International Team Determines Geographic Origin of Leprosy

The international team of investigators, who identified rare genetic variations among strains of the bacterium that causes leprosy, included Patrick J. Brennan, Ph.D., of Colorado State University in Fort Collins. Dr. Brennan is a grantee of the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.

"Using modern genetic techniques, these researchers uncovered clues to the origin of a disease that, since ancient times, has been one of the most stigmatizing," notes NIAID Director Anthony S. Fauci, M.D. "Their findings may help public health officials better track and treat leprosy, which remains a significant problem in some parts of the world today."

The research team included scientists from institutions in the United States, France and seven other countries. Led by Stewart T. Cole, Ph.D., of the Institut Pasteur in Paris, the investigators scanned the genetic material of Mycobacterium leprae, the bacterium that causes leprosy, for tiny variations known as single nucleotide polymorphisms (SNPs). SNPs, pronounced "snips," are variations in a single "letter" of DNA's four-letter code. Scientists can use SNPs to trace the lineage of an organism, in this case M. leprae, and to develop a picture of how leprosy spread from its point of origin. The team looked for SNPs in 171 clinical specimens of M. leprae taken from people infected with the bacterium. The specimens came from 21 countries representing five continents.

Four types of SNP appeared in the samples, but their distribution was not random. Instead, the investigators discovered a fairly close correlation between SNP type and geographic location of the leprosy patient. Type 2, predominant in a small region of East Africa and Central Asia, is the rarest and oldest, the scientists believe. Type 1, present in Asia and the Pacific region, represents the eastward migration of leprosy, while type 3, seen in Europe, North Africa and the Americas, is the form that migrated west. The most recently evolved, type 4, is predominant in West Africa. Because type 4 leprosy is more closely related to type 3 than it is to either type 1 or 2, the researchers concluded that North Africans or Europeans probably brought the disease to West Africa.

Compared with other disease-causing organisms, M. leprae has very few SNPs — only one in every 28,400 letter pairs. The rarity of SNPs is an indication of extreme genetic stability: all the strains of leprosy throughout the world are essentially identical.

The discovery of the four SNP types could help health officials better understand leprosy in present day human populations, says Christine Sizemore, Ph.D., of NIAID's Division of Microbiology and Infectious Diseases. Aggressive therapy with multiple drugs has helped drive down the number of registered leprosy cases around the world, notes Dr. Sizemore. However, despite drug treatment, the number of new cases of leprosy detected each year has stayed the same or risen. The new understanding of the genetic makeup of the leprosy bacterium will allow clinicians to characterize at a molecular level the M. leprae strain infecting a leprosy patient, which will show whether the patient has a new infection or if the previous infection was incompletely treated and has returned. This, in turn, will aid efforts to fully treat patients so that the bacteria are completely eliminated.

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