Browsing by Author "McCormick, Carl"
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Item A new phylodynamic model of Mycobacterium bovis transmission in a multi-host system uncovers the role of the unobserved reservoir(Public Library of Science, 2021-06-25) O'Hare, Anthony; Balaz, Daniel; Wright, David M.; McCormick, Carl; McDowell, Stanley W.J.; Trewby, Hannah; Skuce, Robin A.; Kao, Rowland r.For single host pathogens, pathogen genetic data have been transformative for understanding the transmission and control of many diseases, particuarly rapidly evolving RNA viruses. However garnering similar insights where pathogens are multi-host is more challenging, particularly when the evolution of the pathogen is slower and pathogen sampling often heavily biased. This is the case for Mycobacterium bovis, the causative agent of bovine Tuberculosis (bTB) and for which the Eurasian badger plays an as yet poorly understood role in transmission and spread. Here we have developed a computational model that incorporates M. bovis genetic data from cattle only with a highly abstracted model of an unobserved reservoir. Our research shows that a model in which the reservoir does not contribute to pathogen diversity, but is a source of infection in spatially localised areas around each farm, better describes the patterns of outbreaks observed in a population-level sample of a single M. bovis genotype in Northern Ireland over a period of 15 years, compared to models in which either the reservoir has no role, disease spread is spatially extensive, or where they generate considerable diversity on their own. While this reservoir model is not explicitly a model of badgers, its characteristics are consistent with other data that would suggest a reservoir consisting of infected badgers that contribute substantially to cattle infection, but could not maintain disease on their own.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 Relative abundance of Mycobacterium bovis molecular types in cattle: a simulation study of potential epidemiological drivers(BMC, 2017-08-22) Trewby, Hannah; Wright, David M.; Skuce, Robin A.; McCormick, Carl; Mallon, Thomas R.; Presho, Eleanor L.; Kao, Rowland R.; Haydon, Daniel T.; Biek, RomanBackground: The patterns of relative species abundance are commonly studied in ecology and epidemiology to provide insights into underlying dynamical processes. Molecular types (MVLA-types) of Mycobacterium bovis, the causal agent of bovine tuberculosis, are now routinely recorded in culture-confirmed bovine tuberculosis cases in Northern Ireland. In this study, we use ecological approaches and simulation modelling to investigate the distribution of relative abundances of MVLA-types and its potential drivers. We explore four biologically plausible hypotheses regarding the processes driving molecular type relative abundances: sampling and speciation; structuring of the pathogen population; historical changes in population size; and transmission heterogeneity (superspreading). Results: Northern Irish herd-level MVLA-type surveillance shows a right-skewed distribution of MVLA-types, with a small number of types present at very high frequencies and the majority of types very rare. We demonstrate that this skew is too extreme to be accounted for by simple neutral ecological processes. Simulation results indicate that the process of MVLA-type speciation and the manner in which the MVLA-typing loci were chosen in Northern Ireland cannot account for the observed skew. Similarly, we find that pathogen population structure, assuming for example a reservoir of infection in a separate host, would drive the relative abundance distribution in the opposite direction to that observed, generating more even abundances of molecular types. However, we find that historical increases in bovine tuberculosis prevalence and/or transmission heterogeneity (superspreading) are both capable of generating the skewed MVLA-type distribution, consistent with findings of previous work examining the distribution of molecular types in human tuberculosis. Conclusion: Although the distribution of MVLA-type abundances does not fit classical neutral predictions, our simulations show that increases in pathogen population size and/or superspreading are consistent with the pattern observed, even in the absence of selective pressures acting on the system.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.