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The aim of this study was to explore the related factors linked to the development and infectivity of tuberculosis. This was achieved by comparing the clinical characteristics of patients with pulmonary tuberculosis (TB) who tested positive in smear Mycobacterium tuberculosis tests with this who tested negative in smear mycobacterium tests but positive in sputum Gene Xpert tests. We gathered clinical data of 1612 recently hospitalized patients diagnosed with pulmonary tuberculosis who tested positive either in sputum Gene-Xpert test or sputum smear Mycobacterium tuberculosis tests. The data was collected from January 1, 2018 to August 5, 2023, at Sichuan Provincial People's Hospital. We conducted separately analyzes and comparisons of the clinical characteristics between the two groups of patients, aiming to discussed the related factors influencing the development and infectivity of tuberculosis. In comparison to the GeneXpert positive group, the sputum smear positive group exhibited a higher proportion of elderly patients (aged 75–89) and individuals classified as underweight (BMI < 18.5 kg/m2). Furthermore, this group was more prone to experiencing symptoms such as weight loss, coughing and sputum production, hemoptysis, shortness of breath, and difficulty breathing. Moreover, they are also more likely to develop extrapulmonary tuberculosis, such as tuberculous meningitis, tuberculous pleurisy, and tuberculous peritonitis. These clinical features, when present, not only increase the likelihood of a positive result in sputum smear tests but also suggest a high infectivity of pulmonary tuberculosis. Elderly individuals (aged 75 to 89) who are underweight (BMI < 18.5 kg/m2), display symptom of cough, expectoration, hemoptysis and dyspnea-particularly cough and expectoration-and those with extra pulmonary tuberculosis serve as indicators of highly infectious pulmonary tuberculosis patients. These patients may present with more severe condition, carrying a higher bacteria, and being more prone to bacterial elimination. Identification of these patients is crucial, and prompt actions such as timely and rapid isolation measures, cutting off transmission routes, and early empirical treatment of tuberculosis are essential to control the development of the disease. [ABSTRACT FROM AUTHOR]

Objectives: Diabetes has been related to higher risk and poor prognosis of patients with tuberculosis, while the influence of prediabetes on the treatment outcome of patients with tuberculosis remains not determined. A meta‐analysis was performed to evaluate the influence of prediabetes on treatment outcome of patients with tuberculosis. Methods: Relevant cohort studies were acquired through a search of Medline, Embase, and Web of Science databases. To minimise the influence of between‐study heterogeneity, a randomised‐effects model was used to pool the results. Results: Eight prospective cohort studies including 3001 patients with tuberculosis were available for the meta‐analysis. Among them, 752 (25.1%) were with prediabetes at baseline, and the patients were followed for a mean duration of 17.7 months. It was shown that compared to patients with normoglycemia, those with prediabetes were associated with a higher incidence of unfavourable treatment outcome (risk ratio [RR]: 1.41, 95% confidence interval [CI]: 1.02 to 1.96, p = 0.04; I2 = 56%). Subgroup analysis did not support that difference in study country (Asian or non‐Asian), diagnosis (pulmonary tuberculosis only or also with extrapulmonary tuberculosis), mean age, follow‐up duration, or study quality score had significant influence on the results (p for subgroup difference all >0.05). However, prediabetes at baseline was not associated with an increased risk of all‐cause mortality during follow‐up (RR: 1.59, 95% CI: 0.75 to 3.38, p = 0.23; I2 = 54%). Conclusions: Patients with tuberculosis and prediabetes may have a higher risk of unfavourable treatment outcome compared to patients with normoglycemia. [ABSTRACT FROM AUTHOR]

Tuberculous pleurisy is one of the most common types of extra-pulmonary tuberculosis, but the sensitivity of conventional mycobacterial culture (Culture) or Xpert MTB/RIF assay (Xpert) is not satisfying. This multicentre cohort study evaluated the accuracy of a new cell-free DNA droplet digital PCR assay (cf-ddPCR) for diagnosing tuberculous pleurisy. Patients with suspected tuberculosis (≥5 years of age) with pleural effusion were consecutively recruited from nine research sites across six provinces in China between September 2020 to May 2022. Culture, Xpert, Xpert MTB/RIF Ultra assay (Ultra), real-time PCR, and cf-ddPCR were performed simultaneously for all specimens. A total of 321 participants were enrolled, and data from 281 (87.5%) participants were available, including 105 definite tuberculous pleurisy, 113 possible tuberculous pleurisy and 63 non-tuberculous pleurisy according to the composite reference standard. The sensitivity of cf-ddPCR was 90.5% (95/105, 95% CI, 82.8–95.1%) in the definite tuberculous pleurisy group, which was significantly higher than those of Culture (57.1%, 60/105, 95% CI, 47.1–66.6%, p < 0.001), Xpert (46.7%, 49/105, 95% CI, 37.0–56.6%, p < 0.001), Ultra (69.5%, 73/105, 95% CI, 59.7–77.9%, p < 0.001) and real-time PCR (75.2%, 79/105, 95% CI, 65.7–82.9%, p < 0.001). In possible tuberculous pleurisy, whose results of Culture and Xpert were both negative, the sensitivity of cf-ddPCR was 61.1% (69/113, 95% CI, 51.4–70.0%), which was still significantly higher than that of Ultra (27.4%, 31/113, 95% CI, 19.7–36.8%, p < 0.001) and real-time PCR (38.9%, 44/113, 95% CI, 30.0–48.6%, p < 0.001). The performance of cf-ddPCR is superior to Culture, Xpert, Ultra, and real-time PCR, indicating that improved diagnostic accuracy can be anticipated by incorporating this new assay. [ABSTRACT FROM AUTHOR]

Introduction: Antimicrobial resistance in Mycobacterium tuberculosis (MTB) poses a significant challenge to tuberculosis (TB) management worldwide. Rifampicin resistance (RR) has been associated with the rpoB gene mutation. No study was conducted in Tanzania to determine the commonest mutation. The inconsistent findings from various studies support the need to determine whether reported mutation patterns are applicable in our setting. We determined the frequency of rpoB gene mutation and factors associated with RR, which were detected using GeneXpert MTB/RIF assay. Methods: We conducted a retrospective cross-sectional study involving data from the National Tuberculosis and Leprosy Program database from 2020 to 2022 for cases investigated using GeneXpert MTB/RIF assay. Descriptive analysis was performed to determine the frequency of categorical variables. The chi-square test and logistic regression analysis assessed the relationship between the independent variables and outcome. The 95% confidence interval and a significance level of p<0.05 were used to assess the strength of association. Results: A total of 56,004 participants had a status of MTB and RR, where 38,705/56,004 (69.11%) were males. Probe E mutation (codon 529–533), 89/219 (40.64%) was predominant. Human immunodeficiency virus (HIV)-positive patients had a higher gene mutation, 134/10601 (1.26%) than HIV-negative, 306/45016 (0.68%) (p<0.001). Patients with both pulmonary and extra-pulmonary TB had about four times greater odds of developing rifampicin resistance (AOR 3.88, 95%CI: 1.80–8.32). RR was nearly nine times higher in previously treated patients than new patients (AOR 8.66, 95% CI: 6.97–10.76). HIV-positive individuals had nearly twice the odds of developing RR than HIV-negative individuals (AOR 1.91, 95%CI: 1.51–2.42). Conclusion: The rate of RR was lower compared to other studies in Tanzania, with probe E mutations the most prevalent. Patients with disseminated TB, HIV co-infection and those with prior exposure to anti-TB had more risk of RR. The findings highlight the need to strengthen surveillance of multidrug-resistant TB among high risk patients. [ABSTRACT FROM AUTHOR]

AbstractBackgroundObjectivesMethodsResultsConclusionComorbidities complicate the management of tuberculosis (TB) and have become an essential part of the end TB strategy to eradicate TB. However, pulmonary TB has received the most attention, and little is known about the impact of comorbidities and other factors on outcomes in patients with extrapulmonary tuberculosis (EPTB).Our aim was to analyze the factors associated with hospitalization and mortality in EPTB at a hospital in Central India, using non-TB patients with similar clinical presentations as a comparison.Patients with presumptive EPTB were prospectively enrolled and followed up until the end of treatment or for at least 6 months. Detailed demographic and clinical information was collected for all participants, and patients were categorized as TB or non-TB using a composite reference standard. Multivariate logistic regression was used to analyze the impact of various clinical findings and risk factors on hospitalization and mortality.A total of 276 patients were categorized as TB cases and 175 as non-TB cases. Factors associated with hospitalization in children were younger age and non-adenitis site of disease. In adults, factors associated with mortality were older age, non-adenitis site of disease and HIV infection regardless of TB diagnosis, while diabetes mellitus increased the odds of mortality in EPTB patients.Our results show that comorbidities increase the odds of death in both TB and non-TB patients in low-resource settings. This argues for a shift away from the traditional vertical management of diseases in these areas and supports a continued focus on building robust healthcare systems. [ABSTRACT FROM AUTHOR]

