Antónia Marcsik

Co–infection of Mycobacterium tuberculosis and Mycobacterium leprae in human archaeological samples: a possible explanation for the historical decline of leprosy

Both leprosy and tuberculosis were prevalent in Europe during the first millennium but thereafter leprosy declined. It is not known why this occurred, but one suggestion is that cross–immunity protected tuberculosis patients from leprosy. To investigate any relationship between the two diseases, selected archaeological samples, dating from the Roman period to the thirteenth century, were examined for both Mycobacterium leprae and Mycobacterium tuberculosis DNA, using PCR. The work was carried out and verified in geographically separate and independent laboratories. Several specimens with palaeopathological signs of leprosy were found to contain DNA from both pathogens, indicating that these diseases coexisted in the past. We suggest that the immunological changes found in multi–bacillary leprosy, in association with the socio–economic impact on those suffering from the disease, led to increased mortality from tuberculosis and therefore to the historical decline in leprosy.

New skeletal tuberculosis cases in past populations from Western Hungary (Transdanubia)

The distribution, antiquity and epidemiology of tuberculosis (TB) have previously been studied in osteoarchaeological material in the eastern part of Hungary, mainly on the Great Plain. The purpose of this study is to map the occurrence of skeletal TB in different centuries in the western part of Hungary, Transdanubia, and to present new cases we have found. Palaeopathological analysis was carried out using macroscopic observation supported by radiographic and molecular methods. A large human osteoarchaeological sample (n=5684) from Transdanubian archaeological sites ranging from the 2nd to the 18th centuries served as a source of material. Spinal TB was observed in seven individuals (in three specimens with Potts disease two of which also had cold abscess) and hip TB was assumed in one case. The results of DNA for Mycobacterium tuberculosis were positive in seven of the eight cases identified by paleopathology, and negative in the assumed case of hip TB. However, the molecular results are consistent with highly fragmented DNA, which limited further analysis. Based on the present study and previously published cases, osteotuberculosis was found in Transdanubia mainly during the 9th-13th centuries. However, there are no signs of TB in many other 9th-13th century sites, even in those that lie geographically close to those where osteotuberculous cases were found. This may be due to a true absence of TB caused by the different living conditions, way of life, or origin of these populations. An alternative explanation is that TB was present in some individuals with no typical paleopathology, but that death occurred before skeletal morphological features could develop.

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.

A case of spinal tuberculosis from the Middle Ages in Transylvania (Romania)

Study Design. Case report. Objective. To characterize the paleopathology presented in the skeleton of a 45- to 50-year-old man indicative of tuberculous spondylitis and to confirm by the detection of ancient DNA. Summary of Background Data. Tuberculosis (TB) is an infectious disease prevalent in both present and ancient human populations. The disease is primarily located within the lungs; although characteristic bone lesions can lead to a clear diagnosis, skeletal TB occurs in only 5% to 6% of TB infections, even in historical cases. In addition, the visual appearance of human skeletal remains may be influenced by the environmental conditions at the burial site. However, it is important to recognize ancient skeletal TB because it can provide important data on the history of Mycobacterium tuberculosis and give a unique opportunity for physicians to observe the natural outcome of the infection of the preantibiotic era. Methods. Paleopathological analysis was carried out using careful visual observation supported by ancient DNA analysis. Approximately 60 mg of bone powder from rib fragments was examined and DNA from the M. tuberculosis complex was detected by polymerase chain reaction (PCR) targeting specific genetic loci of the IS6110 and IS1081 regions. Results. The skeleton is part of a human osteoarchaeological collection (n = 274) from the 12th- to 13th-century Transylvanian archaeological site of Peteni, in modern-day Romania. The individual, a 45- to 50-year-old man, showed gross pathology typical of tuberculous spondylitis. The paleopathological diagnosis was supported by analysis for M. tuberculosis complex ancient DNA. Conclusions. This case demonstrates that TB was present in Transylvania (Romania) during the 12th and 13th centuries and adds to the growing body of knowledge on the history of this disease.

