The paradox of tolerance: Parasite extinction due to the evolution of host defence

Host defence against parasite infection can rely on two broad strategies: resistance and tolerance. The spread of resistance traits usually lowers parasite prevalence and decreases selection for higher defence. Conversely, tolerance mechanisms increase parasite prevalence and foster selection for more tolerance. Here we examine the potential for the host to drive parasites to extinction through the evolution of one or other defence mechanism. We analysed theoretical models of resistance and tolerance evolution in both the absence and the presence of a trade-off between defence and reproduction. In the absence of costs, resistance evolves towards maximisation and, consequently, parasite extinction. Tolerance also evolves towards maximisation but the positive feedback between tolerance and disease prevents the disappearance of the parasite. On the contrary, when defence comes with costs it is impossible for the host to eliminate the infection through resistance, because costly resistance is selected against when parasites are at low prevalence. We uncover that the only path to disease clearance in the presence of costs is through tolerance. Paradoxically, however, it is by lowering tolerance -and hence increasing disease-induced mortality- that extinction can occur. We also show that such extinction can occur even in the case of parasite counter-adaptation. Our results emphasise the importance of tolerance as a defence strategy, and identify key questions for future research.