In medieval England, leprosy spread between red squirrels and people, genome evidence shows

Evidence from archaeological sites in the medieval English city of Winchester shows that English red squirrels once served as an important host for Mycobacterium leprae strains that caused leprosy in people, researchers report May 3 in the journal Current Biology.

“With our genetic analysis we were able to identify red squirrels as the first ancient animal host of leprosy,” says senior author Verena Schuenemann of the University of Basel in Switzerland. “The medieval red squirrel strain we recovered is more closely related to medieval human strains from the same city than to strains isolated from infected modern red squirrels. Overall, our results point to an independent circulation of M. leprae strains between humans and red squirrels during the Medieval Period.”

“Our findings highlight the importance of involving archaeological material, in particular animal remains, into studying the long-term zoonotic potential of this disease, as only a direct comparison of ancient human and animal strains allows reconstructions of potential transmission events across time,” says Sarah Inskip of the University of Leicester, UK, a co-author on the study.

Leprosy is one of the oldest recorded diseases in human history and is still prevalent to this day in Asia, Africa, and South America. While scientists have traced the evolutionary history of the mycobacterium that causes it, they didn’t know how it may have spread to people from animals in the past beyond some hints that red squirrels in England may have served as a host.

In the new study, the researchers studied 25 human and 12 squirrel samples to look for M. leprae at two archaeological sites in Winchester. The city was well known for its leprosarium (a hospital for people with leprosy) and connections to the fur trade. In the Middle Ages, squirrel fur was widely used to trim and line garments. Many people also kept squirrels trapped wild squirrels as kits in the wild and raised them as pets.

The researchers sequenced and reconstructed four genomes representing medieval strains of M. leprae, including one from a red squirrel. An analysis to understand their relationships found that all of them belonged to a single branch on the M. leprae family tree. They also showed a close relationship between the squirrel strain and a newly constructed one isolated from the remains of a medieval person. They report that the medieval squirrel strain is more closely related to human strains from medieval Winchester than to modern squirrel strains from England, indicating that the infection was circulating between people and animals in the Middle Ages in a way that hadn’t been detected before.

“The history of leprosy is far more complex than previously thought,” Schuenemann said. “There has been no consideration of the role that animals might have played in the transmission and spread of the disease in the past, and as such, our understanding of leprosy’s history is incomplete until these hosts are considered. This finding is relevant to today as animal hosts are still not considered, even though they may be significant in terms of understanding the disease’s contemporary persistence despite attempts at eradication.” 

“In the wake of COVID-19, animal hosts are now becoming a focus of attention for understanding disease appearance and persistence,” Inskip said. “Our research shows that there is a long history of zoonotic diseases, and they have had and continue to have a big impact on us.”

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This work was supported by the Swiss State Secretariat for Education, Research and Innovation SERI funded ERC Consolidator Project “RESERVOIR,” the University of Zurich’s University Research Priority Program “Evolution in Action: From Genomes to Ecosystems,” and the Fondation Raoul Follereau and the Heiser Program of the New York Community Trust for Research in Leprosy.

Current Biology, Urban, Blom, and Avanzi et al.: “Ancient Mycobacterium leprae genome reveals medieval English red squirrels as animal leprosy host.” https://www.cell.com/current-biology/fulltext/S0960-9822(24)00446-9 

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