Osteoarticular Tuberculosis Patients Research Articles

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.

Novel Potential Diagnostic Serum Biomarkers of Metabolomics in Osteoarticular Tuberculosis Patients: A Preliminary Study.

Osteoarticular tuberculosis is one of the extrapulmonary tuberculosis, which is mainly caused by direct infection of Mycobacterium tuberculosis or secondary infection of tuberculosis in other parts. Due to the low specificity of the current detection method, it is leading to a high misdiagnosis rate and subsequently affecting the follow-up treatment and prognosis. Metabolomics is mainly used to study the changes of the body’s metabolites in different states, so it can serve as an important means in the discovery of disease-related metabolic biomarkers and the corresponding mechanism research. Liquid chromatography tandem mass spectrometry (LC-MS/MS) was used to detect and analyze metabolites in the serum with osteoarticular tuberculosis patients, disease controls, and healthy controls to find novel metabolic biomarkers that could be used in the diagnosis of osteoarticular tuberculosis. Our results showed that 68 differential metabolites (p<0.05, fold change>1.0) were obtained in osteoarticular tuberculosis serum after statistical analysis. Then, through the evaluation of diagnostic efficacy, PC[o-16:1(9Z)/18:0], PC[20:4(8Z,11Z,14Z,17Z)/18:0], PC[18:0/22:5(4Z,7Z,10Z,13Z,16Z)], SM(d18:1/20:0), and SM[d18:1/18:1(11Z)] were found as potential biomarkers with high diagnostic efficacy. Using bioinformatics analysis, we further found that these metabolites share many lipid metabolic signaling pathways, such as choline metabolism, sphingolipid signaling, retrograde endocannabinoid signaling, and sphingolipid and glycerophospholipid metabolism; these results suggest that lipid metabolism plays an important role in the pathological process of tuberculosis. This study can provide certain reference value for the study of metabolic biomarkers of osteoarticular tuberculosis and the mechanism of lipid metabolism in osteoarticular tuberculosis and even other tuberculosis diseases.

Efficacy of Short Term Intermittent Chemotherapy in DOTS Regimen in Extra Spinal Tuberculosis

Noncompliance is one of the major issues with the treatment of tuberculosis (TB), which can lead to treatment failure. A short-course of chemotherapy as recommended by World Health Organization under the umbrella term of Directly Observed Treatment Short Course (DOTS) therapy seems to be effective. The main aim in present study was done to evaluate the efficacy of short term intermittent chemotherapy in DOTS regimen in patients with extra spinal osteoarticular TB. The present prospective study was conducted in the Department of Ortho &amp; Spine Surgery, National Institute of Traumatology &amp; Orthopaedic Rehabilitation (NITOR), Dhaka, Bangladesh over a period of one year between January 2018 to February 2019. 21 patients included in our Study. All the patients were given the DOTS regime as recommended by WHO and followed up at intervals of one month during the treatment for assessing the clinical improvement and compliance of the patient. The results in present study, there were 85.71% males and 14.29% were females. 42.86% were students followed by the labourer (28.57%). Hip (47.62%) was the most commonly involved joint followed by short bones of hand and foot (19.5%). All (100%) patients had an elevated ESR at the time of presentation. Eighty percent patients had shown increase in weight at the end of 6 month of treatment. All patients of extra spinal osteoarticular TB showed improvement. Treatment was found sufficient for 80% of the patients. In 20% cases treatment duration was extended. In discussion the Short term intermittent chemotherapy in DOTS regimen was optimum for the treatment of extra spinal osteoarticular TB and was associated with good compliance.

Diagnosis of osteoarticular tuberculosis by immuno-PCR assay based on mycobacterial antigen 85 complex detection.

Diagnosis of osteoarticular tuberculosis (OATB) exhibits serious challenges owing to paucibacillary nature of specimens and localization of disease at sites that are difficult to access. We recently developed indirect immuno-PCR (I-PCR) and real-time I-PCR (RT-I-PCR) assays for the detection of mycobacterial antigen 85 complex (Ag85) in OATB patients. Detection limits for the purified Ag85 protein were found to be 1 and 41 fg ml-1 by I-PCR and RT-I-PCR, respectively, which were at least 105 -fold lower than respective ELISA. While spiking synovial fluids of non-TB control subjects with the purified Ag85 protein, LODs of 100 and 120 fg ml-1 were obtained by I-PCR and RT-I-PCR, respectively, thus demonstrating the sample matrix effect. Sensitivities of 87·5 and 70·5% were observed in bodily fluids of confirmed (n = 8) and clinically suspected (n = 51) OATB cases, respectively, by I-PCR, with a specificity of 93·9% (n = 33). Markedly, the sensitivities obtained by I-PCR/RT-I-PCR were significantly higher (P < 0·05-0·01) than ELISA and GeneXpert assay (n = 30). However, no substantial difference in sensitivity was observed between the I-PCR and RT-I-PCR assays. After further improving the accuracy of I-PCR, this test may lead to development of an attractive diagnostic kit.

