The interaction between host demography and tuberculosis transmission: disease dynamics, control and evolution.

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TB is the leading single cause of death in humans due to an infectious agent. Approximately 30% of the world's population is latently infected and 0.1% has active disease. TB is characterised by long-term asymptomatic infection that can progress to active disease years or decades after exposure. Active disease can produce a persistent cough, fever, weight loss and, if untreated, death in approximately 50% of cases. In recent years rates have escalated due to the interaction with the HIV epidemic and the emergence of drug resistant strains. TB affects many other mammals as well as humans. Bovine TB is endemic in many domestic cattle populations. Transmission to humans can occur via contaminated milk or direct contact. In Great Britain, bovine TB is one of the most complex and persistent problems facing the cattle industry, with an estimated annual cost of 90 million. Transmission of bovine TB between farms occurs via a combination of local infection and the movement of infected animals. While much less is understood about the natural history of disease in cattle, many of the principles involved in understanding TB spread apply to both humans and cattle. Mathematical models are used to predict how TB will spread in a population and the kind of interventions that might lead to eradication. Models include factors that are known to affect the spread of TB such as stress or overcrowding. Furthermore, progression rates are highly dependent on age of infection. This means that an ageing population is very different, in terms of TB, than a population with high birth rates. The effect of changing demography on TB spread has not been investigated in TB models, and so predictions about how to control the disease are not as accurate as they could be. This project will develop a new, comprehensive framework to understand the transmission dynamics and evolution of chronic diseases, with a particular focus on TB. The framework will be flexible to the needs of TB epidemiologists by incorporating transmission, age-dependent immune response, demographic changes and variation in genetic susceptibility.