A brief history of tuberculosis in the Czech Lands.

Tuberculosis currently remains a serious medical problem, therefore increased attention is being paid to this disease. Paleopathological studies focused on the monitoring of morbid changes in skeletal remains of historical populations facilitate a detailed study of the development of this disease. They provide direct evidence of the existence of tuberculosis and its past forms. In addition to literary and iconographic sources, the present study is focused on recording the findings of bone tuberculosis in historical osteological sets from the Czech Lands and is the starting point for their detailed review. Approximately 76 cases of bone tuberculosis from the Czech Lands have been published and more or less reliably documented from 20 archeological sites dated back from the Eneolithic to the modern period.

A 6500-year-old Middle Neolithic child from Pollera Cave (Liguria, Italy) with probable multifocal osteoarticular tuberculosis.

Clear skeletal evidence of prehistoric tuberculosis (TB) is rare, especially in children. We describe and differentially diagnose the pathological changes displayed by a five-year-old child, Pollera 21 (PO21) dated to the Middle Neolithic of Liguria (Italy), or 5740±30 BP (Beta-409341; 6635-6453cal BP, 2σ, OxCal 4.2). PO21 shows a number of osteoarticular lesions, mainly of a lytic nature with very little bone proliferation: the vertebral column, the shoulder and pelvic girdles, and the ribcage are involved. Given the nature and pattern of the lesions, we propose a diagnosis of multifocal (or multiple) bone TB. Attempts to detect TB aDNA through molecular analysis gave negative results, but this alone is not sufficient to prove that PO21 was not infected with TB. The lesions observed in PO21 share similarities with other published evidence, such as spinal and joint involvement, and disseminated cyst-like lesions. Conversely, PO21 does not show diffuse bone deposition, such as hypertrophic osteoarthropathy (HOA) or endocranial modifications such as serpens endocrania symmetrica (SES). PO21 adds to our knowledge of patterns of TB manifestation in archaeological skeletal remains, which is especially important considering the variability in types and patterns of osteoarticular lesions seen today in people with TB.

AG 85, a major secretion protein of Mycobacterium tuberculosis, can be identified in ancient bone.

For the confirmation of Ag 85 in ancient and recent ECM of native macerated human bone, five cases were investigated. In three individuals, highly positive results for Ag 85 were identified in Western blot: 1) a male from Arzhan, South Siberia, dating from the 7th century BC, 2) a male from Kirchberg in Hesse, Germany, dating from the 10th - 12th century AD and 3) a recent female with a proven diagnosis of TB. As a negative control, a recent male is presented who did not suffer from TB. In another recent male, Ag 85 could be identified only very weakly. From cases in the literature it is well-known that highly positive results for Ag 85 indicate active TB, however, weakly positive results indicate a silent initial infection with Mtb. Thus, apparently, also in ancient individuals, it might well be possible to differentiate between diseased persons and disease carriers using paleoproteomic techniques.

Tuberculosis in Late Neolithic-Early Copper Age human skeletal remains from Hungary.

Alsónyék-Bátaszék in Southern Hungary is one of the largest late Neolithic settlements and cemeteries excavated in Central Europe. In total, 2359 burials from the Late Neolithic - Early Copper Age Lengyel culture were found between 2006 and 2009 [1]. Anthropological investigations previously carried out on individuals from this site revealed an interesting paleopathological case of tuberculosis in the form of Pott's disease dated to the early 5(th) millennium BC. In this study, selected specimens from this osteoarcheological series were subjected to paleomicrobiological analysis to establish the presence of MTBC bacteria. As all individuals showing clear osteological signs of TB infection belonged to a single grave group, 38 individuals from this grave group were analysed. The sample included the case of Pott's disease as well as individuals both with and without osseous TB manifestations. The detection of TB DNA in the individual with Pott's disease provided further evidence for the occurrence of TB in Neolithic populations of Europe. Moreover, our molecular analysis indicated that several other individuals of the same grave group were also infected with TB, opening the possibility for further analyses of this unique Neolithic skeletal series.

Tuberculosis and survival in past populations: A paleo-epidemiological appraisal.

