Bilateral BBSRC-SFI: Tackling a multi-host pathogen problem - phylodynamic analyses of the epidemiology of M. bovis in Britain and Ireland

感染不止一个宿主物种的疾病可能特别难以控制，众所周知的例子包括禽流感(在野生鸟类、家禽和人类中)、狂犬病(在狗和人中)、布鲁氏菌病(在牲畜和人中)和埃博拉病毒(在灵长类动物和人中)。如果其中一个或多个是野生动物物种，控制可能会被证明是特别困难的。野生动物更难观察，更难接近疾病控制的目的，我们往往需要平衡疾病控制的要求和野生动物保护的需要。由于所有这些原因，在这些“多宿主”系统中，确定疾病传播的根本原因并量化疾病控制的影响是一个具有挑战性的问题，当人类管理导致本身增加疾病风险的生态干扰时，这个问题就会加剧。在理清潜在的传播来源和途径方面，一个日益重要的工具是对从感染者身上提取的致病病原体进行大规模“全基因组测序”。通过跟踪疾病病原体在个人之间传播过程中遗传密码的变化，并将其与计算机模型结合起来，这些计算机模型考虑了我们拥有的关于疾病传播的其他信息(例如，谁与谁接触过，何时，以及个人感染了多长时间)，这些数据提供了识别“谁感染了谁”的最佳机会--如果不是在个人层面上，那么至少在没有这种信息的情况下是不可能的水平。重要的是，它帮助我们确定不同物种在这些多物种系统中的重要性，并帮助我们最好地确定如何控制疾病。然而，由于这些技术和它们的这些用途仍然是相对较新的，重要的是有好的、经过充分研究的系统，我们可以在上面测试和了解如何最好地使用它们。一个表现出所有这些特征的疾病问题是牛和獾的牛结核病(BTB)，它具有特殊的信息，本身也是一个重要的问题。据估计，BTB每年给英国造成约1亿GB的损失，导致每年数千头牛被屠宰，对农民、兽医，特别是现有感染(如艾滋病毒/艾滋病)的个人来说，是一种人畜共患风险。众所周知，獾参与了这种疾病向牛的传播，如果没有某种形式的针对獾的疾病控制，就不可能根除这种疾病。由于任何有效的疫苗还需要很多年的时间，獾的扑杀是一种重要的潜在控制手段，但因为獾是受保护和深受喜爱的物种，所以它极具争议性。关于扑杀价值的相互矛盾的证据加剧了这一争议，英格兰的审判表明，它引发了一种社会‘扰动效应’，使扑杀变得不切实际，而爱尔兰共和国的审判表明，它可以有效。在这个项目中，我们的目标是在现有工作的基础上，利用爱尔兰牛和獾对獾种群的特殊记录，生成爱尔兰牛和獾的btb序列。利用基于“社会网络”原理的数学模型来帮助我们理解这些数据，我们的目标是对比爱尔兰和英格兰对btb的控制，爱尔兰长期以来一直广泛使用獾扑杀，而北爱尔兰和英格兰则没有。这将使我们能够估计獾扑杀在英格兰可能产生的潜在好处，以及如果爱尔兰停止扑杀努力的潜在影响。因此，该项目不仅对控制牛的结核病有直接的好处，而且在开发新的方法和见解方面也有长期的好处，这些方法和见解将提高我们对多宿主疾病的概念性理解，以及生态干扰在人畜共患病发生和传播中所起的作用。

Diseases that infect more than one host species can be particularly difficult to control, and well known examples include avian influenza (in wild birds, poultry and humans), rabies (in dogs and humans), Brucellosis (in livestock and humans) and Ebola virus (in primates and humans). If one or more of those is a wildlife species, control can prove particularly difficult. Wildlife are harder to observe, harder to access for purposes of disease control, and often we need to counterbalance the requirements of disease control with the needs of wildlife conservation. For all these reasons, identifying the root causes of disease transmission and quantifying the impact of disease control is a challenging problem in these 'multi-host' systems, a problem that is exacerbated when human management results in ecological disturbances that in themselves increase disease risk. An increasingly important tool in disentangling potential sources and routes of transmission is the deployment of mass "whole genome sequencing" of the causative agent of disease, taken from infected individuals. By tracking changes in the genetic code of the disease agent as it passes from individual to individual, and combining them with computer models that take into account other information we have on the transmission of disease (e.g. who was in contact with whom, and when, and how long individuals are infectious for) these data provide the best opportunity to identify 'who infected whom' - if not on the individual level, then at least at a level that is impossible without this kind of information. Importantly, it helps us to identify how important the different species are in these multi-species systems and also helps us to best identify how to control the disease. However, because these technologies and these uses of them are still relatively new, it is important to have good, well studied systems on which we can test and understand how best to use them.One disease problem which exhibits all these characteristics, has exceptional information and also represents an important problem in itself is bovine Tuberculosis (bTB) in cattle and badgers. BTB is estimated to cost the UK about £100 million per year, results in thousands of cattle slaughtered every year, and is a zoonotic risk to farmers, veterinarians and in particular individuals with compromising existing infections (e.g. HIV/AIDS). Badgers are known to be involved in the transmission of the disease to cattle and without some form of badger-targeted disease control, it will be impossible to eradicate. With any effective vaccine still many years away, badger culling is an important potential means of control but because badgers are a protected and much-loved species, it is highly controversial. This controversy is made worse by conflicting evidence regarding the value of culling, with trial culls in England suggesting that it induces a social 'perturbation effect' that makes culling impractical, while trials in the Republic of Ireland indicating it can be effective. In this project, we shall aim to build upon existing work and generate sequences for bTB in Irish cattle and badgers, taking advantage of the exceptional record they have of their badger population. Using mathematical models based on principles of 'social networks' to help us understand these data, we aim to contrast the control of bTB in Ireland, where badger culling has long been extensively used, with Northern Ireland and England, where it is not. This will allow us to estimate the potential benefit, if any, that badger culling could play in England, and the potential impact should culling efforts cease in Ireland. Thus this project will be of both immediate benefit to the control of bTB in cattle, but also have long term benefit in developing new approaches and insights that will improve our conceptual understanding of multi-host diseases, and the role that ecological disturbance plays in zoonotic disease emergence and spread.