Aims and Obctives: To compare FNAC, microscopy (ZN staining), histopathology and CBNAAT for diagnosis of head and neck tuberculosis, and to evaluate efficacy of CBNAAT in early diagnosis of tuberculosis in head and neck region. Materials and methods: This prospective study was carried out in the department of otorhinolaryngology, JLN Medical College and attached hospital, Ajmer from August 2020 to September 2022. Thorough history and clinical examination of all patients presented with neck swelling was done. All relevant investigations including chest x-ray, mantoux test, ESR, FNAC, ZN staining, CBNAAT and histopathology were done and their efficacy was compared. Results: Sensitivity and specificity of CBNAAT in detecting extra pulmonary tuberculosis was 85.19% and 91.30% respectively, and diagnostic accuracy was consistent with findings of FNAC and ZN staining (p < 0.001) for diagnosis of cervical lymphadenopathy. Conclusion: CBNAAT has a promising role in early diagnosis of head and neck tuberculosis as well as other cases of smear negative tuberculosis such as MDR TB and TB-HIV and is optimal for the diagnosis of lymph node tuberculosis and helps in early identification and initiation of treatment. Sensitivity of CBNAAT scored twice as high in comparison with microscopy thus doubling the proportion of rapid diagnoses with important effect on the patient's outcome. [ABSTRACT FROM AUTHOR]

Background and Objectives: This study evaluated the efficacy of the TrueLab™ Real Time mini-PCR system in providing rapid and accurate diagnostic results for tuberculosis (TB) detection in India. The goal is to improve case detection and accelerate treatment in settings with limited resources. Materials and Methods: This prospective study was conducted by the Department of Microbiology on 120 patients, age ranging from >=15 years with at least two clinical symptoms of pulmonary TB. Molbio and Universal Cartridge Based Sample Prep were the 2 methods used for processing sputum samples. The diagnosis was based on the MTB Real Time PCR test, which has a detection limit of 100 CFU/mL. Patients under 15 years, samples lacking clinical background, saliva specimens or extra-pulmonary TB cases were excluded from the study. Results: A total of 44.17% samples were positive for TB with maximum positivity in the age group 31-45 years. Positivity rate was found to be higher in females. In 4.17% of cases there was rifampicin resistance, which was significantly high in previously treated cases. Comparison of Truenat with Ziehl-Neelsen and fluorescent method revealed that it was more sensitive and less time consuming. Conclusion: Truenat MTB/RIF is a sensitive detection system for TB with rapid results, which serves as an important tool in the early management of tuberculosis patients and drug-resistant-TB cases. [ABSTRACT FROM AUTHOR]

Truenat MTB Plus assay was evaluated for diagnosing ocular tuberculosis (OTB) and detecting multi-drug resistant (MDR) and extremely-drug resistant (XDR) OTB. A total of 75 vitreous fluid specimens [five confirmed OTB, 40 clinically suspected OTB and 30 controls] were subjected to Truenat MTB Plus, multiplex PCR, and Xpert Ultra. Chips of Truenat were used for detecting rifampicin, isoniazid, fluoroquinolone and bedaquiline resistance. The performance was compared against culture, composite reference standard, and gene sequencing. The overall sensitivity of TruePlus, MPCR, and Ultra in diagnosing OTB was 66.6%, 73.3%, and 55.5%, respectively. Out of six cases with mutations in rpoB gene, RifR was detected in five by TrueRif and four by Ultra. Three MDR and one XDR-OTB were reported by Truenat. Truenat assay along with its strategic chips is a rapid and reliable tool for diagnosis of OTB and detection of drug resistance, including MDR and XDR-OTB. Abbreviations: OTB: Ocular tuberculosis; XDR: Extremely drug resistant; Ultra: Xpert MTB/RIF Ultra; Xpert: Xpert MTB/RIF; PCR: polymerase chain reaction; NAATs: Nucleic acid amplification tests; MDR: Multi Drug Resistant; NSP: National Strategic plan for elimination of tuberculosis; FqR: Fluoroquinolone resistant; BdqR: bedaquiline resistant; TrueRif: Truenat MTB Rif Dx; TruePlus: Truenat Plus; INH: Isoniazid; DST: Drug susceptibility testing; MGIT: Mycobacterial growth indicator tube; CRF: Composite reference standard; PPV: positive predictive value; NPV: negative predictive value; EPTB: extrapulmonary tuberculosis; VF: vitreous fluid; DNA: deoxyribonucleic acid; ATT: antitubercular therapy; RifR: Rifampicin resistance; RifS: Rifampicin susceptible; RifI: Rifampicin indeterminate. [ABSTRACT FROM AUTHOR]

To report a case of disseminated TB presenting as ciliary body and thyroid mass lesions. A 17-year-old male patient presented with a thyroid mass and blurring of vision in the left eye. A diagnosis of ciliary body granuloma was made. Although the Mantoux was negative, the HRCT chest showed evidence of miliary TB, and the fine needle aspiration cytology from the thyroid mass revealed AFB. On initiation of Antitubercular therapy(ATT), a paradoxical worsening of ciliary body granuloma was noted which resolved on starting steroids. Involvement of thyroid gland and ciliary body although rare in tuberculosis, may be the presenting feature of disseminated TB. Paradoxical reactions seen after initiation of ATT in these cases may respond well to oral steroids. [ABSTRACT FROM AUTHOR]

Background: Tuberculosis (TB) is one of the significant health concerns in Egypt, necessitating rapid, affordable, and accurate diagnosis to aid in its control. This study presents data collected over five years (2017-2021) to explore different diagnostic TB methods in our lab. Methods: A total of 33700 non-repetitive samples were subjected to different diagnostic methods; 30000 were stained by Ziehl–Neelsen (ZN), of which 2819 were cultured on Löwenstein-Janssen (LJ) media, and 456 were analyzed by GeneXpert; 3700 samples were tested by interferon-gamma release assay (IGRA) Quantiferon. Moreover, 3650 patients underwent the tuberculin skin test (TST). Results: GeneXpert displayed the highest positivity (23.9%), while ZN smear microscopy was the lowest (4.8%). The detection capability between pulmonary and extrapulmonary samples was not statistically significant using LJ culture but significant using GeneXpert MTB/RIF. Rifampicin resistance was 17.4% among the GeneXpert Mycobacterium tuberculosis (MTB)-positive samples. Conclusions: GeneXpert MTB/RIF assay is a user-friendly, rapid, and efficient method for identifying pulmonary and extrapulmonary TB with the simultaneous detection of rifampicin-resistant strains. However, culture and smear microscopy remain the most dominant diagnostic methods in developing countries due to their low cost and relatively acceptable specificity. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) causes major public health problems worldwide. Fighting TB requires sustained efforts in health prevention, diagnosis and treatment. Previous literature has shown that conventional diagnostic methods like X-ray and sputum microscopy often miss early or extrapulmonary TB due to their limited sensitivity. Blood tests, while useful, lack the anatomical detail needed for precise localization of TB lesions. A possible step forward in the fight against TB could be the use of Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) and Computed Tomography (CT). This meta-analysis discusses the current literature, including the methods, results and implications of using FDG-PET-CT in the early diagnosis of TB. Analysis of the studies showed that the sensitivity of FDG-PET-CT as a potential method for early detection of TB was 82.6%. [ABSTRACT FROM AUTHOR]

