification of phylogenetic diversity and associated nomenclature, beyond the
clade level, is not standardised and how varied terminologies (subtypes, subclades, subclasses, clusters etc.)
are used. In most publications from Africa and Asia, groupings were designated numbers or letters based on
subjectively defined clusters in phylogenies, while Latin American studies often employed antigenic variant
classification rather than evolutionary (phylogenetic) relationships. Inconsistent terminology hampered a
clear understanding of circulating lineages and their geographic distribution, and hindered their use as
reference points for further research . Many studies used nomenclature only meaningful within the
[15]
context of that particular study and classifications often differed across related studies [Supplementary
Table 1]; employing RABV-GLUE to classify minor clades revealed these inconsistencies [Figure 4]. The
[15]
significance of discerning lineages lies in implications for control, for example, differentiating incursions
from undetected local transmission and identifying the scale of circulation. Variations in the portion of the
genome sequenced (gene-specific) and sequence length contributed to inconsistencies. Most publications
used partial genome sequencing, often targeting the N gene, a relatively conserved region used as a
diagnostic marker. But, this limited sampling missed important variation, which may define rare and
divergent lineages or improve resolution across narrower spatio-temporal windows. Just 20% of
publications used WGS, which can provide deeper understanding.