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

点击翻译按钮获取中文摘要

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.