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Objective: Osteoarticular tuberculosis (OATB) is one of the most common forms of extrapulmonary tuberculosis; however, limited epidemiological data are available on this public health concern worldwide, especially in developing countries. This study aimed to analyze the clinical epidemiology and drug resistance characteristics of OATB cases in Hunan province which located in South-central China., Methods: We retrospectively enrolled OATB patients with Mycobacterium tuberculosis culture positive at Hunan Chest Hospital from January 2013 through March 31, 2022. The multiple demographic, clinical variables and drug susceptibility data of the patients were collected from the hospital's electronic patient records. Descriptive statistical methods, Chi-square test and logistic regression analysis were employed as statistical methods., Results: Of the 269 OATB cases, 197 (73.23%) were males, 206 (76.85%) were farmers; patients' ages ranged from 5 to 85 years, 57 (21.19%) aged at 20-29 years old and 52 (19.33%) aged at 60-69 years old. In terms of the disease, 177 (65.80%) had spinal TB with most occurrence in lumbar vertebrae (26.02%, 70/269), multiple spinal sites (18.96%, 51/269) and thoracic vertebrae (15.24%, 41/269). Outside of the spine, OATB mainly occurred in the lower limb (13.38%, 36/269). In terms of drug resistance, 40 (14.87%) and 72 (26.77%) were resistant to rifampicin (RFP) and isoniazid (INH) respectively; 38 (14.13%) were multi-drug resistant (MDR), and a total of 78 (29.00%) isolates were drug resistant. OATB patients aged 40-49 years old (compared to those aged ≥70 years) and from the west of Hunan province, China (compared to those from the center of Hunan) were at risk for developing RR/MDR (ORs were 5.057 and 4.942, respectively; 95% CIs were 1.009-25.342 and 1.458-16.750, respectively)., Conclusion: In South-central China, OATB mainly affected males, farmers and those aged 20-29 and 60-69 years old. Spinal TB is prone to occur in the lumbar and multiple spinal sites. The resistance situation of OATB was serious, and people aged 40-49 years old and patients from the west of Hunan were risk factors of RR/MDR. All these findings will help to improve the prevention, diagnosis and treatment strategies of OATB., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Fang, Yang, Liu, Li, Sun, Liu, Yu, Xiang, Li, Guo, Li, Zhao, Zhao, Wan, Li, Yuan and Tan.)

Introduction. Bone and joint tuberculosis (BJTB) is rare in developed countries, particularly in the paediatric population. Hypothesis/Gap Statement. The clinical features and sequelae of paediatric BJTB in Europe are not well characterized and should be assessed to achieve a better approach. Aim. To assess the management and outcomes of paediatric BJTB. Methodology. Longitudinal observational study of all paediatric patients (0-17 years old) diagnosed with BJTB between 2008 to 2020 in a tertiary-care hospital. Results. We identified 18 patients with BJTB, with a median age of 10 years (IQR 6-14.8), 66.7 % male. Most (72 %) were diagnosed after 2015 and were foreign-born (88.9 %), mainly from Portuguese-speaking African countries, and none had HIV. The most common symptoms were pain (77.8 %), fever (50 %) and bone deformity (44.4 %). Spinal TB (STB) affected 13 (72.2 %) and extra-spinal TB (ESTB) 9 (50 %) patients, and 4 (27.7 %) had both conditions. Diagnostic positive procedures included positive nucleic acid amplification technique (NAAT) (44.4 %), Mycobacterium tuberculosis isolation (44.4 %) and compatible histology (33.3 %). All completed antituberculous drugs for a median of 12 months (IQR 12-13) and nine (50 %) had surgery. Overall, acute complications occurred in 16 (88.9 %) patients - 11/13 (84.6 %) with STB and 5/5 (100 %) with ESTB - and included abscesses, spinal compression, spine deformity and pathological fractures. Sequelae were still present at the 12-month follow-up in seven cases (46.7 %), and were more common in foreign-born patients sent to Portugal to receive medical treatment (66.7 vs 20 %). Conclusions. Paediatric BJTB is difficult to diagnose and has high morbidity, requiring long-term follow-up. Over the last decade, foreign-born TB seems to be increasing, with still longer treatment courses and more acute complications and sequelae.