Background: As disseminated extrapulmonary tuberculosis infection can involve multiple systems and result in atypical clinical manifestations that mimic other diseases, the diagnosis may be difficult, especially in elderly patients. Delaying treatment can adversely affect the prognosis. And to achieve better prognosis, early detection and diagnosis are necessary, as well as early initiation of comprehensive treatment. Case presentation: We present the case of a 78-year-old man with disseminated tuberculosis who developed the uncommon complication of urinary retention due to a psoas abscess, meningoencephalitis, and the rare secondary hemophagocytic lymphohistiocytosis syndrome. The patient achieved a favorable outcome following targeted therapy with antitubercular medications. Conclusions: This case highlights that disseminated extrapulmonary tuberculosis infection can present with a variety of manifestations, and may exhibit many rare and complex clinical presentations. Prompt and accurate diagnosis and treatment play a crucial role in improving prognosis for the patients with persistent fever. [ABSTRACT FROM AUTHOR]

Background: The lineage 4 (L4) of Mycobacterium tuberculosis (MTB) is not only globally prevalent but also locally dominant, surpassing other lineages, with lineage 2 (L2) following in prevalence. Despite its widespread occurrence, factors influencing the expansion of L4 and its sub-lineages remain poorly understood both at local and global levels. Therefore, this study aimed to conduct a pan-genome and identify genomic signatures linked to the elevated prevalence of L4 sublineages among extrapulmonary TB (EPTB) patients in western Ethiopia. Methods: A cross-sectional study was conducted at an institutional level involving confirmed cases of extrapulmonary tuberculosis (EPTB) patients from August 5, 2018, to December 30, 2019. A total of 75 MTB genomes, classified under lineage 4 (L4), were used for conducting pan-genome and genome-wide association study (GWAS) analyses. After a quality check, variants were identified using MTBseq, and genomes were de novo assembled using SPAdes. Gene prediction and annotation were performed using Prokka. The pan-genome was constructed using GET_HOMOLOGUES, and its functional analysis was carried out with the Bacterial Pan-Genome Analysis tool (BPGA). For GWAS analysis, Scoary was employed with Benjamini-Hochberg correction, with a significance threshold set at p-value ≤ 0.05. Results: The analysis revealed a total of 3,270 core genes, predominantly associated with orthologous groups (COG) functions, notably in the categories of '[R] General function prediction only' and '[I] Lipid transport and metabolism'. Conversely, functions related to '[N] Cell motility' and '[Q] Secondary metabolites biosynthesis, transport, and catabolism' were primarily linked to unique and accessory genes. The pan-genome of MTB L4 was found to be open. Furthermore, the GWAS study identified genomic signatures linked to the prevalence of sublineages L4.6.3 and L4.2.2.2. Conclusions: Apart from host and environmental factors, the sublineage of L4 employs distinct virulence factors for successful dissemination in western Ethiopia. Given that the functions of these newly identified genes are not well understood, it is advisable to experimentally validate their roles, particularly in the successful transmission of specific L4 sublineages over others. [ABSTRACT FROM AUTHOR]

The article focuses on the increased risk and diagnostic challenges of tuberculosis in individuals with untreated HIV infection. Topics include the impact of HIV on tuberculosis risk and outcomes, complications in treating both diseases simultaneously, and recent advances in research and international guidelines for managing these conditions in high-burden areas.

Background: Tuberculosis (TB) lymphadenitis is the most common form of extra-pulmonary TB, and the treatment duration is six months. This non-inferiority based randomized clinical trial in South India evaluated the efficacy and safety of a four-month ofloxacin containing regimen in tuberculosis lymphadenitis (TBL) patients. Methods: New, adult, HIV-negative, microbiologically and or histopathologically confirmed superficial lymph node TB patients were randomized to either four-month oflaxacin containing test regimen [ofloxacin (O), isoniazid (H), rifampicin (R), pyrazinamide (Z) -2RHZO daily/ 2RHO thrice-weekly] or a six-month thrice-weekly control regimen (2HRZ, ethambutol/4RH). The treatment was directly observed. Clinical progress was monitored monthly during and up to 12 months post-treatment, and thereafter every three months up to 24 months. The primary outcome was determined by response at the end of treatment and TB recurrence during the 24 months post-treatment. Results: Of the 302 patients randomized, 298 (98.7%) were eligible for modified intention-to-treat (ITT) analysis and 294 (97%) for per-protocol (PP) analysis. The TB recurrence-free favourable response in the PP analysis was 94.0% (95% CI: 90.1–97.8) and 94.5% (95% CI: 90.8–98.2) in the test and control regimen respectively, while in the ITT analysis, it was 92.7% and 93.2%. The TB recurrence-free favourable response in the test regimen was non-inferior to the control regimen 0.5% (95% CI: -4.8-5.9) in the PP analysis based on the 6% non-inferiority margin. Treatment was modified for drug toxicity in two patients in the test regimen, while one patient had a paradoxical reaction. Conclusion: The 4-month ofloxacin containing regimen was found to be non-inferior and as safe as the 6-month thrice-weekly control regimen. [ABSTRACT FROM AUTHOR]

Background: Tuberculosis remains a global health challenge, with central nervous system tuberculosis (CNSTB) affecting 5–10% of extrapulmonary tuberculosis cases, leading to severe complications in children aged 2 to 4 years. Despite timely diagnosis and intervention, management of CNSTB is a challenge. Thalidomide, a TNF-α inhibitor, is a potential therapeutic option in cases resistant to adjuvant corticosteroid therapy. This case report describes the management of complicated CNSTB utilising thalidomide, a less commonly used drug, with a favourable outcome. Clinical presentation: A 3-year-old boy diagnosed with CNSTB and having a ventriculoperitoneal shunt presented with left-sided hemiparesis. He was previously diagnosed with tubercular meningitis at 2.5 years of age. On anti-tubercular treatment and corticosteroid, he had a complicated course with drug-induced liver injury (DILI) and paradoxical reaction. Despite a year of anti-tubercular therapy, there was a deterioration in neurological symptoms, accompanied by an increase in the number of tuberculomas observed on MRI. Adjuvant treatment with thalidomide proved effective in suppressing immunological activation, leading to a reduction in tuberculomas. Conclusion: This case highlights the intricacies of CNSTB, including complications and refractory tuberculomas. Thalidomide was effective in managing these challenges, offering a potential therapeutic option in challenging CNSTB cases. Positive clinical and radiological responses underscore the need to further explore thalidomide as an adjunctive therapy in similar paediatric cases. [ABSTRACT FROM AUTHOR]

Background: The clinical presentation of extrapulmonary tuberculosis (EPTB) is atypical and it is easily confused with other diseases such as common infections, making prompt diagnosis a great challenge. This study aimed to evaluate the accuracy of targeted nanopore sequencing (TNS) in the diagnosis of EPTB. The diagnostic accuracy of TNS using different types of extrapulmonary specimens was also evaluated. Methods: We reviewed the clinical data of patients with suspected EPTB for whom TNS was conducted and who were hospitalized at our center. The true positive, false positive, false negative, and true negative values were determined. Indices of diagnostic accuracy were computed, including sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the curve (AUC) for TNS and acid-fast bacilli (AFB) culture, and compared with those from clinical diagnosis. Results: 149 patients were included in the analysis. The overall sensitivity, specificity, PPV, NPV, and AUC of TNS for the diagnosis of EPTB were 86.4%, 87.5%, 97.3%, 55.3%, and 0.87, respectively. For diagnosis by AFB culture, these values were 25.6%, 100.0%, 100.0%, 20.5%, and 0.63, respectively. The most common specimens used were lymph node tissue, cerebrospinal fluid, pleural effusion, and pleural tissue. The diagnostic accuracy of TNS using all types of extrapulmonary specimens was good. Conclusions: TNS demonstrates good diagnostic accuracy in the rapid diagnosis of EPTB and this was true across different types of extrapulmonary specimens. [ABSTRACT FROM AUTHOR]

