Every year, the World Health Organization reports 500,000 new cases of drug-resistant tuberculosis (TB), which poses a serious global danger. The increased number of XDR-TB and MDR-TB cases reported worldwide necessitates the use of new therapeutic approaches. The main issues with the antitubercular medications now in use for the treatment of multidrug-resistant tuberculosis are their poor side effect profile, reduced efficacy, and antimicrobial resistance. One possible remedy for these problems is bedaquiline. The need for better treatment strategies is highlighted by the strong minimum inhibitory concentrations that bedaquiline (BDQ), a novel anti-TB medicine, exhibits against both drug-resistant and drug-susceptible TB. Bedaquiline may be able to help with these problems. Bedaquiline is a medication that is first in its class and has a distinct and particular mode of action. Bedaquiline is an ATP synthase inhibitor that is specifically directed against Mycobacterium tuberculosis and some nontuberculous mycobacteria. It is metabolized by CYP3A4. Bedaquiline preclinical investigations revealed intralesional drug biodistribution. The precise intralesional and multi-compartment pharmacokinetics of bedaquiline were obtained using PET bioimaging and high-resolution autoradiography investigations. Reduced CFU counts were observed in another investigation after a 12-week course of therapy. Meta-analyses and systematic reviews of phase II trials on bedaquiline\'s efficacy in treating drug-resistant tuberculosis in patients reported higher rates of cure, better culture conversion, and lower death rates when taken in conjunction with a background regimen. Here is a thorough medication profile for bedaquiline to aid medical professionals in treating individuals with tuberculosis.

Respiratory tuberculosis (RTB), a global health concern affecting millions of people, has been observationally linked to the gut microbiota, but the depth and nature of this association remain elusive. Despite these findings, the underlying causal relationship is still uncertain. Consequently, we used the Mendelian randomization (MR) method to further investigate this potential causal connection. We sourced data on the gut microbiota from a comprehensive genome-wide association study (GWAS) conducted by the MiBioGen Consortium (7686 cases, and 115,893 controls). For RTB, we procured 2 distinct datasets, labeled the Fingen R9 TBC RESP and Fingen R9 AB1 RESP, from the Finnish Genetic Consortium. To decipher the potential relationship between the gut microbiota and RTB, we employed MR on both datasets. Our primary mode of analysis was the inverse variance weighting (IVW) method. To ensure robustness and mitigate potential confounders, we meticulously evaluated the heterogeneity and potential pleiotropy of the outcomes. In the TBC RESP (RTB1) dataset related to the gut microbiota, the IVW methodology revealed 7 microbial taxa that were significantly associated with RTB. In a parallel vein, the AB1 RESP (RTB2) dataset highlighted 4 microbial taxa with notable links. Notably, Lachnospiraceae UCG010 was consistently identified across both datasets. This correlation was especially evident in the data segments designated Fingen R9 TBC RESP (OR = 1.799, 95% CI = 1.243-2.604) and Finngen R9 AB1 RESP (OR = 2.131, 95% CI = 1.088-4.172). Our study identified a causal relationship between particular gut microbiota and RTB at the level of prediction based on genetics. This discovery sheds new light on the mechanisms of RTB development, which are mediated by the gut microbiota.

BACKGROUND: This study aimed to effectively evaluate the diagnostic performance of the EasyNAT Mycobacterium tuberculosis complex (MTC) assay for tuberculosis (TB) detection from sputum.
METHODS: The retrospectively analyzed data was collected from September 1, 2021, to November 1, 2023, in our hospital.
RESULTS: Forty EasyNAT-positive sputum specimens were simultaneously detected using the GeneXpert MTB/ rifampicin (RIF) assay. The concordance rate between the EasyNAT and GeneXpert MTB/RIF assays was 100%.
CONCLUSIONS: Because of the complexity of detecting RIF resistance data information, the rapid EasyNAT system used in conjunction with GeneXpert might be a better choice for the detection of TB in hospitals.

Despite its historical decline, TB remains a significant cause of infectious disease-related global deaths. The lack of reliable diagnostic tests for vulnerable groups, such as children and immunocompromised patients, remains a challenge for TB control. For decades, it has been recognised that exhaled breath has great potential as a non-invasive and universally accessible clinical alternative to sputum and invasive sampling methods. Although translation into clinical practice has not yet occurred, there has been significant progress with promising results in various applications, including diagnosis, estimation of infectiousness, and monitoring of treatment response. More recently, the COVID-19 pandemic reignited global interest in this field and technological advances have further accelerated its development. In the coming decade, breath sampling will enhance our understanding of respiratory infectious diseases and host-immune responses, which may lead to clinical applications. Here we discuss the diagnostic landscape of TB and the current state of the art of breath sampling.

