Genomic epizoology of a Brucella abortus outbreak in Northern Ireland (1997-2012).

In the recent past (1997-2012), Northern Ireland (NI) in the United Kingdom (UK), suffered an outbreak of Brucella abortus, which at its height affected over 200 cattle herds. Initially, isolates were characterized using multi locus variable number tandem repeats analysis (MLVA). Whilst informative in this setting, hyper-variability in some loci, limited the resolution necessary to infer fine-scale disease transmission networks. Consequently, we applied whole genome sequencing to isolates from this outbreak to evaluate higher resolution markers for disease epizoology.Phylogenetic analysis revealed the B. abortus outbreak in NI was caused by two distinct pathogen lineages. One contained isolates from an endemic infection previously believed to have been eradicated, consistent with the 1997-2012 outbreak being linked to a previously thought eradicated endemic infection. The dominant second lineage exhibited little genetic diversity throughout the recrudescent outbreak, with limited population sub-structure evident. This finding was inconsistent with prior MLVA molecular characterizations that suggested the presence of seven clonal complexes. Spatio-temporal modeling revealed a significant association of pairwise SNP differences between isolates and geographic distances, however effect sizes were very small owing to reduced pathogen diversity.Genome sequence data suggested that MLVA hyper-variability in some MLVA loci contributed to an overestimate of pathogen diversity in the most recent outbreak. The low diversity observed in our genomic dataset made it inappropriate to apply phylodynamic methods to these data. We conclude that maintaining data repositories of genome sequence data will be invaluable for source attribution/epizoological inference should recrudescence ever re-occur. However genomic epizoological methods may have limited utility in some settings, such as when applied to recrudescent/re-emergent infections of slowly evolving bacterial pathogens.