Pre-European contact leprosy in the Americas and its current persistence.

Leprosy, primarily caused by Mycobacterium leprae, is considered a disease introduced into the Americas during European colonization. However, the recent discovery of a second pathogen causing leprosy, M. lepromatosis, mainly found in the Americas, challenges this view. Here, we show that M. lepromatosis infected humans in the Americas before European contact. By screening 389 ancient and 408 contemporary samples, we have expanded the genetic data available for the species. Phylogenetic analyses revealed distinct human-infecting clades of M. lepromatosis, with one dominating North America since colonial times. The presence of millennia-old strains in North and South America indicates M. lepromatosis may have been widespread during the Late Holocene, demonstrating M. lepromatosis leprosy has a long-standing history in the Americas before European arrival.