The antiquity of tuberculosis in Hungary: the skeletal evidence

The analysis of the skeletons of past human populations provides some of the best biological data regarding the history of significant diseases such as tuberculosis. The purpose of this study is to present the pathological alterations of the bones in this disease deriving from the ancient time of the territory of the Hungarian Great Plain on the basis of the earlier references and new cases. The bone changes in tuberculosis were mainly manifested in the vertebrae and less frequently in the hip, however, further alterations were observed on the surface of the endocranium and the ribs.

Appearance of hyperostosis frontalis interna in some osteoarcheological series from Hungary.

Hyperostosis frontalis interna (HFI) is a generalised pathological condition with an unknown etiology and variable clinical association. It is characterized by excess bone growth and manifested on the inner table of the frontal bone, occasionally extending onto the temporals, parietals and the occipital. The etiology of HFI is uncertain: it may be an unknown genetic predisposition, a common environmental exposure, or special metabolic diseases. The purpose of the present study is to report cases of HFI in some osteoarcheological series from Hungary and to emphasize the importance of the investigation of HFI in ancient populations. Twenty out of 803 adults with observable frontal bones exhibited HFI, ranging from early to mid-type, including 15 females and 5 males. Some overgrowths with edges were blending into the endocranial surface, and some were prominently protruding from the surface. Advanced cases of HFI (type C) were observed after age 40-60 years.

Linear Measurements of the Neurocranium Are Better Indicators of Population Differences than Those of the Facial Skeleton: Comparative Study of 1,961 Skulls

Abstract The aim of this study is to individualize potential differences between two cranial regions used to differentiate human populations. We compared the neurocranium and the facial skeleton using skulls from the Great Hungarian Plain. The skulls date to the 1st–11th centuries, a long space of time that encompasses seven archaeological periods. We analyzed six neurocranial and seven facial measurements. The reduction of the number of variables was carried out using principal components analysis. Linear mixed-effects models were fitted to the principal components of each archaeological period, and then the models were compared using multiple pairwise tests. The neurocranium showed significant differences in seven cases between nonsubsequent periods and in one case, between two subsequent populations. For the facial skeleton, no significant results were found. Our results, which are also compared to previous craniofacial heritability estimates, suggest that the neurocranium is a more conservative region and that population differences can be pointed out better in the neurocranium than in the facial skeleton.

Skeletal Metastatic Carcinomas from the Roman Period (1st to 5th Century AD) in Hungary

Objectives: According to paleopathological records, tumors have a great antiquity. The prevalence of cancer in ancient populations might have differed from that in modern humans because of substantial differences in environmental factors, life expectancy and the availability of treatment. This study presents 3 cases of probable skeletal metastatic carcinoma from the Roman period (1st-5th century AD) in Hungary, showing the development of bone metastases of cancer without chemo- and radiotherapy. Methods: All skeletons were subjected to a careful macroscopic investigation, which was extended by radiological, stereo- and scanning electron microscopic analyses. Results: In 1 case, the mixed nature and localization of the lesions, as well as the sex and age of the individual, suggested breast cancer as the primary focus. In the other 2 cases, based on the mostly osteoblastic nature and the localization of the lesions as well as on the sex and age of the individuals, the most probable diagnostic option is prostate carcinoma with skeletal metastases. Conclusions: In view of the scarcity of cancer metastases that have been diagnosed in archeological specimens in general, identification of all examples of cancer in antiquity represents an important contribution both to paleopathology and to modern medicine.

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.

Childhood bone tuberculosis from Roman Pécs, Hungary

A child from a Roman necropolis in Pécs, Hungary (4th century CE) was initially diagnosed with severe spinal osteomyelitis. The post-cranial skeleton displayed bone alterations in the lower thoracic and upper lumbar segments, including vertebral body destruction, collapse and sharp kyphosis, and additional multiple rib lesions, suggesting a most likely diagnosis of pulmonary and spinal tuberculosis. This study discusses a number of selected diagnoses in the context of our pathological findings, complementing the macroscopic examination with radiological and biomolecular analyses.