Objective: Diagnosing tuberculosis (TB) can be particularly challenging in the absence of sputum for pulmonary tuberculosis cases and extrapulmonary TB (EPTB). This study evaluated the utility of nanopore-based targeted nextgeneration sequencing (tNGS) for diagnosing TB in tissue samples, and compared its efficacy with other established diagnostic methods. Methods: A total of 110 tissue samples from clinical cases were examined. The sensitivity and specificity of tNGS were benchmarked against a range of existing diagnostic approaches including hematoxylin and eosin (HE) staining in conjunction with acid-fast bacilli (AFB) detection, HE staining combined with PCR, HE staining paired with immunohistochemistry (IHC) using anti-MPT64, and the Xpert Mycobacterium tuberculosis (MTB)/rifampicin (RIF) assay. Results: The sensitivity and specificity of tNGS were 88.2 and 94.1%, respectively. The respective sensitivities for HE staining combined with AFB, HE staining combined with PCR, HE staining combined with IHC using anti-MPT64, and Xpert MTB/RIF were 30.1, 49.5, 47.3, and 59.1%. The specificities for these methods were 82.4, 88.2, 94.1, and 94.1%, respectively. Analysis of drug resistance based on tNGS results indicated that 10 of 93 TB patients (10.75%) had potential drug resistance. Conclusion: Targeted next-generation sequencing achieved higher accuracy than other established diagnostic methods, and can play a crucial role in the rapid and accurate diagnosis of TB, including drug-resistant TB. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) is a communicable, airborne infection caused by the bacillus Mycobacterium tuberculosis. Pulmonary tuberculosis (PTB) is the most common presentation, although infection can spread anywhere to cause extra-pulmonary tuberculosis (EPTB). In this paper, a novel fractional order mathematical model is designed for the transmission dynamics of tuberculosis. Uninfected vulnerable individuals are categorized into the following: susceptible with underline ailment and susceptible without underline ailment. The research seeks to qualitatively and quantitatively analyze the proposed model and suggests comprehensive intervention measures for the control of tuberculosis among individuals with underline ailment. Some of the major highlights from the numerical investigation points out that TB vaccination is key to reducing the spread of TB among individuals with underline ailment. Furthermore, efforts to step down the spread of TB through awareness campaigns could significantly reduce the burden of the disease among individuals with co-morbidity. [ABSTRACT FROM AUTHOR]

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Background: We aimed to assess serum 25-hydroxyvitamin D3 (25(OH)D3) concentrations in extrapulmonary tuberculosis (EPTB) patients and to evaluate the effect of vitamin D3 supplementation on their treatment course. Methods: Serum 25(OH)D3concentrations were measured in 47 newly diagnosed EPTB patients and 42 controls. Vitamin D-deficient EPTB patients were randomly assigned to receive 50,000 IU of vitamin D3 (cholecalciferol) orally once a week for 6 weeks (total 300,000 IU), followed by maintenance doses of 1000 IU a day besides anti-TB drugs or the first line anti-TB treatment only. Follow up serum 25(OH)D3 concentrations were measured after 3 months of starting vitamin D3 supplementation. Both groups were evaluated for clinical, laboratory, and radiological outcomes after treatment. Results: Serum 25(OH)D3 concentrations were significantly lower among TB cases (17.1 ± 5.5 nmol/L) compared to healthy controls (51.8 ± 27.3 nmol/L), and vitamin D deficiency was observed in all EPTB patients (n = 47). Patients in VD3 supplementation group had significantly higher weight gain and serum albumin level at 2 months and end of treatment, higher hemoglobin concentration at the end of treatment, significantly lower CRP and ESR at 2 months and at the end of treatment. In cases with TB pleurisy, a significant higher rate of full resolution of pleural fluid after 6 months of anti-TB treatment and shorter treatment duration were noted compared to the other group. Conclusions: Vitamin D deficiency is prevalent in EPTB patients, in whom, vitamin D supplementation is a useful adjunctive therapy to anti-TB drugs and improves treatment course. [ABSTRACT FROM AUTHOR]

Extra-pulmonary TB (EPTB) is difficult to diagnose due to paucibacillary nature of disease. Current study evaluated accuracy of Truenat MTB and MTB-Rif Dx (TN), for detection of Mycobacterium tuberculosis and resistance to rifampicin. Samples were collected from 2103 treatment naive adults with presumptive EPTB, and tested by smear microscopy, liquid culture (LC) (MGIT-960) and GeneXpert MTB/RIF (GX) (Microbiological Reference Standards, MRS). TN results were compared to MRS and Composite Reference Standards (CRS, Microbiology, histopathology, radiology, clinical features prompting decision to treat, response to treatment). CRS grouped patients into 551 confirmed, 1096 unconfirmed, and 409 as unlikely TB. TN sensitivity and specificity was 73.7% and 90.4% against GX. Against LC, Overall sensitivity of GX was 67.6%, while that of TN was 62.3%. Highest sensitivity by TN was observed in pus samples (89%) and highest specificity (92%) in CSF samples, similar to GX. TN sensitivity was better in fluid and biopsy samples and slightly inferior for lymph node aspirates compared to GX. TN sensitivity for RIF resistance detection was slightly superior to GX. TN and GX results were further compared to Clinical Reference Standards. TN detected 170 TB patients initiated on treatment missed by GX, while GX detected 113 such patients missed by TN. Of 124 samples with RIF resistance discordance between GX and TN, GX reported 103/124 as sensitive, 3/124 as indeterminate and 18 as resistant (13/18 samples had low/very low DNA load) while TN reported RIF resistance indeterminate in 103/111 low/very low DNA load samples. Due to paucibacillary nature of EPTB samples, culture yield was poor and phenotypic drug susceptibility testing failed to resolve the discordance. The study establishes TN at par with GX and can be utilized for quick and accurate diagnosis of EPTB. [ABSTRACT FROM AUTHOR]

We assessed the diagnostic yield of urine GeneXpert MTB/RIF Ultra and factors associated with a positive test among adult patients suspected to have extrapulmonary tuberculosis. Urine Ultra was positive in 14% of participants with definite or probable tuberculosis. Hospitalization, disseminated tuberculosis, and human immunodeficiency virus infection were associated with a positive result. [ABSTRACT FROM AUTHOR]

Tuberculosis lesion of the upper respiratory tract in most cases is a secondary disease and develops as a result of the introduction of a specific pathogen in patients suffering from pulmonary tuberculosis. Against the background of the deterioration of the general epidemiological situation of tuberculosis, its course has changed in the direction of aggravation of the process and an increase in diseases of extrapulmonary tuberculosis. It is known that silver nanoparticles restore the sensitivity of drug-resistant strains of tuberculosis microbacteria to chemotherapy drugs, and their growth is suppressed. The purpose of the study is to evaluate the effectiveness of the use of silver--containing drugs for the treatment of patients with tuberculosis of the upper respiratory tract. As a result of the study, it was found that silver nanoparticles demonstrate anti-tuberculosis activity. At the same time, the dose-dependent nature of the suppressive activity of nanoparticles was established. Argitos at a concentration of 3.3% showed higher therapeutic activity in the treatment of laryngeal tuberculosis compared with standard anti-tuberculosis drugs. [ABSTRACT FROM AUTHOR]

Background: Tuberculosis (TB) persists as a global health challenge, with its treatment hampered by the side effects of long-term combination drug therapies and the growing issue of drug resistance. Therefore, the development of novel therapeutic strategies is critical. This study focuses on the role of immune checkpoint molecules (ICs) and functions of CD8+ T cells in the search for new potential targets against TB. Methods: We conducted differential expression genes analysis and CD8+ T cell functional gene analysis on 92 TB samples and 61 healthy individual (HI) samples from TB database GSE83456, which contains data on 34,603 genes. The GSE54992 dataset was used to validated the findings. Additionally, a cluster analysis on single-cell data from primates infected with mycobacterium tuberculosis and those vaccinated with BCG was performed. Results: The overexpression of LAG-3 gene was found as a potentially important characteristic of both pulmonary TB (PTB) and extrapulmonary TB (EPTB). Further correlation analysis showed that LAG-3 gene was correlated with GZMB, perforin, IL-2 and IL-12. A significant temporal and spatial variation in LAG-3 expression was observed in T cells and macrophages during TB infection and after BCG vaccination. Conclusion: LAG-3 was overexpressed in TB samples. Targeting LAG-3 may represent a potential therapeutic target for tuberculosis. [ABSTRACT FROM AUTHOR]

Introduction: Gastrointestinal tuberculosis (TB), specifically gastric TB, is a rare form of extrapulmonary TB. Diagnosis proves challenging with nonspecific signs and symptoms. In this case report, a 22-year-old male came in with complaints of recurrent hematemesis and melena. Case Presentation: We found a submucosal mass with ulceration in the stomach cardia on esophagoduodenoscopy (EGD). The endoscopic ultrasound (EUS) finding was a hypoechoic submucosal lesion with a clear margin; specimens were taken using fine needle aspiration (FNA) for further histopathological examination. The result indicated granuloma of Mycobacterium Tuberculosis in pathology, suggesting that the diagnosis was gastric TB. The patient was then treated with antitubercular therapy regimen for 9 months. The previously documented mass in the stomach cardia was no longer visible on the follow-up endoscopy examination, and the patient was considered cured. Conclusion: This case shows that gastric tuberculosis should be considered in patients with gastrointestinal symptoms, especially those living in TB endemic regions. Endoscopic examinations, such as EGD and EUS, may aid in the diagnosis of gastric tuberculosis.

