Academic literature on the topic 'Skeletal tuberculosis'

Mycobacterium tuberculosis is a disease that is being reported much more frequently in the literature, primarily because of the rapid increase in severely immunocompromised patients, but also because of the development of multiple drug-resistant tuberculosis strains. Extrapulmonary M. tuberculosis is also reportedly on the rise, and may manifest itself at a number of sites in the body, including the peripheral skeleton. It is important to recognize peripheral tuberculosis osteomyelitis early because early treatment can effectively eliminate long-term morbidity. The authors present a review of the diagnosis and treatment of extrapulmonary M. tuberculosis, with special emphasis on peripheral skeletal tuberculous osteomyelitis. A case study involving peripheral skeletal tuberculous osteomyelitis in the foot is presented.

Tuberculosis (TB) has killed millions of people throughout history and still isone of the leading causes of death. Since the early 1990s, ancient DNA(aDNA) research has made considerable contributions to the study of thisinfectious disease in the past. While early studies used polymerase chainreactions (PCRs) solely to identify the TB-causing organisms, namely theMycobacterium tuberculosis complex (MTBC), later approaches extended thefocus to assign the actual disease-causing species or strains of the MTBCbut were either directed at single or few individuals or only provided few data. This research project has screened a large set of European skeletaland dental samples from individuals of the 1st–19th centuries AD for IS6110,an insertion sequence believed to be specific to the MTBC, and has identifieda number of individuals that may indeed have suffered from TB. Reports ofIS6110-like elements in other mycobacteria, however, challenge thesuitability of IS6110 for detecting MTBC. Two sequences similar but notidentical to IS6110 were revealed from several of the samples analysed,supporting the proposal that IS6110 should not serve as the sole target foridentifying MTBC from archaeological material. It cannot be establishedwhere these sequences derive from, but application of a MycobacteriumspecificPCR and targeting of genomic regions of the MTBC that containsingle nucleotide polymorphism (SNPs) indicate that at least some of thesamples contain a range of unknown, most likely environmental, bacterialand/or mycobacterial species. Yet, screening for IS6110 together with thedetection of large sequence polymorphisms (LSPs) and SNPs in othergenomic regions has identified eight individuals to unambiguously containMycobacterium tuberculosis aDNA. Apart from one individual which wasrecovered from Northern France, these skeletons derived from Britisharchaeological excavation sites. The SNP and LSP results enabled theallocation of infecting MTBC strains into various classification systemsreported in clinical literature and revealed that M. tuberculosis strains variedthroughout different time periods, thereby mainly confirming evolutionarypathways suggested in previous studies. Additionally, it was found thatdistinct strains co-existed temporally, and maybe even spatially, in Britainand that at least one individual harboured two different MTBC strains,suggesting a mixed infection. Application of next generation sequencingenabled one of the 19th century strains from Britain to be characterised ineven more detail, revealing closest similarity to a M. tuberculosis strainisolated at the beginning of the 20th century in North America.

The study of human palaeopathology has developed considerably in the last three decades resulting in a structured and standardised framework of practice, based upon skeletal lesion patterning and differential diagnosis. By comparison, disarticulated zooarchaeological assemblages have precluded the observation of lesion distributions, resulting in a dearth of information regarding differential diagnosis and a lack of standard palaeopathological recording methods. Therefore, zoopalaeopathology has been restricted to the analysis of localised pathologies and ‘interesting specimens’. Under present circumstances, researchers can draw little confidence that the routine recording of palaeopathological lesions, their description or differential diagnosis will ever form a standard part of zooarchaeological analysis. This has impeded the understanding of animal disease in past society and, in particular, has restricted the study of systemic disease. This research tackles this by combining the disciplines of human palaeopathology and zoopalaeopathology and focusing on zoonotic disease. The primary aim of this research was to investigate the skeletal manifestation of bTB in cattle, sheep/goat and pig to establish differential diagnostic criteria for its identification in zooarchaeological assemblages. Methods commonplace in human palaeopathology were adapted and applied to zoopalaeopathology, in addition to radiography and aDNA analysis. The results emphasise the difficulties but also the potential associated with the identification of systemic diseases in zooarchaeological assemblages. An approach to the classification of potentially infectious lesions is presented that enables the calculation of crude prevalence in disarticulated assemblages. In addition, the potential for a DNA analysis to shed further light on animal disease in the past is emphasised.<br>Arts and Humanities Research Council (AHRC)<br>Many of the images have been removed from the online version due to copyright restrictions. The embargo period for the thesis ended: 16th January 2018.