The Mycobacterium tuberculosis complex (MTC) has affected South American populations since ca. 200 years BCE. In Argentina, possible cases date from ca. 1000-1400 Common Era (CE). This paper describes the oldest (905-1030 CE) confirmed case of tuberculosis (TB) in a young adult male from Lomitas de Saujil (Tinogasta, Catamarca, Argentina). Osteolytic lesions on the bodies of the lower spine were macroscopically and radiographically identified. Bilateral new bone formation was seen on the visceral vertebral third of several ribs and in long bones, compatible with hypertrophic osteoarthropathy. Representative rib and hand bones gave profiles for MTC-specific C 27 -C 32 mycocerosic acid lipid biomarkers; these were strongest in one heavily-lesioned lower rib, which also had MTC-diagnostic C 76 -C 89 mycolic acids and positive amplification of MTC-typical IS6110 aDNA fragments. During the first millennium CE, the intense social interaction, the spatial circumscription of villages among the pre-Hispanic societies in the mesothermal valleys of Catamarca and the fluid contacts with the Eastern lowlands, valleys and puna, were factors likely to favor disease transmission. It is proposed that TB arrived from northern Chile and dispersed towards the northeast into the Yocavil valley, where several cases of TB infection were macroscopically identified for a later chronology., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Brazil is one of the highest tuberculosis (TB) burden countries of the world. Cutaneous tuberculosis (CTB) is a rare form of extrapulmonary manifestation of tuberculosis. This study aimed to describe the clinico-evolutive, laboratory and therapeutic aspects of CTB cases among patients from a cohort with TB in Rio de Janeiro, Brazil., Methods: Cases of diagnosed CTB with microbiologic confirmation or clinical response to anti-tuberculous treatment associated with positive smear or histopathological findings between the years 2000 and 2016 were selected., Results: Seventy-five patients with CTB were included, most were women (58.7%) with a median age of 42 years. CTB diagnosis was based on culture in only 42.7% of the cases. Scrofuloderma represented 50.7% of the cases, followed by erythema induratum of Bazin (EIB) (18.7%), tuberculous gumma (13.3%), lupus vulgaris (8%), TB verrucosa cutis (4%), orificial TB (2.7%) and associated forms (2.7%). Other TB presentations were pulmonary (22.7%), mammary (6.6%) and osteoarticular (4%). All patients who completed the treatment (97.3%) had their lesions healed. Only two patients (2.6%) needed to change the therapy due to adverse reactions. Fifty percent of EIB patients presented recurrence., Conclusions: These data highlight the diversity of CTB presentations and the importance of the skin to assist in early identification and treatment of TB. More studies are necessary to improve the knowledge on EIB for a better approach towards these patients, mainly in cases of recurrence., (© 2019 The International Society of Dermatology.)

Mycobacterial bone marrow (BM) infection is the most common diagnosis established by BM examinations for fever of unknown origin. In this study, clinical features and outcomes of patients who fulfilled the criteria for BM infection due to Mycobacterium tuberculosis (MTB) and non-tuberculous mycobacteria (NTM) at a medical centre in Taiwan from 2001 to 2009 were investigated. The BM histopathological findings were also analysed. A total of 24 patients (16 men, eight women) with mycobacterial BM infections were found. Of these, nine (38%) were positive for human immunodeficiency virus (HIV) and six (25%) had no pre-existing immunocompromised conditions. MTB isolates were obtained from 11 (46%) patients and NTM species were isolated from 10 (42%) patients, including M. avium complex (MAC, n = 7) and M. kansasii (n = 3). Patients with MTB infections were significantly older than those with NTM infections (60·5 vs. 47·7 years, P = 0·043) and were less likely to have a positive BM culture (45% vs. 100%, P = 0·012). The 90-day survival rates for MTB and NTM BM infections were 68% and 60%, respectively (P = 0·61). In addition, the presence of BM granulomas was significantly more common in patients with MTB BM infections than in those with NTM infections (82% vs. 30%, P = 0·030). In Taiwan, the importance of NTM was not inferior to MTB and besides MAC, M. kansasii might be an important pathogen in non-HIV-infected patients. The presence of BM granulomas and caseation provides valuable information regarding early treatment pending culture results.

