White plague among the "forgotten people" from the Barbaricum of the Carpathian Basin-Cases with tuberculosis from the Sarmatian-period (3rd-4th centuries CE) archaeological site of Hódmezovásárhely-Kenyere-ér, Bereczki-tanya (Hungary).

Tuberculosis (TB) is a bacterial infection that is well-known in the palaeopathological record because it can affect the skeleton and consequently leaves readily identifiable macroscopic alterations. Palaeopathological case studies provide invaluable information about the spatio-temporal distribution of TB in the past. This is true for those archaeological periods and geographical regions from when and where no or very few TB cases have been published until now-as in the Sarmatian period (1st-5th centuries CE) in the Barbaricum of the Carpathian Basin. The aim of our paper is to discuss five newly discovered TB cases (HK199, HK201, HK225, HK253, and HK309) from the Sarmatian-period archaeological site of Hódmezovásárhely-Kenyere-ér, Bereczki-tanya (Csongrád-Csanád county, Hungary). Detailed macromorphological evaluation of the skeletons focused on the detection of bony changes likely associated with different forms of TB. In all five cases, the presence of endocranial alterations (especially TB-specific granular impressions) suggests that these individuals suffered from TB meningitis. Furthermore, the skeletal lesions observed in the spine and both hip joints of HK225 indicate that this juvenile also had multifocal osteoarticular TB. Thanks to the discovery of HK199, HK201, HK225, HK253, and HK309, the number of TB cases known from the Sarmatian-period Carpathian Basin doubled, implying that the disease was likely more frequent in the Barbaricum than previously thought. Without the application of granular impressions, the diagnosis of TB could not have been established in these five cases. Thus, the identification of TB in these individuals highlights the importance of diagnostics development, especially the refinement of diagnostic criteria. Based on the above, the systematic macromorphological (re-)evaluation of osteoarchaeological series from the Sarmatian-period Carpathian Basin would be advantageous to provide a more accurate picture of how TB may have impacted the ancestral human communities of the Barbaricum.

More than one millennium (2nd-16th century CE) of the White Plague in the Carpathian Basin - New cases, expanding knowledge.

The causative agent of tuberculosis is still a widespread pathogen, which caused the death of ca. 1.6 million people globally in 2021. The paleopathological study of human remains revealed the antiquity of the disease and its continuous presence throughout the history of humankind. The Carpathian Basin has always been a biocultural melting pot, since it has seen several migrations over the centuries, and served as a location of admixture and interaction for numerous populations of different cultures. Thus, this geographical territory is ideal for the examination of the coevolutionary processes of hosts and their pathogens. We aimed to reveal the spatial and temporal distribution of tuberculosis cases excavated inside the borders of Hungary between the 2nd and 16th centuries CE. We established a comprehensive database by collecting 114 already published cases and introducing 39 new cases. The involved cases include those that have been confirmed by different molecular methods, as well as possible infections that were identified based on the presence of macromorphological and radiological alterations. The progress of future molecular and paleopathological studies can be facilitated by our dataset, as it presents spatial and temporal information concerning the spread of the disease in the Carpathian Basin, as well as the biological profile and detailed paleopathological description of lesions illustrated by photo- and radiographs.

Tuberculosis in prehistory in Eastern Central Europe (Hungary) - Chronological and geographical distribution.

Tuberculosis (TB) has long been a major scourge of humankind. Paleopathological and paleomicrobiological studies have revealed the past presence of the disease on a large spatial and temporal scale. The antiquity of the disease has extensively been studied in the Carpathian Basin, given its dynamic population and cultural changes since prehistory. These studies, however, have mainly focused on the populations living during the Common Era. The aim of this paper is to present the published and the recently discovered cases of prehistoric TB, from the Neolithic (6000-4500/4400 BCE) to the Bronze Age (2600/2500-800 BCE) Central Carpathian Basin (Hungary). We summarize 18 published cases and present new cases dating to the Neolithic period and introduce 3 newly discovered Bronze Age cases of TB. Despite extensive research, TB has not yet been identified from the Copper and Iron Ages in the Carpathian Basin. Considering the state of TB research, and supplemented by our prehistoric dataset, the spatio-temporal pattern of the disease can be further elucidated, thus advancing future molecular and paleopathological studies. Our dataset offers comprehensive spatial and temporal information on the spread of the disease in the Carpathian Basin, along with a detailed biological profile of the demonstrated cases and extensive paleopathological descriptions of the observed lesions, complemented by photographic evidence. This invaluable resource paves the way for enhanced understanding and progress in the field.

