Multiscale Modelling of Hepatic Viral Infection

Abstract

The multiscale modelling of hepatic viral infection was introduced in this work and various approaches were carried out to contribute effectively to the control and eradication of viral hepatitis in sub-saharan Africa. A nested multiscale model was developed by applying the Replication-Transmission Theory at the cell level of biological organisation. In addition, a hybrid model was developed with the inclusion of the life-cycle of the pathogen which represents the within-cell submodel of the nested multiscale model and the comparative analysis of the two models were carried out. Stochasticity was incorporated into the nested multiscale modeling and it was analysed mathematically and computationally to understand their effects and influences on the control and eradication of the pathogen in the study of infectious disease systems. The mathematical and numerical analysis of various models developed were carried out and the effects of within-scale were analysed to justify the preferability of multiscale model over single scale model of infectious disease system. The heterogeneity of the models were also considered by introducing stochasticity to the multiscale model addresses the problem of the emergence of resistance in the treatment of viral heptitis as well as drug resistance. Throughout the study, the focus was on process-based multiscale modeling, which is rooted in the Replication-Transmission Relativity Theory. This approach aimed to determine the suitability of nested multiscale models compared to hybrid models for a comprehensive and detailed understanding of multiscale modelling in hepatic viral infection studies. The multiscale models developed have the potential to assess the efficacy of control and preventive interventions, especially when integrated with mechanism-based multiscale modelling of hepatic viral infections. The formulated models showed that the within-cell time scale, the between-cell time scale and the age of infection should be taken into consideration in the formulation of a model that will incorporate both medical and health interventions for the effective treatment of hepatic viral infections. This study gives a better description of dynamics of the disease with significant complex behaviours observed at different level of biological organisation compared to when the dynamics of the disease is investigated at only one time scale.