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Page 28 Jaswant et al. One Health Implement Res 2024;4:15-37 https://dx.doi.org/10.20517/ohir.2023.61

We found an urgent need to increase in-country sequencing capacity in endemic countries, with relatively
few generating sequences in-country. Regionally, Africa lagged behind Latin America and Asia in terms of
capacity, but had a higher output than Latin America, likely because few countries in the region remain
endemic for dog-mediated rabies. Most sequencing was driven by research, with routine sequencing not yet
part of surveillance in endemic regions. Consequently, there is a shortage of sequences, with largest
contributions from China and Brazil (upper-middle-income countries with existing networks and
resources), whereas several countries had limited representation; some with just one publication. The
scarcity of sequences, which poses a challenge to characterising RABV diversity and understanding
transmission, could be due to different cultural, intrinsic and socio-economic factors. In the aftermath of
the COVID-19 pandemic, sequencing capabilities have expanded, becoming more affordable and accessible.
[149]
This increased capacity has practical applications for responding to rabies outbreaks .
Although dogs were identified as the primary host responsible for most transmission in regions with
endemic dog-mediated rabies which were the focus of this study, RABVs broad host range means it is
capable of transmission among multiple species. This versatility creates potential for new reservoirs, raising
concerns about the effectiveness of control measures, and about these reservoirs being a source of re-
emergence . In areas where dog-mediated rabies has largely been eliminated, there were several examples
[160]
of transmission cycles in wildlife, some of which resulted from spillover from dogs. In Latin America, where
canine rabies incidence has reduced dramatically from coordinated regional control, intriguing reservoir
dynamics have emerged. For example, three major enzootic cycles, distinct from dog rabies foci in Mexico
[165]
(skunks, coyotes and gray foxes) highlight a complex maintenance dynamic . Similarly, transmission
cycles have established in ferret badgers independently in both Taiwan and China [118,119,166] . These findings
underscore the complex reservoir dynamics of RABV and importance of understanding host associations
and cross-species transmission. As dog-mediated rabies declines, this understanding will be necessary to
enable targeted control, either directing efforts at blocking transmission and spread between source and
target populations or controlling infection within new reservoirs. The risk of rabies spillover from wildlife
foci to dogs is a serious challenge for “Zero by 30”. When such reservoirs exist, tailored surveillance and
control measures are crucial to mitigate the threat of re-emergence in dog populations as a result of
spillover. This may eventually require countries to undertake control measures in wildlife reservoirs, but
more imminently underscores the need to eliminate rabies from dog populations before wildlife foci can
establish.

Underreporting and misdiagnosis of human rabies remains a significant issue and can create a false
impression of low burden in rabies endemic settings across Africa and Asia. While enhancing diagnostic
capacity and overall surveillance is crucial to address underreporting, we also emphasise the pivotal role that
genetic data can play in strengthening human rabies surveillance. Rabies-free countries experience imported
human cases from exposures in endemic countries [167-169] . Oftentimes, these imported cases were confirmed
through epidemiological investigation, but genetic data identified the sources of infections, as well as
ambiguous cases, without a clear route of exposure (e.g., no bite history) or origin (e.g., the migrant from
Mexico and the veterinarian in Brazil), or with unusually long incubation periods [133,135-137] . These human
cases identified from countries that are free from dog-mediated rabies highlight how these technologies
could be applied to strengthen human rabies diagnosis and source attribution within endemic countries.

Unlike infections in humans, which are effectively dead-end hosts, movement of infected animals is the
predominant factor contributing to RABV establishment in new geographic settings. Publications
highlighted both local host movement and long-distance human-mediated movements, however, evidence
on transmission links and directionality were sparse, with only a few studies (25%) employing