Abstract Background The clinical presentation of extrapulmonary tuberculosis (EPTB) is atypical and it is easily confused with other diseases such as common infections, making prompt diagnosis a great challenge. This study aimed to evaluate the accuracy of targeted nanopore sequencing (TNS) in the diagnosis of EPTB. The diagnostic accuracy of TNS using different types of extrapulmonary specimens was also evaluated. Methods We reviewed the clinical data of patients with suspected EPTB for whom TNS was conducted and who were hospitalized at our center. The true positive, false positive, false negative, and true negative values were determined. Indices of diagnostic accuracy were computed, including sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the curve (AUC) for TNS and acid-fast bacilli (AFB) culture, and compared with those from clinical diagnosis. Results 149 patients were included in the analysis. The overall sensitivity, specificity, PPV, NPV, and AUC of TNS for the diagnosis of EPTB were 86.4%, 87.5%, 97.3%, 55.3%, and 0.87, respectively. For diagnosis by AFB culture, these values were 25.6%, 100.0%, 100.0%, 20.5%, and 0.63, respectively. The most common specimens used were lymph node tissue, cerebrospinal fluid, pleural effusion, and pleural tissue. The diagnostic accuracy of TNS using all types of extrapulmonary specimens was good. Conclusions TNS demonstrates good diagnostic accuracy in the rapid diagnosis of EPTB and this was true across different types of extrapulmonary specimens.

Abstract Background We aimed to assess serum 25-hydroxyvitamin D3 (25(OH)D3) concentrations in extrapulmonary tuberculosis (EPTB) patients and to evaluate the effect of vitamin D3 supplementation on their treatment course. Methods Serum 25(OH)D3concentrations were measured in 47 newly diagnosed EPTB patients and 42 controls. Vitamin D-deficient EPTB patients were randomly assigned to receive 50,000 IU of vitamin D3 (cholecalciferol) orally once a week for 6 weeks (total 300,000 IU), followed by maintenance doses of 1000 IU a day besides anti-TB drugs or the first line anti-TB treatment only. Follow up serum 25(OH)D3 concentrations were measured after 3 months of starting vitamin D3 supplementation. Both groups were evaluated for clinical, laboratory, and radiological outcomes after treatment. Results Serum 25(OH)D3 concentrations were significantly lower among TB cases (17.1 ± 5.5 nmol/L) compared to healthy controls (51.8 ± 27.3 nmol/L), and vitamin D deficiency was observed in all EPTB patients (n = 47). Patients in VD3 supplementation group had significantly higher weight gain and serum albumin level at 2 months and end of treatment, higher hemoglobin concentration at the end of treatment, significantly lower CRP and ESR at 2 months and at the end of treatment. In cases with TB pleurisy, a significant higher rate of full resolution of pleural fluid after 6 months of anti-TB treatment and shorter treatment duration were noted compared to the other group. Conclusions Vitamin D deficiency is prevalent in EPTB patients, in whom, vitamin D supplementation is a useful adjunctive therapy to anti-TB drugs and improves treatment course.

Abstract Extra-pulmonary TB (EPTB) is difficult to diagnose due to paucibacillary nature of disease. Current study evaluated accuracy of Truenat MTB and MTB-Rif Dx (TN), for detection of Mycobacterium tuberculosis and resistance to rifampicin. Samples were collected from 2103 treatment naive adults with presumptive EPTB, and tested by smear microscopy, liquid culture (LC) (MGIT-960) and GeneXpert MTB/RIF (GX) (Microbiological Reference Standards, MRS). TN results were compared to MRS and Composite Reference Standards (CRS, Microbiology, histopathology, radiology, clinical features prompting decision to treat, response to treatment). CRS grouped patients into 551 confirmed, 1096 unconfirmed, and 409 as unlikely TB. TN sensitivity and specificity was 73.7% and 90.4% against GX. Against LC, Overall sensitivity of GX was 67.6%, while that of TN was 62.3%. Highest sensitivity by TN was observed in pus samples (89%) and highest specificity (92%) in CSF samples, similar to GX. TN sensitivity was better in fluid and biopsy samples and slightly inferior for lymph node aspirates compared to GX. TN sensitivity for RIF resistance detection was slightly superior to GX. TN and GX results were further compared to Clinical Reference Standards. TN detected 170 TB patients initiated on treatment missed by GX, while GX detected 113 such patients missed by TN. Of 124 samples with RIF resistance discordance between GX and TN, GX reported 103/124 as sensitive, 3/124 as indeterminate and 18 as resistant (13/18 samples had low/very low DNA load) while TN reported RIF resistance indeterminate in 103/111 low/very low DNA load samples. Due to paucibacillary nature of EPTB samples, culture yield was poor and phenotypic drug susceptibility testing failed to resolve the discordance. The study establishes TN at par with GX and can be utilized for quick and accurate diagnosis of EPTB.

Multiple strains of Mycobacteria cause tuberculosis (TB), a chronic, specific infectious granulomatous disease. It mainly occurs with pulmonary involvement when compared to extrapulmonary involvement. Primary oral occurrence is uncommon and oral lesions are usually secondary to pulmonary involvement. When there are no active pulmonary clinical manifestations of TB, the diagnosis of the very rare entity of primary gingival TB poses a great challenge to clinicians. In this case report, we discuss a case of primary gingival TB in a 24-year-old lactating mother. This article briefs the onset and course of the lesion during pregnancy and postpartum, elaborates the pathway to diagnosis, various investigations performed and the regimen of antitubercular therapy for 6 months, followed by complete resolution of the lesion without recurrence. This report also describes the significance of considering TB as a differential diagnosis in oral lesions and the various diagnostic methods available. It also emphasizes the sole importance of histopathology in the early detection of the lesion and its management.

Background: Extrapulmonary tuberculosis (EPTB) makes for 25% of all instances of tuberculosis (TB) patients. The enigmatic clinical presentation of EPTB makes identification difficult since it simulates other chronic conditions such as neoplastic and inflammatory disorders and could culminate in treatment that is either insufficient or not required. For an affirmative and confirmed diagnosis, a substantial level of suspicion is imperative. The paucibacillary feature of EPTB makes diagnosis extremely difficult and necessitates the use of many diagnostic methods to arrive at a precise diagnosis. In December 2010, the World Health Organization recommended using GeneXpert/cartridge-based nucleic acid amplification test (CBNAAT) for the initial assessment of suspected cases of EPTB. Furthermore, fine-needle aspiration cytology (FNAC), Ziehl–Neelsen (ZN) stain, and the CBNAAT have to be utilized to exclude other possible origins of granulomatous inflammation. The goal of the current investigation is to comprehend how FNAC and ZN stains relate to CBNAAT and their diagnostic value. Methods: The evaluation included all suspected instances of tubercular lymphadenopathy, and adequate aspirates were obtained from the site of the enlarged cervical lymph nodes. Smears were made following FNAC and stained with ZN stain as well as hematoxylin and eosin stain. Simultaneously, CBNAAT and culture evaluations were conducted on the same aspirates. This cross-sectional study took place at a tertiary care center and encompassed 200 individuals with clinical manifestations of EPTB. Results: There were 200 cases of suspected tubercular lymphadenitis (TBLN). According to the FNAC results, TBLN was detected in 71 (47.6%) of these 200 cases, followed by necrotizing lymphadenitis in 56 (37.5%), chronic caseating granulomatous lymphadenitis in 47 (31.5%), and reactive lymphadenitis in 26 (17.4%). They were correlated with CBNAAT results, which showed that all instances of tuberculous lymphadenitis, 85.71% of cases of necrotizing lymphadenitis, 55.32% of cases of chronic caseating granulomatous lymphadenitis, and 2 (7.69%) cases of reactive lymphadenitis were CBNAAT positive. Conclusion: CBNAAT should be utilized with FNAC and ZN staining to diagnose EPTB. The CBNAAT assay demonstrated a significant advantage in the identification of previously unidentified FNAC patients. Despite being a simple diagnostic tool, FNAC has a lower specificity and significantly lower precision than CBNAAT in correctly identifying cases of EPTB because it exhibits similar cytomorphological characteristics with lesions that are not associated with TB.