Tuberculosis is one of most ancient diseases affecting human populations. Although numerous studies have tried to detect pathogenic DNA in ancient skeletons, the successful identification of ancient tuberculosis strains remains rare. Here, we describe a study of 140 ancient subjects inhumed in Yakutia (Eastern Siberia) during a tuberculosis outbreak, dating from the 16(th)-19(th) century. For a long time, Yakut populations had remained isolated from European populations, and it was not until the beginning of the 17(th) century that first contacts were made with European settlers. Subsequently, tuberculosis spread throughout Yakutia, and the evolution of tuberculosis frequencies can be tracked until the 19(th) century. This study took a multidisciplinary approach, examining historical and paleo-epidemiological data to understand the impact of tuberculosis on ancient Yakut population. In addition, molecular identification of the ancient tuberculosis strain was realized to elucidate the natural history and host-pathogen co-evolution of human tuberculosis that was present in this population. This was achieved by the molecular detection of the IS6110 sequence and SNP genotyping by the SNaPshot technique. Results demonstrated that the strain belongs to cluster PGG2-SCG-5, evocating a European origin. Our study suggests that the Yakut population may have been shaped by selection pressures, exerted by several illnesses, including tuberculosis, over several centuries. This confirms the validity and necessity of using a multidisciplinary approach to understand the natural history of Mycobacterium tuberculosis infection and disease.

Purpose: Granulomas in bone marrow are an infrequent finding related to various disorders. The aim of this study was to review our clinical experience with granulomatous bone marrow disease and to describe the contributions of recent diagnostic tools, such as (18)F-Fluorodeoxyglucose positron emission tomography ((18)F-FDG-PET) and molecular biology., Methods: Clinical, laboratory and morphological data on patients with a granuloma based on bone marrow biopsy analysed in the University Hospital Lyon from May 2004 to July 2010 were reviewed., Results: We identified 57 cases among 9641 bone marrow biopsies, representing an incidence of 0.59% in the series and an annual incidence of 9.5 cases per year. Nine biopsies performed for staging a known pathology were excluded from further analysis. Among the 48 remaining patients, associated disease was demonstrated in 79%, with infections being the most common (33%), following by sarcoidosis (21%), malignancy (19%) and therapy-induced granulomas (6%). One previously unpublished entity is described: infection with Bartonella henselae diagnosed using molecular biology from node and skin biopsies in two renal transplant patients. (18)F-FDG-PET, performed in 13 cases, showed hypermetabolic foci consistent with sarcoidosis in two cases. Positive PCR result for an infectious pathogen was obtained in three bone marrow samples (Mycobacterium tuberculosis, n=1; Mycobacterium genavense, n=2)., Conclusion: In comparison to previous research, our study reports high proportions of cases caused by sarcoidosis and unknown causes. (18)F-FDG-PET could show signs consistent with sarcoidosis and molecular biology is useful for the detection of fastidious bacteria in immunocompromised patients., (Copyright © 2012. Published by Elsevier B.V.)

The prevalence of tuberculosis (TB) continues to rise worldwide. Current migration patterns and increased travel to high-prevalence TB countries will result in more frequent presentations of less common forms of TB. Tuberculous dactylitis, a form of tuberculous osteomyelitis, is well recognised in countries with a high prevalence of TB. We provide a systematic review of all published cases of tuberculous dactylitis in children and adolescents and describe a case to illustrate the typical features of the disease. Our review revealed 37 cases of tuberculous dactylitis in children and adolescents, all reported in the last 17 years. Children less than 10 years of age are most frequently affected and the hand is the most commonly affected site. Concurrent pulmonary TB is present in a fifth of cases and systemic symptoms are usually absent. Positive TST and IGRA support the presumptive diagnosis, but cannot be used as rule-out tests. The definitive diagnosis relies on the detection M. tuberculosis by PCR or culture. Treatment should comprise of a standard three to four drug anti-tuberculous regimen. The optimal treatment duration remains unknown. Surgery has a limited role in the treatment in general but may play a supportive role, and curettage of the cavity has been recommended for avascular lesions.

Background: We conducted a study of osteoarticular tuberculosis in patients from private and public settings in a disease endemic area. Our objective was to assess the role of mycobacterial culture and polymerase chain reaction (PCR) in the diagnosis of osteoarticular tuberculosis (TB) in settings where only clinical and imaging diagnosis form the basis for treatment., Methodology: Ninety-three consecutive specimens collected from clinically suspected patients of osteoarticular TB were screened for bacterial culture, mycobacterial culture and in-house nested PCR. In addition, specimens were examined by imaging and histopathology. Ten specimens collected from patients suffering from other bone diseases were included as negative controls., Results: Of the 93 clinically suspected TB patients, mycobacterial culture was positive for Mycobacterium tuberculosis (MTB) in 47 (51%) patients who were confirmed as definite TB cases. Of the remaining patients, 16 (17%) were diagnosed as probable, 19 (20%) as possible, and 11 (12%) as only clinically suspected TB cases. In-house nested PCR was positive in 65 (70%) cases. Fifteen patients were resistant to one or more anti-tuberculous drugs; twelve patients were multi-drug resistant, two of whom were extensively drug resistant., Conclusion: Mycobacterial cultures using liquid media with susceptibility should form the backbone of management of osteoarticular TB. Nested PCR enhances the sensitivity if performed in addition to culture.

