Osteoarticular Tuberculosis Research Articles

Osteoarticular tuberculosis: imaging findings in pediatric patients.

Osteoarticular tuberculosis (TB) is an uncommon form of extrapulmonary TB that has the potential to damage joints and bones, generating long-term impairment. Mainly, the initial diagnosis of osteoarticular TB relies on clinical findings and imaging. When required, imaging can aim for less invasive tissue or fluid sampling for pathology, microbiology, and molecular biology analysis. Most TB diagnosis tests have variable and frequently poor sensitivities; however, bone biopsy samples have demonstrated a high percentage of culture positivity. Clinical and imaging findings of osteoarticular TB often mimic other processes, such as rheumatoid arthritis or chronic recurrent multifocal osteomyelitis. When the infection affects the growth plates, angular deformities and extremity length discrepancies can arise. Unfortunately, several osteoarticular TB cases are detected late due to the nonspecific nature of clinical symptoms and non-characteristic imaging findings. This article reviews the most common and atypical osteoarticular TB imaging presentations to increase awareness of osteoarticular TB.

Metagenomic next-generation sequencing of osteoarticular tissue for the diagnosis of suspected osteoarticular tuberculosis.

In the detection of unknown infectious disease pathogens, the overall efficacy of traditional detection methods, such as culture, is low, and traditional PCR testing is also limited to the gene sequences of known pathogenic microorganisms. Metagenomic next-generation sequencing (mNGS) performs DNA sequencing by studying the entire microbial community genome in a given sample, without the need for isolation and culture. Previous studies have shown that mNGS performs better on pulmonary and extrapulmonary samples when compared with Xpert, traditional pathogenetic tests, and even parallel diagnostics. However, it should be emphasized that only a few studies have explored the performance of mNGS in detecting Mycobacterium tuberculosis in clinical samples associated with bone and joint infections. We conducted this retrospective study to provide additional data to support the use of mNGS in the clinical setting to identify pathogens within abscesses or tissue samples associated with bone and joint infections.

Reevaluating Pediatric Osteomyelitis with Osteoarticular Tuberculosis: Addressing Diagnostic Delays and Improving Treatment Outcomes

Background: Pediatric osteoarticular tuberculosis (TB) remains a significant global health challenge, particularly in resource-limited settings, where delayed diagnosis and treatment frequently lead to severe long-term complications. Despite advancements in TB control, skeletal TB in children is often misdiagnosed due to its non-specific clinical presentation, contributing to poor outcomes such as joint deformities, growth disturbances, and chronic pain. The complexity of diagnosing osteoarticular TB is further exacerbated by the limited sensitivity of conventional diagnostic tools and the overlap with other musculoskeletal conditions. This study seeks to evaluate the impact of early detection and multidisciplinary management on treatment outcomes in pediatric patients with osteoarticular TB. Methods: A retrospective review was conducted at the Pediatric Orthopedics Department of the “Grigore Alexandrescu” Children’s Hospital in Romania from 2009 to 2023. Case data included clinical, imaging, and microbiological findings, and treatment outcomes in children aged 0–18 years diagnosed with tuberculous osteomyelitis. Results: The study identified varied clinical presentations, with delayed diagnosis often linked to misinterpretation of symptoms as non-TB infections. Multimodal diagnostic approaches combining imaging, microbiological testing, and histopathology improved diagnostic accuracy. Early surgical intervention alongside anti-TB therapy proved effective in reducing long-term complications. Conclusions: Timely, accurate diagnosis and multidisciplinary treatment are critical to improving outcomes in pediatric osteoarticular TB. Vaccination status and comprehensive diagnostic tools significantly influence disease progression and treatment success. The study underscores the need for enhanced screening and diagnostic methods to prevent delays in treatment.

