Mathematical models for within-host competition of malaria parasites.

In this paper, we formulate two within-host infection models to simulate dynamics of the drug sensitive and drug resistant malaria parasites, where the first model solely considers the within-host competition between these two strains, and the second model further considers the immune re-sponse. Detailed theoretical analysis of the second model are made, including the existence, stability and bifurcation of the equilibrium, which have also been verified by numerical simulations. Both theoretical and numerical results show that competition or chronic control of drug sensitive parasites could inhibit the evolution of drug resistant ones to some extent. However, if the immune response is considered, periodic solution could be observed, and they will persist for all relatively small treatment rate. This may lead to the recurrence of resistance for the chronic control strategy, even though it could delay the resistance emergence. In addition, global sensitivity analysis is implemented to provide the information on the significance of model parameters on the state variables.