COVID-19 transmission dynamics and the impact of vaccination: modelling, analysis and simulations.

Despite the lifting of COVID-19 restrictions, the COVID-19 pandemic and its effects remain a global challenge including the sub-Saharan Africa (SSA) region. Knowledge of the COVID-19 dynamics and its potential trends amidst variations in COVID-19 vaccine coverage is therefore crucial for policy makers in the SSA region where vaccine uptake is generally lower than in high-income countries. Using a compartmental epidemiological model, this study aims to forecast the potential COVID-19 trends and determine how long a wave could be, taking into consideration the current vaccination rates. The model is calibrated using South African reported data for the first four waves of COVID-19, and the data for the fifth wave are used to test the validity of the model forecast. The model is qualitatively analysed by determining equilibria and their stability, calculating the basic reproduction number R0 and investigating the local and global sensitivity analysis with respect to R0. The impact of vaccination and control interventions are investigated via a series of numerical simulations. Based on the fitted data and simulations, we observed that massive vaccination would only be beneficial (deaths averting) if a highly effective vaccine is used, particularly in combination with non-pharmaceutical interventions. Furthermore, our forecasts demonstrate that increased vaccination coverage in SSA increases population immunity leading to low daily infection numbers in potential future waves. Our findings could be helpful in guiding policy makers and governments in designing vaccination strategies and the implementation of other COVID-19 mitigation strategies.

Mathematical Analysis of a Mathematical Model of Chemovirotherapy: Effect of Drug Infusion Method.

A mathematical model for the treatment of cancer using chemovirotherapy is developed with the aim of determining the efficacy of three drug infusion methods: constant, single bolus, and periodic treatments. The model is in the form of ODEs and is further extended into DDEs to account for delays as a result of the infection of tumor cells by the virus and chemotherapeutic drug responses. Analysis of the model is carried out for each of the three drug infusion methods. Analytic solutions are determined where possible and stability analysis of both steady state solutions for the ODEs and DDEs is presented. The results indicate that constant and periodic drug infusion methods are more efficient compared to a single bolus injection. Numerical simulations show that with a large virus burst size, irrespective of the drug infusion method, chemovirotherapy is highly effective compared to either treatments. The simulations further show that both delays increase the period within which a tumor can be cleared from body tissue.

Mathematical analysis of a tumour-immune interaction model: A moving boundary problem.

A spatio-temporal mathematical model, in the form of a moving boundary problem, to explain cancer dormancy is developed. Analysis of the model is carried out for both temporal and spatio-temporal cases. Stability analysis and numerical simulations of the temporal model replicate experimental observations of immune-induced tumour dormancy. Travelling wave solutions of the spatio-temporal model are determined using the hyperbolic tangent method and minimum wave speeds of invasion are calculated. Travelling wave analysis depicts that cell invasion dynamics are mainly driven by their motion and growth rates. A stability analysis of the spatio-temporal model shows a possibility of dynamical stabilization of the tumour-free steady state. Simulation results reveal that the tumour swells to a dormant level.

Enhancement of chemotherapy using oncolytic virotherapy: Mathematical and optimal control analysis.

Oncolytic virotherapy has been emerging as a promising novel cancer treatment which may be further combined with the existing therapeutic modalities to enhance their effects. To investigate how virotherapy could enhance chemotherapy, we propose an ODE based mathematical model describing the interactions between tumour cells, the immune response, and a treatment combination with chemotherapy and oncolytic viruses. Stability analysis of the model with constant chemotherapy treatment rates shows that without any form of treatment, a tumour would grow to its maximum size. It also demonstrates that chemotherapy alone is capable of clearing tumour cells provided that the drug efficacy is greater than the intrinsic tumour growth rate. Furthermore, virotherapy alone may not be able to clear tumour cells from body tissue but would rather enhance chemotherapy if viruses with high viral potency are used. To assess the combined effect of virotherapy and chemotherapy we use the forward sensitivity index to perform a sensitivity analysis, with respect to chemotherapy key parameters, of the virus basic reproductive number and the tumour endemic equilibrium. The results from this sensitivity analysis indicate the existence of a critical dose of chemotherapy above which no further significant reduction in the tumour population can be observed. Numerical simulations show that a successful combinational therapy of the chemotherapeutic drugs and viruses depends mostly on the virus burst size, infection rate, and the amount of drugs supplied. Optimal control analysis was performed, by means of the Pontryagin's maximum principle, to further refine predictions of the model with constant treatment rates by accounting for the treatment costs and sides effects. Results from this analysis suggest that the optimal drug and virus combination correspond to half their maximum tolerated doses. This is in agreement with the results from stability and sensitivity analyses.

Modelling the spatiotemporal dynamics of chemovirotherapy cancer treatment.

Chemovirotherapy is a combination therapy with chemotherapy and oncolytic viruses. It is gaining more interest and attracting more attention in the clinical setting due to its effective therapy and potential synergistic interactions against cancer. In this paper, we develop and analyse a mathematical model in the form of parabolic non-linear partial differential equations to investigate the spatiotemporal dynamics of tumour cells under chemovirotherapy treatment. The proposed model consists of uninfected and infected tumour cells, a free virus, and a chemotherapeutic drug. The analysis of the model is carried out for both the temporal and spatiotemporal cases. Travelling wave solutions to the spatiotemporal model are used to determine the minimum wave speed of tumour invasion. A sensitivity analysis is performed on the model parameters to establish the key parameters that promote cancer remission during chemovirotherapy treatment. Model analysis of the temporal model suggests that virus burst size and virus infection rate determine the success of the virotherapy treatment, whereas travelling wave solutions to the spatiotemporal model show that tumour diffusivity and growth rate are critical during chemovirotherapy. Simulation results reveal that chemovirotherapy is more effective and a good alternative to either chemotherapy or virotherapy, which is in agreement with the recent experimental studies.

Analysis of virotherapy in solid tumor invasion.

Cancer treatment is an inexact science despite traditional cancer therapies. The traditional cancer treatments have high levels of toxicity and relatively low efficacy. Current research and clinical trials have indicated that virotherapy, a procedure which uses replication-competent viruses to kill cancer cells, has less toxicity and a high efficacy. However, the interaction dynamics of the tumor host, the virus, and the immune response is poorly understood due to its complexity. We present a mathematical analysis of models that study tumor-immune-virus interactions in the form of differential equations with spatial effects. A stability analysis is presented and we obtained analytical traveling wave solutions. Numerical simulations were obtained using fourth order Runge-Kutta and Crank-Nicholson methods. We show that the use of viruses as a cancer treatment can reduce the tumor cell concentration to a very low cancer dormant steady state or possibly deplete all tumor cells in body tissue. The traveling waves indicated an exponential increase and decrease in the cytotoxic-T-lymphocytes (CTLs) density and tumor load in the long term respectively.

Effect of immunotherapy on the response of TICLs to solid tumour invasion.

There is clinical evidence that some people have lived with a benign tumour for their entire life time. This is explained by cancer dormancy which is attributed to the interaction of tumour infiltrating cytotoxic lymphocytes (TICLs) with tumour cells. We present two mathematical models to study the mechanism of interaction of TICLs with tumour cells, with and without clinical intervention. Stability analysis and numerical simulations of the models reveal the existence of a stable tumour dormant state.