Leprosy was in the Americas long before European settlers arrived

Leprosy’s history has long been misunderstood. New evidence reveals it was present in the Americas more than 1,000 years ago.

Scientists from Colorado State University and the Institut Pasteur in France, working alongside Indigenous communities and over 40 researchers from across the Americas and Europe, uncovered these findings.

New insights into infectious diseases

The collaborative study reframes the story of leprosy and offers new insights into how infectious diseases evolve and spread in human and animal populations.

“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.

“We’re only just beginning to uncover the diversity and global movements of this recently discovered pathogen.”

Tracking leprosy across the Americas

Leprosy affects thousands worldwide, typically caused by the bacterium Mycobacterium leprae. Until now, most believed the disease arrived in the Americas with European colonizers.

“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.”

The team conducted the most extensive screening ever done for this bacterium. They analyzed DNA from nearly 800 samples, including ancient skeletal remains from several regions and clinical samples from Mexico, the U.S., Brazil, Paraguay, and French Guiana.

Mexico and the U.S. had the most positive cases, likely due to a combination of higher pathogen prevalence and more intensive sampling efforts.

Genetic evolution of leprosy

In collaboration with Indigenous communities, the researchers recovered M. lepromatosis DNA from ancient human remains in Canada and Argentina, dating back more than 1,000 years.

The team used a method called long-read sequencing to assemble the first high-quality, complete genome of the bacterium from a modern sample, taken from a leprosy patient in Costa Rica. This genome is crucial for mapping the bacterium’s evolution and spread.

Interestingly, despite the vast distance between Canada and Argentina, the ancient infections fall within a narrow time frame. The strains are genetically similar, suggesting M. lepromatosis spread widely across the continent in just a few centuries.

Whether humans facilitated this spread through trade and travel, or whether animals played a role, remains uncertain.

A pathogen hiding in plain sight

The journey to this discovery began in 2008, when M. lepromatosis was first identified in a patient in Mexico. It came as a surprise to many researchers.

“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. “The idea that such a significant pathogen could go undetected for so long was deeply surprising.”

In 2015, researchers sequenced the genome of M. lepromatosis. This allowed the development of molecular tools to detect the bacterium in human tissue. Still, confirmed information on its distribution remained scarce.

Study co-author Lucio Vera-Cabrera is a microbiologist and researcher at the Autonomous University of Nuevo León in Mexico.

“Genome sequencing enabled the development of specific markers to detect Mycobacterium lepromatosis,” noted Vera-Cabrera. “Since then, numerous cases have been identified in Mexico, raising strong suspicion that North America may be the pathogen’s place of origin. However, until now, its true origin remained unclear.”

Curious connection with squirrels

One of the earlier surprises came in 2016 when researchers found M. lepromatosis in red squirrels in the British Isles – the first confirmed animal reservoir for the pathogen.

“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.”

Building on that discovery, the new research identified five genetically distinct lineages of M. lepromatosis. One of these lineages includes the strains found in red squirrels.

Genetic analysis suggests that the squirrel strain likely came from the Americas, introduced sometime between 4,000 and 100 years ago.

A new chapter in medical history

“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,” said Nicolás Rascovan, a senior author of the study from the Institut Pasteur.

The research offers a deeper understanding of how pathogens move between humans and animals over time.

By studying both ancient and modern DNA, researchers are uncovering hidden stories of the past – and changing how we view infectious diseases today.

The full study was published in the journal Science.

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