Mathematical Model of Drug-Sensitive and Drug-Resistance Malaria Competition With Antimalaria Therapy

The interplay between drug-sensitive and drug-resistant malaria parasites within a host is a complex phenomenon that significantly impacts antimalarial treatment effectiveness and the evolution of resistance. This study analyzes the dynamical behavior of a within-host malaria model incorporating maturation delay τ˜m, immune activation delay τ˜i, and competitive interactions between drug-sensitive and drug-resistant infected red blood cells. Using the next-generation matrix method, we compute the basic reproduction number R0. The qualitative analysis reveals that the disease-free equilibrium is asymptotically stable for any delay τ˜m≥0 whenever R0 1. Conditions for uniform persistence of both strains are established under the Hale–Waltman framework, showing that coexistence occurs when each strain can invade the other’s boundary equilibrium. A Hopf bifurcation analysis with respect to the immune delay yields a first Lyapunov coefficient μ2≈−0.2223, confirming a supercritical transition to stable limit cycles, providing a mechanistic hypothesis for chronic oscillatory infections. Sobol sensitivity analysis identifies sensitive-strain drug efficacy ϵs and resistant-strain death rate δyr as the most influential parameters, suggesting that combined therapy targeting both strains may be more effective than monotherapy for maintaining R0