Leprosy: The age-old companion of humans - Re-evaluation and comparative analysis of Avar-period cases with Hansen's disease from the Danube-Tisza Interfluve, Hungary.

In recent years, our knowledge of leprosy in the past has substantially been enriched. Nonetheless, much still remains to be discovered, especially in regions and periods from where no written sources are available. To fill in some research gaps, we provide the comparative analysis of eight Avar-period leprosy cases from the Danube-Tisza Interfluve (Hungary). In every case, to reconstruct the biological consequences of leprosy, the detected bony changes were linked with palaeopathological and modern medical information. To reconstruct the social consequences of being affected by leprosy, conceptualisation of the examined individuals' treatment in death was conducted. In every case, the disease resulted in deformation and disfigurement of the involved anatomical areas (rhinomaxillary region, feet, and/or hands) with difficulties in conducting certain physical activities. These would have been disadvantageous for the examined individuals and limited or changed their possibilities to participate in social situations. The most severe cases would have required continuous support from others to survive. Our findings indicate that, despite their very visible disease and associated debility, the examined communities did not segregate leprosy sufferers but provided and cared for them, and maintained a strong enough social network that made their survival possible even after becoming incapable of self-sufficiency.

The two extremes of Hansen's disease-Different manifestations of leprosy and their biological consequences in an Avar Age (late 7th century CE) osteoarchaeological series of the Duna-Tisza Interfluve (Kiskundorozsma-Daruhalom-dulo II, Hungary).

To give an insight into the different manifestations of leprosy and their biological consequences in the Avar Age of the Hungarian Duna-Tisza Interfluve, two cases from the 7th-century-CE osteoarchaeological series of Kiskundorozsma-Daruhalom-dulo II (Hungary; n = 94) were investigated. Based on the macromorphology of the bony changes indicative of Hansen's disease, KD271 (a middle-aged male) and KD520 (a middle-aged female) represent the two extremes of leprosy. KD271 appears to have an advanced-stage, long-standing near-lepromatous or lepromatous form of the disease, affecting not only the rhinomaxillary region but also both upper and lower limbs. This has led to severe deformation and disfigurement of the involved anatomical areas of the skeleton, resulting in his inability to perform the basic activities of daily living, such as eating, drinking, grasping, standing or walking. The skeleton of KD520 shows no rhinomaxillary lesions and indicates the other extreme of leprosy, a near-tuberculoid or tuberculoid form of the disease. As in KD271, Hansen's disease has resulted in disfigurement and disability of both of the lower limbs of KD520; and thus, the middle-aged female would have experienced difficulties in standing, walking, and conducting occupational physical activities. KD271 and KD520 are amongst the very few published cases with leprosy from the Avar Age of the Hungarian Duna-Tisza Interfluve, and the only examples with detailed macromorphological description and differential diagnoses of the observed leprous bony changes. The cases of these two severely disabled individuals, especially of KD271 -who would have required regular and substantial care from others to survive-imply that in the Avar Age community of Kiskundorozsma-Daruhalom-dulo II there was a willingness to care for people in need.

The genetic origin of Huns, Avars, and conquering Hungarians.

Huns, Avars, and conquering Hungarians were migration-period nomadic tribal confederations that arrived in three successive waves in the Carpathian Basin between the 5th and 9th centuries. Based on the historical data, each of these groups are thought to have arrived from Asia, although their exact origin and relation to other ancient and modern populations have been debated. Recently, hundreds of ancient genomes were analyzed from Central Asia, Mongolia, and China, from which we aimed to identify putative source populations for the above-mentioned groups. In this study, we have sequenced 9 Hun, 143 Avar, and 113 Hungarian conquest period samples and identified three core populations, representing immigrants from each period with no recent European ancestry. Our results reveal that this "immigrant core" of both Huns and Avars likely originated in present day Mongolia, and their origin can be traced back to Xiongnus (Asian Huns), as suggested by several historians. On the other hand, the "immigrant core" of the conquering Hungarians derived from an earlier admixture of Mansis, early Sarmatians, and descendants of late Xiongnus. We have also shown that a common "proto-Ugric" gene pool appeared in the Bronze Age from the admixture of Mezhovskaya and Nganasan people, supporting genetic and linguistic data. In addition, we detected shared Hun-related ancestry in numerous Avar and Hungarian conquest period genetic outliers, indicating a genetic link between these successive nomadic groups. Aside from the immigrant core groups, we identified that the majority of the individuals from each period were local residents harboring "native European" ancestry.

