A mathematical immuno-epidemiological framework for co-infection

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With the advent of the germ theory of disease, understanding the mechanisms of pathogen propagation and survival has formed a major branch of the natural sciences. Mathematical immunology (in a host) and epidemiology (in a population) have contributed to the study of infectious diseases. Recently, the field of immuno-epidemiology, whereby immunological characteristics are incorporated into epidemiological models, has been developed so that a better understanding of effects of pathogen and immune system interactions on disease transmission and persistence in a population can be gained. This applied mathematics proposal focuses on the development of a mathematical immuno-epidemiological framework for co-infection, when two pathogens simultaneously infect a host, and a population. Our overriding objective is to understand how synergism between co-infecting pathogens influence disease progression and propagation. As a model system, we will focus on the globally relevant Human Immunodeficiency Virus- mycobacterium Tuberculosis (HIV-TB) co-infection. TB and HIV are both diseases which plague the globe. These diseases also contribute to the propagation of the other in-host and in a population. By defining the parameters critical to HIV-TB co-infection, this work will provide an enhanced understanding of the effects of synergy in pathogenesis and, ultimately, a basis for the improved care of HIV/TB patients. The primary research outcome of the proposed work will be a mathematically tractable and biologically relevant immuno-epidemiological modelling framework of co-infection. New mathematical and computational tools will result in the areas of global stability analysis, bifurcation theory, moment closure and stochastic modelling. Theory and techniques for qualitative analysis of the large systems are developed, as well as robust and efficient numerical and stochastic tools. These approaches can readily be translated to other co-infection systems (i.e. Leishmaniasis-HIV, HIV-HBV, etc), extended to study drug therapy and vaccination limitations/effectiveness, and to study infection spread in a network of populations linked by travel.