Tuberculosis is a chronic granulomatous transmitting type of disease caused by the Mycobacterium tuberculosis complex. It can affect any part of the body, including the oral cavity. Oral tuberculosis can be primary or secondary, In oral cavity, tongue, buccal mucosa, lip, and palate may involve. Here, the authors present a case of a 50-year-old male patient of tuberculosis of palate, manifesting as a non healing ulcer. The ulcer was present in the middle part of the palate, having undermined edge and a non indurated margin. Though it was tender on palpation, there was no evidence of palatal perforation or bony erosion on radiographic examination. A chest radiograph revealed consolidation in the apex and right upper zone, and Cartridge Based Nucleic Acid Amplification Test (CBNAAT) of sputum was positive, but biopsy of the lesion could not be performed because of problem in patient’s consent. The authors took a chance and started antitubercular drugs. They observed the changes of ulcer at regular intervals. No topical medication was given for the ulcer. After taking antitubercular drugs, the condition improved rapidly and The ulcer healed completely after completing the Intensive Phase (IP) only. Tuberculosis is a transmitting and fatal disease. Early diagnosis with proper treatment can prevent complications and the transmission of the disease to others.

Introduction: Tuberculosis (TB) is caused by Mycobacterium tuberculosis (MTB) and now represents a significant global health concern, with an estimated 10 million people infected with TB in 2022, equivalent to 133 incident cases per 100,000 population. Indonesia faces a substantial burden. The World Health Organization (WHO) estimates 969,000 TB cases, with 717,941 confirmed cases reported. Extrapulmonary TB, contributing to 15% of TB cases, affects various areas such as bones, pleura, lymph nodes, genitourinary system, peritoneum, and meninges. Tuberculous epididymo-orchitis, a rare type of extrapulmonary TB, is characterized by MTB infection in the epididymis or testis. Case: A 31-year-old male was presented to the Emergency Department of Budi Rahayu General Hospital, Pekalongan, with a fever, bitter taste, body aches, and cough. Initially hospitalized for five days and discharged upon improvement of symptoms, the patient returned with fatigue, cough, and black stools. After being admitted under internist and pulmonary specialist care due to a suspected left lung TB apical lesion, biomolecular testing (GeneXpert) was performed. Consultation with a urologist revealed scrotal pain, prompting further tests including urine acid-fast bacilli (AFB) examination, testicular ultrasound, and aspiration culture. The patient was diagnosed with TB epididymo-orchitis and treated with a Category 1 TB regimen. Conclusion: TB epididymo-orchitis is a rare case requiring thorough diagnostic evaluation encompassing anamnesis, physical examination, and diagnostic procedures. Early detection and appropriate management are vital in combating this challenging disease.

Background: Ocular tuberculosis is a relatively rare extrapulmonary manifestation of tuberculosis. This vision-threatening disease is extremely challenging to diagnose, particularly because it can mimic other diseases. We report a case of tuberculous ciliary body granuloma initially diagnosed as bullous retinal detachment. Case report: A 52-year-old female presented with bullous retinal detachment in her left eye, and ultrasound biomicroscopy (UBM) verified the presence of a lesion with ciliary body granulomatous inflammation. The T-SPOT was positive, and the purified protein derivative (PPD) test was strongly positive (diameter of 20 mm). Following the administration of oral anti-tuberculosis regimen combined with prednisone, the retina gradually became reattached, the ciliary body granuloma became significantly reduced in size, and the visual acuity of the patient noticeably improved. Conclusions: Tuberculous ciliary body granulomas can cause bullous exudative retinal detachment and can be diagnosed with UBM. Early and full-course anti-tuberculosis treatment (ATT) combined with corticosteroid therapy can improve the patient prognosis. [ABSTRACT FROM AUTHOR]

HIV is a disease which reduces human resistant to fight. When our immunity becomes so weak that we are not able to fight even the common commensals of our body, this leads to what is called as an opportunistic infection. Tuberculosis is one of those most common type of opportunistic infection and in this pulmonary tuberculosis is more common. Extrapulmonary tuberculosis with HIV is the area of lesser research. In this study we tried to prove the Prevalence of extrapulmonary tuberculosis in AIDS patients and also the effect of combined HAART and ATT on prevalence of extrapulmonary tuberculosis and also its effect on Quality of life of the patient. This is a retrospective study conducted in a tertiary centre in the Department of Otorhinolaryngology & head and neck surgery from January 2020 to December 2020. A total of 80 patients were studied for 1 year. Confirmed cases of AIDS with extra pulmonary tuberculosis in head and neck region were studied, keeping all ethical issues in mind and after complete treatment of ATT along with HAART. After treatment, a significant number of patients got resolved with EPTB and gave positive response on their quality of life. Not only pulmonary tuberculosis, extrapulmonary tuberculosis with HIV is on the rise nowadays. Combined treatment of both can help in decreasing prevalence of extrapulmonary tuberculosis and improves quality of life. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) constitutes 15–20% of TB cases in general practice among HIV-negative adults in India. The head and neck region provides an impressive field of research because of its varied presentations and different sites of involvement. TB may often mimic malignancy and is misdiagnosed, which leads to an unnecessary delay in diagnosis. Through this study, we aim to draw focus on the various ways in which isolated extrapulmonary TB manifests in today's clinical practice in the head and neck region. Prospective analysis of 60 patients diagnosed with TB in a simple random sampling over 1 year. The period of study was from July 2022 to June 2023. All those patients who presented to the ENT OPD of Civil Hospital of Asarwa. Patients with complete clinical data were included in the study. In our study patients in the 3rd and 4th decade of life were most commonly affected and a male preponderance of the disease was seen. The most common presentation of EPTB in the head and neck region is cervical lymphadenitis, followed by tuberculous otitis media and laryngeal TB. Each of these has a characteristic clinical presentation that helps to identify this disease. Fine needle aspiration cytology is a very efficient cytopathological examination method that helps in the diagnosis of the disease. Special care should be taken in patients in whom other routine conventional medical and surgical therapy fail to show the desired outcome. Special care and a high degree of suspicion are needed to diagnose extrapulmonary TB. Once rightly diagnosed, it will prevent the progression of the disease and its complications. [ABSTRACT FROM AUTHOR]

Background: Tuberculosis (TB) is a common infection in chronic kidney disease. The prolonged therapy of TB can delay kidney transplantation in patients on antitubercular therapy (ATT). Methods: This was a retrospective single‐center study to analyze the safety of kidney transplantation and its outcomes in patients undergoing transplantation while on the continuation phase of ATT. Results: Between 2013 and 2022, 30 patients underwent kidney transplantation while on ATT. Median age was 38 years and 70% were males. Majority of the patients (86.7%) had extrapulmonary tuberculosis, most common site of involvement being tubercular lymphadenitis. 14/30 patients had microbiological/histopathological diagnosis of TB and the rest were diagnosed by ancillary tests. Patients were treated with 4 drug ATT (isoniazid, rifampicin, pyrazinamide, ethambutol) before transplantation for aminimum of 2 months. Post‐transplantation fluoroquinolone‐based non‐rifamycin ATT was used (median duration 11 months). All patients completed therapy. At 2 years, there was 100% patient survival and 96.7% graft survival. Median eGFR at 6, 12, and 24 months post‐transplantation was 71.9, 64.7, and 67 mL/min/1.73m2, respectively. The percentage of patients suffering a biopsy proven acute rejection at 6, 12, and 24 months was 3.3%, 6.7%, and 6.7%. Conclusion: Kidney transplantation can be done in patients with TB who have a satisfactory response to the intensive phase of the ATT. The decision for transplantation while on the continuation phase of ATT should be individualized. In our experience, there is excellent patient and graft survival in these patients with a low risk of failure of ATT or relapse of TB. [ABSTRACT FROM AUTHOR]

