French Researchers Detail New Insights On Leprosy In Science

A French study that compares the genetic differences among strains of leprosy-causing bacteria has revealed some surprising insights into how the pathogen evolved and how it was spread across the continents by human migrations. The research, led by scientists at the Pasteur Institute in Paris, appears in the 13 May issue of the journal Science, published by AAAS.

The findings indicate that the world's existing leprosy infections are all caused by a single bacterial clone that has spread yet barely mutated for centuries. They also show that the disease may have begun in East Africa, as opposed to India as previously thought, and then spread to the other continents in part through European colonialism and later the slave trade.

A French study that compares the genetic differences among strains of leprosy-causing bacteria has revealed some surprising insights into how the pathogen evolved and how it was spread across the continents by human migrations. The research, led by scientists at the Pasteur Institute in Paris, appears in the 13 May issue of the journal Science, published by AAAS.

The findings indicate that the world's existing leprosy infections are all caused by a single bacterial clone that has spread yet barely mutated for centuries. They also show that the disease may have begun in East Africa, as opposed to India as previously thought, and then spread to the other continents in part through European colonialism and later the slave trade.

One of the oldest known human diseases, leprosy is still a significant problem in parts of the developing world, especially India. According to the World Health Organization, roughly 500,000 new cases were detected in 2003.

"Leprosy is still very real and devastating to patients who aren't treated appropriately," said Caroline Ash, senior editor at Science. "The better we can understand this pathogen's genome and the subtle differences among its various strains worldwide, the better position we'll be in to ultimately eliminate the disease."

The ability to trace an infection back to a certain region may help public health workers monitor the movement of the disease over time and determine the geographic source of new infections, said study author Stewart Cole of the Pasteur Institute.

Historically, it's been thought that leprosy originated in the Indian subcontinent and was then introduced to Europe by Greek soldiers returning from the Indian campaign of Alexander the Great, according to Cole. More research will be necessary to confirm this, but the new findings indicate that the disease actually originated in East Africa or perhaps the Near East, then migrated eastward and westward.

Europeans and North Africans then spread Leprosy to West Africa, and the slave trade brought the disease from West Africa to the Caribbean and South America, the study suggests. Europeans also introduced leprosy to North America.

"Colonialism was extremely bad for parts of the world in terms of human health," said Cole.

The disease, caused by Mycobacterium leprae, primarily affects the skin and nervous system, particularly the limbs and digits. It's not especially contagious, as people once widely believed, but it can cause permanent disability and disfigurement and is still a source of social stigma. The disease is treatable with a combination of antibiotics.

The bacterium has long puzzled researchers because its genome is filled with an unusually high proportion of damaged, nonfunctional genes. This is probably why it grows exceedingly slowly, making it difficult for researchers to study because they can't grow it in culture. In fact, M. leprae only lives in humans and in armadillos (which might have acquired the bacterium by eating infected human cadavers), and it can also grow in the footpads of mice.

Cole and his international research team compared the genomes of seven strains of M. leprae taken from patients around the world and then grown in armadillos until the samples were large enough to analyze. They focused on genetic sequences known to be dynamic—to move around, copy themselves or disappear—and thus most likely to reflect evolutionary change. But the researchers found strikingly little variation.

Next, the authors looked for mutations known as "single nucleotide polymorphisms" or "SNPs," which are substitutions of single nucleotides or "letters" at a specific spot in the genome. They found only three spots where useful SNPs occurred.

"Finding so few SNPs is pretty unusual. It's the least number of SNPs I'm aware of in any bacterium," Cole said.

At each of the three SNP locations, one of four different nucleotides can be substituted, making for a possible 64 different combinations in the genetic sequence. In a study of 175 different bacteria samples from 21 countries, the researchers found only four of these combinations.

Overall, the genetic similarity between the different samples suggests that the bacterium's genome is exceedingly stable.

"It seems that there was only a single source of the bacterium that was at the origin of this global pandemic," Cole said.

Each of the four SNP combinations was most common in a certain geographic region, allowing the researchers to trace how the pathogen had spread from its original source.

The study was funded by the Pasteur Institute; the Association Française Raoul Follereau; Lepra; the Consortium National de Recherche en Génomique; and the National Institute of Allergy and Infectious Diseases.

Kathy Wren

12 May 2005