Treating symptomatic infections and the co-evolution of virulence and drug resistance

Abstract

Antimicrobial therapeutic treatments are by definition applied after the onset of symp-toms, which tend to correlate with infection severity. Using mathematical epidemiology models, I explore how this link affects the coevolutionary dynamics between the virulence of an infection, measured via host mortality rate, and its susceptibility to chemotherapy. I show that unless resistance pre-exists in the population, drug-resistant infections are initially more virulent than drug-sensitive ones. As the epidemic unfoldsvirulence is more counter-selected in drug-sensitive than in drug-resistant infectionsThis difference decreases over time and, eventually, the exact shape of genetic trade-offs govern long-term evolutionary dynamics. Using adaptive dynamics, I show that two types of evolutionary stable strategies (ESS) may be reached in the context of this sim-ple model and that, depending on the parameter values, an ESS may only be locally sta-ble. In general, the more the treatment rate increases with virulence, the lower the ESS value. Overall, both on the short-term and long-term, having treatment rate depend on infection virulence tend to favour less virulent strains in drug-sensitive infections. These results highlight the importance of the feedbacks between epidemiology, public health policies and parasite evolution, and have implications for the monitoring of virulence evolution.