Correction: Life and death of a leprosy sufferer from the 8th-century-CE cemetery of Kiskundorozsma-Kettoshatár I (Duna-Tisza Interfluve, Hungary)-Biological and social consequences of having Hansen's disease in a late Avar Age population from Hungary.

[This corrects the article DOI: 10.1371/journal.pone.0264286.].

Ancient genomes reveal origin and rapid trans-Eurasian migration of 7th century Avar elites.

The Avars settled the Carpathian Basin in 567/68 CE, establishing an empire lasting over 200 years. Who they were and where they came from is highly debated. Contemporaries have disagreed about whether they were, as they claimed, the direct successors of the Mongolian Steppe Rouran empire that was destroyed by the Turks in ∼550 CE. Here, we analyze new genome-wide data from 66 pre-Avar and Avar-period Carpathian Basin individuals, including the 8 richest Avar-period burials and further elite sites from Avar's empire core region. Our results provide support for a rapid long-distance trans-Eurasian migration of Avar-period elites. These individuals carried Northeast Asian ancestry matching the profile of preceding Mongolian Steppe populations, particularly a genome available from the Rouran period. Some of the later elite individuals carried an additional non-local ancestry component broadly matching the steppe, which could point to a later migration or reflect greater genetic diversity within the initial migrant population.

Life and death of a leprosy sufferer from the 8th-century-CE cemetery of Kiskundorozsma-Kettoshatár I (Duna-Tisza Interfluve, Hungary)-Biological and social consequences of having Hansen's disease in a late Avar Age population from Hungary.

The aim of our paper is to demonstrate a middle-aged male (KK61) from the 8th-century-CE cemetery of Kiskundorozsma-Kettoshatár I (Duna-Tisza Interfluve, Hungary), who appears to represent the lepromatous form of Hansen's disease. Leprosy has affected not only the rhinomaxillary region of his face but also his lower limbs, with severe deformation and disfigurement of the involved anatomical areas (saddle-nose and flat-foot deformity, respectively). Consequently, he would have experienced disability in performing the basic activities of daily living, such as eating, drinking, standing or walking; and thus, he would have required regular and substantial care from others to survive. Despite his very visible disease and associated debility, it seems that KK61 was accepted as a member of the community in death, since he has been buried within the cemetery boundaries, among others from his community. In addition, his grave has conformed to the mortuary practices characteristic of the Kiskundorozsma-Kettoshatár I cemetery (e.g., burial orientation, position of the body in the grave, and type and quantity of accompanying grave goods). Although distinction or segregation in life do not preclude normative treatment in death, the long-lasting survival of KK61 with Hansen's disease implies that he would not have been abandoned but cared for by others. KK61 is one of the few published historic cases with leprosy from the Avar Age of the Hungarian Duna-Tisza Interfluve. His case gives us a unique insight into the biological consequences of living with Hansen's disease and illustrates the social attitude toward leprosy sufferers in early mediaeval Hungary.

Maternal Lineages from 10-11th Century Commoner Cemeteries of the Carpathian Basin.

Nomadic groups of conquering Hungarians played a predominant role in Hungarian prehistory, but genetic data are available only from the immigrant elite strata. Most of the 10-11th century remains in the Carpathian Basin belong to common people, whose origin and relation to the immigrant elite have been widely debated. Mitogenome sequences were obtained from 202 individuals with next generation sequencing combined with hybridization capture. Median joining networks were used for phylogenetic analysis. The commoner population was compared to 87 ancient Eurasian populations with sequence-based (Fst) and haplogroup-based population genetic methods. The haplogroup composition of the commoner population markedly differs from that of the elite, and, in contrast to the elite, commoners cluster with European populations. Alongside this, detectable sub-haplogroup sharing indicates admixture between the elite and the commoners. The majority of the 10-11th century commoners most likely represent local populations of the Carpathian Basin, which admixed with the eastern immigrant groups (which included conquering Hungarians).

Author Correction: Genetic insights into the social organisation of the Avar period elite in the 7th century AD Carpathian Basin.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Genetic insights into the social organisation of the Avar period elite in the 7th century AD Carpathian Basin.

