Within-host pathogen dynamics: Some ecological and evolutionary consequences of transients, dispersal mode, and within-host spatial heterogeneity

The ecology and evolution of infectious disease occur at multiple spatial scales. In this paper, we explore some consequences of transient dynamics of pathogens within individual hosts. If infected hosts die quickly, relative to internal equilibration in pathogen dynamics, within-host transients may influence between-host transmission and spread. We develop a formulation for characterizing the overall growth rate of an infectious disease, which includes both within-host dynamics and between-host transmission, when the disease is sufficiently rare that the supply of available hosts can be viewed as a constant. This formulation is analogous to the familiar Euler equation in age-structured demography. We suggest that the pathogen growth rate estimated this way may be a better measure of pathogen fitness than is R0. We point out that even simple models of within-host pathogen dynamics can have phases in which numbers overshoot the final equilibrium, and that such phases may influence pathogen evolution. We touch on the potential importance of within-host spatial heterogeneities in pathogen dynamics, and suggest that an interesting question for future work is understanding the interplay of spatial structure and transient dynamics in the within-host infection process.