Tese de doutoramento em Antropologia, apresentada à Faculdade de Ciências e Tecnologia da Universidade de Coimbra<br>A tuberculose é uma doença infecto-contagiosa cuja origem e evolução pode ser tratada pelo cruzamento da interpretação de fontes documentais e iconográficas, com os resultados decorrentes das recentes técnicas moleculares de pesquisa de biomarcadores e, também, através de métodos macroscópicos e radiológicos. Estas foram as metodologias utilizadas no estudo de 329 indivíduos de ambos os sexos, com idades compreendidas entre os 7 e os 87 anos, pertencentes Colecção de Esqueletos Humanos Identificados (CEI) do Museu Antropológico da Faculdade de Ciências e Tecnologia da Universidade de Coimbra. Da investigação realizada, a pesquisa documental confirmou as variáveis de identificação constantes no livro de registo da CEI e permitiu adicionar novos dados relativos a estes indivíduos. No campo osteológico foram descritas e discutidas as lesões observadas, considerado o diagnóstico diferencial dos diferentes tipos de tuberculose, nomeadamente o significado das lesões nas costelas com base em critérios utilizados na paleopatologia e na medicina. Este estudo pretendeu, ainda, dar um contributo na comparação e validação dos biomarcadores como sejam, o HPLC para a pesquisa de ácidos micólicos e o PCR para a amplificação de ADN antigo de origem bacteriana. Considerando que os indivíduos estudados faleceram no início do século XX, período anterior ao desenvolvimento dos antibióticos, mas em que os conhecimentos médicos de diagnóstico da tuberculose eram já bastantes satisfatórios, os dados decorrentes deste trabalho poderão contribuir para a identificação desta doença em esqueletos não identificados, tanto juvenis como adultos, provenientes de contextos arqueológicos e históricos.<br>The aim of this dissertation was to examine the evidence, and consider the differential diagnosis for tuberculosis (TB) in individuals from early 20th century Coimbra Human Identified Skeletal Collection (CISC), curated by the Anthropological Museum, from the Faculty of Sciences and Technology at the University of Coimbra. The methodologies were from macroscopic observation, radiological examination, biomarker analysis (mycobacterial ancient DNA amplification by PCR and mycolic acids identification by HPLC) and documentary assessment, in order to confirm the authenticity and complement the information of the CISC records. This work, based on data arising before antibiotics became available for treatment, can contribute to the future diagnosis of TB in nondocumented skeletal material, and will facilitate a more reliable diagnosis of TB in both juveniles and adult individuals, in archaeological and historical contexts.

