Introduction of these variants into non-reservoir animals increases the risk of human exposures and threatens current advances toward rabies control.Many pathogens are thought to have host specialization, which explains the maintenance of distinct strains in host species. Pathogens would have to overcome their host specificity to cross to a new host species. Some studies have argued that host specializations may be exaggerated, and pathogens are more likely to exhibit CST than previously thought. Original hosts usually have low death rates when infected with a pathogen, with fatality rates tending to be much higher in new hosts

Between non-human primates and humans
Due to the close relation of nonhuman primates (NHP) and humans, disease transmission between NHP and humans is relatively common and can become a major public health concern. Diseases such as HIV and human adenoviruses have been associated with NHP interactions.In places where contact between humans and NHPs is frequent, precautions are often taken to prevent disease transmission. Simian foamy viruses (SFV) is an enzootic retrovirus that has high rates of cross-species transmission and has been known to affect humans bitten by infected NHPs. It has caused health concerns in places like Indonesia where visitors at monkey temples can contract SFV from temple macaques (Macaca fascicularis). TMAdV (titi monkey adenovirus) is a highly divergent, sharing <57% pairwise nucleotide identity with other adenoviruses, NHP virus that had a high fatality rate (83%) in monkeys and is capable of spreading through human hosts.
The process of using genetic markers to estimate CST rates should take into account several important factors to reduce bias. One is that the phylogenetic tree constructed in the analysis needs to capture the underlying epidemiological process generating the tree. The models need to account for how the genetic variability of a pathogen influences a disease in a species, not just general differences in genomic structure. Two, the strength of the analysis will depend on the amount of mutation accumulated since the pathogen was introduced in the system. This is due to many models using the number of mutations as an indicator of CST frequency. Therefore, efforts are focused on estimating either time since the introduction or the substitution rate of the marker (from laboratory experiments or genomic comparative analysis). This is important not only when using the MPR method but also for Likelihood approaches that require an estimation of the mutation rate. Three, CST will also affect disease prevalence in the potential host, so combining both epidemiological time series data with genetic data may be an excellent approach to CST study

Bayesian analysis
Bayesian frameworks are a form of maximum likelihood-based analyses and can be very effective in cross-species transmission studies. Bayesian inference of character evolution methods can account for phylogenetic tree uncertainty and more complex scenarios, with models such as the character diffusion model currently being developed for the study of CST in RNA viruses. A Bayesian statistical approach presents advantages over other analyses for tracking CST origins.