Genome analysis reveals how leprosy spread


Leprosy, also called Hansen’s diasease, likely originated in East Africa and spread to Asia and Europe before being imported into West Africa by explorers.

The findings enrich the historical understanding of leprosy's global migration and contradict a commonly held view that leprosy spread to West Africa directly from East Africa.

Leprosy is a chronic infectious disease that usually affects the skin and peripheral nerves but has a wide range of possible clinical manifestations.
Patients are classified as having paucibacillary or multibacillary leprosy.
Paucibacillary leprosy is milder and characterized by one or more hypopigmented skin macules.
Multibacillary leprosy is associated with symmetric skin lesions, nodules, plaques, thickened dermis, and frequent involvement of the nasal mucosa resulting in nasal congestion and epistaxis.

Investigators, led by Stewart T. Cole, of the Institut Pasteur in Paris, identified rare genetic variations among strains of the bacterium that causes leprosy, Mycobacterium leprae.

The genetic material of the bacterium was scanned for tiny variations known as single nucleotide polymorphisms ( SNPs ).

SNPs 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 Mycobacterium leprae, and to develop a picture of how leprosy spread from its point of origin.

Researchers looked for SNPs in 171 clinical specimens of Mycobacterium 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, Mycobacterium 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 scientists better understand leprosy in present day human populations, “ says Christine Sizemore, 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 Mycobacterium 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. “

The study has been published in Science.

Source: NIH, 2005


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