Threshold Dynamics of Within-Host CHIKV Infection: A Delay Differential Equation Model with Persistent Infected Monocytes and Humoral Immunity

In this paper, we present a mathematical analysis of within-host CHIKV dynamics by developing and studying a novel delay differential equation model that incorporates persistent infected monocytes, discrete time delays, and an antibody-mediated humoral immune response. The model includes five compartments: susceptible monocytes, persistent infected monocytes, actively infected monocytes, CHIKV pathogens, and neutralizing antibodies. To reflect key biological latencies, we introduce four distinct discrete delays accounting for the periods between viral entry and the emergence of infected cell populations, intracellular virion production, and antibody activation. We analyze the model, establishing the positivity, boundedness, and invariance of solutions, and derive the basic reproduction number R0 via the next-generation matrix method. Using Lyapunov functions and LaSalle’s Invariance Principle, we prove a threshold dynamic: the infection-free equilibrium is globally asymptotically stable (GAS) when R0≤1, while a unique endemic equilibrium is GAS when R0>1. Numerical simulations validate the analytical results and illustrate threshold behavior. A detailed local sensitivity analysis of R0 identifies the most influential parameters, offering theoretical insights into potential intervention strategies. We further investigate the effects of antiviral therapy as a theoretical intervention, deriving a treatment-dependent reproduction number and the critical drug efficacy required for eradication, and explore how the intracellular production delay can itself serve as a critical threshold for infection clearance. The study provides a rigorous theoretical framework that highlights the roles of latency, immune response, and biological delays in CHIKV pathogenesis and offers qualitative insights that may inform future experimental and treatment design studies.