Joint estimation of epidemiological and genetic processes for Mycobacterium bovis transmission dynamics in cattle and badgers

联合评估牛和獾中牛分枝杆菌传播动态的流行病学和遗传过程

• 批准号: BB/L010569/1
• 负责人: Rowland Kao
• 金额: $ 98.55万
• 依托单位: University of Glasgow
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2014
• 资助国家: 英国
• 起止时间: 2014 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FL010569%2F1
• 关键词: Joint; estimation; epidemiological; genetic; processes; Joint; estimation; epidemiological; genetic; processes

The control and eradication of infectious diseases can be difficult for pathogens that are able to persist in multiple host species. This is the case for bovine tuberculosis (bTB), a disease primarily affecting cattle but also found in a number of wildlife species; in Britain and Ireland, the most important of these is the Eurasian badger (Meles meles). While Ireland has had a persistent bTB problem in cattle, by the 1970's bTB had been almost eradicated from Great Britain but since then the has been a dramatically re-emerging disease in cattle. BTB is a zoonosis with implications for both human and animal health, though chronic cases of either in Britain and Ireland are few. Control of bTB also places a severe strain on individual farmers, the farming industry and government, with a projected cost in England and Wales alone of over £1bn over the next decade. While it has long been suspected that badgers are involved, research efforts to date have not determined the extent to which badgers are responsible for eradicating bTB from cattle, and this topic is the subject of great social and political controversy. One of the most important developments in epidemiology of the last few decades has been the increased use of 'genetic fingerprinting' to identify patterns of disease spread. Until recently, this has largely been done using only a small number of selected regions in the genome. While this kind of "genetic fingerprinting" has been very useful and shows that cattle and badgers in the same region are usually infected by the same bTB strain, the fingerprints are far from unique: many cattle and many badgers share the same type, making it impossible to determine who infected whom. In this project, we will take advantage of novel technology making it feasible and affordable to sequence the entire M. bovis genome for large numbers of samples. Because the bacterium occasionally makes mistakes while replicating its genome, new mutations constantly arise not seen using traditional fingerprinting methods but with the new technology creating a much more unique and discriminatory genetic fingerprint of transmission. Using samples collected over decades from cattle and badgers in Great Britain and Northern Ireland, we will sequence the genomes of hundreds of isolates to genetically track the spread of the pathogen and to test whether it is predominantly maintained in cattle, in badgers, or both. The unique opportunity exploited in this proposal is the availability of extraordinarily dense sampling of cattle and badgers infection together with entire life histories of individual cattle, including movement to other farms and whether it became infected with bTB at some point of its life. This creates an exceptional resource, allowing us to compare our very detailed understanding of contacts between cattle and between herds with the genetic fingerprint information. Based on this information, we will use mathematical models linked directly to statistical inference methods to simulate how the infection may have spread through cattle populations in Britain and Ireland and how it may have genetically changed in the process. This will be done under various different assumptions about the multiple possible sources and mechanisms of infection. By comparing our simulated results to the actual observations (e.g. the number of infected cattle and the type of bTB they carry, etc), we will gain unprecedented insight into the drivers for the spread of the disease and what may prevent its current control.

对于能够在多种宿主物种中持续存在的病原体而言，传染病的控制和放疗可能很难。牛结核病（BTB）就是这种情况，这种疾病主要影响牛，但在许多野生动植物物种中也发现。在英国和爱尔兰，其中最重要的是欧亚badge（Meles Meles）。虽然爱尔兰在牛的BTB问题持续存在，但到1970年代，BTB几乎从英国放射了放射性，但是从那时起，这种BTB一直是一种动态重新出现的牛的疾病。 BTB是人畜共患病，对人类和动物健康都有影响，尽管在英国和爱尔兰的慢性病很少。 BTB的控制还给个别农民，农业和政府带来了严重的压力，在未来十年中，英格兰和威尔士预计的成本将超过10亿英镑。虽然长期以来一直怀疑参与了badge，但迄今为止的研究工作尚未确定badge从牛根除BTB的程度，而这个话题是巨大的社会和政治争议的主题。过去几十年流行病学中最重要的发展之一是增加使用“遗传指纹”来识别疾病传播模式。直到最近，这在很大程度上仅使用基因组中的少数选定区域进行。尽管这种“遗传指纹”非常有用，并且表明同一地区的牛和badge通常被同一BTB菌株感染，但指纹远非独特：许多牛和许多badge犬共享相同的类型，使得无法确定谁感染了谁。在这个项目中，我们将利用新颖的技术，使其可行且负担得起，可以为整个Bovis基因组对大量样品进行测序。由于细菌偶尔会在复制其基因组的同时犯错误，因此不断出现新的突变，而没有使用传统的指纹方法，而是通过新技术创造了更独特和歧视性的传播遗传指纹。使用数十年来从牛和英国和北爱尔兰收集的样品，我们将对数百种分离株的基因组进行序列，以在遗传上跟踪病原体的传播，并测试它是否主要在牛，badge中或两者兼而有之。该提案中探索的独特机会是，对牛和badge虫感染的非常密集的采样以及单个牛的整个生活历史，包括向其他农场的运动以及它是否在其生活的某个时候感染了BTB。这创建了一个非凡的资源，使我们能够比较我们对牛之间和牛群之间的接触的非常详细的理解与遗传指纹信息。基于这些信息，我们将使用与统计推断方法直接相关的数学模型来模拟感染如何通过英国和爱尔兰的牛群传播，以及在此过程中它如何在基因上改变。这将在各种关于感染的多种可能来源和机制的不同假设下进行。通过将我们的模拟结果与实际观察结果进行比较（例如，感染的牛的数量和携带的BTB的类型等），我们将获得对疾病传播的驱动因素的前所未有的见解，以及可能阻止其当前控制的疾病。