Mechanism research of Tollip negative feedback regulation in TLR4 signaling pathways based on spinal tuberculosis: Detection of Tollip and NF-κB expression levels

The emergence of drug-resistant mycobacterium tuberculosis (MTB, or TB) strains has led to an increasing incidence of TB. Spinal tuberculosis is the most common extrapulmonary tuberculosis. In the present study, tollip, a negative feedback regulatory factor in TLR4 signaling pathway was chosen based on previous studies on osteoarticular tuberculosis. U937 cells were transfected with recombinant lentivirus containing shRNA (RNA interference, RNAi) or overexpression vector containing Tollip gene and tested in vitro. The expression levels of Tollip and TLR4 were detected by Real-time PCR and immunofluorescence techniques, and the cell morphology and infection effect were observed by DAPI staining. The results suggested that Tollip gene could negatively inhibit the expression of related factors in TLR4 signaling pathway, and thus is a potential biomarker for early diagnosis.

Decoding the hidden realm: Molecular pioneering unravelling osteoarticular tuberculosis diagnosis

Osteoarticular tuberculosis (TB), a form of extrapulmonary tuberculosis, refers to the involvement of Mycobacterium tuberculosis (M.tb) in the bones and joints. While pulmonary tuberculosis is the most common form, osteoarticular TB represents a relatively rare but significant manifestation, accounting for approximately 1–3% of all TB cases. Accurate and timely diagnosis plays a pivotal role in the management of osteoarticular TB. Conventional diagnostic methods for osteoarticular TB, such as acid-fast bacilli smear microscopy and culture, have limitations in terms of sensitivity, specificity, and turnaround time. The purpose of this review is to comprehensively evaluate and synthesize the existing literature on molecular pioneering in osteoarticular TB diagnosis. Molecular techniques, such as nucleic acid amplification tests and gene-based assays, have emerged as promising tools for diagnosing TB. These techniques target specific genetic sequences of M.tb, enabling rapid and sensitive detection of the pathogen. However, the diagnostic accuracy, advantages, and limitations of these molecular techniques in the context of osteoarticular TB diagnosis require further investigation and consolidation of evidence. Furthermore, this review aims to identify areas for future research and development in the field of molecular diagnostics for osteoarticular TB.

Single-cell transcriptomic analysis reveals a decrease in the frequency of macrophage-RGS1high subsets in patients with osteoarticular tuberculosis

BackgroundCell subsets differentially modulate host immune responses to Mycobacterium tuberculosis (MTB) infection. However, the nature and functions of these subsets against osteoarticular tuberculosis (OTB) are unclear. Here, we aimed to understand the phenotypes and functions of immune cell subsets in patients with OTB using single-cell RNA sequencing (scRNA-Seq).MethodsPathological and healthy adjacent tissues were isolated from patients with OTB and subjected to scRNA-Seq. Unsupervised clustering of cells was performed based on gene expression profiles, and uniform manifold approximation and projection was used for clustering visualization.ResultsThirteen cell subsets were identified in OTB tissues. scRNA-seq datasets of patients and healthy controls (HCs) showed that infection changed the frequency of immune cell subsets in OTB tissues. Myeloid cell examination revealed nine subsets. The frequency of macrophage-RGS1high subsets decreased in OTB tissues; this increased MTB susceptibility in an SLC7A11/ferroptosis-dependent manner. Immunohistochemistry assays and flow cytometry for patients with OTB and osteoarticular bacterial infection (OBI) and HCs verified that the frequency of macrophage-RGS1high subset decreased in OTB tissues and blood samples, thereby distinguishing patients with OTB from HCs and patients with OBI.ConclusionThe macrophage-RGS1high subset levels were decreased in patients with OTB, and would be up-regulated after effective treatment. Therefore, the clinical significance of this study is to discover that macrophage-RGS1high subset may serve as a potential biomarker for OTB diagnosis and treatment efficacy monitoring.

Serum Protein Electrophoresis Patterns in Patients with Osteoarticular Tuberculosis.

