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

结核病是传染性病原体导致人类死亡的主要单一原因。世界上大约30%的人口处于潜伏感染状态，0.1%的人口处于活动性疾病。结核病的特点是长期无症状感染，可在接触后数年或数十年发展为活动性疾病。活动性疾病可导致持续咳嗽、发烧、体重减轻，如果不治疗，约50%的病例会死亡。近年来，由于与艾滋病毒流行的相互作用和耐药菌株的出现，发病率有所上升。结核病不仅影响人类，也影响许多其他哺乳动物。牛结核病在许多家畜种群中流行。人类可通过受污染的牛奶或直接接触传播。在英国，牛结核病是养牛业面临的最复杂和最持久的问题之一，估计每年花费9000万英镑。牛结核病在农场之间的传播是通过当地感染和受感染动物的移动共同发生的。虽然人们对牛患病的自然历史知之甚少，但了解结核病传播的许多原则同时适用于人类和牛。数学模型被用来预测结核病将如何在人群中传播，以及可能导致根除结核病的干预措施。模型包括已知影响结核病传播的因素，如压力或过度拥挤。此外，进展率高度依赖于感染年龄。这意味着，就结核病而言，老龄化人口与高出生率人口是非常不同的。人口结构变化对结核病传播的影响还没有在结核病模型中进行研究，因此关于如何控制这种疾病的预测并不像它们可能的那样准确。该项目将制定一个新的全面框架，以了解慢性病的传播动态和演变，特别侧重于结核病。该框架将结合传播、年龄依赖性免疫反应、人口统计学变化和遗传易感性变异，灵活适应结核病流行病学家的需要。

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.