Background: Tuberculosis (TB) remains the number one cause of adult deaths by a curable infectious disease. Mycobacterium tuberculosis bacilli (MTB) is the most common causative organism isolated from mycobacterial lymphadenitis. Accurate and speedy diagnosis is required, especially in paucibacillary extrapulmonary TB. In this study, we compared the efficacy of CBNAAT with line probe assay and liquid culture in the evaluation of tubercular lymph node abscesses. Materials and Methods: This is a hospital‑based observational cross‑sectional study conducted at Gandhi Medical College and Hospital, Secunderabad, TS, in patients who presented with lymph node abscesses over a period of 18 months after obtaining clearance from the ethics committee and obtaining informed consent. Each sample was evaluated and analyzed in association with the clinical findings, AFB staining, CBNAAT, LPA, and AFB culture, and the results were compared. Results: Fifty patients with TB lymph node abscess diagnosed through FNAC were included in the present study. AFB smear was positive in 29 samples, CBNAAT was positive in 43 samples, LPA was positive in 44 samples, and liquid culture was positive in 39 samples. CBNAAT could detect TB in 16 smear‑negative cases, 10 liquid culture‑negative cases, and one LPA‑negative case. In our study, CBNAAT was more effective in diagnosing TB lymph node abscess than AFB smear. No significant results were obtained when comparing CBNAAT with LPA and liquid culture. Conclusion: This study demonstrates excellent diagnostic accuracy of the Xpert MTB/RIF test in patients with tuberculous lymphadenitis, with a sensitivity of 86%, specificity of 83.33%, negative predictive value of 95.56%, and positive predictive value of 58.82%. Thus, it can be a rule in testing for lymph node TB. These efforts will contribute to the attainment of the TB elimination goal. [ABSTRACT FROM AUTHOR]

Orbital tuberculosis is a manifestation of extra-pulmonary tuberculosis that is challenging to diagnose and treat. Here, we describe the pivotal role of serial imaging in the diagnosis and treatment of orbital tuberculosis. A 28-year-old male presented with recurrent right upper eyelid swelling and a supraduction deficit associated with a firm painless orbital mass, seen on initial computed tomography to be an extensive superomedial lesion producing mass effect. Biopsy revealed a tuberculosis-like granulomatous inflammation, which, coupled with a positive QuantiFERON gold test, led to empiric anti-tuberculin treatment. Serial radiologic imaging following initiation of treatment showed progressive reduction in mass size, supporting the diagnosis and determining the length of treatment. This rare case demonstrates the utility of serial radiologic exams in the diagnosis and treatment of orbital tuberculosis. [ABSTRACT FROM AUTHOR]

Tuberculosis is a chronic granulomatous transmitting type of disease caused by the Mycobacterium tuberculosis complex. It can affect any part of the body, including the oral cavity. Oral tuberculosis can be primary or secondary, In oral cavity, tongue, buccal mucosa, lip, and palate may involve. Here, the authors present a case of a 50-year-old male patient of tuberculosis of palate, manifesting as a non healing ulcer. The ulcer was present in the middle part of the palate, having undermined edge and a non indurated margin. Though it was tender on palpation, there was no evidence of palatal perforation or bony erosion on radiographic examination. A chest radiograph revealed consolidation in the apex and right upper zone, and Cartridge Based Nucleic Acid Amplification Test (CBNAAT) of sputum was positive, but biopsy of the lesion could not be performed because of problem in patient's consent. The authors took a chance and started antitubercular drugs. They observed the changes of ulcer at regular intervals. No topical medication was given for the ulcer. After taking antitubercular drugs, the condition improved rapidly and The ulcer healed completely after completing the Intensive Phase (IP) only. Tuberculosis is a transmitting and fatal disease. Early diagnosis with proper treatment can prevent complications and the transmission of the disease to others. [ABSTRACT FROM AUTHOR]

Introduction: Tuberculous meningitis (TBM) is a severe extra-pulmonary tuberculosis with high fatality. This meta-analysis aimed to assess the impact of linezolid on TBM treatment outcomes. Methods: We searched multiple databases for studies published up to May 18, 2024 comparing the effects of linezolid on TBM. Meta-analysis was conducted using Review Manager 5.4. Results: Our findings indicated that linezolid may reduce treatment failure risk (RR = 0.42 (0.20, 0.89), p = 0.02) and improve temperature recovery (RR = 1.56 (1.21, 2.02), p < 0.001) in TBM patients. Conclusions: The analysis suggests a positive association between linezolid treatment and therapeutic improvements, with no significant adverse reactions reported. [ABSTRACT FROM AUTHOR]

Background: Tuberculosis (TB) is a global public health problem. Evaluation of TB treatment outcome enables health institutions to measure and improve the effectiveness of TB control programs. This study aimed to assess treatment outcomes of tuberculosis and identify associated factors among TB patients registered at Alemgena Health Center, Oromia, Ethiopia. Method: A retrospective study was conducted; Secondary data were collected from medical records of 1010 TB patients treated at Alemgena Health Center between September 2012 and August 2018, inclusively. Logistic regression was used to identify factors associated with TB treatment outcomes. P-value less than 0.05 was considered statistically significant. Results: The proportion of males and females was almost equal. Among the patients 64.7% were in the age group 15–34, 98% were new cases, 31.2% were smear positive, 13% were HIV positive and 40.3% had extra-pulmonary tuberculosis. 94.2% of the patients had successful treatment outcome, with 26.9% cured and 67.3% treatment completed, whereas 5.8% had unsuccessful treatment outcomes, of whom 4.2% died and 1.5% defaulted. Death rate was higher among patients older than 44 years (10.4%) than among children (0%). In bivariate logistic regression analysis, treatment success rate was 3.582 (95% CI 1.958–6.554, p-value =.000) times higher in the age group 44 and below compared to the age group 45 and above. Conclusion: Treatment success rate exceeded the one targeted by WHO. Age was found to be associated with treatment outcome. Success rate has to be improved for TB patients in the age group greater than 45 years of age. [ABSTRACT FROM AUTHOR]

Epithelial cells function as the primary line of defense against invading pathogens. However, bacterial pathogens possess the ability to compromise this barrier and facilitate the transmigration of bacteria. Nonetheless, the specific molecular mechanism employed by Mycobacterium tuberculosis (M.tb) in this process is not fully understood. Here, we investigated the role of Rv2569c in M.tb translocation by assessing its ability to cleave E-cadherin, a crucial component of cell-cell adhesion junctions that are disrupted during bacterial invasion. By utilizing recombinant Rv2569c expressed in Escherichia coli and subsequently purified through affinity chromatography, we demonstrated that Rv2569c exhibited cell wall–associated serine protease activity. Furthermore, Rv2569c was capable of degrading a range of protein substrates, including casein, fibrinogen, fibronectin, and E-cadherin. We also determined that the optimal conditions for the protease activity of Rv2569c occurred at a temperature of 37°C and a pH of 9.0, in the presence of MgCl2. To investigate the function of Rv2569c in M.tb, a deletion mutant of Rv2569c and its complemented strains were generated and used to infect A549 cells and mice. The results of the A549-cell infection experiments revealed that Rv2569c had the ability to cleave E-cadherin and facilitate the transmigration of M.tb through polarized A549 epithelial cell layers. Furthermore, in vivo infection assays demonstrated that Rv2569c could disrupt E-cadherin, enhance the colonization of M.tb, and induce pathological damage in the lungs of C57BL/6 mice. Collectively, these results strongly suggest that M.tb employs the serine protease Rv2569c to disrupt epithelial defenses and facilitate its systemic dissemination by crossing the epithelial barrier. Author summary: Mycobacterium tuberculosis (M.tb) causes tuberculosis (TB), a highly contagious respiratory disease and a leading cause of death worldwide. Following the inhalation of aerosol particles, the bacteria often establish a persistent infection within the lungs, leading to the development of the characteristic pulmonary TB syndrome. Additionally, M.tb can breach alveolar barrier, thereby initiating extrapulmonary TB. The pathogenesis of M.tb heavily relies on systemic dissemination, although the precise underlying mechanism remains incompletely elucidated. The alveolar epithelial barrier, composed of tight junctions and adherens junctions, plays a crucial role in safeguarding against invading pathogens. In this study, we present groundbreaking discoveries pertaining to the extracellular serine protease Rv2569c of M.tb, which facilitates bacterial transmigration through the cleavage of E-cadherin. Furthermore, we ascertain that Rv2569c elicits profound pathological harm and enhances M.tb colonization within murine pulmonary tissues. These findings contribute to a deeper comprehension of the pathogenic mechanisms employed by M.tb and hold potential for informing future strategies aimed at controlling TB infections. [ABSTRACT FROM AUTHOR]

