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

We presented a cross-scale model for evolutionary emergence of novel pathogens, linking explicit representations of viral growth and competition within host individuals to viral transmission between individuals. Our work identifies four steps to evolutionary emergence summarized in Figure 5 and four ingredients (see, equation (4)) that govern these steps: (i) the reproductive number of the wild type which determines the size of a minor outbreak of this strain, (ii) the rate at which individuals infected initially with the wild-type strain transmit the mutant strain, and (iii) the cross-scale reproductive number α of a mutant virion which corresponds to the mean number of mutant virions transmitted by an individual whose initial infection only included one mutant virion, and (iv) the reproductive number of the mutant strain. Prior studies of evolutionary emergence [12] [13] [14] [15] identified the importance of the single strain reproductive numbers, R m and R w , and a phenomenological 'mutation rate', but ingredients (iii)-(iv) are new mechanistic insights arising from the cross-scale dynamics. By analyzing these ingredients of evolutionary emergence, we show how the probability of emergence is governed by selection pressures at within-host and between-host scales, the width of the transmission bottleneck, and the infection duration. We also map the conditions under which different broad-scale patterns are observed, from rapid selective sweeps to slower diffusion of new types. While our study has focused on within-host and between-host scales of selection, it could be generalized readily to other types of cross-scale dynamics where selection may act differently at different scales, such as within-farm and between-farm scales where genetic data have given insights into the emergence of high-pathogenicity avian influenza strains [93] .