Cross-scale dynamics and the evolutionary emergence of infectious diseases

Sebastian J. Schreiber; Ruian Ke; Claude Loverdo; Miran Park; Priyanna Ahsan; James O. Lloyd-Smith

Our analysis also focuses on a simple "logistic-like" model for within-host viral dynamics. This simplification allows us to study how evolutionary emergence is limited by different factors for pathogens dominated by exponential versus saturated phases of viral growth, while maintaining analytical tractability. Future important extensions would be to allow within-host fitness to alter the carrying capacity in the saturated phase, as well as identifying the relative contributions of stochastic within-host dynamics [17] , immune responses, and host heterogeneity on viral emergence. Some of these aims would be addressed by using a more mechanistic model for the within-host dynamics, incorporating resource limitation [72, 73] or immune pressure [107] . We have assumed that the bottleneck width N is fixed for a given pathogen. This is broadly consistent with currently available data [44, 47, 48] , but it will be important to explore the consequences of variation in bottleneck width arising from different routes of transmission, or possibly from changing viral loads [38, 39] . Among other possible impacts, this may alter the conclusion that emergence probability is minimally affected by the functional dependence of transmission probability on viral load. The computational and analytical framework developed here can be extended to account for these additional complexities. Other important extensions can explore the impact of clonal competition on emergence probabilities [108] [109] [110] [111] or the potential for complementation to rescue pathogen strains from deep fitness valleys-a mechanism that depends on wide transmission bottlenecks [112] .