Historical assessments of the last two centuries consistently placed tuberculosis as the leading cause of mortality. However, for earlier periods, we can only calculate the frequencies of archaeological bone lesions, which tell us little about the real impact of the disease on mortality. These lesions are usually observed in individuals who have developed immune resistance, which is visible as healed osteo-articular lesions. This study aimed to test the differential impacts of tuberculosis, cribra orbitalia and cribra femoris on adult survival and sex-based survival. We analyzed 28 French adult samples from the Antiquity and the Early Middle Ages. The age-at-death of 1480 individuals was estimated using cementochronology. Survival curves and median age-at-death were calculated to test new hypotheses that challenge the parasitic and deficiency theories of bone stress markers. Comparisons between carriers and non-carriers provided new information concerning the plausible causes of bone stress markers related to infections and TB. The most likely hypothesis is skeletal demineralization and osteoclastic resorption, which are usually observed close to tubercular granuloma or distant from active lesions. The bone marrow niche of Mycobacterium tuberculosis within CD271(+) BM-MSCs stem cells is the proposed explanation for the localized cortical resorption that is observed in bone stress markers.

7000 year-old tuberculosis cases from Hungary - Osteological and biomolecular evidence.

This study derives from the macroscopic analysis of a Late Neolithic population from Hungary. Remains were recovered from a tell settlement at Hódmezovásárhely-Gorzsa from graves within the settlement as well as pits, ditches, houses and as stray finds. One of the most important discoveries from these remains was evidence of tuberculosis. Pathological analysis of the seventy-one individuals revealed numerous cases of infections and non-specific stress indicators on juveniles and adults, metabolic diseases on juveniles, and evidence of trauma and mechanical changes on adults. Several cases showed potential signs of tuberculosis and further analyses were undertaken, including biomolecular studies. The five individuals were all very young adults and included a striking case of Hypertrophic Pulmonary Osteopathy (HPO) with rib changes, one case with resorptive lesions on the vertebrae, two cases with hypervascularisation on the vertebrae and periosteal remodelling on the ribs, and one case with abnormal blood vessel impressions and a possible lesion on the endocranial surface of the skull. The initial macroscopic diagnosis of these five cases was confirmed by lipid biomarker analyses, and three of them were corroborated by DNA analysis. At present, these 7000-year-old individuals are among the oldest palaeopathological and palaeomicrobiological cases of tuberculosis 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.

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 Pott's 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.

Tuberculosis de la muñeca y de la mano / Tuberculosis of the hand and wrist

Introducción: La tuberculosis osteoarticular se observa en la columna, la rodilla y la cadera y, menos a menudo,en las vainas tenosinoviales, y en los huesos de la mano y la muñeca. El objetivo del presente trabajo es analizar esta patología y su tratamiento, y valorar la técnica de reconstrucción simultánea a largo plazo. Materiales y métodos: El estudio abarca a 19 pacientes tratados en 45 años, correspondientes a: 3 espinas ventosas, 10 tenosinovitis de flexores, 4 tenosinovitis de extensores y 2 artritis de muñeca. Empleamos una metodología diagnóstica moderna y el estudio retrospectivo de los pacientes, sus tratamientos y resultados. Resultados: El tratamiento farmacológico correcto es eficaz en 99 por ciento de los casos para la infección tuberculosa. El quirúrgico acelera la curación y consiste en la resección de los tejidos necróticos y la reconstrucción funcional, primaria o secundaria. La curación de la infección se logra siempre; la recuperación funcional estará en relación con el tipo, la. gravedad y la extensión de la lesión. Conclusiones: Se demuestra la frecuencia de estas patologías en los trabajadores de la carne o que están en contacto diario con hacienda. Se destacan los procedimientos modernos de diagnóstico. Se enfatiza en un tratamiento médico completo en calidad, duración y tipo de fármacos. Se destacan las bondades de los tratamientos quirúrgicos y de la reconstrucción funcional simultánea que propusimos en 1965.

