Ancient Plague Genomes Point to Sources of Outbreaks in Europe After Black Death Pandemic

NEW YORK – A genomic analysis of a handful of ancient Yersinia pestis isolates from different parts of Europe has revealed potential reintroduction sources for the pathogen, which continued to crop up for centuries following the initial Black Death pandemic in the 1300s. It also uncovered characteristic genetic features in a 'Second Plague' strain that was detected as recently as the early 19th century.

"Combined with our analysis of historical data, our results point toward the existence of a reservoir outside of Western Europe responsible for the post-Black Death lineage," co-senior authors Barbara Bramanti, a researcher affiliated with the University of Oslo, the University of Tartu, and the University of Ferrara, and N.C. Stenseth, an investigator at the University of Oslo, and their colleagues wrote in a paper published in the Proceedings of the National Academy of Sciences on Monday.

The researchers sequenced the genomes of nine Y. pestis isolates collected from four sites in Europe, using phylogenetic and historical clues to interpret the relationships between the strains and to retrace potential sources of human disease. In particular, they pointed to a Chechnyan isolate from the 18^th century that contained a 49,000-base pair deletion that marked both 18^th century isolates from the Second Plague Pandemic they studied, consistent with a potential Y. pestis reservoir in this region.

"Our analysis shows that, following a 'diversification,' the post-Black Death lineage gave rise to four more outbreaks sporting the same deletion," the authors reported, noting that non-European centers seemed to make key contributions to these subsequent plague waves.

Prior studies suggest that plague dynamics began to change sometime during the mid-17^th century, the team explained, and Europe's Second Plague Pandemic appeared to include far more localized disease outbreaks than the Black Death plague, which wiped out an estimated 30 to 60 percent of the populations in Europe relatively quickly. Even so, detailed plague dynamics during the 18^th and 19^th century have remained elusive, prompting the group's more extensive genomic analysis.

"The introduction of post-Black Death plague to Europe has been subject to debate in previous studies," the authors explained. "The main points of contention are the number of introductions from outside of Western Europe and the location of the reservoir(s) feeding the Y. pestis lineage, which established itself following the Black Death epidemic."

Using whole-genome sequence data and available historical insights, the researchers analyzed half a dozen 17^th century Y. pestis isolates from Italy, two 18^th century representatives from Sweden and Chechnya, along with an earlier Y. pestis strain from 14^th century Italy.

Together, their results highlighted the presence of Second Plague pathogens outside of Western Europe in the 18^th century, suggesting that wildlife reservoirs in the Caucasus area may have helped fuel Y. pestis introductions and reintroductions in Western Europe — a notion that appeared to be supported by phylogenetic data on strains sequenced so far.

"Based on our historical synthesis, we … speculate that this lineage kept on introducing plague to Eastern Europe and Western Asia long after the last large outbreaks documented in Western Europe," the authors concluded, "indicating the need for additional sampling in these regions to gain a better understanding of the complex processes involved in plague dynamics during the Second Plague Pandemic."