Epidemiology of Serovar Dublin in Cattle and Humans in Denmark, 1996 to 2016: a Retrospective Whole-Genome-Based Study.

serovar Dublin is a cattle-adapted serovar causing both intestinal and systemic infection in its bovine host, and it is also a serious threat to human health. The present study aimed to determine the population structure of Dublin isolates obtained from Danish cattle herds and to investigate how cattle isolates relate to Danish human isolates, as well as to non-Danish human and bovine isolates. Phylogenetic analysis of 197 Danish cattle isolates from 1996 to 2016 identified three major clades corresponding to distinct geographical regions of cattle herds. Persistence of closely related isolates within the same herd and their circulation between epidemiologically linked herds for a period of more than 20 years were demonstrated. These findings suggest that a lack of internal biosecurity and, to some extent, also a lack of external biosecurity in the herds have played an important role in the long-term persistence of Dublin in Danish cattle herds in the period investigated. Global population analysis revealed that Danish cattle isolates clustered separately from bovine isolates from other countries, whereas human isolates were geographically spread. Resistance genes were not commonly demonstrated in Danish bovine isolates; only the isolates within one Danish clade were found to often harbor two plasmids of IncFII/IncFIB and IncN types, the latter plasmid carrying , , , and antibiotic resistance genes. Dublin causes economic losses in cattle production, and the bacterium is a public health concern. A surveillance and control program has been in place in Denmark since 2002 with the ultimate goal to eradicate Dublin from Danish cattle herds; however, a small proportion of herds have remained positive for many years. In this study, we demonstrate that herds with persistent infection often were infected with the same strain for many years, indicating that internal biosecurity has to be improved to curb the infection. Further, domestic cases of Dublin infection in humans were found to be caused both by Danish cattle isolates and by isolates acquired abroad. This study shows the strength of whole-genome sequencing to obtain detailed information on epidemiology of Dublin and allows us to suggest internal biosecurity as a main way to control this bacterium in Danish cattle herds.