Browsing by Author "Skuce, Robin"
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Item Bayesian latent class estimation of sensitivity and specificity parameters of diagnostic tests for bovine tuberculosis in chronically infected herds in Northern Ireland(Elsevier, 2018-05-01) Lahuerta-Marin, Angela; Milne, Georgina; McNair, James; Skuce, Robin; McBride, S.H.; Menzies, F.D.; McDowell, Stanley; Byrne, A.W.; Handel, I.G.; Bronsvoort, B.M. de C.In the European Union, the recommended ante-mortem diagnostic methods for bovine tuberculosis (bTB) include the single intradermal cervical comparative tuberculin (SICCT) test and the interferon-gamma (IFN- g) test as an ancillary test. The SICCT test has a moderate sensitivity (Se) and high specificity (Sp), while the IFN-g test has good Se, but a lower Sp than the SICCT test. A retrospective Bayesian latent class analysis was conducted on 71,185 cattle from 806 herds chronically infected with bTB distributed across Northern Ireland (NI) to estimate the Se and Sp of the common ante-mortem tests and meat inspection. Analyses were also performed on data stratified by farming type and herd location to explore possible differences in test performance given the heterogeneity in the population. The mean estimates in chronically infected herds were: (1) ‘standard’ SICCT: Se 40.5–57.7%, Sp 96.3–99.7%; (2) ‘severe’ SICCT: Se 49.0%–60.6%, Sp 94.4–99.4%; (3) IFN-g(bovine–avian) using a NI optical density (OD) cut-off difference of 0.05: IFN-g(B–A)NI: Se 85.8– 93.0%, Sp 75.6–96.2%; (4) IFN-g(bovine–avian) using a standard ‘commercial’ OD cut-off difference of 0.1: IFN-g(B–A)0.1: Se 83.1–92.1%, Sp 83.1–97.3%; and (5) meat inspection: Se 49.0–57.1% Se, Sp 99.1–100%. Se estimates were lower in cattle from dairy farms than from beef farms. There were no notable differences in estimates by location of herds. Certain population characteristics, such as production type, might influence the ability of bTB tests to disclose truly infected cases.Item Can We Breed Cattle for Lower Bovine TB Infectivity?(Frontiers Media, 2018-12-07) Tsairidou, Smaragda; Allen, Adrian; Banos, Georgios; Coffey, Mike; Anacleto, Osvaldo; Byrne, Andrew W.; Skuce, Robin; Glass, Elizabeth J.; Woolliams, John A.; Doeschl-Wilson, Andrea B.Host resistance and infectivity are genetic traits affecting infectious disease transmission. This Perspective discusses the potential exploitation of genetic variation in cattle infectivity, in addition to resistance, to reduce the risk, and prevalence of bovine tuberculosis (bTB). In bTB, variability in M. bovis shedding has been previously reported in cattle and wildlife hosts (badgers and wild boars), but the observed differences were attributed to dose and route of infection, rather than host genetics. This article addresses the extent to which cattle infectivity may play a role in bTB transmission, and discusses the feasibility, and potential benefits from incorporating infectivity into breeding programmes. The underlying hypothesis is that bTB infectivity, like resistance, is partly controlled by genetics. Identifying and reducing the number of cattle with high genetic infectivity, could reduce further a major risk factor for herds exposed to bTB. We outline evidence in support of this hypothesis and describe methodologies for detecting and estimating genetic parameters for infectivity. Using genetic-epidemiological predictionmodels we discuss the potential benefits of selection for reduced infectivity and increased resistance in terms of practical field measures of epidemic risk and severity. Simulations predict that adding infectivity to the breeding programme could enhance and accelerate the reduction in breakdown risk compared to selection on resistance alone. Therefore, given the recent launch of genetic evaluations for bTB resistance and the UK government’s goal to eradicate bTB, it is timely to consider the potential of integrating infectivity into breeding schemes.Item Fine-mapping host genetic variation underlying outcomes to Mycobacterium bovis infection in dairy cows(BMC, 2017-06-24) Wilkinson, S.; Bishop, S.C.; Allen, Adrian; McBride, S.H.; Skuce, Robin; Bermingham, M.; Woolliams, J.A.Background: Susceptibility to Mycobacterium bovis infection in cattle is governed in part by host genetics. However, cattle diagnosed as infected with M. bovis display varying signs of pathology. The variation in host response to infection could represent a continuum since time of exposure or distinct outcomes due to differing pathogen handling. The relationships between host genetics and variation in host response and pathological sequelae following M. bovis infection were explored by genotyping 1966 Holstein-Friesian dairy cows at 538,231 SNPs with three distinct phenotypes. These were: single intradermal cervical comparative tuberculin (SICCT) test positives with visible lesions (VLs), SICCT-positives with undetected visible lesions (NVLs) and matched controls SICCT-negative on multiple occasions. Results: Regional heritability mapping identified three loci associated with the NVL phenotype on chromosomes 17, 22 and 23, distinct to the region on chromosome 13 associated with the VL phenotype. The region on chromosome 23 was at genome-wide significance and candidate genes overlapping the mapped window included members of the bovine leukocyte antigen class IIb region, a complex known for