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

基本信息

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

项目摘要

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来说，控制和根除传染病可能很困难，牛结核病（bTB）就是这种疾病，这种疾病主要影响牛，但在英国的许多野生动物物种中也发现了这种疾病。在爱尔兰和爱尔兰，其中最重要的是欧亚獾（Meles meles），虽然爱尔兰牛的 bTB 问题一直存在，但到 1970 年代，bTB 已在英国几乎根除。 BTB 是一种在牛中重新出现的疾病，它是一种对人类和动物健康都有影响的人畜共患病，尽管在英国和爱尔兰，BTB 的慢性病例很少，但 BTB 的控制也给个体农民和农业带来了严重的压力。预计未来十年，仅英格兰和威尔士的成本就将超过 10 亿英镑。虽然长期以来人们一直怀疑獾参与其中，但迄今为止的研究工作尚未确定獾在多大程度上对根除 bTB 负有责任。来自牛，这个话题是过去几十年来，流行病学最重要的发展之一是越来越多地使用“基因指纹”来识别疾病传播模式，直到最近，这在很大程度上仅使用一种方法来完成。虽然这种“基因指纹”非常有用，并且表明同一区域的牛和獾通常感染相同的 bTB 菌株，但指纹远非唯一：许多牛和獾都感染了相同的 bTB 菌株。许多獾具有相同的类型，因此在这个项目中，我们将利用新技术，使对大量样本的整个牛分枝杆菌基因组进行测序变得可行且经济实惠，因为这种细菌在复制其基因组时偶尔会犯错误，产生新的突变。使用传统指纹识别方法无法看到的病毒不断出现，但随着新技术创造出更加独特和更具歧视性的传播基因指纹，我们将使用数十年来从英国和北爱尔兰的牛和獾身上收集的样本，对数百个分离株的基因组进行测序。从基因上追踪病毒的传播该提案利用的独特机会是对牛和獾感染进行极其密集的采样以及个体牛的整个生活史，包括迁徙。其他农场以及它是否在其生命的某个阶段感染了 bTB，这创造了一个特殊的资源，使我们能够将我们对牛之间和牛群之间的接触的非常详细的了解与基因指纹信息进行比较。使用与统计推断直接相关的数学模型通过比较我们的模拟结果，模拟感染如何在英国和爱尔兰的牛群中传播以及在此过程中如何发生基因变化。根据实际观察结果（例如受感染的牛的数量和它们携带的bTB类型等），我们将对疾病传播的驱动因素以及可能阻碍其当前控制的因素获得前所未有的洞察。

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Using whole genome sequencing to investigate transmission in a multi-host system: bovine tuberculosis in New Zealand.

DOI：
10.1186/s12864-017-3569-x
发表时间：
2017-02-16
期刊：
BMC genomics
影响因子：
4.4
作者：
Crispell J;Zadoks RN;Harris SR;Paterson B;Collins DM;de-Lisle GW;Livingstone P;Neill MA;Biek R;Lycett SJ;Kao RR;Price-Carter M
通讯作者：
Price-Carter M

Measurably evolving pathogens in the genomic era.

DOI：
10.1016/j.tree.2015.03.009
发表时间：
2015-06
期刊：
Trends in ecology & evolution
影响因子：
16.8
作者：
Biek R;Pybus OG;Lloyd-Smith JO;Didelot X
通讯作者：
Didelot X

Genome-Wide Diversity and Phylogeography of Mycobacterium avium subsp. paratuberculosis in Canadian Dairy Cattle.

DOI：
10.1371/journal.pone.0149017
发表时间：
2016
期刊：
PloS one
影响因子：
3.7
作者：
Ahlstrom C;Barkema HW;Stevenson K;Zadoks RN;Biek R;Kao R;Trewby H;Haupstein D;Kelton DF;Fecteau G;Labrecque O;Keefe GP;McKenna SL;Tahlan K;De Buck J
通讯作者：
De Buck J

Genome epidemiology of Mycobacterium bovis infection in contemporaneous, sympatric badger and cattle populations in Northern Ireland