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Keywords:

  • Nested models;
  • pathogen;
  • pathogenesis;
  • transmission-virulence tradeoff;
  • virulence

A significant goal of recent theoretical research on pathogen evolution has been to develop theory that bridges within- and between-host dynamics. The main approach used to date is one that nests within-host models of pathogen replication in models for the between-host spread of infectious diseases. Although this provides an elegant approach, it nevertheless suffers from some practical difficulties. In particular, the information required to satisfactorily model the mechanistic details of the within-host dynamics is not often available. Here, we present a theoretical approach that circumvents these difficulties by quantifying the relevant within-host factors in an empirically tractable way. The approach is closely related to quantitative genetic models for function-valued traits, and it also allows for the prediction of general characteristics of disease life history, including the timing of virulence, transmission, and host recovery. In a companion paper, we illustrate the approach by applying it to data from a model system of malaria.