Persistence of Brucella abortus lineages revealed by genomic characterization and phylodynamic analysis.

Brucellosis, caused by Brucella abortus, is a major disease of cattle and humans worldwide distributed. Eradication and control of the disease has been difficult in Central and South America, Central Asia, the Mediterranean and the Middle East. Epidemiological strategies combined with phylogenetic methods provide the high-resolution power needed to study relationships between surveillance data and pathogen population dynamics, using genetic diversity and spatiotemporal distributions. This information is crucial for prevention and control of disease spreading at a local and worldwide level. In Costa Rica (CR), the disease was first reported at the beginning of the 20th century and has not been controlled despite many efforts. We characterized 188 B. abortus isolates from CR recovered from cattle, humans and water buffalo, from 2003 to 2018, and whole genome sequencing (WGS) was performed in 95 of them. They were also assessed based on geographic origin, date of introduction, and phylogenetic associations in a worldwide and national context. Our results show circulation of five B. abortus lineages (I to V) in CR, phylogenetically related to isolates from the United States, United Kingdom, and South America. Lineage I was dominant and probably introduced at the end of the 19th century. Lineage II, represented by a single isolate from a water buffalo, clustered with a Colombian sample, and was likely introduced after 1845. Lineages III and IV were likely introduced during the early 2000s. Fourteen isolates from humans were found within the same lineage (lineage I) regardless of their geographic origin within the country. The main CR lineages, introduced more than 100 years ago, are widely spread throughout the country, in contrast to new introductions that seemed to be more geographically restricted. Following the brucellosis prevalence and the farming practices of several middle- and low-income countries, similar scenarios could be found in other regions worldwide. Author summary Brucellosis caused by Brucella abortus is an important disease of cattle and humans, highly prevalent in middle- and low-income countries worldwide. Determining the prevalent B. abortus lineages as well as the sources and timing of strain introductions into a country, is necessary for understanding the epidemiology and the natural history of the disease. Our results, derived from 188 B. abortus isolates from Costa Rica and 221 genomes from the same species worldwide, showed that in spite of being a small country (similar to 51,100 km(2)), there are at least five B. abortus lineages circulating in its territory. Furthermore, regardless of control measures, the lineages introduced more than 100 years ago are still present and widespread throughout the country, in contrast to more recent introductions that seemed to be geographically restricted. By means of our analysis, we constructed a road map based on an integrative approach that may improve the understanding of the disease dynamics. Following the brucellosis prevalence and the farming practices of several middle- and low-income countries, similar scenarios could be found in other regions worldwide, where our methods could be useful and similarly applied.