Tuberculosis de la muñeca y de la mano / Tuberculosis of the hand and wrist

Introducción: La tuberculosis osteoarticular se observa en la columna, la rodilla y la cadera y, menos a menudo,en las vainas tenosinoviales, y en los huesos de la mano y la muñeca. El objetivo del presente trabajo es analizar esta patología y su tratamiento, y valorar la técnica de reconstrucción simultánea a largo plazo. Materiales y métodos: El estudio abarca a 19 pacientes tratados en 45 años, correspondientes a: 3 espinas ventosas, 10 tenosinovitis de flexores, 4 tenosinovitis de extensores y 2 artritis de muñeca. Empleamos una metodología diagnóstica moderna y el estudio retrospectivo de los pacientes, sus tratamientos y resultados. Resultados: El tratamiento farmacológico correcto es eficaz en 99 por ciento de los casos para la infección tuberculosa. El quirúrgico acelera la curación y consiste en la resección de los tejidos necróticos y la reconstrucción funcional, primaria o secundaria. La curación de la infección se logra siempre; la recuperación funcional estará en relación con el tipo, la. gravedad y la extensión de la lesión. Conclusiones: Se demuestra la frecuencia de estas patologías en los trabajadores de la carne o que están en contacto diario con hacienda. Se destacan los procedimientos modernos de diagnóstico. Se enfatiza en un tratamiento médico completo en calidad, duración y tipo de fármacos. Se destacan las bondades de los tratamientos quirúrgicos y de la reconstrucción funcional simultánea que propusimos en 1965.(AU)

[Contribution of paleopathology to defining the pathocoenosis of infectious diseases (Part one)]. / Apporti della paleopatologia alla definizione della patocenosi delle malattie infettive (prima parte).

Studying the remains of mummies obtained by archaeological research may provide key information concerning historical pathocoenosis. Paleopathology makes it possible to recognise, characterise and connect different features involved in human pathocoenosis, such as epidemiology, in a historical perspective, and cultural development, via the introduction of new livestock farming techniques and agriculture in general. Several distinct pathologies may produce direct and indirect changes in the skeleton of affected individuals. Therefore bone remains represent very important sources of information to study such diseases. Changes related to trauma and nutrition deficiency as well as secondary signs, induced by tuberculosis, brucellosis, leprosy, syphilis, malaria, periostitis and aspecific osteomyelitis, persist in bones. In addition, other diseases may cause indirect alterations and subsequent secondary bone in the skeleton via different mechanisms. A secondary bone dimorphism may be induced by poliomyelitis. Aspecific lesions may arise in a skeletal bone and then cause secondary alterations in near-bone segments. Reviewing studies of paleopathologic research found in the literature, we emphasize the relationship between the appearance of major infectious diseases and the development of human activities; whereas it is clear that the introduction of livestock farming had a key role in the pathocoenosis of distinct infections such as tuberculosis, brucellosis and leprosy, some doubts and uncertainty remain in relation to the origin of others with epidemiologically important pathologies, such as syphilis.

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.

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.

Leprosy and tuberculosis in Iron Age Southeast Asia?

The recent excavation of a sample of 120 human skeletons from an Iron Age site in the valley of the Mun River, a tributary of the Mekong River on the Khorat Plateau in northeast Thailand, has provided the largest sample from this period in the region to date. This paper reviews three individuals from the sample with pathological changes for which the differential diagnosis includes systemic infectious disease. In two of these, both males with lesions of the hands and feet, leprosy and psoriatic arthritis are discussed as differential diagnoses, with leprosy the most probable. In the third, a female with lesions of the spine, the differential diagnosis includes tuberculosis and nonspecific osteomyelitis. Tuberculosis is the most probable diagnosis. Although the focus of this paper is a presentation of the evidence for infectious disease at Noen U-Loke, the significance of probable diagnoses of mycobacterial diseases for the history of the diseases and for prehistory in mainland Southeast Asia is also briefly discussed.

Outbreak of tuberculosis in a 2000-year-old Chinese population.

The molecular identification of Mycobacterium tuberculosis DNA in ancient human remains has been achieved mainly in mummies with macroscopic changes but not in the skeletons without bone tuberculosis. Using polymerase chain reaction studies, we identified mycobacterial DNA in 2000-year-old human skeletons without pathological changes. Our findings suggest that these people suffered from an outbreak of tuberculosis. Molecular examinations for mycobacterial DNA in the bone marrow of skeletons may contribute to the clarification of ancient diseases in old human populations.

Rib lesions in a prehistoric Puebloan sample from southwestern Colorado.

