For Immediate Release
Thursday, May 12, 2005
Leprosy Traced to Origin Centuries Ago Through Dna Fingerprints in Colorado State, Global Study
FORT COLLINS - Colorado State University's leprosy research facility and experts, along with other scientists from around the globe, have traced the origin of the ancient disease to East Africa, which spread to Asia and Europe, then into West Africa by explorers. In a study released today in Science magazine, the experts present DNA evidence of where the disease began and how it spread across the globe thousands of years ago, debunking some long-held beliefs about the migration of the disease directly from East Africa to West Africa.
The international group identified rare genetic variations among strains of the bacterium that cause the disease. Using DNA, the study presents new evidence that leprosy likely originated in East Africa and spread to Asia and Europe before being imported into West Africa by explorers. It was then transmitted to North America, South American and the Caribbean islands through the slave trade and colonialism.
"This facility and experts such as Dr. Brennan and Dr. Spencer are among world leaders in solving the problem of global disease, and their accomplishments set a high standard for excellence at the university," said Anthony Frank, provost and senior vice president at Colorado State.
The study involved Colorado State University's Mycobacteria Research Laboratories, including Patrick J. Brennan, principal investigator at the lab, who has been conducting research in tuberculosis and leprosy for more than 30 years, and John Spencer, senior scientist.
"The identification of these 'fingerprints' for the leprosy pathogen represents a very important new tool for medical experts," said Jeffrey Wilusz, department head of Microbiology, Immunology and Pathology. "This information can be used to help scientists eventually eliminate this disease, which continues today to infect a significant number of people in countries across the globe."
The study's DNA information traces migration of the disease through simple mutations, called single nucleotide polymorphisms, or SNPs. Despite its status as an ancient disease, Mycobacterium leprae, the bacterium that causes leprosy, is known to have mutated these particular SNPs only four times. By studying populations across the globe and identifying which of the four established strains of the bacteria causes the disease in separate populations, the researchers were able to identify a timeline and geographical map of how the disease spread. Through Colorado State's National Institute of Allergy and Infectious Diseases-funded leprosy research and the university's cache of the bacterium that causes leprosy, researchers were able to obtain DNA of rare strains of the disease. The NIAID, part of the National Institutes of Health, funds leprosy research and research resources through the Department of Microbiology's Mycobacteria Research Laboratories. The laboratory is one of the preeminent leprosy research facilities in the world, and, along with the National Hansen's Disease Laboratory at Louisiana State University in Baton Rouge, LA, provides leprosy research material to leprosy researchers around the world free of charge.
"We can track human migration patterns based on the dominate type of leprosy in regions," said John Spencer, senior scientist at the Mycobacteria Research Laboratories. "This historical record of bacteria provides us with significant information about how the disease spread through migration, since leprosy only affects humans."
Researchers had believed that leprosy spread from East Africa directly to West Africa via contact among those populations, for example, but the study's DNA evidence suggests that the disease was actually introduced into West Africa by European explorers, colonists and slave traders. In turn, the slave trade introduced leprosy from West Africa into Brazil, the Caribbean islands and other parts of South America.
Brennan and Spencer collaborated with scientists from institutions in the United States, France and seven other countries. Colorado State supplied DNA samples of the disease from eight regions which were used in comparison to the samples obtained from other individuals in the study.
The study was led by Stewart T. Cole of the Institut Pasteur in Paris. Researchers scanned the genetic material of M. leprae for tiny variations known as single nucleotide polymorphisms, or SNPs. SNPs, pronounced "snips," are variations in a single "letter" of DNA's four-letter code. The distribution of SNPs in a population gives researchers an understanding of relatedness among individuals and clues to the geographic origin and movements of a population.
Compared with other disease-causing organisms, M. leprae has very few SNPs, at a rate of only one in every 28,000 letters of genetic code. For example, the bacterium that is linked to causing stomach ulcers in humans, H. pylori, has an SNP rate of one in every 32 letters of genetic code. The low number of SNPs in M. leprae indicates extreme genetic stability; all the strains of leprosy throughout the world are essentially identical.
The team looked at 171 specimens of the bacterium from people infected from 21 different countries representing five continents. They found four distinct SNP varieties in the samples.
There is a fairly strict correlation between the geographical location of the leprosy patient and SNP type, the investigators discovered. Based on the degree of similarity among the four SNP types, the researchers could trace leprosy's spread around the globe. 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.
Colorado State's leprosy lab within the Mycobacteria Research Laboratories in the Department of Microbiology, Immunology and Pathology is at the forefront in developing rapid diagnostic tests and skin tests for leprosy that can be used to diagnose the disease before individuals show symptoms. Leprosy may take several months to 15 years to exhibit symptoms after a person is exposed to the disease, which can make prevention of the spread of the disease a challenge.
While the World Health Organization has focused on eliminating leprosy and the global prevalence has fallen, the rate of new infections each year continues to be steady. Leprosy remains a significant public health problem in 10 countries, compared to 122 countries in 1985. Leprosy can be treated with a combination of drugs. The latest information from the WHO shows that 620,672 new cases were diagnosed in 2002. The disease is thought to be spread by nasal discharge, such as through coughing or sneezing, but is not considered highly contagious. Those at highest risk are also thought to have a genetic pre-disposition to the disease.