Reservoir population dynamics and pathogen epidemiology drive pathogen genetic diversity, spillover, and emergence

Abstract

When several factors align, pathogens that normally infect wildlife can spill over into the human population. If pathogen transmission within the human population is self-sustaining, or rapidly evolves to be self sustaining, novel human pathogens can emerge. Although many factors influence the likelihood of spillover and emergence, the rate of contact between humans and wildlife is critical. Thus, for those pathogens inhabiting wildlife reservoirs with pronounced seasonal fluctuations in population density, it is broadly recognized that spillover risk also varies with season. What remains unknown, however, is the extent to which seasonal fluctuations in reservoir populations influence the evolutionary dynamics of pathogens in ways that affect the likelihood of emergence. Here, we use mathematical models and stochastic simulations to show that seasonal fluctuations in reservoir population densities lead to seasonal increases in genetic variation within pathogen populations and thus influence the waiting time for mutations capable of sustained human-to-human transmission. These seasonal increases in genetic variation also lead to elevated risk of emergence at predictable times of year.

Evolution of pathogen tolerance and emerging infections: A missing experimental paradigm

“…However, in these examples, in addition to spillover via phylogenetic relatedness or spatial proximity, arguably, another important condition can be the circulation of a stable, large, and diverse zoonotic pool in the reservoir species. Indeed, this is corroborated by recent analyses and mathematical models indicating that the number of zoonotic viruses with spillover risk might increase proportionally with the total number ( Mollentze and Streicker, 2020 ) as well as the genetic diversity ( Remien and Nuismer, 2020 ) of viruses maintained inside reservoir animals.…”

“…Finally, once the pathogen establishes infection in the novel host by evading the immune responses, it then needs to spread effectively in the population ( Plowright et al, 2015 ; Subudhi et al, 2019 ). At each step of this transmission chain, the duration of the host’s infectivity, population density, and size might dictate the success of the consecutive step ( Remien and Nuismer, 2020 ; Wolfe et al, 2007 ). However, before all these fine-scale micro-evolutionary downstream processes can begin, potentially an important precondition can be the maintenance of a sufficiently large ( Mollentze and Streicker, 2020 ) and diverse ( Remien and Nuismer, 2020 ) zoonotic pathogen pool with the potential to overcome the species barrier.…”

“…At each step of this transmission chain, the duration of the host’s infectivity, population density, and size might dictate the success of the consecutive step ( Remien and Nuismer, 2020 ; Wolfe et al, 2007 ). However, before all these fine-scale micro-evolutionary downstream processes can begin, potentially an important precondition can be the maintenance of a sufficiently large ( Mollentze and Streicker, 2020 ) and diverse ( Remien and Nuismer, 2020 ) zoonotic pathogen pool with the potential to overcome the species barrier. Although the causal link is absent, large populations of reservoir animals harboring large pathogen populations have been predicted to serve as fertile sources of zoonotic diseases ( Han et al, 2016 ).…”

“…Although not mutually exclusive, the emergence of novel zoonotic pathogens might also depend on the genetic diversity of the pathogen pool ( Wolfe et al, 2007 ). Pathogen genetic diversity is likely to be greatest within large reservoir populations when they also harbor proportionally large pathogen populations ( Remien and Nuismer, 2020 ). Increased strain diversity might enhance the pathogen’s prospect of jumping across species barrier by harboring the pool of useful mutations to establish infection in a new host ( Dennehy et al, 2010 ; i.e., production of specific rare variants that are inherently more competent to establish cross-species infection; Mandl et al, 2015 ).…”