Subnational TB estimates are crucial for making informed decisions to tailor TB control activities to local TB epidemiology.A cross-sectional survey was conducted among 143,005 individuals in Tamil Nadu, India. Participants were screened for symptoms and underwent chest X-ray (CXR). Participants with symptoms of TB and/or abnormal CXR were tested for TB using Xpert, smear, and liquid culture.The prevalence of microbiologically confirmed pulmonary TB (MCPTB) was 212 (95% CI 184-239) per 100,000 population. The prevalence-to-notification ratio (P:N) in the state was 2.05 (95% CI 1.8-2.29). Low body mass index and diabetes together had a population attributable fraction of 54.15 (95% CI 45.68-61.97). Approximately 39% of the TB cases were asymptomatic and were identified only by CXR screening. In the general population, only 26.9% sought care at a health facility among those with symptoms suggestive of TB.The programme needs to prioritise screening with CXR to potentially detect cases earlier and curtail the transmission and upscale molecular tests in the selected population to increase the yield of case finding. Innovative health education strategies must be devised to address health-seeking behaviour..

Tuberculosis is one of the oldest known diseases and it remains one of the main causes of morbidity and mortality, especially in developing countries. It is associated with social inequalities and affects different age groups. Tuberculosis in children and adolescents should be considered a sentinel event, since it is linked to a recent infection through contact with bacilliferous adults. We report an immunocompetent 15-year-old adolescent with tuberculosis, exhibiting pulmonary, osteoarticular, and cutaneous involvement. Conventional treatment with tuberculostatic drugs for a year had satisfactory results without sequelae.

UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: LAG-3 was overexpressed in TB samples. Targeting LAG-3 may represent a potential therapeutic target for tuberculosis.

BACKGROUND: Tuberculosis is a global health problem that causes 1. 4 million deaths every year. It has been estimated that sputum smear-negative diagnosis but culture-positive pulmonary TB diagnosis contribute to 12.6% of pulmonary TB transmission. TB diagnosis by smear microscopy smear has a minimum detection limit (LOD) of 5,000 to 10,000 bacilli per milliliter (CFU/ml) of sputum result in missed cases and false positives. However, GeneXpert technology, with a LOD of 131-250 CFU/ml in sputum samples and its implementation is believe to facilitate early detection TB and drug-resistant TB case. Since 2013, Ghana health Service (GHS) introduce GeneXpert MTB/RIF diagnostic in all regional hospitals in Ghana, however no assessment of performance between microscopy and GeneXpert TB diagnosis cross the health facilities has been reported. The study compared the results of routine diagnoses of TB by microscopy and Xpert MTB from 2016 to 2020 at the Cape Coast Teaching Hospital (CCTH).
METHODS: The study compared routine microscopic and GeneXpert TB diagnosis results at the Cape Coast Teaching Hospital (CCTH) from 2016 to 2020 retrospectively. Briefly, sputum specimens were collected into 20 mL sterile screw-capped containers for each case of suspected TB infection and processed within 24 h. The samples were decontaminated using the NALC-NaOH method with the final NaOH concentration of 1%. The supernatants were discarded after the centrifuge and the remaining pellets dissolved in 1-1.5 ml of phosphate buffer saline (PBS) and used for diagnosis. A fixed smears were Ziehl-Neelsen acid-fast stain and observed under microscope and the remainings were used for GeneXpert MTB/RIF diagnosis. The data were analyze using GraphPad Prism.
RESULTS: 50.11% (48.48-51.38%) were females with an odd ratio (95% CI) of 1.004 (0.944-1.069) more likely to report to the TB clinic for suspected TB diagnosis. The smear-positive cases for the first sputum were 6.6% (5.98-7.25%), and the second sputum was 6.07% (5.45-6.73%). The Xpert MTB-RIF diagnosis detected 2.93% (10/341) (1.42-5.33%) in the first and 5.44% (16/294) (3.14-8.69%) in the second smear-negative TB samples. The prevalence of Xpert MTB-RIF across smear positive showed that males had 56.87% (178/313) and 56.15% (137/244) and females had 43.13% (135/313) and 43.85% (107/244) for the first and second sputum. Also, false negative smears were 0.18% (10/5607) for smear 1 and 0.31% (16/5126) for smear 2.
CONCLUSIONS: In conclusion, the study highlights the higher sensitivity of the GeneXpert assay compared to traditional smear microscopy for detecting MTB. The GeneXpert assay identified 10 and 16 positive MTB from smear 1 and smear 2 samples which were microscopic negative.

