Mathematical modelling of the role of mucosal vaccine on the within-host dynamics of Chlamydia trachomatis.

A mathematical model of the within-host replicative dynamics of C. trachomatis infection and its interactions with the immune system, in the presence of a mucosal vaccine, is presented. Our aim is to estimate the requisite efficacy of an efficacious mucosal vaccine that could promote a stable disease-free state in vivo. Sensitivity analysis was used to quantify how variability in the model parameters influence the value of the disease threshold R0. This shows that the two most important factors to be considered for achieving a disease-free state state in vivo, based on their influence on R0, are the efficacy of the Chlamydia vaccine, and the rate at which the humoral immune response protects healthy epithelial cells from infection. Numerical simulations of the model show that a vaccine with a minimum efficacy of 86% may be required for the in vivo control of Chlamydia burden. Such effective but imperfect Chlamydia vaccine could confer long-term protective immunity to genital Chlamydia infections. Conditions under which lower vaccine efficacies may suffice are also explored.

STI-GMaS: an open-source environment for simulation of sexually-transmitted infections.

BACKGROUND: Sexually-transmitted pathogens often have severe reproductive health implications if treatment is delayed or absent, especially in females. The complex processes of disease progression, namely replication and ascension of the infection through the genital tract, span both extracellular and intracellular physiological scales, and in females can vary over the distinct phases of the menstrual cycle. The complexity of these processes, coupled with the common impossibility of obtaining comprehensive and sequential clinical data from individual human patients, makes mathematical and computational modelling valuable tools in developing our understanding of the infection, with a view to identifying new interventions. While many within-host models of sexually-transmitted infections (STIs) are available in existing literature, these models are difficult to deploy in clinical/experimental settings since simulations often require complex computational approaches. RESULTS: We present STI-GMaS (Sexually-Transmitted Infections - Graphical Modelling and Simulation), an environment for simulation of STI models, with a view to stimulating the uptake of these models within the laboratory or clinic. The software currently focuses upon the representative case-study of Chlamydia trachomatis, the most common sexually-transmitted bacterial pathogen of humans. Here, we demonstrate the use of a hybrid PDE-cellular automata model for simulation of a hypothetical Chlamydia vaccination, demonstrating the effect of a vaccine-induced antibody in preventing the infection from ascending to above the cervix. This example illustrates the ease with which existing models can be adapted to describe new studies, and its careful parameterisation within STI-GMaS facilitates future tuning to experimental data as they arise. CONCLUSIONS: STI-GMaS represents the first software designed explicitly for in-silico simulation of STI models by non-theoreticians, thus presenting a novel route to bridging the gap between computational and clinical/experimental disciplines. With the propensity for model reuse and extension, there is much scope within STI-GMaS to allow clinical and experimental studies to inform model inputs and drive future model development. Many of the modelling paradigms and software design principles deployed to date transfer readily to other STIs, both bacterial and viral; forthcoming releases of STI-GMaS will extend the software to incorporate a more diverse range of infections.

A mathematical model of chlamydial infection incorporating movement of chlamydial particles.

We present a spatiotemporal mathematical model of chlamydial infection, host immune response, and movement of infectious particles. The resulting partial differential equations model both the dynamics of the infection and changes in infection profile observed spatially along the length of the host genital tract. This model advances previous Chlamydia modelling by incorporating spatial change. Numerical solutions and model analysis are carried out, and we present a hypothesis regarding the potential for treatment and prevention of infection by increasing chlamydial particle motility.

Chlamydial infection and spatial ascension of the female genital tract: a novel hybrid cellular automata and continuum mathematical model.

Sexually transmitted chlamydial infection initially establishes in the endocervix in females, but if the infection ascends the genital tract, significant disease, including infertility, can result. Many of the mechanisms associated with chlamydial infection kinetics and disease ascension are unknown. We attempt to elucidate some of these processes by developing a novel mathematical model, using a cellular automata-partial differential equation model. We matched our model outputs to experimental data of chlamydial infection of the guinea-pig cervix and carried out sensitivity analyses to determine the relative influence of model parameters. We found that the rate of recruitment and action of innate immune cells to clear extracellular chlamydial particles and the rate of passive movement of chlamydial particles are the dominant factors in determining the early course of infection, magnitude of the peak chlamydial time course and the time of the peak. The rate of passive movement was found to be the most important factor in determining whether infection would ascend to the upper genital tract. This study highlights the importance of early innate immunity in the control of chlamydial infection and the significance of motility-diffusive properties and the adaptive immune response in the magnitude of infection and in its ascension.