Ancient genomes reveal a high diversity of Mycobacterium leprae in medieval Europe.

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.

A migration-driven model for the historical spread of leprosy in medieval Eastern and Central Europe.

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.

The health status of the early medieval population of Greater Moravia in relations to social and economic structures.

The Greater Moravian Empire (9th-10th century AD) was the first early state formation of the Slavonic populations in Central Europe. The focus of this research is the comparative assessment of the health status of three cemeteries of different socio-economic status in the area surrounding the Mikulcice castle. We have compared about 850 skeletons from (1) the castle cemetery and (2) non-castle cemeteries in Mikulcice and (3) a cemetery from the poor village of Josefov located eight kilometres from Mikulcice. The following characteristics were examined: linear enamel defects, dental caries, cribra orbitalia, Harris lines, trauma, degenerative joint disease and occupation stress markers, sexual dimorphism and demographic estimators. Hypoplastic defects of enamel determined on the permanent dentition of children appear with high frequency (over 80%). As the incidence of these defects is found mostly in individuals between the ages of 2 to 4 years, it is interpreted to be a consequence of weaning stress. Cribra orbitalia appears more frequently in the rural Josefov cemetery. Inhabitants at the extramural settlement exhibit poorer dental health than people buried inside the castle. Demographic estimators showed also clear the differences between the cemeteries in the Mikulcice settlement and inside the castle. The results show that there were significant differences between the health status of early Slavonic populations from South Moravia.

Harris lines in the non-adult Great Moravian population of Mikulcice (Czech Republic).

Harris lines have been recognised as an indicator of the stress since the thirties of the last century, when the work of dr. H. A. Harris was published. Despite seventy years of interest, the aetiology of this marker remains unclear. The lines are generally interpreted as being the consequence of a temporary interruption or arrest of bone growth during ontogenesis. Various factors as a trauma, malnutrition and protein deficiency can be the cause of HL's development [e.g. 1]. Clinical studies, have not confirmed these connections unequivocally [e.g. 2, 3]. The lines form in the region of the metaphyses, where the bones grow. Their position vis-a-vis the bone enables to deduce, more or less, the time of their formation [e.g. 4, 5, 6]. The aim of our research was to study the Harris line's formarion in the non-adult population of the Great-Moravian settlement agglomeration at Mikulcice-Valy. We focused only on the non-adult population because it is impossible to rule out the possibility of re-modelling (obliteration) of these lines in adults [e.g. 7]. We recorded the incidence of these markers using X-rays of the long bones of the upper (Hu) and lower (Fe, Ti) extremities. We evaluated a total of 132 individuals. In the first phase, we calculated the intra-observer and inter-observer errors [e.g. 8]. After determining the incidence of these markers on individual bones, we observed the difference in the incidence of markers among individual bones, as well as differences in the distribution of lines in the proximal and distal parts of the bone under study. We also studied the intensity of line formation, which, together with the density of the lines themselves, could indicate the degree of intensity and duration of the stress [e.g. 9]. Finally, we evaluated, the period in the child's life when bone growth was most frequently disrupted [e.g. 6].

Case reports: Legg-Calvé-Perthes disease in Czech archaeological material.

Legg-Calvé-Perthes disease (osteochondrosis of the femoral head) has been recognized in archaeological material for nearly a century but is extremely rare. We describe two Czech cases from archaeological findings. The first case was diagnosed in the skeleton of a man older than 50 years with the left hip affected. The skeleton was in grave Number 2 of the Langobard cemetery at Luzice (Moravia) and dated to the end of the fifth century and the beginning of the sixth century AD. The second case was described by J. Chochol in 1957 on the left femur and half of the pelvis of a skeleton from an archaeological investigation in Brandýsek (Bohemia), ninth to tenth centuries AD. Using the diagnostic criteria of Ortner and Putschar, we excluded slipped capital femoral epiphysis in both cases. We discuss the differential diagnosis of Legg-Calvé-Perthes disease versus unilateral and bilateral osteochondroses of the femoral head in archaeological and current clinical material.