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article imageDNA genome sequencing shows leprosy pathogen unchanged in 1000yrs

By JohnThomas Didymus     Jun 17, 2013 in Science
Researchers have sequenced the genome of the bacterial pathogen that caused leprosy in Medieval times and found that the genome and virulence of the pathogen have not changed significantly in 1,000 years.
The team of researchers led by Verena Schuenemann from the University of Tübingen in Tübingen, Germany, obtained nearly complete genomes of Myboacterium leprae from five skeletal remains in Medieval graves (10th-14th century A.D.) in the United Kingdom, Sweden and Denmark. The UK samples were collected from skeletal remains found at the Medieval leprosy hospital of St. Mary Magdalen in Winchester.
The remains contained only very tiny amounts of the bacterial DNA. But using extremely sensitive methods and new technology the researchers were able to sequence the genomes of M. leprae found in five Medieval skeletons.
They then compared the genomes to sequenced genomes of modern strains of M. leprae.
Discovery that the strains of bacteria which caused leprosy in Medieval times have not changed much in 1,000 years gives researchers fresh insights in the origins, evolution and spread of the disease since Medieval times.
According to one of the researchers Stewart Cole, co-director of the study, and the head of the École Polytechnique Fédérale de Lausanne’s Global Health Institute, leprosy was endemic in Europe in Medieval times but disappeared mysteriously in the 16th Century.
Smithsonian Magazine reports Cole said that at the height of its incidence, leprosy affected one in 30 people in some regions of Europe and by the 13th century, the disease had peaked with the number of leper hospitals at 19,000.
It is estimated that more than 225,000 cases of leprosy arise worldwide every year, mostly in less developed countries. The researchers compared the genome sequences of the five Medieval samples they obtained to 11 modern strains extracted at different geographic regions of the world and found that leprosy-causing bacteria have not changed in genetic makeup in the last 1,000 years. The researchers found only 800 mutations in 16 genomes. They also found that genes linked to virulence of the bacteria have remained largely intact over the centuries.
According to Schuenemann and his colleagues in a paper titled "Genome-Wide Comparison of Medieval and Modern Mycobacterium leprae," published on 13 June, 2013 in the journal Science, "ancient M. leprae sequences were compared with those of 11 modern strains, representing diverse genotypes and geographic origins. The comparisons revealed remarkable genomic conservation during the past 1000 years, a European origin for leprosy in the Americas, and the presence of an M. leprae genotype in medieval Europe now commonly associated with the Middle East. The exceptional preservation of M. leprae biomarkers... in ancient skeletons has major implications for palaeomicrobiology and human pathogen evolution."
Excavation of the St. Mary Magdalen leprosarium in Winchester  UK  with in situ skeletons.
Excavation of the St. Mary Magdalen leprosarium in Winchester, UK, with in situ skeletons.
University of Winchester
The findings of the team suggest that the disappearance of the disease in Europe in the 1500s was not due to the bacteria losing virulence, but increased host resistance, better living conditions and medical care.
According to Smithsonian Magazine, Cole said: "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."
Cole told the BBC: "It's been proposed that bubonic plague killed off a large part of the European population, including those suffering from leprosy. One of the interesting things about this paper is that the medieval and current strains are the same, whereas leprosy disappeared fairly rapidly from Europe. It's clear that leprosy has created a strong selective pressure on the immune system. The European Caucasian populations have acquired resistance to leprosy, they have certain characteristic mutations in genes that make them less susceptible."
According to the researchers, one of the reasons why the incidence of leprosy in Europe is very low today is because an estimated 95% of the population has developed resistance to infection.
The researchers also found that the Medieval European strains were nearly identical to strains found today in the Middle East and in the Americas.
Although researchers interpret available evidence as suggesting that the Crusades played a major role in the dissemination of the disease between the Middle East and Europe they are uncertain where the pathogen originated. But according to one of the authors of the study, Johannes Krause, of the University of Tubingen, Germany, "lines of evidence suggest an Asian origin of the disease" based on the fact that the earliest evidence of leprosy comes from a 4,000-year old Indian skeleton. Krause told the BBC: "This skeleton can only tell us it was present in Asia around 4,000 years ago, but we do not know where the origin of the disease is."
Researchers believe, however, that the modern American strains were introduced from Europe.
Scientists conclude that apart from the fact that Europeans developed resistance to the disease, the strict policy of isolation of infected persons played a major role in its disappearance. Although the cause of leprosy was not well understood, with some saying it was hereditary and others believing it was punishment from God, people with leprosy were treated as outcasts, segregated from society and confined to quarantined colonies called leprosaria. There was a strong social stigma associated with the disease. Sufferers were forced to wear bells that rang as they walked. The bells warned healthy people that a sufferer was approaching.
With developments in modern medicine, the disease can be cured if treated early, otherwise it leads to permanent deformity. Krause noted that "the bacterium is still pathogenic, the same way it was 1,000 years ago, but our social conditions have changed and we have much better medical treatment. But at the same time, it's still a very prevalent disease."
The BBC reports that Professor Monica Green, a specialist in medical history at the Arizona State University, said: "The important thing to remember is that leprosaria were religious institutions, showing both a major material investment and adherence to a religious rule of life. Leprosy was the only disease in medieval Europe that elicited a specific institutional response. In its full-blown form, it was grossly disfiguring and maiming. Stigma might be reserved for persons with the most serious cases."
She continued: "There was a general decline towards the later middle ages, in part because the segregation provided by leprosaria 'worked' in removing the most seriously affected individuals from open society."
The pathogen that causes leprosy was first isolated in 1873, bringing an end to centuries of speculations about its cause. Historical records and remains indicate it has been around since very early in human history. The earliest written records about leprosy date back to 600 B.C.,China, according to the BBC. Greek, Egyptian, and Indian records acknowledged the incidence of the disease. The oldest proven case comes from DNA analysis of the remains of a first-century man carried out in 2009.
The research is part of a series of recent studies aimed at using DNA sequencing technology to learn more about historic epidemics. A recent study using DNA sequencing technology found that a different strain of Phytophtora infestans caused the devastating potato blight that led to the 1845 Irish potato famine.
Scientists are hoping that future studies will confirm the pathogen that caused the Black Death which ravaged Europe and peaked in the years 1347-1351
More about leprosy genome, Dna sequencing, Myboacterium leprae, leprosaria
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