Tese de doutoramento em Antropologia, na especialidade de Antropologia Biológica, apresentada à Faculdade de Ciências e Tecnologia da Universidade de Coimbra<br>Paleopathology, summarily defined as the study of past diseases, has on the differential diagnosis a major challenge. Taking into account the difficulties faced by paleopathologists on the study of ancient conditions, especially those of infectious origin involving periosteal new bone formation (PNBF), an investigation was conducted combining macroscopic and histological techniques. The purpose of this research was twofold: firstly, to analyze the macroscopic distribution of periosteal reactions by age and cause of death, anatomical location, laterality, symmetry, bone dispersion and type of new bone; and secondly, to microscopically examine and compare thin sections of periosteal new bone, in order to evaluate the existence (or not) of microstructural differences in individuals who died from: (1) tuberculosis infections-TB (Group 1, n=114); (2) non-TB infections (Group 2, n=89); and (3) other conditions (Group 3, n=50). For the macroscopic analysis an assemblage of 253 individuals from the Human Identified Skeletal Collection from the Bocage Museum (Lisbon, Portugal), 136 males and 117 females, comprising individuals with an age at death ranging from 2.5 months to 94 years old, was chosen. A total of 34 dry bone specimens: 26 belonging to 23 individuals from the Bocage Museum, and eight from eight individuals from archaeological contexts (14th-19th centuries) were prepared for histological examination under transmitted and polarized light. Analysis of the macroscopic results revealed a high frequency (71.2%) of PNBF in individuals younger than 45 years old ( =22.64 years old). Deposits of new bone were most commonly found in individuals who died from TB (Group 1=82.5%) in comparison with those who died from non-TB disorders (Group 2=42.7%) or from other conditions (Group 3=46%), and the results were highly significant. Only the PNBF located on ribs had a positive relationship with TB as the cause of death (Group 1). Individuals who died from TB infection were also those who showed a broader involvement of the rib cage. Here periosteal lesions were most frequently observed in the upper to middle segment (R1R6, 60.2% [405/673]), mainly in the left-side (41.2%). In the ribs, a predominance of diffuse lesions combining woven and lamellar foci was recurrently seen. In spite of the apparent relationship between periosteal rib lesions and TB, the presence of similar lesions in individuals who died from other diseases does not allow for the establishment of a definitive association. The frequency of PNBF in the appendicular bones was higher in the tibia (T) and fibula (Fi) of the individuals from Group 2 (T=36.7%; Fi=17.4%) and Group 3 (T=41.2%; Fi=17.1%), and in those older than 45 years of age (T=38.8%; Fi=17.5%). The analysis of the individuals with multiple periosteal bone involvement did not reveal significant differences among cause of death groups. The younger individuals from Group 1 were those with more deposits of new bone in the humerus, radius and ulna. With regard to the distribution of the periosteal lesions, symmetric foci were most often seen in the scapula and radius (n=5, respectively), whereas left-sided ones more common in the ulna (n=5), and right-sided ones in the humerus (n=4). In the lower limb bones, a predominance of symmetric lesions was observed in the tibia (n=37), femur (n=28) and fibula (n=15). Localized foci of new bone were commonly observed in the upper limb bones. In contrast, a high frequency of diffuse lesions was found on the shaft of the lower limb bones (e.g. tibia and fibula). Only the femur (n=28) showed a high prevalence of localized lesions. Differences in the type of new bones were also found between the upper (predominance of woven and woven/lamellar foci) and the lower limb bones (lamellar and woven/lamellar foci). In the appendicular skeleton, the lack of association between new bone formation, particularly in the tibia and fibula, and the underlying cause of death seems to corroborate the non-specificity of periosteal lesions, challenging their usefulness as an indicator of physiological stress. Furthermore, it may point out to the existence of inaccurate records of cause of death, or the coexistence of multiple conditions not identified in the obituary certificate. The value of the histological analysis on the study of bone lesions was observed at three main levels: (1) diagnosis of pathological conditions; (2) description of bone lesions; and (3) assessment to bone tissue quality. With regard to the diagnosis of pathological conditions, differences in the microstructure of PNBF were seen between Group 1 and Group 2 of cause of death and within groups. Multiple layers of “appositional bone” enclosing numerous primary vascular canals were the pattern most commonly observed (n=4) in the samples from Group 1. In contrast, three samples (one from Group 1, two from Group 2) presented a microstructure compatible with subperiosteal hematomas. These observations suggest that beyond pulmonary diseases other mechanisms may stimulate PNBF on the visceral surface of ribs. Histological analysis was also fundamental in the description and characterization of bone changes. For example, of the five samples with “consolidated” fracture callus, only two presented a truly mature and remodeled microstructure. This means that the outer surface of a bone lesion may not give a complete picture of the tissues response. In spite of the good preservation of some bone samples, massive diagenetic changes due to the action of bacteria and fungi were observed at microscopic level. This clearly suggests that gross inspection is not a good measure of the bone tissue quality. In contrast, microscopy is essential to differentiate between pseudopathology and physiological or pathological signs. This study demonstrated the difficulties in using periosteal lesions, especially those of the lower limb bones to ascertain the diagnosis of particular conditions. Furthermore, it also revealed the limitations and possible misinterpretations found in the macroscopic study of identified skeletal collections. In contrast, the histological analysis showed surprising results that reinforce the pertinence of applying histological techniques in the description and diagnosis of bone changes in human remains. Future studies based on well-documented collections with accurate medical records and/or samples retrieved from clinical cases will eventually solve some of the problems and limitations detected in this investigation. Increasing the sample size will also improve our understanding of the entire spectrum of new bone variation associated with a particular condition. It is possible that further research in the field of bone biochemistry, immunology and cell communication will shed light on the exact mechanism (or mechanisms) behind PNBF.

This dissertation deals with the study of ancient diseases mentioned in the historical period of the Scriptures in the region of Syro-Palestine. The definition, history, methodology and etymology of the terms relating to biblical diseases are discussed. Leprosy, syphilis, plague and anaemia amongst other diseases leave skeletal signs and lesions. Paleopathologists may reveal these diseases by studying skeletal remains of the population of Syro-Palestine. Criticisms and recommendations are offered for the practical paleopathologist, anthropologist or archaeologist. More interest should be taken in the study of coprolite in every new discovery of human remains. The scarcity of skeletal remains in the region is well known. The past and present law structure, the Halakah, may partly be to blame. The future of paleopathology worldwide is undisputedly the biochemical science of DNA analysis. With this new science the role for macromorphological examination may diminish. The diseases mentioned in the Bible are finding it increasingly difficult to hide behind the words in the Scriptures.<br>Old Testament and Ancient Near Eastern Studies<br>MA (Biblical Archaeology)