Objective: To explore the characteristics of adverse drug reactions during the 24-week therapy with delamanid-containing regimen for patients with multidrug-resistant and rifampicin-resistant pulmonary tuberculosis (MDR/RR-PTB). Methods: The prospective multicenter study was conducted from June 2020 to June 2023. A total of 608 eligible patients with MDR/RR-PTB were enrolled in 26 tuberculosis medical institutions in China including 364 males and 79 females, aged 39.6(19.0-68.0) years. Patients were treated with chemotherapy regimens containing delamanid. Patients were closely supervised during treatment of medication, and all adverse reactions occurring during treatment were monitored and recorded. The clinical characteristics of adverse reactions were evaluated by descriptive analysis. Chi-square test and multivariate logistic regression were used to analyze the related factors of QTcF interval prolongation (QT corrected with Fridericia\'s formula). Results: Of the 608 patients enrolled in this study, 325 patients (53.5%) reported 710 adverse events within 24 weeks of treatment. The top 6 most common complications were hematological abnormalities (143 patients, 23.5%), QT prolongation (114 patients, 18.8%), liver toxicity (85 patients, 14.0%), gastrointestinal reaction (41 patients, 6.7%), peripheral neuropathy (25 patients, 4.1%) and mental disorders (21 patients, 3.5%). The prolongation of QT interval mostly occurred in the 12th week after the first dose of medication. Serious adverse reactions occurred in 21 patients (3.5%). There were 7 patients (1.2%) with mental disorders, including 2 patients (0.3%) with severe mental disorders. Conclusions: The safety of dalamanid-based regimen in the staged treatment of MDR/RR-PTB patients was generally good, and the incidence of adverse reactions was similar to that reported in foreign studies. This study found that the incidence of QT interval prolongation in Chinese patients was higher than that reported overseas, suggesting that the monitoring of electrocardiogram should be strengthened when using drugs containing delamanid that may cause QT interval prolongation.
目的： 探讨含德拉马尼方案治疗耐多药和利福平耐药肺结核（MDR/RR-PTB）患者24周治疗过程中药物不良反应发生的特点。 方法： 前瞻性多中心研究。2020年6月至2023年6月，在全国26家结核病医疗机构纳入符合条件的MDR/RR-PTB患者608例，其中男364例，女244例，年龄39.6（19.0~68.0）岁。给予含德拉马尼的化疗方案进行治疗，全程密切督导患者服药，监测并记录治疗过程中发生的所有不良反应，通过描述性分析评价不良反应发生的临床特点，用χ2检验及多因素logistic回归分析QTcF（采用Fridericia公式校正的QT值）间期延长的相关影响因素。 结果： 纳入本研究的608例患者在24周治疗期间内共有325例（53.5%）报告了710例次不良反应。发生频率最高的前6位依次是血液系统损害（143例，23.5%）、心电图QT间期延长（114例，18.8%）、肝毒性（85例，14.0%）、胃肠道反应（41例，6.7%）、周围神经病（25例，4.1%）、精神障碍（21例，3.5%）。心电图QT间期延长大多发生在距首次服药的第12周，其中严重不良反应21例（3.5%）。精神障碍患者7例（1.2%），其中严重精神障碍者有2例（0.3%）。 结论： 含德拉马尼方案阶段性治疗MDR/RR-PTB患者的安全性总体良好，不良反应发生率与国外研究相当。研究发现我国患者人群中QT间期延长的发生率高于国外的相关报道，提示在使用含德拉马尼等可能引起QT间期延长的药物时要加强心电图的监测。.

OBJECTIVE: To evaluate cytokine profiles and interferon-gamma release assay (IGRA) for their diagnostic capabilities in the differentiation of tuberculosis (TB) from non-TB conditions, as well as smear-negative pulmonary tuberculosis (SNPT) from smear-positive pulmonary tuberculosis (SPPT).
METHODS: A total of 125 participants were included, 77 of whom had TB and 48 who didn\'t, and demographic, clinical, and laboratory data were collected, including cytokine levels and IGRA results. The TB patients were further divided into 2 subgroups: SNPT (n=42) and SPPT (n=35).
RESULTS: Compared to non-TB, the TB group had lower BMI, higher WBC, neutrophils, monocytes, ESR and CRP (p<0.05). TB patients showed higher IL-2, IL-6, IFN-γ, IL-8 (p<0.001) and higher IGRA positivity (88.3% versus [vs.] 29.2%, p<0.001). Between SNPT and SPPT, moderate effect sizes were observed for IFN-α, IL-2, IL-10, IL-8 (Cohen\'s d 0.59-0.76), with lower IGRA positivity in SNPT (81.0% vs. 97.1%, p=0.015). ROC analysis indicated IFN-α, IL-2, IL-10, IL-8 had moderate accuracy for SNPT diagnosis (AUCs 0.668-0.734), and combining these improved accuracy (AUC 0.759, 80% sensitivity, 64.2% specificity).
CONCLUSIONS: A multi-biomarker approach combining these cytokines demonstrates enhanced diagnostic accuracy for tuberculosis.