Virulence management: Closing the feedback loop between healthcare interventions and virulence evolution.

We study the evolution of virulence of an endemic pathogen in response to healthcare interventions which affect host recovery and pathogen transmission. By anticipating the evolutionary response of the pathogen we may develop effective long-term management strategies for controlling the impact of the endemic on the society. To that end, we use standard Adaptive Dynamics techniques in an SIS model. The recovery rate and the transmission rate, both of which can be affected by healthcare interventions, are used as evolutionary control variables. The effect of interventions may be density-independent (self-help based on healthcare instructions) or density-dependent (when assistance of a healthcare worker is required). We consider the evolutionary response of the pathogen both to abrupt changes and to gradual changes in the level of healthcare intervention. Healthcare intervention is optimised for three alternative objectives: minimisation of virulence, minimisation of the probability that an infected individual dies of the disease, and total eradication of the endemic. We find that the optimal strategy may depend on the objective. High levels of healthcare intervention may eradicate the pathogen, but this option may not be available for budgetary reasons or otherwise. Counterintuitively, to minimise virulence, one should keep healthcare interventions at a minimum, while to minimise the probability for an infected individual to die of the disease, both low and high levels of healthcare intervention suffice. Changes in the level of healthcare intervention should be implemented fast (not gradually) in order to avoid sudden changes in pathogen evolution and the possible emergence of multiple simultaneously coexisting pathogen strains.