Tuberculosis (TB) is a leading cause of infectious disease deaths in India. It is also one of the most challenging diseases to diagnose and treat effectively. TB can occur both in the lungs and in extrapulmonary locations through hematogenous spread. Osteoarticular TB is a type of extrapulmonary characterized by atypical presentation. If diagnosed early, it can be treated effectively with reduced risk of mortality. At Nalanda medical college and hospital, an 18-month prospective research was undertaken. The study included a total of 120 patients with osteoarticular TB. Serum electrophoresis of blood samples was performed at baseline, 2 months, and 4 months following antitubercular medication administration. The fractions of albumin, α1, α2, β, and γ globulins were estimated and compared with the baseline value. It was observed that as the disease progressed and became more chronic, there was a decrease in albumin and an increase in α1, α2, β, and γ globulin percentages of serum proteins. Upon follow-up, the serum electrophoresis revealed that these values observed during baseline could be reversed by the administration of antitubercular drugs. This study suggests that analyzing serum protein fractions could be a cost-effective strategy to determine the presence of osteoarticular TB and also aid in initiating antitubercular treatment.

Clinical case of bone tuberculosis in the foot: involvement of the calcaneus. Diagnostic challenge and possible primary infection

Osteoarticular tuberculosis is a rare form of extrapulmonary tuberculosis, and represents a real diagnostic challenge due to its atypical presentation and similarity with other bone pathologies. The case of a 20-year-old male patient with a history of pulmonary tuberculosis treated 5 years ago, who came to the emergency room due to edema, pain and functional difficulty in the ankle and heel, is presented. The computed tomography of the left foot showed a hypodense osteolytic-type lesion that affected two thirds of the calcaneus, thinning of the cortices and involvement in the support area of the calcaneus. Surgical treatment and sample collection were performed, the anatomopathological analysis of which showed the presence of granulomatous cells inside. Tuberculostatic treatment was started, achieving the patient's improvement. The objective is to highlight the importance of early diagnosis based on clinical and radiological findings to facilitate timely intervention and minimize adverse outcomes.

TUBERCULOSIS OF THE WRIST

INTRODUCTIONTuberculosis (TB) is a public health challenge. However, musculoskeletal involvement represents 10–15% of all extrapulmonary cases. Upper extremity involvement is extremely rare. The slow progressive course of clinical symptoms and lack of radiological signs lead to difficulties in establishing early diagnosis. Hence, the patients who have tuberculosis of the wrist are usually misdiagnosed. We report 5 cases of tuberculosis of the wrist seen in our unit from the year 2012 to 2021.METHODSCases were retrospectively evaluated on demographics, nature of history, clinical presentation, culture finding, and histopathological findings from 2012 to 2021 at our unit.RESULTSA total of 5 cases were evaluated retrospectively. Three patients were more than 60 years old and two were less than 30 years old. Four of the patients presented with wrist swelling 2 of them had wrist pain and only 1 patient had discharge from the wound. The duration of the symptoms ranges from 2 months to 3 years. Only one of the patients had a history of pulmonary TB contact whereas the others didn't. All patients underwent surgery. All of the patients had positive cultures for Mycobacterium tuberculosis complex and histopathological examination showed necrotizing granulomatous inflammation from specimens taken intraoperatively, which confirmed the diagnosis of tuberculosis of the wrist.DISCUSSIONSOur cases show that the common presentation of tuberculosis of the wrist was comparable to other literature. Most of the patients presented with chronic wrist swelling with or without wrist pain. The diagnosis of the disease was delayed an average of 10 - 12 months from symptoms onset to diagnosis. S. Bayram et al reported a case where the diagnosis was made 45 months later. Due to its rarity, it often is misdiagnosed, resulting in delays in the proper treatment.CONCLUSIONThe diagnosis of the TB wrist remains difficult because of insidious and non-specific. presentation. However, early diagnosis is essential to avoid delays in treatment and complications. Hence, chronic wrist pain, and swelling with or without unexplained bone erosion around the wrist area must be highly suspected of being osteoarticular tuberculosis.

Osteoarticular TB specimen yield rates. Large joint analysis at a single centre.