Diagnosis of osteoarticular tuberculosis: multi-targeted loop-mediated isothermal amplification assay versus multiplex PCR.

Aim: Diagnosis of osteoarticular tuberculosis (OATB) is quite challenging and there is an urgent need to design a prompt and precise diagnostic test. Methods: We developed a multi-targeted loop-mediated isothermal amplification (LAMP) assay using mpt64 (Rv1980c) and pstS1 (Rv0934) targets for the detection of Mycobacterium tuberculosis in OATB patients. Results: The sensitivities of 100 and 82.4% were obtained in confirmed (n=10) and suspected (n=57) OATB cases, respectively by multi-targeted LAMP with a specificity of 96.9% (n=33). Moreover, the sensitivities attained by multi-targeted LAMP in total OATB cases were significantly higher (p<0.05-0.01) than multiplex PCR (mpt64 +pstS1) and GeneXpert assay. Conclusion: Our LAMP is simple, reliable and cost-effective method, which may develop into an attractive diagnostic kit for early detection of OATB cases.

Immune status changing helps diagnose osteoarticular tuberculosis.

This study is aimed to develop a new nomogram for the clinical diagnosis of osteoarticular tuberculosis (TB). xCell score estimation to obtained the immune cell type abundance scores. We downloaded the expression profile of GSE83456 from GEO and proceed xCell score estimation. The routine blood examinations of 326 patients were collected for further validation. We analyzed univariate and multivariate logistic regression to identified independent predicted factor for developing the nomogram. The performance of the nomogram was assessed using the receiver operating characteristic (ROC) curves. The correlation of ESR with lymphocytes, monocytes, and ML ratio was performed and visualized in osteoarticular TB patients. Compared with the healthy control group in the dataset GSE83456, the xCell score of basophils, monocytes, neutrophils, and platelets was higher, while lymphoid was lower in the EPTB group. The clinical data showed that the cell count of monocytes were much higher, while the cell counts of lymphocytes were lower in the osteoarticular TB group. AUCs of the nomogram was 0.798 for the dataset GSE83456, and 0.737 for the clinical data. We identified the ML ratio, BMI, and ESR as the independent predictive factors for osteoarticular TB diagnosis and constructed a nomogram for the clinical diagnosis of osteoarticular TB. AUCs of this nomogram was 0.843. We demonstrated a significant change between the ML ratio of the EPTB and non-TB patients. Moreover, we constructed a nomogram for the clinical diagnosis of the osteoarticular TB diagnosis, which works satisfactorily.

Bone penetration of linezolid in osteoarticular tuberculosis patients of China

BackgroundLinezolid presents strong antimicrobial activity against multidrug-resistant (MDR) pulmonary tuberculosis (TB), but its application in osteoarticular tuberculosis treatment remains understudied. Our objective was to analyze the bone penetration efficiency of linezolid in osteoarticular TB patients. MethodsOsteoarticular TB patients, treated with 600 mg q 24 h linezolid-containing regimens and undergoing surgery, were prospectively and consecutively enrolled. One dose linezolid was administered before surgery. Blood and bone samples were collected simultaneously during operation, and their linezolid concentrations were then detected using high-performance liquid chromatography-tandem mass spectrometry. Pus samples were subjected to mycobacterial culture and GeneXpert MTB/RIF assay. The minimum inhibition concentrations (MICs) and drug susceptibility testing were performed with the recovered isolates. ResultsA total of 36 eligible osteoarticular TB patients were enrolled, including five MDR/rifampicin-resistant cases. All the 12 recovered isolates had MICs ≤0.5 μg/mL for linezolid. Mean concentrations in plasma, collected 100−510 min after the preoperative dosing, were 10.43 ± 4.83 μg/mL (range 3.29−22.26 μg/mL), and median concentrations in bone were 3.93 μg/mL (range 0.61−16.34 μg/mL). The median bone/plasma penetration ratio was 0.42 (range 0.14−0.95 μg/mL). Linezolid concentration in bone had a linear correlation with the drug concentration in plasma (r = 0.7873, p < 0.0001), while plasma concentration could explain 61.98% of the variation of concentration in bone (R2 = 0.6198). Notably, stratification analysis by sampling time demonstrated that samples collected 200−510 min after dosing had very good linear relationships between their bone and plasma concentrations (r = 0.9323). ConclusionsLinezolid penetrates from blood to bone efficiently, and the penetration further stabilizes ∼3 h after dosing.