After 568 AD the Avars settled in the Carpathian Basin and founded the Avar Qaganate that was an important power in Central Europe until the 9th century. Part of the Avar society was probably of Asian origin; however, the localisation of their homeland is hampered by the scarcity of historical and archaeological data. Here, we study mitogenome and Y chromosomal variability of twenty-six individuals, a number of them representing a well-characterised elite group buried at the centre of the Carpathian Basin more than a century after the Avar conquest. The studied group has maternal and paternal genetic affinities to several ancient and modern East-Central Asian populations. The majority of the mitochondrial DNA variability represents Asian haplogroups (C, D, F, M, R, Y and Z). The Y-STR variability of the analysed elite males belongs only to five lineages, three N-Tat with mostly Asian parallels and two Q haplotypes. The homogeneity of the Y chromosomes reveals paternal kinship as a cohesive force in the organisation of the Avar elite strata on both social and territorial level. Our results indicate that the Avar elite arrived in the Carpathian Basin as a group of families, and remained mostly endogamous for several generations after the conquest.

Y-chromosome haplogroups from Hun, Avar and conquering Hungarian period nomadic people of the Carpathian Basin.

Hun, Avar and conquering Hungarian nomadic groups arrived to the Carpathian Basin from the Eurasian Steppes and significantly influenced its political and ethnical landscape, however their origin remains largely unknown. In order to shed light on the genetic affinity of above groups we have determined Y chromosomal haplogroups and autosomal loci, suitable to predict biogeographic ancestry, from 49 individuals, supposed to represent the power/military elit. Haplogroups from the Hun-age are consistent with Xiongnu ancestry of European Huns. Most of the Avar-age individuals carry east Eurasian Y haplogroups typical for modern north-eastern Siberian and Buryat populations and their autosomal loci indicate mostly un-admixed Asian characteristics. In contrast the conquering Hungarians seem to be a recently assembled population incorporating un-admixed European, Asian as well as admixed components. Their heterogeneous paternal and maternal lineages indicate similar supposed phylogeographic origin of males and females, derived from Central-Inner Asian and European Pontic Steppe sources.

Osteoarcheological and biomolecular evidence of leprosy from an 11-13th century CE Muslim cemetery in Europe (Orosháza, Southeast Hungary).

Orosháza site no. 10 (Southeast Hungary) contains the partially excavated archaeological remains of an 11-13th century CE Muslim merchant village and its cemetery located in close proximity to Christian villages of the same era. The skeleton of a young woman (grave no. 16) from the last phase of the cemetery use was identified with rhinomaxillary lesions associated with lepromatous leprosy. The right parietal bone also exhibited signs of cranial trauma, possibly caused by symbolic trepanation, a well-known ritual practice in the 9-11th century CE Carpathian Basin. The retrospective diagnosis of the disease was supported by ancient DNA analysis, as the samples were positive for Mycobacterium leprae aDNA, shown to be of genotype 3. Contrary to the general practice of the era, the body of the young female with severe signs of leprosy was interred among the regular graves of the Muslim cemetery in Orosháza, which may reflect the unique cultural background of the community.

Hyperostosis frontalis interna in ancient populations from the Carpathian Basin - A possible relationship between lifestyle and risk of development.

OBJECTIVE: The prevalence of hyperostosis frontalis interna (HFI) was examined in different periods of the Carpathian Basin from 4900 BCE to 17th century AD. The study seeks to evaluate temporal changes in HFI and the possible impact of lifestyle on it. MATERIALS: The studied material consisted of 4668 crania from Hungary and Serbia. METHODS: The crania were analyzed employing macroscopic and endoscopic examination. RESULTS: In historic periods, sex and age played a pivotal role in HFI development. Among predominantly pastoralist populations of the 5th-8th and 10th centuries, prevalence of HFI was considerably higher than in the medieval populations of the 9th-17th centuries. CONCLUSIONS: In addition to age and sex, other factors could be implicated in HFI development. The physiological effects of the pastoralist lifestyle and diet on insulin regulation could explain the increased risk of developing HFI in the 5th-8th and 10th-century populations. SIGNIFICANCE: The study provides the first comprehensive dataset of HFI from different archaeological periods from the Carpathian Basin. It has implications for lifestyle and risk of HFI development in past populations. LIMITATIONS: The archaeological periods are not equally represented. SUGGESTIONS FOR FURTHER RESEARCH: In order to better understand the etiology of HFI, lifestyle factors can be used to elucidate the risk of developing HFI in ancient populations.

