An optimal control model of the treatment of chronic Chlamydia trachomatis infection using a combination treatment with antibiotic and tryptophan

Abstract

We develop a mathematical model of within-host Chlamydia dynamics to investigate the effects of different treatment combinations on the within-host dynamics of chronic genital chlamydial infections characterised by the presence of IFN-γ-induced chlamydial persistence. Our modelling framework is informed by recent studies which have demonstrated that tryptophan and some of its biosynthetic analogues are able to both reverse and inhibit IFN-γ-induced chlamydial persistence. Our aim is to find the optimal combination of treatments/drugs that will minimise the systemic cost of two controls/treatments, the concentration of extracellular Chlamydia, infected epithelial host cells, and importantly the development of chlamydial persistence. Pontryagin’s Maximum Principle is used to characterise the optimal controls and the resulting optimal control system is numerically solved. Optimal control solutions that eradicate the pathogen and its persistence are demonstrated. Our numerical results indicate that the optimal way to clear and truncate the progression of a chronic Chlamydia infection may be the administration of a combination therapy that is bacteriostatic to chlamydial particles and that concurrently inhibits and reverses chlamydial persistence, using a cocktail of tryptophan supplementation and levo-1-methyl tryptophan. Our approach provides a framework for the design of new therapeutic regimens and guidelines for the treatment of chronic chlamydial infections.