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<ol><li>Quantify the spatial scale at which M. bovis circulates locally in cattle and badgers - usiing the concept of a cosical network community to organise the clade structure of thiinferred phylogeny. Characteristic spatial scoales for local cirucuation of M. bovis will be identified and a sampling strategy to capture the spatial patterns willb e determined.</li>
<li>Quantify transmission arisinig from cattle only epidemics using genetic and epidemiological data. An estimate will be made for the role of unobserved infections in cattle for the within-herd persistence of M. bovis. Different models of M. bovis murtation rates will be compared. Parameter distributions will be infered for use as priors for cattle to cattle transmissionin High Incidence Areas (HIA's)</li>
<li>Characterise the badger-cattle interaction. Unsing data from Woodchester Park and the Northern Irelend TVR study, genetic diversity of M. bovis in symatric catttle and badger populations will be compared. the relationsheips between badger and cattle isolates will be characterised in terms of spatio-temporal network and builiing on (2) and other work, a herd/social-group scale model of badger-cattle interactionsw ill be developed.</li>
<li>An integrated miltiscale modelling framework combining genetic and epidemiological date will be developed and used to predict the spatial spread and persistence of bTB in the combined two-host system. </li></ol>
<p>The control and eradication of infectious diseases can be difficult for pathogens that are able to perisit in multiple host species. This is the case for bovine tuberculosis (bTB), a disease primarily of cattle but also found in a number of wildife 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 GB but since then there has been a dramatically re-emerging disease in cattle. Bovine TB is a zoonosis with implications for both humans 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 & 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 determied the extent to which badgers are responsible for bTB in cattle.</p>
<p>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 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 which are not seen using traditional fingerprinting methods but with the new technolgoy creating a much more unique and discriminatory genetic fingerprint of transmission. Using samples collected over decades from cattle and badgers in GB and NI 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 badger infection together with entire life histories of individual cattle, inlciuding movement to other farms and whether it became infected with bTB at some point in 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 it's current control. </p>