Adaptive virulence evolution: the good old fitness-based approach

Infectious diseases could be expected to evolve towards complete avirulence to their hosts if given enough time. However, this is not the case. Often, virulence is maintained because it is linked to adaptive advantages to the parasite, a situation that is often associated with the hypothesis known as the transmission virulence trade-off hypothesis. Here, we argue that this hypothesis has three limitations, which are related to how virulence is defined, the possibility of multiple trade-offs, and the difficulty of testing the hypothesis empirically. By adopting a fitness-based approach, where the relation between virulence and the fitness of the parasite throughout its life cycle is directly assessed, it is possible to address these limitations and to determine directly whether virulence is adaptive.