its role in immunity and disease resistance. Chromosome heritability analysis attributed variance to six and thirteen chromosomes for the VL and NVL phenotypes, respectively, and four of these chromosomes were found to explain a proportion of the phenotypic variation for both the VL and NVL phenotype. By grouping the M. bovis outcomes (VLs and NVLs) variance was attributed to nine chromosomes. When contrasting the two M. bovis infection outcomes (VLs vs NVLs) nine chromosomes were found to harbour heritable variation. Regardless of the case phenotype under investigation, chromosome heritability did not exceed 8% indicating that the genetic control of bTB resistance consists of variants of small to moderate effect situated across many chromosomes of the bovine genome. Conclusions: These findings suggest the host genetics of M. bovis infection outcomes is governed by distinct and overlapping genetic variants. Thus, variation in the pathology of M. bovis infected cattle may be partly genetically determined and indicative of different host responses or pathogen handling. There may be at least three distinct outcomes following M. bovis exposure in dairy cattle: resistance to infection, infection resulting in pathology or no detectable pathologyItem Genomic epidemiology of Mycobacterium bovis infection in sympatric badger and cattle populations in Northern Ireland(Microbiology Society, 2023-05-25) Akhmetova, Assel; Guerrero, Jimena; McAdam, Paul; Salvador, Liliana C. M.; Crispell, Joseph; Lavery, John; Presho, Eleanor; Kao, Rowland R.; Biek, Roman; Menzies, Fraser; Trimble, Nigel; Harwood, Roland; Pepler, P. Theo; Oravcova, Katarina; Graham, Jordon; Skuce, Robin; du Plessis, Louis; Thompson, Suzan; Wright, Lorraine; Byrne, Andrew W.; Allen, AdrianBovine tuberculosis (bTB) is a costly, epidemiologically complex, multi-host, endemic disease. Lack of understanding of transmission dynamics may undermine eradication efforts. Pathogen whole-genome sequencing improves epidemiological inferences, providing a means to determine the relative importance of inter- and intra-species host transmission for disease persistence. We sequenced an exceptional data set of 619 Mycobacterium bovis isolates from badgers and cattle in a 100 km2 bTB 'hotspot' in Northern Ireland. Historical molecular subtyping data permitted the targeting of an endemic pathogen lineage, whose long-term persistence provided a unique opportunity to study disease transmission dynamics in unparalleled detail. Additionally, to assess whether badger population genetic structure was associated with the spatial distribution of pathogen genetic diversity, we microsatellite genotyped hair samples from 769 badgers trapped in this area. Birth death models and TransPhylo analyses indicated that cattle were likely driving the local epidemic, with transmission from cattle to badgers being more common than badger to cattle. Furthermore, the presence of significant badger population genetic structure in the landscape was not associated with the spatial distribution of M. bovis genetic diversity, suggesting that badger-to-badger transmission is not playing a major role in transmission dynamics. Our data were consistent with badgers playing a smaller role in transmission of M. bovis infection in this study site, compared to cattle. We hypothesize, however, that this minor role may still be important for persistence. Comparison to other areas suggests that M. bovis transmission dynamics are likely to be context dependent, with the role of wildlife being difficult to generalize.Item Phylodynamic analysis of an emergent Mycobacterium bovis outbreak in an area with no previously known wildlife infections(Wiley on behalf of British Ecological Society, 2021-11-01) Rossi, Gianluigi; Crispell, Joseph; Brough, Tanis; Lycett, Samantha J.; White, Piran C. L.; Allen, Adrian; Ellis, Richard J.; Gordon, Stephen V.; Harwood, Roland; Palkopoulou, Eleftheria; Presho, Eleanor; Skuce, Robin; Smith, Graham C.; Kao, Rowland R.1. Understanding how emergent pathogens successfully establish themselves and persist in previously unaffected populations is a crucial problem in disease ecology, with important implications for disease management. In multi-host pathogen systems this problem is particularly difficult, as the importance of each host species to transmission is often poorly characterised, and the disease epidemiology is complex. Opportunities to observe and analyse such emergent scenarios are few. 2. Here, we exploit a unique dataset combining densely collected data on the epidemiological and evolutionary characteristics of an outbreak of Mycobacterium bovis (the causative agent of bovine tuberculosis, bTB) in a population of cattle and badgers in an area considered low risk for bTB, with no previous record of either persistent infection in cattle, or of any infection in wildlife. We analyse the outbreak dynamics using a combination of mathematical modelling, Bayesian evolutionary analyses and machine learning. 3. Comparison to M. bovis whole-genome sequences from Northern Ireland confirmed this to be a pathogen single introduction from the latter region, with evolutionary analysis supporting an introduction directly into the local cattle population 6 years prior to its first discovery in badgers. 