Objectives: To evaluate the clinical and diagnostic features of osteoarticular tuberculosis (OT) from a series of cases seen over 30 years in a large university hospital in Naples, Italy., Methods: We reviewed the files of all patients admitted to our department from 1975 to 2004 with a diagnosis of osteoarticular tuberculosis., Results: We identified 136 patients with 140 osteoarticular tuberculosis lesions. Fifty-three cases were diagnosed from 1975 to 1984, 36 cases from 1985 to 1994, and 47 cases from 1995 to 2004. Eleven patients (8%) were from high-incidence areas outside of Italy. The mean delay until diagnosis was 216.6 days. Pain, low-grade fever, and loss of weight were the most common presenting symptoms. Neurological involvement was present in 11 cases out of 79 spinal lesions (13.9%). Serological methods were used to study antimycobacterial antibodies using enzyme-linked immunosorbent assays (ELISA-TB test) in 59 patients (42.1%). Positive results on this test were obtained in 43 patients (72.9%). ELISA-TB test was the only diagnostic test associated with a shorter diagnostic delay in a model of multivariate regression analysis (p=0.001). Tc-99m MDP bone scans were obtained from 83 patients with 84 lesions and increased uptake in the affected area was noted in 72 lesions (85.7%). Histological and microbiological examinations were positive in 97 (69.3%) and 57 (40.7%) lesions, respectively. In 43 (30.7%) lesions, we could not definitively confirm the diagnosis. In these cases chemotherapy was nevertheless initiated., Conclusions: Thorough and even invasive diagnostic work-up is mandatory for the proper and timely management of patients with OT. Tc-99m MDP bone scanning and ELISA-TB test are useful diagnostic tools. We always used microbiological testing and histological examination to confirm the diagnosis of OT, but empirical antituberculosis treatment was nevertheless initiated in the patients with high clinical suspicion in order to limit the potentially permanent destruction of affected skeletal segments.

Objective: To study clinical features of skeletal tuberculosis diagnosed in our laboratory over the last 10 years., Methods: We carried out a retrospective observational study of 26 patients with osteoarticular tuberculosis recording clinical and microbiological data., Results: Pain was the main clinical presentation. The median time from the onset of symptoms to the diagnosis was 8 months. Synovial fluid was the most common sample obtained. Bone disease and previous or concurrent pulmonary tuberculosis were the most important predisposing factors. The tuberculin test reaction was positive in 83.3% of the patients. The outcome was favorable in 69% of the patients. Weight-bearing joints were the most commonly involved sites., Conclusions: A high degree of suspicion is still needed to avoid a delayed diagnosis that might complicate the outcome.

Multifocal skeletal tuberculosis is an uncommonly reported entity, Unanimity on terminology is lacking in the literature. The article presents a series of 18 such patients encountered in our institution. All the patients were below 15 y of age. Male to female ratio was 13:5. Most of the cases presented with swellings, discharging sinuses and/or ulcers. Appendicular involvement was seen in 17 of these cases. All the cases were diagnosed histopathologically as tuberculosis. All the cases were treated with multi-drug anti-tubercular therapy with additional procedures such as incision and drainage or sinus tract curettage performed in 9 of the patients. All the lesions healed. Their clinical behaviour, result and outcome are analysed with available international literature.

Tuberculosis (TB) is a serious disease of global importance, with a rising incidence in the developed world in recent years. Tuberculous lymphadenitis, tuberculous meningitis, osteoarticular tuberculosis and miliary tuberculosis are some of the more well-recognised manifestations of non-pulmonary TB in childhood. The diagnosis of non-pulmonary TB poses a particular challenge for clinicians because of the protean ways in which the disease presents. The omission of tuberculosis from the differential diagnosis of patients with obscure illnesses and the relatively insensitive bacteriological methods for detecting Mycobacterium tuberculosis add to the complexity of the problem. A high index of suspicion is required in order to avoid delays in diagnosis which may influence treatment outcome. The advent of DNA amplification techniques such as the polymerase chain reaction may herald a promising new era in the prompt and accurate management of extrapulmonary tuberculosis.

