Mixed infections and the evolution of virulence: effects of resource competition, parasite plasticity, and impaired host immunity.

Mixed-genotype parasite infections are common in nature. Theoretical studies analyze the effects of such infections over evolutionary time and predict an increase in virulence due to the competitive advantage of virulent parasites. In contrast, experimental studies compare the overall virulence of mixed and single infections within one generation. Although these within-generation comparisons have limited relevance to existing theory, they demonstrate that within-host parasite interactions are not restricted to competition for resources, as envisaged by theory. Instead, mixed infections may result in phenotypic changes in growth rate or impaired immune clearance. Developing and using a two-parasite epidemiological model with recovery, we confirm that within-host competition for resources selects for higher virulence. However, parasite phenotypic plasticity and impaired host immunity can select for lower virulence. Because these latter two mechanisms would be detected by experimentalists as an increase in pathology, our results warn against the temptation to draw inferences on virulence evolution on the basis of single-generation experiments.