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Jaswant et al. One Health Implement Res 2024;4:15-37 https://dx.doi.org/10.20517/ohir.2023.61 Page 17

Table 1. Definitions of key terms in the context of RABV
Term Definition
Cross-species Transmission events from one (host) species to another, that occasionally result in a host shift, whereby a new
transmission transmission cycle is established, but more frequently leading to short-lived chains of transmission or dead-end infections
[5,6]
with no onward transmission
Reservoir One or more epidemiologically connected populations in which the pathogen persists and from which infection is
[7]
transmitted to a population of concern i.e., a target population . Domestic dogs are considered maintenance hosts in the
reservoir for rabies in many regions, while humans, endangered wildlife, and livestock are often considered target
populations [8]
Variant A viral population maintained within a particular reservoir host in a geographically defined area that differs from other viral
[9]
populations due to either a host shift or diversification within a host species or population i.e., host-association
[4]
(sometimes called a biotype ). RABV variants often show host-associations. Here we differentiate dog- vs. wildlife-
[10]
associated RABV variants
Directionality of The predominant direction of transmission from one host species, population or location to another. Genomic data can be
[11]
transmission used to identify how infected hosts are linked to each other, and to infer the source of infection . Transmission networks
involve mapping transmission routes or pathways to ascertain who infected whom and have been inferred for RABV using
[11]
parsimony-based approaches and advanced Bayesian frameworks
Transboundary pathogen spread across administrative boundaries. We differentiate human-mediated spread, often over long distances
spread e.g., > 50 km, from local dispersal due to host behaviour (rabid dogs typically bite animals within 1 km of their location, but
can sometimes run over 20 km) [12] . An incursion (or introduction) is the spread of a pathogen into a new area, either where
that pathogen was historically absent, had been previously eliminated (i.e., re-introduction), or where the pathogen is
already present. In the latter example, an incursion might be identified from genetic data when a distinct viral lineage is
found in an area where other lineages are circulating [13,14]
Phylogeny or A branching diagram or tree showing the evolutionary relationships between sequences or species. These generally
phylogenetic tree incorporate nucleotide substitution models, and can include taxonomic and temporal information. The most widely applied
methods for tree building are Neighbour Joining, Maximum Parsimony, Maximum Likelihood and Bayesian Inference
RABV-GLUE Is a flexible software system for interpreting sequencing data with functionality for storage and interpretation. The software
[15]
is freely available and can be directly downloaded for viral sequence analysis or can be used via the web interface : http:/
/rabv-glue.cvr.gla.ac.uk
[16]
Clade A monophyletic group with a single common ancestor . Shared ancestry therefore defines the initial pathogen emergence
[17]
and spread . RABV is designated into clades or subclades (sometimes referred to as major and minor clades), usually
associated with specific geographic areas and/or hosts. A lineage (sometimes referred to as a subtype) is a group of related
sequences (typically a smaller monophyletic group contained within a larger subclade) defined by statistical support of
their phylogenetic placement and genetic differences from their most recent common ancestor (mrca) [18] . Clades and
subclades can be classified differently depending on the hosts and geographical location. In this review, publications may
have designated clades/subclades/lineages according to the author’s naming system. To allow for comparison between
publications, a table of publication-specific names and corresponding RABV-GLUE designations is available in
Supplementary Table 1
Phylodynamics The study of how epidemiological, immunological, and evolutionary processes (inter)act to shape viral phylogenies.
Examples include studies of spatial diffusion, sometimes incorporating geographical or population structure i.e.,
[19]
phylogeography
Genomic/genetic Surveillance involving sequence data to characterise an infectious agent and infer additional information about its
surveillance dynamics. Genomic refers specifically to WGS i.e., the entire pathogen genome (> 10 kb for RABV), whereas partial genome
sequencing is the generation of a sequence of a specified genetic region that can be used to identify the organism. For
RABV, 400 bp fragments are used for diagnostics, and many phylogenetic studies sequence the N gene, G gene and/or G-L
intergenic regions
1st generation (or Type of sequencing which produces DNA fragments labelled by chemical modified nucleotides (dideoxynucleotides) during
[20]
Sanger) nucleotide elongation. Sanger sequencing sequences one fragment at a time
sequencing
NGS Parallel approaches that sequence millions of fragments simultaneously, hence have higher throughput than 1st generation
approaches. NGS technologies are divided into 2nd generation technologies which analyse clonal representations of the
input DNA before sequencing amplified DNA clones, e.g., Illumina MiSeq and Ion Torrent, vs. 3rd generation single
molecule sequencing technologies, which can produce longer reads than 2nd generation platforms but typically have higher
error rates, e.g., Oxford Nanopore and PacBio [20]
RABV: Rabies virus; GLUE: gene-linked by underlying evolution; WGS: Whole Genome Sequencing; NGS: next generation sequencing.
over recent decades due to coordinated regional dog vaccination programs . In contrast, most LMICs in
[25]
Asia and Africa have not allocated sufficient budget to control this disease, and access to dog vaccines
remains limited. Confounding the lack of vaccines, typically, rabies surveillance has also been poor.
Additional challenges to rabies control include lack of understanding of dog ownership patterns, population
sizes, and accessibility for vaccination as well as cultural practices including dog meat consumption . To
[27]
address these challenges, international organisations joined forces under the United Against Rabies