A paleomicrobiological study was performed on 37 skeletal tissue specimens from cadavers in the necropolis of Thebes-West, Upper Egypt, (2120-500 BC) and four from the necropolis of Abydos (3000 BC). The subjects had typical macromorphological evidence of osseous tuberculosis (n = 3), morphological alterations that were not specific, but probably resulted from tuberculosis (n = 17), or were without morphological osseous changes (n = 21). DNA was extracted from these bone samples and amplified by PCR with a primer pair that recognised the Mycobacterium tuberculosis complex insertion sequence IS6110. To confirm specificity of the analysis, the amplification products of several samples were subjected to restriction enzyme digestion, or direct sequencing, or both. In 30 of the 41 cases analysed, ancient DNA was demonstrated by amplification by the presence of the human beta-actin or the amelogenin gene and nine of these cases were positive for M. tuberculosis DNA. The results were confirmed by restriction endonuclease digestion and sequencing. A positive result for M. tuberculosis DNA was seen in two of the three cases with typical morphological signs of tuberculosis and amplifiable DNA, in five of 13 non-specific, but probable cases (including two cases from c. 3000 BC), but also in two of 14 cases without pathological bone changes. These observations confirm that tuberculosis may be diagnosed unequivocally in skeletal material from ancient Egypt, even dating back to c. 3000 BC. As a positive molecular reaction was observed in most of the typical cases of skeletal tuberculosis, in about one-third of non-specific, but probable tuberculous osseous changes and, surprisingly, in about one-seventh of unremarkable samples, this suggests that infection with M. tuberculosis was relatively frequent in ancient Egypt.

This survey was conducted in 1969/70 in a random sample of 15 of the 61 administrative districts in Tanzania. It included clinics with a long established tuberculosis service (A group), those with a tuberculons service of recent inception (B group) and those with no specialised tuberculosis service (C group), and 3 additional centres of special interest. The aim was to obtain, for tuberculous patients newly registered for treatment during a specified 6-month period, information on: a) the proportions of patients with pulmonary and/or extra-pulmonary tuberculosis; b) the history of previous chemotherapy with antituberculosis drugs: c) the prevalence of bacteriologically-positive pulmonary tuberculosis; d) the prevalence of initial and acquired resistance to the standard antituberculosis drugs; e) the radiographic extent and type of disease and of cavitation. Of 1884 patients in the random sample, 87.4 per cent had pulmonary tuberculosis only, 2.5 per cent had pulmonary and extra-pulmonary tuberculosis and 10.1 per cent had extra-pulmonary tuberculosis only. Although there were differences in the proportions with extra-pulmonary disease in individual districts in each group there were no important differences in the average levels for the A, B and C groups. Of 256 extra-pulmonary tuberculous lesions in 237 patients, 58 per cent were lymph node, 26 per cent bone and joint and 12 per cent pleural, pericardial or peritoneal. Of 1694 patients with pulmonary tuberculosis with or without extra-pulmonary tuberculosis, 96.3 per cent gave no history of previous chemotherapy and 3.6 per cent a definite history. A sputum specimen from each of 1338 patients with pulmonary tuberculosis was examined by direct smear; 675 (50 per cent) were positive as were 694 (55 per cent) of 1257 cultures. For the patients with no history of previous chemotherapy the positivity rates were 59 per cent on smear and 66 per cent on culture for the A group, 53 per cent and 57 per cent for the B group and 35 per cent and 38 per cent for the C group. Of 636 patients with no history of previous chemotherapy and sensitivity test results, 9 per cent had a strain resistant to isoniazid and/or streptomycin. The total prevalence of resistance to isoniazid was 6 per cent and to streptomycin 4 per cent. Of 1278 patients aged 5 or more with a postero-anterior chest radiography available and a diagnosis of intra-thoracic tuberculosis in Tanzania, 86 per cent were reported at an independent assessment in London as having a lung lesion. Among the 1171 patients of all ages reported as having a lung lesion, gross extensive or moderate disease was present in 73 per cent of the radiographs and cavitation in 66 per cent. The type of radiographic disease was assessed as acute in 36 per cent, mixed-acute in 40 per cent, mixed in 19 per cent and chronic in 5 per cent. There was no evidence of associations between drug resistance and the extent or type of disease of presence of cavitation...