Leprosy has been present in the Americas for more than 1,000 years, long before the arrival of European settlers, according to a groundbreaking new finding published this week in the journal Science.
The major international study was co-led by scientists at Colorado State University and the Institut Pasteur in France, in collaboration with Indigenous communities and more than 40 scientists from institutions across the Americas and Europe. The study reframes the history of leprosy in the Americas and has implications for better understanding how infectious diseases spread, persist and evolve in human and animal populations over time.
"This study is a powerful example of how ancient and modern DNA can rewrite medical history and deepen our understanding of contemporary infectious diseases," said Charlotte Avanzi, co-lead author and assistant professor at CSU, who led the analysis of modern clinical samples for the study. "We're only just beginning to uncover the diversity and global movements of this recently discovered pathogen."
Leprosy is a disease that affects thousands of people worldwide, with M. leprae being the most common species of leprosy-causing bacteria. Scientists have long thought that the disease was introduced to the Americas by European colonizers. This new study, however, shows that a lesser-known species of leprosy-causing bacteria, Mycobacterium lepromatosis, infected humans in the Americas centuries before European contact.
"This discovery changes how we understand the history of leprosy in the Americas," said co-lead author Maria Lopopolo from Institut Pasteur. "It tells us that a form of the disease had been endemic among Indigenous populations long before European ships arrived."
Extensive screening
For this study, the team conducted the most extensive screening done for this pathogen, analyzing DNA from nearly 800 samples, including ancient skeletal remains from different regions and clinical samples from five countries: Mexico, the U.S., Brazil, Paraguay and French Guiana. The most positive cases were identified in Mexico and the U.S., which, according to the authors, likely reflects a combination of a higher prevalence of the pathogen in those regions as well as more intensive sampling in those countries.
Working in collaboration with Indigenous communities, the team recovered M. lepromatosis DNA from ancient human remains in Canada and Argentina that dated back over 1,000 years. Using a DNA sequencing method known as long-read sequencing, the team also generated the first high-quality, complete genome for the bacterium from a modern sample, a leprosy patient from Costa Rica — an essential step for mapping evolution and spread.
Despite being separated by over 10,000 kilometers, the infections from the Canadian and Argentinian remains fell within a relatively narrow time frame, and the corresponding strains were similar, suggesting the bacterium had spread widely across the continent in a few centuries. Whether this rapid dispersal was human-mediated, such as through networks of trade and contact, or animal-driven, remains an open question, the authors said.
"Our findings significantly alter the historical narrative of leprosy in the Americas," said Nicolás Rascovan, a senior author from the Institut Pasteur. "This discovery not only reshapes our understanding of the pathogen's origins but also raises the possibility that this pathogen may have been introduced in various geographic regions and highlights the complex interplay between human populations and pathogens over time."
Altering the historical narrative
The road to this discovery began in 2008 when M. lepromatosis was first identified in a patient in Mexico — an unexpected revelation at the time.
"It was hard for many in the field to accept that a second agent of leprosy had been hiding in plain sight," said John Spencer, an associate professor at CSU who contributed to the original discovery of M. lepromatosis. "The idea that such a significant pathogen could go undetected for so long was deeply surprising."
In 2015, the genome of M. lepromatosis was sequenced , which enabled scientists to develop molecular tools to detect the bacterium in human tissue. Despite this progress, confirmed data on the geographic distribution of M. lepromatosis remained sparse.
"Genome sequencing enabled the development of specific markers to detect Mycobacterium lepromatosis. Since then, numerous cases have been identified in Mexico, raising strong suspicion that North America may be the pathogen's place of origin," said co-author Lucio Vera-Cabrera, microbiologist and researcher at the Autonomous University of Nuevo León, Mexico. "However, until now, its true origin remained unclear."
One of the study's earlier breakthroughs came in 2016, when M. lepromatosis was unexpectedly found in red squirrels in the British Isles — the first confirmed animal reservoir of the pathogen, also reported in Science.
"At that time, we were puzzled," Avanzi said. "We had detected the pathogen mostly in the Americas, and it was unclear how red squirrels in Europe had become infected."
The new research builds on that finding and found five genetically distinct lineages of M. lepromatosis, including one lineage formed by the red squirrel strains. Analyses suggest that the strain infecting squirrels likely originated from a strain introduced from the Americas between 4,000 and 100 years ago.
