Variation in Mycobacterium bovis genetic richness suggests that inwards cattle movements are a more important source of infection in beef herds than in dairy herds

Publication history: Accepted - 25 June 2019; Published online - July 2019Background We used genetic Multi-Locus VNTR Analysis (MLVA) data gathered from surveillance efforts to better understand the ongoing bovine tuberculosis (bTB) epidemic in Northern Irish cattle herds. We modelled the factors associated with Mycobacterium bovis MLVA genotype richness at three analytical scales; breakdown level, herd level, and patch level, and compared the results between dairy and non-dairy production types. Results In 83% of breakdowns and in 63% of herds, a single MLVA genotype was isolated. Five or more MLVA genotypes were found in less than 3 % of herds. Herd size and the total number of reactors were important explanatory variables, suggesting that increasing MLVA genotype richness was positively related to increases in the number of host animals. Despite their smaller relative size, however, the highest MLVA genotype richness values were observed in non-dairy herds. Increasing inwards cattle movements were important positive predictors of MLVA genotype richness, but mainly in non-dairy settings. Conclusions The principal finding is that low MLVA genotype richness indicates that small-scale epidemics, e.g. wildlife, contiguous farms, and within-herd recrudescence, are important routes of M. bovis infection in cattle herds. We hypothesise that these mechanisms will maintain, but may not explicitly increase, MLVA genotype richness. The presence of elevated MLVA richness is relatively rare and likely indicates beef fattening enterprises, which purchase cattle from over long distances. Cattle movements were furthermore an important predictor of MLVA genotype richness in non-dairy herds, but not in dairy herds; this may represent reduced cattle purchasing levels in dairy enterprises, compared to beef. These observations allude to the relative contribution of different routes of bTB infection between production types; we posit that infection associated with local factors may be more evident in dairy herds than beef herds, however in beef herds, inwards movements offer additional opportunities for introducing M. bovis into the herd

Phylodynamic analysis of an emergent Mycobacterium bovis outbreak in an area with no previously known wildlife infections

1. Understanding how an emergent pathogen successfully establishes itself and persists in a previously unaffected population 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 single introduction of the pathogen from the latter region, with evolutionary analysis supporting an introduction directly into the local cattle population six 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 raw data object of this analysis were used to support decisions regarding the control of a M. bovis emergent outbreak, of considerable concern because of the geographical distance from previously known high-risk areas. Our further analyses, estimating the time of introduction (and therefore the likely magnitude of any hidden outbreak) and the rates of cross-species transmission, provided valuable confirmation that the extent and focus of the imposed controls were appropriate. Not only 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

Relative abundance of Mycobacterium bovis molecular types in cattle:a simulation study of potential epidemiological drivers

Background: 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