Tuberculosis (TB) remains endemic in South Africa. The spine, hip, and knee joints are common extra-pulmonary TB sites. Sound history taking, clinical examination, and basic laboratory and pathological tests remain key important steps in osteoarticular TB diagnosis. In our resources-stricken context cost is everything, if we can make a diagnosis cheaply that would go a long way. The diagnostic yield of standard laboratory tests compared to a real-time polymerase chain reaction (PCR) for osteoarticular TB diagnosis in a single orthopaedic unit has not been analysed. We conducted a retrospective record review of extra-spinal osteoarticular TB infection at our hospital from 01 June 2016 to 31 December 2021. Patient demographics, clinical history, and laboratory test results were analysed. A total of 34 cases were identified, with 32 of the cases being articular and two osseous involvement. The knee was the most common joint affected followed hip joint. Acid Fast Bacilli were detected in 32% of cases with microscopy, while TB culture was positive in 29% of samples. Histopathological examination and real-time PCR diagnosed TB in 66% and 63% of the cases, respectively. Our findings suggest that in the right context of a suggestive history and examination, histological analysis is as good as PCR for diagnosing osteoarticular TB.

Reviewing imaging discoveries in tuberculosis affecting extraspinal osteoarticular regions

Abstract Tuberculosis (TB) remains a significant global health concern, affecting both pulmonary and extrapulmonary systems. While musculoskeletal TB represents a small portion of cases (1%–3%), it remains particularly problematic in developing regions like Asia and Africa. Tuberculous spondylitis, affecting the vertebral column, comprises about half of all musculoskeletal TB cases. Although large joint involvement and para-articular regions are common, isolated soft tissue TB is rare. The introduction of advanced imaging techniques, with magnetic resonance imaging as the preferred method, has revolutionized the diagnosis of musculoskeletal TB. Early detection of bone and joint TB is vital for optimizing treatment outcomes and reducing the risk of complications, including deformities. This review article consolidates clinical and radiological insights into extraspinal osteoarticular TB, stressing the importance of heightened awareness among radiologists and clinicians. It underscores the role of advanced imaging in ensuring accurate diagnoses, particularly in regions with high TB prevalence, and in initiating timely and effective patient management to prevent complications.

Treatment Outcome of Drug-Resistant Skeletal Tuberculosis: A Retrospective Analysis.

Management outcomes of drug-resistant (DR) osteoarticular tuberculosis (OATB) is dismal as in pre-ATT era (1905). The studies documenting treatment outcome of DR-OATB are scarce; hence, present retrospective analysis was conducted to evaluate outcome of consecutive cases of DR-OATB. 45 consecutive patients of suspected DR-OATB were treated from 2010 onwards. Tissue samples were submitted for AFB smear, cytology/histology, liquid culture, CBNAAT/LPA besides gram's staining and aerobic/anaerobic culture. Patients were treated by individualized second-line ATT till documenting healed status by contrast MRI/PET. The changes in neurological deficit, deformities, and drug-induced adverse events were documented. 37/45 patients, 15 males and 22 females, mean age 26.89years were followed. DR was suspected observing poor clinico-radiological response/appearance of fresh lesions on ATT. All showed no growth on aerobic/anaerobic pyogenic culture. 29 (78%) had microbiologically proven drug resistance and 8 (22%) were labeled as clinical drug resistance (CDR). 18/29 had multi-drug resistance. Mean prior ATT intake was 12.03months 15 (40%) underwent surgical decompression. Mean duration of second-line ATT was 22.5months (9-36months). All patients achieved healed status with 8 (21%) developed side effects, most commonly hepatotoxicity, ototoxicity, and psychiatric disturbances. Average follow-up after completion of ATT was 40.5months. We report a large series where patients of DR-OATB were suspected on clinical criteria, investigated by DST, and treated. Patients with proven drug resistance were treated by individualized second-line ATT. CDR cases were treated by MDR protocol. Genotypic DST (CBNAAT/LPA) improved demonstration of DR. We demonstrated healed status on MRI/PET with no recurrence at minimum 2-year follow-up.