Mycobacterium culturing and drug resistance of osteoarticular tuberculosis in Xinjiang, China.

This study aims to elucidate the strains and drug resistance of mycobacterium isolated from osteoarticular tuberculosis (OATB) patients and provide a reference for the diagnosis and treatment of OATB.Sixty-nine clinically diagnosed and surgically treated OATB patients were collected in time period of January 2017 to December 2018 at the First Affiliated Hospital of Xinjiang Medical University. The BACTEC MGIT 960 system was used for mycobacteria culturing, strain identification, and drug susceptibility testing, and the mycobacteria culture positive rate, species distribution, and drug resistance were analyzed.Within 4 weeks, 24 (34.78%) isolates of mycobacteria culture were positive; 40 (57.97%) isolates were positive, when culturing time was expanded to 8 weeks, and the difference was statistically significant (P < .05). Among the 40 isolates, 24 (60%) were identified as mycobacterium tuberculosis (MTB), 10 (25%) were Mycobacterium bovis, and 6 (15%) were non-tuberculous mycobacteria (NTM). Among total 69 isolates, 40 were enrolled in drug sensitivity test, and 15 (37.5%) isolates were confirmed drug resistant strains, in which 5 isolates were MTB, 4 isolates were M. bovis, and 6 isolates of NTM.The pathogen of clinically diagnosed OATB was mainly MTB. However, M. bovis and NTM also accounted for a considerable proportion, and their drug resistance rate was higher. Extending the culturing time appropriately could improve the culture positive rate. NTM was a drug resistant strain, and mycobacteria culturing, strain identification, and drug resistance analysis should be carried out to serve as a guide for individual treatment.

Vitamin D deficiency among pediatric osteoarticular tuberculosis patients.

We prospectively investigated serum 25 hydroxy vitamin D concentrations in children suffering from osteoarticular tuberculosis. The age or sex correlation to vitamin D levels in affected subjects was also calculated. Twenty five untreated children with osteoarticular tuberculosis were taken as cases along with equal number of age and sex matched 'healthy' controls. The following laboratory references for defining the vitamin D status were used (<30nmol/L=deficiency; 30-75nmol/L=insufficiency; >75nmol/L=sufficiency). The cases were further grouped based on gender differences and age (<5 or >5 years). Out of 25 cases, there were 14 (56%) with deficiency of vitamin D. In 'apparently' healthy subjects, all 25 controls (100%) had hypovitaminosis D. The osteoarticular tuberculosis patients had significant lower levels of vitamin D when compared with their healthy peers irrespective of gender or age differences. The osteoarticular tuberculosis cases had low serum vitamin D levels compared to healthy controls. The low vitamin D levels were persistent irrespective of gender and age in osteoarticular tuberculosis children. There was widespread vitamin D insufficiency in apparently healthy controls.

Association of tumor necrosis factor-α gene polymorphism with osteoarticular tuberculosis prognosis in a Hebei population.

This study investigated the association of tumor necrosis factor-α (TNF-α)-308, -238, and -863 polymorphisms with osteoarticular tuberculosis (OA-TB) prognosis in a Hebei population. Genomic DNA was extracted from venous blood samples of 120 OA-TB patients and 100 healthy volunteers. TNF-α-308, -238, and -863 were analyzed by PCR-restriction fragment length polymorphism; genotype and allele frequencies were calculated. Serum TNF-α level was significantly higher in OA-TB patients (283.16 ± 51.68 ng/L) than in control (122.54 ± 54.65 ng/L; P < 0.05). Higher frequency of TNF-α-308 GG genotype in healthy volunteers (91.0%) than in OA-TB patients (79.2%) indicated that it was a protective factor against OA-TB (OR = 0.405, 95%CI = 0.147-0.657, P = 0.007). Higher frequencies of TNF-α-308 GA genotype and TNF-α-308 allele (A) in OA-TB patients (20.8 and 10.4%, respectively) than in healthy volunteers (8.0 and 5.0%, respectively) indicated an association with increased risk of OA-TB (OR = 3.112, 95%CI = 1.520-6.343, P = 0.003; OR = 3.109, 95%CI = 1.676-6.538, P = 0.006; respectively). Haplotype association analysis of TNF-α polymorphisms (-308/-238/-863) showed a higher frequency of TNF-α AGA in OA-TB patients (12.1%) than in healthy volunteers (3.5%), indicating that it was a risk factor for OA-TB (OR = 4.201, 95%CI = 1.80-9.91, P = 0.010). TNF-α-308 G/A and TNF-α AGA (-308/-238/-863) were associated with a predisposition to OA-TB, which could aid clinical detection, prevention, and prognosis of OA-TB.

