A general theory for the evolutionary dynamics of virulence.

Most theory on the evolution of virulence is based on a game-theoretic approach. One potential shortcoming of this approach is that it does not allow the prediction of the evolutionary dynamics of virulence. Such dynamics are of interest for several reasons: for experimental tests of theory, for the development of useful virulence management protocols, and for understanding virulence evolution in situations where the epidemiological dynamics never reach equilibrium and/or when evolutionary change occurs on a timescale comparable to that of the epidemiological dynamics. Here we present a general theory similar to that of quantitative genetics in evolutionary biology that allows for the easy construction of models that include both within-host mutation as well as superinfection and that is capable of predicting both the short- and long-term evolution of virulence. We illustrate the generality and intuitive appeal of the theory through a series of examples showing how it can lead to transparent interpretations of the selective forces governing virulence evolution. It also leads to novel predictions that are not possible using the game-theoretic approach. The general theory can be used to model the evolution of other pathogen traits as well.