An unusually high frequency of periosteal lesions of visceral rib surfaces was observed in a small, prehistoric skeletal series from southwestern Colorado. Lesions of this type have been concordant with pulmonary tuberculosis in three studies of human skeletal collections with known cause of death, and in a recent clinical investigation of rib dimensions in living patients with lung disorders. Diseases such as pneumonia and actinomycosis have also been found to cause these lesions, but in much lower frequencies. Archaeological evidence suggests that Puebloan farmers of Sleeping Ute Mountain's southern piedmont, from which the sample is drawn, endured unusually harsh environmental conditions punctuated by severe drought and exacerbated by escalating warfare. It is argued here that these environmental stressors increased susceptibility to an opportunistic respiratory infection reminiscent of tuberculosis, and possibly also some form of pneumonia, resulting in high rates of active disease previously noted only in historic Puebloan peoples.

Paleopathological and molecular evidence of human bone tuberculosis in Iron Age Lithuania.

Skeletal remains of two individuals, showing lesions suggestive of bone tuberculosis, from the archaeological sites of Marvele and Sukioniai in Lithuania were analyzed at the DNA level. The diagnosis of bone tuberculosis was confirmed in the remains from Marvele by amplifiying a 245-bp fragment of a repetitive insertion element-like sequence (IS 6110) of Mycobacterium tuberculosis DNA. This is direct evidence for the presence of tuberculosis in Lithuania at the beginning of the first millennium AD. The individual from Sukioniai was found to be tuberculosis-negative. No PCR product was obtained for the 245-bp target sequence or for a smaller 123-bp DNA fragment specific for Mycobacterium tuberculosis. However, amplifiable ancient DNA appeared to be present in the examined specimen as was shown by the results of the DNA-based sex identification, which indicated, consistent with the bone morphology, a male individual.

Tuberculosis in the native American: indigenous or introduced?

An analysis of the current and historical literature is presented in order to assess the weight of evidence for the existence of tuberculosis among the Native Americans of North America before the time of Columbus. Literature related to pertinent artifacts, biologic specimens, geographic and geologic history, epidemiology, and early travelogues and histories in considered. While the evidence does not convincingly confirm or deny the presence of this disease in America's earliest human history, an understanding of the factors related to the epidemiology of tuberculosis is of value for both social and public health reasons.

Paleopathology in an Iroquoian ossuary, with special reference to tuberculosis.

Pathological skeletal remains from the Uxbridge Ossuary (1490 +/- 80 A.D., N = 457) are classified into four broad categories: trauma, congenital disability, tumor, and infection. Traumatic injuries are relatively common (fractures in 5-9.4% of total), considering the date and subsistence pattern of the population. Congenital disabilities and tumors are rare, affecting approximately 2% of the population. Nonspecific periosteitis and osteitis affect 5% of the sample. By far the most common pathological skeletal changes are lytic lesions leading to cavitation of cancellous bone, especially in the lower vertebral and sacro-iliac regions. It is argued that the changes seen and their distribution are most consistent with a diagnosis of tuberculosis. Applying clinical observations regarding bone involvement, it is estimated that a minimum of 26 skeletons were affected. This in turn indicates a very high population tuberculosis incidence. The Uxbridge sample is neither the only nor the earliest Iroquoian ossuary to display apparent tuberculosis (Hartney 1981). The common presence of this disease in some communities and its low incidence in others are discussed in the context of the epidemic wave phenomenon. There is strong evidence for warfare at Uxbridge, and this warfare may have produced crowding, poor hygiene and diet, such that the disease could flourish.

Human treponematosis and tuberculosis: evidence from the New World.

The purpose of this study has been first, to critically review the evidence for the presence of human treponematosis and tuberculosis in the skeletal remains of prehistoric natives in the New World, and second, to report on nine new cases dated to before contact and suggesting the presence of these two disease conditions. A review of the medical history and findings by human paleopathologists leaves little doubt that both diseases originated in the Old World. The findings of this study lend further support to the fact that, although rare, human treponematosis and tuberculosis were indeed endemic in the pre-Columbia New World before contact. There is no evidence that these two diseases could have arisen independently and de novo, especially during the relatively short time since man's arrival in the New World. Where a disease has been endemic for quite some time as appears to be the case with human treponematosis and tuberculosis, milder forms of the disease and improved host response could have developed in which only the most severe cases would be observable. This explains the rarity of skeletal lesions suggestive of these two human disease conditions in prehistoric human populations.