Osteoarticular tuberculosis in infants: A diagnostic and management challenge

Objectives: Musculoskeletal manifestations of tuberculosis in infants are rare and different both in etiopathological mechanism and clinical presentation. Radiological diagnosis of osteoarticular tuberculosis (TB) in infants is tricky due to the various differentials of a cystic lesion. Literature also mention it only in isolated case reports. We carried out this study with an aim to collate and study patterns of osteoarticlular TB in the appendicular skeleton and to highlight the difficulties in diagnosis and management. Material and Methods: We retrospectively reviewed the data at our hospital over the past 8 years. Microbiologically confirmed osteoarticular tuberculosis affecting appendicular skeleton in children below 1 year of age were included in the study. Cases with spine involvement were excluded. The delay to diagnosis from the onset of symptoms, the initial diagnosis and treatment given were noted. The resolution of radiological presentation and occurrence of deformities at the final follow up (atleast 1 year) were noted. Results: During the study period, 8 infants were diagnosed to have osteoarticular tuberculosis with median age at presentation of 8.7 months (range 3 to 12 months). Average duration of follow up was 4 years (range 1 to 8 years). Cystic, Erosive, infiltrative, spina ventosa and mortar pestle were the radiological appearances found. Three of the 8 cases were referred as suspected malignancy. All but one case were vaccinated with BCG. Curettage and anti-tubercular therapy (ATT) were the treatment in all cases. Three cases with a delay in diagnosis of more than 2 months, developed complications: 1 had limb length discrepancy (LLD) due to physeal involvement, 1 developed angular deformity and 1 child had perthe’s disease as a sequelae. Conclusion: Osteoarticular tuberculosis is an increasing possibility, shockingly, even in infancy and should be a differential in an endemic country like India. A delay to diagnosis of even 2 months of this condition can lead to devastating complications. Being mindful of the diagnosis and early treatment gives rewarding results.

Analysis on the epidemiological and drug resistance characteristics of osteoarticular tuberculosis in South-central China.

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. 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. 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). 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.

Surgical Treatment of Thoracolumbar Pott’s Disease at Niamey National Hospital (HNN) about 34 Cases

Pott's disease or tuberculous spondylodiscitis is one of the most serious forms of osteoarticular tuberculosis, responsible for spinal cord compression and/or "cauda equina" syndrome due to granulomatous and/or abscessed tuberculous epiduritis. Surgery therefore plays a key role in the management of this pathology, although surgical techniques vary widely from one author to another and from one department to another.
 The aim of our work is to describe the different techniques used in our department during the study period, and to evaluate the results.
 This is a prospective study concerning 34 cases of dorsolumbar and lumbar Pott's disease collised in the neurosurgery department of Niamey National Hospital from January 2020 to December 2021.
 Analysis of our results found 26 men and 8 women with a sex ratio of 3.25; the extreme ages were 11 and 76 years and the mean age was 40.53 years. 20 patients presented with dorsal cord compression syndrome, 12 with cauda equina syndrome, 6 with conus medullaris syndrome and 2 with multifocal localization.
 CT was performed in all patients and MRI in only one. All patients were treated with antibacillary chemotherapy. In 16 patients (47.06%), a posterolateral approach consisting of hemilaminectomy, pediculotomy and unilateral arthrectomy was used; in 9 patients (26.47%) a posterior approach consisting of fenestration; and laminectomy in 4 patients (11.76%). An anterior approach in 3 patients (8.82%), consisting of a corpectomy and an antero-lateral approach (pediculo-artrectomy-corpectomy) in 2 patients (5.89%). All our patients underwent debridement, evacuation of residual pus and sequestrectomy. Out of the debridement filling of the defect was performed in 23 cases with a spinous graft, 2 with fibula, 2 with a rib graft and one with an iliac bone graft.
 At 4 months post-surgery, radicular signs had completely disappeared in all patients, and sensory-motor deficit had improved in 30 patients (88.23%). There was a reduction in kyphosis in all patients who had benefited from an anterior approach, compared with 41.38 % who had undergone a posterior approach.

Unveiling foot tuberculosis as an under-recognized source of foot pain.