Osteoarticular tuberculosis: in search of new biomarkers

Background Our objectives were to evaluate the diagnostic utility of serum and synovial fluid concentration of adenosine deaminase, interlukin-6, tumor necrosis factor-alpha, and interferon-γ in patients of osteoarticular tuberculosis (TB) and define a cutoff limit of these markers in the serum and local fluid for its diagnosis.

Does multiplex Polymerase Chain Reaction increase the diagnostic percentage in osteoarticular tuberculosis? A prospective evaluation of 80 cases

Multiplex Polymerase Chain Reaction (MPCR) is a technique in which two or more gene targets are amplified in a single reaction. This has increased sensitivity of diagnosis as a single gene target may be absent in some Mycobacterium tuberculosis strains. MPCR using two target genes specific for Mycobacterium tuberculosis, that is, IS6110 and MPB 64, ZN staining and Mycobacterial culture were performed on synovial fluid/pus samples of 80 (three confirmed, 77 suspected) patients of osteoarticular tuberculosis and 25 non tuberculosis patients. MPCR had a sensitivity of 100% in confirmed cases and 81.8% in clinically suspected cases. AFB was positive in one patient and Mycobacterial culture was positive in three patients. MPCR also had 100% specificity; MPB64 was positive in five patients in which IS6110 was negative whereas IS6110 was positive in two patients in which MPB64 was negative. MPCR is a sensitive and specific method for diagnosis of paucibacilliary conditions such as osteoarticular tuberculosis.

Osteoarticular tuberculosis – diagnostic solutions in a disease endemic region

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. 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. 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. 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.

Basic science of host immunity in osteoarticular tuberculosis -A clinical study

Background : Osteoarticular tuberculosis is coming back with vengeance. Host immunity plays a major role in either containing the disease or allowing the spread. Number of resistant cases and drug defaulters are on the rise. Immunepotentiation (immunomodulation) has shown beneficial response in pulmonary tuberculosis in various studies. Methods : This study was done to assess immune status of various categories of patients of osteoarticular tuberculosis, to modulate (alter or change) the immune system in non responder patients and to add immunomodulation therapy in some patients from the very beginning of antitubercular chemotherapy and observe their clinical response and objectively assess their immune status. Prospective study was done in two phases involving 103 patients suffering from osteoarticular tuberculosis. In phase one 61 patients (Two Groups - Group 1 called fresh virgin/responder cases given first line antitubercular drugs (ATT) = 41 patients; Group 2 called Non responders immunomodulated with cycles of oral levamisole, BCG and DPT vaccine as an adjuvant to ATT = 20 patients) assessed for their cellular immune profile. In second phase 42 patients (In three Groups - Group 3A who received only ATT = 15 patients; Group 3B who received ATT and immunomodulation from very beginning = 15 patients; Group 4 who were non responders, put on immunomodulation after minimum three months of ATT =12 patients) were assessed for their interleukin profiles at presentation and after three months of therapy in respective groups. The immune parameters of all above mentioned patients (n=103) were correlated with the type of clinical presentation, course of disease, response to therapy and response to immunomodulation. Follow up in all the groups ranges from 24 - 49 months (mean 27.2 months). Results : Group1 (n=41): Thirty nine out of 41 patients showed clinicoradiological response at three months of therapy. The CD4 cell counts in these patients rose to a statistically significant (p=. 000) mean of 1140±452.6 cumm indicating that tuberculosis is an important cause of this reversible CD4 T cell lymphopenia. Group 2 (n=20): Thirteen patients showed favorable clinical response to immunomodulation. The CD4 cell counts showed statistically significant (P Overall, out of total 32 nonresponder patients in the present study, 23 responded to immunomodulation regime. No side effect related to immunomodulation was observed. No patient in this study was diabetic or HIV+ve. Conclusions : Correlation of above immune parameters with the clinical presentation, the course of disease and the response to therapy reflected various patterns of host immune responses in osteoarticular tuberculosis. If immunomodulating drugs (Immunotherapy) are given along with ATT from very beginning, these beneficial changes are quantitatively more (more marked) indicating robust host immune response to infection, helping control the disease early. Adjuvant immunomodulation has the potential of shortening the total duration of antitubercular chemotherapy, besides inducing beneficial clinical and host immune responses.