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

The directionality of the positive feedback is more complex, and depends on multiple factors including the infection duration and the presence or absence of cross-scale conflicts. For long-term infections, mutant frequencies can drop deterministically within a host, and hence prevent emergence, even if the mutant strain has a reproductive number greater than one. This occurs when the mutant strain has a within-host selective disadvantage and between-host selective advantage (upper left quadrant of Fig 2D) ; the long infectious period allows time for the within-host disadvantage to drive the mutant strain to lower frequency and, thereby, set up the positive feedback effectively preventing evolutionary emergence. In contrast, for short-term infections the mutant strain tends to rise in frequency whenever the mutant reproductive number is greater than one, because there is insufficient time for any within-host disadvantage to act. In particular, evolutionary emergence may occur despite within-host selective disadvantages, a possibility excluded by previous theory [15] . Collectively these two results imply that, in the face of cross-scale conflict and wide transmission bottlenecks, longer infectious periods can inhibit, rather than facilitate [14] , evolutionary emergence (Fig 2B,D) . Related to this result, Geoghegan et al. [17] found that longer durations of the infectious period would lower the probability that a donor would infect the recipient. In their case, this occurred because fitness of the mutant was assumed to be lower in the donor host species and higher in the recipient species. Hence, a longer infectious period could purge any mutants arising in the donor and result in the recipient only receiving wild-type virions.