Foot tuberculosis is a rare form of osteoarticular tuberculosis, accounting for less than 1% of cases. It presents unique diagnostic challenges due to its nonspecific clinical features and overlapping symptoms with other conditions. This study aimed to investigate the clinical presentation, radiographic findings, and prognosis of foot tuberculosis, with the goal of improving early recognition and appropriate intervention. A prospective study was conducted between November 2016 and July 2021, involving 39 patients diagnosed with foot tuberculosis. Clinical examinations, laboratory tests, X-rays, and MRI evaluations were performed to aid in the diagnosis. Biopsy was conducted on patients with radiological lesions. Patients were treated with an 18-month course of antitubercular therapy (ATT). Foot Function Index (FFI) scores were recorded before and after treatment. Statistical analysis was conducted to assess factors impacting prognosis. Unilateral foot involvement was observed in all patients, with a male predominance (61.5%) and a mean age of 31.3years. The most common symptoms were pain and edema, with sinus tracts present in 17.9% of patients. Radiographic findings showed cystic and sclerotic lesions, with the "spina ventosa" appearance primarily affecting the metatarsal bones. MRI played a valuable role in early detection. Histopathological examination confirmed tuberculosis in all cases, and acid-fast bacilli were found in 23% of patients. Most patients (79.4%) responded well to ATT without requiring surgery. Factors such as high initial ESR, delayed ATT initiation, multiple lesions, and tarsal involvement were associated with unfavourable outcomes. Foot tuberculosis presents with nonspecific symptoms, leading to misdiagnosis and delays in appropriate treatment. Clinical examination, radiographic evaluation, and biopsy are essential for accurate diagnosis. Early initiation of ATT is crucial for favourable outcomes. Factors such as high initial ESR, delayed treatment initiation, multiple lesions, and tarsal involvement negatively impact prognosis. This study highlights the importance of recognizing foot tuberculosis and provides insights into its clinical presentation, radiographic features, and treatment outcomes, facilitating timely intervention and improved patient management.

Diagnosis and treatment of osteo-articular tuberculosis of the foot and ankle (a five case series)

IntroductionOsteo-articular tuberculosis is a rare manifestation of this disease, often posing diagnostic challenges that necessitate additional diagnostic imaging modalities such as radiography, CT, and MRI. This article presents a series of five cases involving tuberculosis affecting the bones of the foot and ankle, diagnosed at various stages. The patients received appropriate anti-tuberculosis medical treatment following national protocols, along with surgical interventions when necessary. Case studiesIn this series, we describe the clinical characteristics and management of five cases of foot and ankle bone tuberculosis. These cases were diagnosed at different stages, and all patients received standard anti-tuberculosis medical therapy according to national treatment guidelines. Surgical interventions were performed when deemed necessary to optimize patient outcomes. DiscussionThe diagnosis of bone tuberculosis should be considered in any clinical scenario that presents with uncertain features, persistent symptoms, or resistance to conventional treatment approaches. It is crucial to employ a multidisciplinary approach involving medical and surgical management to effectively address this challenging disease. However, it is important to note that surgical intervention cannot replace the necessity of proper medical treatment. ConclusionTuberculosis involving the bones of the foot and ankle remains an infrequent occurrence. However, considering the endemic context, prompt therapeutic interventions are essential to prevent significant osteoarticular damage. Early diagnosis, adherence to established treatment protocols, and a comprehensive approach encompassing both medical and surgical modalities are crucial for successful management of this rare entity.

Drug Resistance in Osteoarticular Tuberculosis: A Study From an Endemic Zone.

The present study was undertaken to determine the incidence of drug resistance against anti-tubercular drugs among patients from an endemic zone. Methodology: Forty consecutive clinico-radiologically diagnosed patients of osteoarticular tuberculosis (29: spine, 11: extraspinal) were enrolled. Pus from needle aspiration was taken in 31 cases, tissue following spinal decompression in seven, synovial in one, and sinus edge biopsy in one. The pus/tissue was subjected to acid-fast bacilli (AFB) staining and liquid culture, sensitivity to 13 anti-tubercular drugs (Isoniazid (INH), rifampicin (RIF), kanamycin (KAN), amikacin (AMK,) capreomycin (CAP), ethionamide (ETH), levofloxacin (LEV), moxifloxacin (MOX), linezolid (LNZ), para-amino-salicylic acid (PAS), bedaquiline (BDQ), delamanid (DLM), and clofazimine (CFO)) were checked, and histopathological/cytopathological examination and molecular tests were performed. Results: The mean age of patients was 29.07(9-65) years; 21 were female and 19 were male. The diagnostic accuracy for tuberculosis was 20% by AFB smear, 65% by liquid culture, 82.5% by histopathology, and 90% by cartridge-based nucleic acid amplification testing (CBNAAT). All culture-positive isolates were identified as Mycobacterium tuberculosis with no non-tubercular Mycobacterium. The drug resistance detected on CBNAAT was 11.1%, line probe assay (LPA) first line was 15.4%, LPA second line was 4%, and liquid drug susceptibility testing (DST) 11.5%. We detected 15.4% INHresistance, 11.1% RIF, 7.6% LEV, 3.8% MOX and PAS. No resistance was detected against second-line injectable drugs (SLID), ETH, LNZ, BDQ, DLM, and CFO. Conclusions: No single laboratory modality can ascertain the diagnosis in all cases; hence, samples should be sent for all tests in tandem. In the presence of insufficient samples, tissue may be subjected to CBNAAT and histopathology to arrive at tissue diagnosis. In this subset, overall drug resistance incidence was 12.5% (5/40) with one patient each of isolated INH and RIF resistance, one of multidrug-resistance (MDR), and two of pre-extensively drug-resistant (pre-XDR). Primary drug resistance came out to be 11.1% (4/36) with one patient each of isolated INH and RIF resistance, one ofMDR, and one Pre-XDR.