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.

5000 years of dietary variations of prehistoric farmers in the Great Hungarian Plain.

The development of farming was a catalyst for the evolution of the human diet from the varied subsistence practices of hunter-gatherers to the more globalised food economy we depend upon today. Although there has been considerable research into the dietary changes associated with the initial spread of farming, less attention has been given to how dietary choices continued to develop during subsequent millennia. A paleogenomic time transect for 5 millennia of human occupation in the Great Hungarian Plain spanning from the advent of the Neolithic to the Iron Age, showed major genomic turnovers. Here we assess where these genetic turnovers are associated with corresponding dietary shifts, by examining the carbon and nitrogen stable isotope ratios of 52 individuals. Results provide evidence that early Neolithic individuals, which were genetically characterised as Mesolithic hunter-gatherers, relied on wild resources to a greater extent than those whose genomic attributes were of typical Neolithic European farmers. Other Neolithic individuals and those from the Copper Age to Bronze Age periods relied mostly on terrestrial C3 plant resources. We also report a carbon isotopic ratio typical of C4 plants, which may indicate millet consumption in the Late Bronze Age, despite suggestions of the crop's earlier arrival in Europe during the Neolithic.

Possible cases of leprosy from the Late Copper Age (3780-3650 cal BC) in Hungary.

At the Abony-Turjányos dulo site, located in Central Hungary, a rescue excavation was carried out. More than 400 features were excavated and dated to the Protoboleráz horizon, at the beginning of the Late Copper Age in the Carpathian Basin, between 3780-3650 cal BC. Besides the domestic and economic units, there were two special areas, with nine-nine pits that differed from the other archaeological features of the site. In the northern pit group seven pits contained human remains belonging to 48 individuals. Some of them were buried carefully, while others were thrown into the pits. The aim of this study is to present the results of the paleopathological and molecular analysis of human remains from this Late Copper Age site. The ratio of neonates to adults was high, 33.3%. Examination of the skeletons revealed a large number of pathological cases, enabling reconstruction of the health profile of the buried individuals. Based on the appearance and frequency of healed ante- and peri mortem trauma, inter-personal (intra-group) violence was characteristic in the Abony Late Copper Age population. However other traces of paleopathology were observed on the bones that appear not to have been caused by warfare or inter-group violence. The remains of one individual demonstrated a rare set of bone lesions that indicate the possible presence of leprosy (Hansen's disease). The most characteristic lesions occurred on the bones of the face, including erosion of the nasal aperture, atrophy of the anterior nasal spine, inflammation of the nasal bone and porosity on both the maxilla and the bones of the lower legs. In a further four cases, leprosy infection is suspected but other infections cannot be excluded. The morphologically diagnosed possible leprosy case significantly modifies our knowledge about the timescale and geographic spread of this specific infectious disease. However, it is not possible to determine the potential connections between the cases of possible leprosy and the special burial circumstances.

Rare Case of an Ancient Craniofacial Osteosarcoma with Probable Surgical Intervention.

Osteosarcoma is the most common primary malignant bone tumor both today and in antiquity. Nevertheless, it is a comparatively rare tumor. This paper describes a case of a highly aggressive craniofacial lesion from the 11th-12th centuries AD, most likely representing osteosarcoma. During the paleopathological study, macroscopic, endoscopic, radiological, scanning-electron and light microscopic investigations were performed. The skull of the approximately 40-50 year-old female revealed several pathological findings. The most impressive macroscopic feature was an extensively spiculated periosteal reaction ("sunburst" pattern) in combination with a massive bone destruction most likely derived from a highly aggressive tumor originating in the ethmoidal area of the medial wall of the orbit. The central parts of the lesion showed excessive new and most probably neoplastic bone formation indicating an underlying high-grade osteosarcoma. The light microscopic examination revealed three different levels of bony structures representing different qualities of bone tissues. Besides the mass lesion, signs of a healed multiple incomplete trephination of the left parietal bone was observed. This case represents a unique example in which the concomitance of a tumor and an incomplete trephination could be observed from the skeletal remains of an ancient individual. The case opens new considerations as to whether surgical interventions, such as incomplete trephination, might have been used already in the Middle Ages as a therapeutic approach.