In certain areas it is estimated that nearly one in 30 people were infected with leprosy, and the image of the leper with skin lesions, wrapped in cloth, and ringing a bell remains culturally powerful.
But at the turn of the 16th century, the disease abruptly and inexplicably receded over most of the European continent.
Biologists and archeologists reconstructed the genomes of medieval strains of Mycobacterium leprae, the pathogen responsible for leprosy, which they exhumed from centuries-old graves. Their results, published in the journal Science, introduce new methods for understanding epidemics.
"We were able to reconstruct the genome without using any contemporary strains as a basis," explained study co-author and EPFL scientist Pushpendra Singh, who worked closely with Johannes Kraus and team from Tubingen University in Germany.
Their results show that the genomes of the medieval strains are almost exactly the same as that of contemporary strains, and the mode of spreading has not changed.
It wasn't the disease that evolved, it was humans who developed resistance, according to the authors.
"If the explanation of the drop in leprosy cases isn't in the pathogen, then it must be in the host, that is, in us; so that's where we need to look," explains Stewart Cole, co-director of the study and the head of EFFL's Global Health Institute.
The study shows intense natural selection in action. While previous studies have shown that Europeans were genetically better-suited to developing resistance, the high prevalence and intense social isolation of diseased individuals sped the process along.
"In certain conditions, victims could simply be pressured not to procreate," Cole said.
Researchers also discovered a medieval strain of Mycobacterium leprae in Sweden and the U.K. that is almost identical to the strain currently found in the Middle East.
"We didn't have the data to determine the direction in which the epidemic spread," Cole said. "The pathogen could have been carried to Palestine during the Crusades. But the process could have operated in the opposite direction, as well."
Leprosy has affected humans for around 4,000 years and still affects more than 200,000 people each year, with leper colonies still found worldwide.