Mathematical analysis of a tuberculosis model with imperfect vaccine

Abstract

Since 1921, the Bacille Calmette–Guerin (BCG) vaccine continues to be the most widely used vaccine for the prevention of Tuberculosis (TB). However, the immunity induced by BCG wanes out after some time making the vaccinated individual susceptible to TB infection. In this work, we formulate a mathematical model that incorporates the vaccination of newly born children and older susceptible individuals in the transmission dynamics of TB in a population, with a vaccine that can confer protection on older susceptible individuals. In the absence of disease-induced deaths, the model is shown to undergo the phenomenon of backward bifurcation where a stable disease-free equilibrium (DFE) co-exists with a stable positive (endemic) equilibrium when the associated reproduction number is less than unity. It is shown that this phenomenon does not exist in the absence of imperfect vaccine, exogenous reinfection, and reinfection of previously treated individuals. It is further shown that a special case of the model has a unique endemic equilibrium point (EEP), which is globally asymptotically stable when the associated reproduction number exceeds unity. Uncertainty and sensitivity analysis are carried out to identify key parameters that have the greatest influence on the transmission dynamics of TB in the population using the total population of latently infected individuals, total number of actively infected individuals, disease incidence, and the effective reproduction number as output responses. The analysis shows that the top five parameters of the model that have the greatest influence on the effective reproduction number of the model are the transmission rate, the fraction of fast disease progression, modification parameter which accounts for reduced likelihood to infection by vaccinated individuals due to imperfect vaccine, rate of progression from latent to active TB, and the treatment rate of actively infected individuals, with other key parameters influencing the outcomes of the other output responses. Numerical simulations suggest that with higher vaccination rate of older susceptible individuals, fewer new born children need to be vaccinated, in order to achieve disease eradication.