Tuberculous Osteomyelitis Presenting as a Sternal Mass in Paediatric Patient: A Case Report

Background: Sternal tuberculosis is an uncommon form of extrapulmonary tuberculosis and it can be a diagnostic challenge for pediatricians.
 Case Presentation: We report the case of a young 14-year-old boy, who had a gradually increasing swelling of the sternum over the past 2 months preceded by weight loss, asthenia and night sweats. Radiological, histological, and microbiological investigations confirmed it as a case of sternal tuberculosis (TB). He was managed with surgical debridement during the sternal biopsy and quadruple antituberculosis therapy with good response.
 Discussion: Tuberculosis (TB) of sternum is one of the rarest forms of skeletal tuberculosis. The incidence of sternal tuberculosis has been calculated to be <1.5% amongst osteo-articular tuberculosis, with very few cases reported in infants. The diagnosis is based on histological and bacteriologic arguments.
 Conclusion: Tuberculous osteomyelitis of the sternum is a rare finding in children. Our aim is to increase awareness around atypical presentations and the uncommon involvement of the sternum in musculoskeletal tuberculosis.

Development of tetracycline-modified nanoparticles for bone-targeted delivery of anti-tubercular drug.

Background: Since the poor response to existing anti-tuberculosis drugs and low drug concentration in local bone tissues, the traditional drug therapy does not result in satisfactory treatment of osteoarticular tuberculosis. Thus, we report a rifapentine release system with imparted bone targeting potential using tetracycline (TC) -modified nanoparticles (NPs). Methods: TC was conjugated to PLGA-PEG copolymer via a DCC/NHS technique. Rifapentine-loaded NPs were prepared by premix membrane emulsification technique. The resulting NPs were characterized in terms of physicochemical characterization, hemolytic study, cytotoxicity, bone mineral binding ability, in vitro drug release, stability test and antitubercular activity. The pharmacokinetic and biodistribution studies were also performed in mice. Results: Rifapentine loaded TC-PLGA-PEG NPs were proved to be 48.8nm in size with encapsulation efficiency and drug loading of 83.3% ± 5.5% and 8.1% ± 0.4%, respectively. The release of rifapentine from NPs could be maintained for more than 60h. Most (68.0%) TC-PLGA-PEG NPs could bind to HAp powder in vitro. The cellular studies revealed that NPs were safe for intravenous administration. In vivo evaluations also revealed that the drug concentration of bone tissue in TC-PLGA-PEG group was significantly higher than that in other groups at all time (p < 0.05). Both NPs could improve pharmacokinetic parameters without evident organ toxicity. The minimal inhibitory concentration of NPs was 0.094μg/mL, whereas this of free rifapentine was 0.25μg/mL. Conclusion: Rifapentine loaded TC-PLGA-PEG NPs could increase the amount of rifapentine in bone tissue, prolong drug release in systemic circulation, enhance anti-tuberculosis activity, and thereby reducing dose and frequency of drug therapy for osteoarticular tuberculosis.