An international team, including assistant professor Charlotte Avanzi’s laboratory in CSU’s Mycobacteria Research Labs, utilized archaeological findings to identify red squirrels (Sciurus vulgaris) in medieval England as hosts for Mycobacterium leprae, the causative agent of leprosy, one of the oldest known infectious disease associated with humans.
“We identified M. leprae in modern red squirrel populations from the British Isles earlier in 2016. At that time, it was the first non-human host for this bacterium outside of the Americas,” said Avanzi, lead author on the subsequent publication. “The unexpected discovery prompted questions regarding how red squirrels became infected. Preliminary data suggested that they might have harbored the infection for centuries.”
Identifying new hosts and their implication in the disease burden, both today and in the past, provides invaluable clues for understanding transmission.
While scientists have elucidated the evolutionary trajectory of M. leprae, until this new study, the means by which it may have historically transferred from animals to humans remained unclear. Previous hints suggested that red squirrels in England might have functioned as hosts, but definitive evidence needed to be provided.
Leprosy in Medieval Life
Researchers in the collaborative study, now published in Current Biology, utilized a combination of paleopathology, paleomicrobiology, and analysis of historical records to investigate 25 human and 12 squirrel samples from medieval archaeological sites in Winchester, England.
Christian Urban, one of the study’s lead authors affiliated with the University of Basel and the University of Zurich, elaborated, “We carried out the genetic analyses on the [medieval] squirrels’ tiny hand and foot bones, which weigh between 20 and 30 milligrams. That is not a lot of material.”
“Our expertise at CSU resides in recovering minuscule amounts of M. leprae DNA out of clinical samples and analyzing M. leprae genomes to understand where the pathogen originates,” Avanzi said.
Together, researchers successfully sequenced and reconstructed four genomes, representing medieval strains of M. leprae, including one obtained from a red squirrel found in a pit used by fur traders.
They unveiled a striking discovery; the leprosy bacteria found in the medieval squirrels exhibited a close genetic relationship to those isolated from medieval human skeletons within the same geographical area.
“This similarity shows us that leprosy bacteria were probably transmitted between animals and humans at that time,” said Verena Schünemann, a paleogeneticist and study co-lead from the University of Basel.
Winchester is renowned for its medieval leprosarium, a hospital catering to individuals with leprosy, as well as its significant ties to the fur trade in the Middle Ages. In that era, squirrel fur frequently adorned and lined garments. Moreover, it was common for individuals to capture squirrels in the wild while they were still young and raise them as pets.
However, Schünemann stressed, that based on current knowledge, it is still not clear precisely how transmission took place. “We don’t know whether the squirrels infected humans or whether humans were the ones to introduce the disease to the animals.” Schünemann said.
Puzzling the One Health Past
“Our findings highlight the importance of involving different archaeological material, in particular, animal remains combined with historical reconstruction, into studying the long-term zoonotic potential of [leprosy],” added Sarah Inskip, osteoarchaeologist and study co-lead from the University of Leicester.
Annually, Mycobacterium leprae still infects around 200,000 people worldwide, with a few cases occurring in the United States. Left untreated, leprosy leads to severe deformities.
The interdisciplinary One Health aspect of the project joined various puzzle pieces to reveal the intricacy of past interactions between humans and animals, which highlights the significance of investigating non-human host reservoirs of the past to gain comprehensive insights into ongoing disease transmission dynamics.
CSU contributed content for this story, which was originally developed by Kristopher Benke at CellPress.