4. Once introduced, the evidence supports M. bovis epidemiological dynamics passing through two phases, the first dominated by cattle-to- cattle transmission before becoming established in the local badger population. 5. Synthesis and applications. The Mycobacterium bovis emergent outbreak that was the object of this study was of considerable concern because of the geographical distance from previously known high-risk areas. Initial decisions about the outbreak control were supported by the whole-genome sequencing data. The further analyses described here were used to estimate the time of introduction (and therefore the likely magnitude of any hidden outbreak) and the rates of cross-species transmission, and provided valuable confirmation that the extent and focus of the imposed controls were appropriate. Not only do these findings strengthen the call for genomic surveillance, but they also pave the path for future outbreaks control, providing insights for more rapid and decisive evidence-based decision-making. As the methods we used and developed are agnostic to the disease itself, they are also valuable for other slowly transmitting pathogens.Item The population and landscape genetics of the European badger (Meles meles) in Ireland(Wiley, 2018-09-12) Guerrero, Jimena; Byrne, Andrew W.; Lavery, John; Presho, Eleanor; Kelly, Gavin; Courcier, Emily A.; O’Keeffe, James; Fogarty, Ursula; O’Meara, Denise B.; Ensing, Dennis; McCormick, Carl; Biek, Roman; Skuce, Robin; Allen, AdrianThe population genetic structure of free-ranging species is expected to reflect landscape-level effects. Quantifying the role of these factors and their relative contribution often has important implications for wildlife management. The population genetics of the European badger (Meles meles) have received considerable attention, not least because the species acts as a potential wildlife reservoir for bovine tuberculosis (bTB) in Britain and Ireland. Herein, we detail the most comprehensive population and landscape genetic study of the badger in Ireland to date—comprised of 454 Irish badger samples, genotyped at 14 microsatellite loci. Bayesian and multivariate clustering methods demonstrated continuous clinal variation across the island, with potentially distinct differentiation observed in Northern Ireland. Landscape genetic analyses identified geographic distance and elevation as the primary drivers of genetic differentiation, in keeping with badgers exhibiting high levels of philopatry. Other factors hypothesized to affect gene flow, including earth worm habitat suitability, land cover type, and the River Shannon, had little to no detectable effect. By providing a more accurate picture of badger population structure and the factors effecting it, these data can guide current efforts to manage the species in Ireland and to better understand its role in bTB.Item Whole-Genome sequencing in routine Mycobacterium bovis epidemiology – scoping the potential(Microbiology Society, 2024-02-14) Allen, Adrian; Magee, Ryan; Devaney, Ryan; Ardis, Tara; McNally, Caitlín; McCormick, Carl; Presho, Eleanor; Doyle, Michael; Ranasinghe, Purnika; Johnston, Philip; Kirke, Raymond; Harwood, Roland; Farrell, Damien; Kenny, Kevin; Smith, Jordy; Gordon, Stephen; Ford, Tom; Thompson, Suzan; Wright, Lorraine; Jones, Kerri; Prodohl, Paulo; Skuce, Robin; Animal Health and WelfareMycobacterium bovis the main agent of bovine tuberculosis (bTB), presents as a series of spatially-localised micro-epidemics across landscapes. Classical molecular typing methods applied to these micro-epidemics, based on genotyping a few variable loci, have significantly improved our understanding of potential epidemiological links between outbreaks. However, they have limited utility owing to low resolution. Conversely, whole-genome sequencing (WGS) provides the highest resolution data available for molecular epidemiology, producing richer outbreak tracing, insights into phylogeography and epidemic evolutionary history. We illustrate these advantages by focusing on a common single lineage of M. bovis (1.140) from Northern Ireland. Specifically, we investigate the spatial sub-structure of 20 years of herd-level multi locus VNTR analysis (MLVA) surveillance data and WGS data from a down sampled subset of isolates of this MLVA type over the same time frame. We mapped 2108 isolate locations of MLVA type 1.140 over the years 2000–2022. We also mapped the locations of 148 contemporary WGS isolates from this lineage, over a similar geographic range, stratifying by single nucleotide polymorphism (SNP) relatedness cut-offs of 15 SNPs. We determined a putative core range for the 1.140 MLVA type and SNP-defined sequence clusters using a 50 % kernel density estimate, using cattle movement data to inform on likely sources of WGS isolates found outside of core ranges. Finally, we applied Bayesian phylogenetic methods to investigate past population history and reproductive number of the 1.140 M. bovis lineage. We demonstrate that WGS SNP-defined clusters exhibit smaller core ranges than the established MLVA type - facilitating superior disease tracing. We also demonstrate the superior functionality of WGS data in determining how this lineage was disseminated across the landscape, likely via cattle movement and to infer how its effective population size and reproductive number has been in flux since its emergence. These initial findings highlight the potential of WGS data for routine monitoring of bTB outbreaks.