Introduction: Tuberculous pleural effusion (TPE) stands as one of the primary forms of extrapulmonary tuberculosis (TB) and frequently manifests in regions with a high prevalence of TB, consequently being a notable cause of pleural effusion in such areas. However, the differentiation between TPE and parapneumonic pleural effusion (PPE) presents diagnostic complexities. This study aimed to evaluate the potential of myeloid-derived suppressor cells (MDSCs) in the pleural fluid as a potential diagnostic marker for distinguishing between TPE and PPE. Methods: Adult patients, aged 18 years or older, who presented to the emergency room of a tertiary referral hospital and received a first-time diagnosis of pleural effusion, were prospectively enrolled in the study. Various immune cell populations, including T cells, B cells, natural killer (NK) cells, and MDSCs, were analyzed in both pleural fluid and peripheral blood samples. Results: In pleural fluid, the frequency of lymphocytes, including T, B, and NK cells, was notably higher in TPE compared to PPE. Conversely, the frequency of polymorphonuclear (PMN)-MDSCs was significantly higher in PPE. Notably, compared to traditional markers such as the neutrophil-to-lymphocyte ratio and adenosine deaminase level, the frequency of PMN-MDSCs emerged as a more effective discriminator between PPE and TPE. PMN-MDSCs demonstrated superior positive and negative predictive values and exhibited a higher area under the curve in the receiver operating characteristic curve analysis. PMN-MDSCs in pleural effusion increased the levels of reactive oxygen species and suppressed the production of interferon-gamma from T cells following nonspecific stimulation. These findings suggest that MDSC-mediated immune suppression may contribute to the pathology of both TPE and PPE. Discussion: The frequency of PMN-MDSCs in pleural fluid is a clinically useful indicator for distinguishing between TPE and PPE. [ABSTRACT FROM AUTHOR]

Chronic immune activation in tuberculosis (TB) associated with human immunodeficiency virus (HIV) infection (HIV/TB) modifies their clinical course. We prospectively measured osteopontin (OPN), full-length galectin-9 (FL-Gal9), and total-Gal9 (T-Gal9) levels in 32 patients with HIV/TB coinfection treated with anti-tuberculosis and antiretroviral therapies over 6–18 months to determine the amelioration of inflammatory conditions in response to the therapies. We observed a significant time-dependent decrease in FL-Gal9 in both pulmonary TB (PTB, n = 20) and extrapulmonary TB (EPTB, n = 12) patients. The levels of T-Gal9, OPN, and CRP decreased significantly after treatment in only PTB patients. We calculated the inflammatory score (INS) indicating immunologic recovery based on the decline in OPN, FL-Gal9, T-Gal9, and CRP levels. Baseline levels of T-Gal9 and OPN positively correlated with INS in all TB and only PTB patients, respectively, indicating that their levels predict better recovery. In contrast, FL-Gal9 levels at the second visit negatively correlated with INS in EPTB patients. The decrease rate in OPN levels at the second visit also correlated positively with INS in PTB patients. Women showed a higher INS and lower levels of FL-Gal9 than men. The patients with moderate grade severity on chest X-ray had higher CD4 cell numbers than those with limited grade severity. Monitoring these markers will help to predict and assess the response to therapy as well as to devise strategies to reduce the complications caused by chronic immune activation in patients with HIV/TB coinfection. [ABSTRACT FROM AUTHOR]

To present a comprehensive analysis of the clinical features and magnetic resonance imaging (MRI) findings of intracranial tuberculomas in Indonesia. This was a retrospective analysis of brain MRI from 58 patients (29 women), mean age ± SD = 39 ± 2 years, diagnosed with intracranial tuberculomas. Clinical data, including symptoms, cerebrospinal fluid examination results, and MRI were also analysed. The diagnosis of intracranial tuberculoma was confirmed based on observed MRI changes following anti-tuberculosis therapy. A total of 603 tuberculomas were fully detected via MRI in all patients. Among these lesions, 507 (84%) were located in the cerebrum, 61 (10%) in the cerebellum, 19 (3%) in the basal ganglia, 12 (2%) in the brain stem, and four (1%) in the thalamus. The MRI signals were classified into two groups: tuberculomas with caseating granulomas and tuberculomas with non-caseating granulomas. Among the patients, 29 had concomitant meningitis, seven had hydrocephalus, and four had cerebral infarction. Evidence of pulmonary tuberculosis was found in 16 patients, with one patient having coexisting thoracic vertebral tuberculosis. The present study confirmed the significance of MRI as a valuable tool in the diagnosis of intracranial tuberculomas and the detection of associated abnormalities. The combination of MRI findings with clinical features can enhance the overall diagnostic accuracy for intracranial tuberculomas. • CNS involvement is one of the most severe symptoms of extrapulmonary tuberculosis. • MRI is modality of choice in detecting of tuberculomas. • Tuberculomas often found between grey and white matter junction. • MRI sequence contrast-enhanced FLAIR sequence can detecting meningitis. • MR-spectroscopy showed a lipid-lactate peak for tuberculomas. [ABSTRACT FROM AUTHOR]

Background: Cerebrospinal fluid (CSF) Xpert MTB/RIF assay is an initial test for the diagnosis of tuberculous meningitis (TBM). Nevertheless, it is not very clear which of the factors govern CSF-Gene Xpert/MTB positivity. Objective: Hence, we aimed to assess the relationship, if any, between the clinical, laboratory and radiological parameters of the central nervous system (CNS) tuberculosis patients and the Gene Xpert study in CSF in such patients. Methods and Material: First, we studied 200 patients with CNS tuberculosis according to the case definition, and subsequently, we performed a Gene Xpert study on the CSF of these patients. Then, we correlated the clinical, radiological, and CSF criteria with the Gene Xpert positivity using the univariate binary logistic regression method via SPSS 20 (P-value <0.05). Results: Seventy-five (37.5%) patients (57.3% females) of median 24 years of age, were CSF-Gene Xpert/MTB-positive and 125 (62.5%) patients were negative. The mean duration of illness (P = 0.017), weight loss or failure to thrive (P < 0.001), loss of consciousness or seizure (P = 0.001), signs of meningeal irritation (P = 0.027), stage III of TBM (P < 0.001), evidence of dissemination (P = 0.003), basal exudates (P = 0.004), hydrocephalus (P = 0.018), CSF lymphocytic predominance (P < 0.001), and reduced CSF glucose (P = 0.011) correlated significantly with positive the Gene Xpert/MTB results. Also, Gene Xpert had a sensitivity of 80% and a specificity of 74.84% against culture Xpert. Conclusions Xpert MTB/RIF might be more useful in the later stages of the disease and those with more severe disease. [ABSTRACT FROM AUTHOR]

Key Clinical Message: In the setting of Fournier's gangrene, atypical clinical manifestations and complications in an immunocompetent patient warrant consideration of perineal tuberculosis as a potential underlying cause. Tuberculosis cutis orificialis is a rare form of extrapulmonary tuberculosis that affects the perianal region. Fournier's gangrene is an aggressive necrotizing fasciitis that primarily involves the perianal area and external genitalia. A previously healthy 38‐year‐old man presented with a left perianal abscess. His condition deteriorated, leading to septic shock and multiorgan dysfunction syndrome. A CT scan displayed extensive necrotizing fasciitis. Treatment included broad‐spectrum antibiotics, numerous surgical perineal debridements, a transverse loop colostomy, and hyperbaric oxygen therapy. We believe the patient had pre‐existing asymptomatic, non‐diagnosed perianal tuberculosis, and a subsequent bacterial superinfection resulted in a perineal local abscess that progressed to severe Fournier's gangrene. The diagnosis of tuberculosis was confirmed through positive cultures and molecular identification in perineal biopsies. The patient experienced a complex clinical course with complications such as myocardial necrosis, acute respiratory distress syndrome, rhabdomyolysis with severe critical illness polyneuromyopathy and internal jugular thrombosis. Fournier's gangrene resulted in air dissection throughout the perineal fasciae, extending to the abdominal wall muscles resulting in an infected extraperitoneal spontaneous hematoma, probably caused by therapeutic anticoagulation. An extraperitoneal surgical drainage was performed. This case emphasizes the complexities in diagnosing and managing both perianal tuberculosis and Fournier's gangrene. [ABSTRACT FROM AUTHOR]