Browsing by Author "Kao, Rowland R."
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Item 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 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.