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 Hódmezővásárhely–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 Hódmezővásárhely–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.


S2 Text: Differential diagnoses of the skeletal lesions indicative of tuberculous involvement of the spine that were detected in HK225.
Although spinal tuberculosis (STB) seems to be the most likely underlying cause of the bony changes that were observed in the vertebral column of HK225, other aetiologies should also be considered in the differential diagnosis.The most relevant ones are pyogenic spinal infections and granulomatous spinal infections other than TB (fungal infectionse.g., aspergillosis and candidiasis; and bacterial infectionse.g., actinomycosis and brucellosis) [1][2][3][4][5].
Pyogenic spondylitis is the most frequent type of spinal infections, with most cases being diagnosed in patients over 50 years of age [6][7][8][9].It is a rare bacterial infection of the vertebral column, which is caused by pyogenic organisms, most commonly Staphylococcus aureus [10][11][12][13].In pyogenic spondylitis, the lumbar region represents the most frequently affected site, followed by the thoracic and cervical spine [6,10,[13][14].The disease typically affects two contiguous vertebrae and the intervening intervertebral disc; unlike in STB, involvement of more than two vertebrae is unusual in pyogenic spondylitis [6][7][8][9][15][16][17].In most cases, it is the anterior portion of the vertebral body that is primarily affected by the pyogenic infection, whereas involvement of the posterior vertebral elements is fairly rare [7,9].Vertebral body collapse and consequent kyphosis formation are not typical features of the disease [7].In contrast to STB, pyogenic spondylitis is characterised by rapid, massive bone regeneration (e.g., sclerosis, reactive new bone formations, and osteophyte-like bony extensions) but formation of extra-vertebral abscesses and sub-ligamentous spread of the infection are less frequent [9][10][11]15,[17][18][19].Based on the young age of HK225, as well as the presence of vertebral body collapse, the evident signs of overlying extra-vertebral abscesses and sub-ligamentous spread of the infection, and the absence of sclerotic repair of the lytic lesion in the spine of HK225, pyogenic spondylitis can be ruled out with high certainty as a diagnostic option in HK225.
Although in recent years, the incidence of fungal granulomatous infections has been increased, they are still extremely rare, with candidiasis and aspergillosis being the most frequent ones with potential spinal involvement [11,[20][21][22][23][24][25].They are caused by Candida and Aspergillus species, respectively [11,21,25].In fungal spondylitis, it is the lumbar region, which is the most commonly involved site, followed by the thoracic and cervical regions [20,[22][23][25][26]. Similar to STB, fungal spondylitis can affect not only one but multiple vertebrae, with multi-level non-contiguous involvement being not unusual [27][28].It can cause vertebral body collapse and consequent kyphosis formation [29].Furthermore, fungal spondylitis is often associated with the formation of extra-vertebral abscesses and sub-ligamentous spread of the infection, and unlike STB, it frequently affects the posterior vertebral elements [27][28][29][30][31]. Based on the rarity of fungal spondylitis, as well as the absence of posterior vertebral element involvement, it is unlikely that it was fungal spondylitis that resulted in the development of the skeletal lesions that were observed in the vertebral column of HK225.

Although actinomycosis, a rare bacterial granulomatous infection caused by
Actinomyces species, can result in vertebral osteomyelitis, actinomycotic involvement of the spine is extremely rare and mainly occurs in adults [29,[32][33][34][35][36].In most cases with actinomycotic spondylitis, the disease affects the cervical and thoracic regions of the vertebral column [33][34][35][36].Usually not one but several contiguous vertebrae are involved, and there is a tendency for the posterior vertebral elements to be affected rather than the vertebral bodies; thus, actinomycotic spondylitis scarcely leads to vertebral body collapse and consequent kyphosis formation [29,33,[37][38][39].The disease is characterised by formation of extra-vertebral abscesses and sub-ligamentous spread of the infection, which can lead to the formation of cortical erosions, sclerosis, and reactive new bone formations; osteolytic lesions and osteophyte-like bony extensions can also occur [29,[33][34][37][38][39].Based on the age preference and rarity of actinomycotic spondylitis, as well as the presence of vertebral body collapse and the absence of posterior vertebral element involvement in HK225, it is unlikely that an infection with Actinomyces spp.resulted in the development of the bony changes that were detected in the vertebral column of HK225.
Brucellosis is a bacterial granulomatous infection caused by Brucella species, which can spread from animals to humans [29,[40][41][42][43]. Spinal involvement, i.e., brucellar spondylitis, mainly occurs in adults, especially those over 50 years of age [29,40,[43][44][45].It is the lumbar region of the vertebral column that is most commonly affected by the disease, followed by the thoracic and cervical spine; usually two contiguous vertebral bodies are involved [40][41]43,[45][46].Unlike in STB, vertebral body collapse and consequent kyphosis formation, as well as development of extra-vertebral abscesses are not typical features of brucellar spondylitis.In cases where there is extra-vertebral abscess formation, they tend to be small, relatively limited, and usually do not spread [29,42,[44][45][47][48]. Brucellar spondyilitis is characterised by concomitant occurrence of reparative and destructive processes, with sclerosis, reactive new bone formations, and osteophyte-like bony extensions [29,40,[44][45][46][47].Based on the young age of HK225, as well as the presence of vertebral body collapse, the evident signs of overlying extra-vertebral abscesses and sub-ligamentous spread of the infection, and the absence of sclerotic repair of the lytic lesion in the spine of HK225, brucellosis seems to be less likely to be responsible for the development of the skeletal lesions that were observed in the vertebral column of HK225.