Studying ancient DNA allows us to retrace the evolutionary history of human pathogens, such as Mycobacterium leprae, the main causative agent of leprosy. Leprosy is one of the oldest recorded and most stigmatizing diseases in human history. The disease was prevalent in Europe until the 16th century and is still endemic in many countries with over 200,000 new cases reported annually. Previous worldwide studies on modern and European medieval M. leprae genomes revealed that they cluster into several distinct branches of which two were present in medieval Northwestern Europe. In this study, we analyzed 10 new medieval M. leprae genomes including the so far oldest M. leprae genome from one of the earliest known cases of leprosy in the United Kingdom-a skeleton from the Great Chesterford cemetery with a calibrated age of 415-545 C.E. This dataset provides a genetic time transect of M. leprae diversity in Europe over the past 1500 years. We find M. leprae strains from four distinct branches to be present in the Early Medieval Period, and strains from three different branches were detected within a single cemetery from the High Medieval Period. Altogether these findings suggest a higher genetic diversity of M. leprae strains in medieval Europe at various time points than previously assumed. The resulting more complex picture of the past phylogeography of leprosy in Europe impacts current phylogeographical models of M. leprae dissemination. It suggests alternative models for the past spread of leprosy such as a wide spread prevalence of strains from different branches in Eurasia already in Antiquity or maybe even an origin in Western Eurasia. Furthermore, these results highlight how studying ancient M. leprae strains improves understanding the history of leprosy worldwide.
- MeSH
- History, Medieval MeSH
- DNA, Bacterial genetics history MeSH
- Phylogeny MeSH
- Phylogeography MeSH
- Genetic Variation MeSH
- Genome, Bacterial MeSH
- Host-Pathogen Interactions genetics MeSH
- Polymorphism, Single Nucleotide MeSH
- Leprosy epidemiology history microbiology MeSH
- Humans MeSH
- Evolution, Molecular MeSH
- Mycobacterium leprae classification genetics pathogenicity MeSH
- Check Tag
- History, Medieval MeSH
- Humans MeSH
- Publication type
- Journal Article MeSH
- Historical Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Geographicals
- Europe epidemiology MeSH
- MeSH
- Dapsone therapeutic use MeSH
- Diagnosis, Differential MeSH
- Emigrants and Immigrants MeSH
- Drug Therapy, Combination MeSH
- Leprosy * diet therapy epidemiology etiology drug therapy classification MeSH
- Humans MeSH
- International Classification of Functioning, Disability and Health MeSH
- Mycobacterium leprae * pathogenicity MeSH
- Disease Transmission, Infectious * MeSH
- Rifamycins therapeutic use MeSH
- Blindness prevention & control MeSH
- Muscle Tonus MeSH
- Check Tag
- Humans MeSH
Leprosy was rare in Europe during the Roman period, yet its prevalence increased dramatically in medieval times. We examined human remains, with paleopathological lesions indicative of leprosy, dated to the 6th-11th century AD, from Central and Eastern Europe and Byzantine Anatolia. Analysis of ancient DNA and bacterial cell wall lipid biomarkers revealed Mycobacterium leprae in skeletal remains from 6th-8th century Northern Italy, 7th-11th century Hungary, 8th-9th century Austria, the Slavic Greater Moravian Empire of the 9th-10th century and 8th-10th century Byzantine samples from Northern Anatolia. These data were analyzed alongside findings published by others. M. leprae is an obligate human pathogen that has undergone an evolutionary bottleneck followed by clonal expansion. Therefore M. leprae genotypes and sub-genotypes give information about the human populations they have infected and their migration. Although data are limited, genotyping demonstrates that historical M. leprae from Byzantine Anatolia, Eastern and Central Europe resembles modern strains in Asia Minor rather than the recently characterized historical strains from North West Europe. The westward migration of peoples from Central Asia in the first millennium may have introduced different M. leprae strains into medieval Europe and certainly would have facilitated the spread of any existing leprosy. The subsequent decline of M. leprae in Europe may be due to increased host resistance. However, molecular evidence of historical leprosy and tuberculosis co-infections suggests that death from tuberculosis in leprosy patients was also a factor.
- MeSH
- History, Medieval MeSH
- Adult MeSH
- Genotype MeSH
- Leprosy epidemiology history transmission MeSH
- Middle Aged MeSH
- Humans MeSH
- Human Migration * MeSH
- Young Adult MeSH
- Mycobacterium leprae genetics MeSH
- Paleopathology MeSH
- Models, Statistical * MeSH
- Check Tag
- History, Medieval MeSH
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Historical Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Geographicals
- Europe MeSH
WHO technical report series, ISSN 0512-3054 968
vii, 61 s. : tab. ; 24 cm
- MeSH
- Leprosy epidemiology prevention & control therapy MeSH
- Leprostatic Agents MeSH
- Mycobacterium leprae MeSH
- Risk Factors MeSH
- Conspectus
- Patologie. Klinická medicína
- NML Fields
- infekční lékařství
- NML Publication type
- publikace WHO
- MeSH
- Adult MeSH
- Leprosy history diagnosis epidemiology MeSH
- Men MeSH
- Mycobacterium leprae isolation & purification MeSH
- Check Tag
- Adult MeSH
- Publication type
- Case Reports MeSH
- Geographicals
- Somalia MeSH
- MeSH
- Agglutination Tests methods MeSH
- Glycolipids MeSH
- Latex MeSH
- Leprosy diagnosis MeSH
- Humans MeSH
- Mycobacterium leprae immunology MeSH
- Serologic Tests methods MeSH
- Antibody Specificity MeSH
- Check Tag
- Humans MeSH
- Publication type
- Comparative Study MeSH
- MeSH
- Latex MeSH
- Leprosy pathology MeSH
- Macrophages physiopathology MeSH
- Mycobacterium leprae MeSH
- Mice MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Animals MeSH
- Publication type
- Comparative Study MeSH
