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A group of TB experts with vast clinical and epidemiological experience were drawn from a pool of doctors, epidemiologists and scientists participating in NATCON 2020 Conference in a closed-door session to discuss, highlight, and prioritize key resolutions that are most pertinent at present to eliminate TB from India and other developing countries in the Covid and post-COVID era. These Scientific experts were non-industry persons who met on 17th December, 2020 and used the prevailing scientific literature along with 2019 Joint Monitoring Mission document as a starting point of the discussion on this specific topic to build an agreement upon the resolutions. After the meeting on the virtual platform, all the attending doctors gave a set of recommendations on rebuilding TB Elimination programme in the Covid and Post-Covid era. Focused scientific roundtable discussion on rebuilding TB Elimination Post-Covid. Develop actionable recommendations for the scientific community and the government leadership to consider in moving forward. To prioritize the recommendations in the categories of Build-Prevent-Detect-Treat., (Copyright © 2021 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.)

We propose to use Twitter data as social-spatial sensors. This study deals with the question whether research papers on certain diseases are perceived by people in regions (worldwide) that are especially concerned by these diseases. Since (some) Twitter data contain location information, it is possible to spatially map the activity of Twitter users referring to certain papers (e.g., dealing with tuberculosis). The resulting maps reveal whether heavy activity on Twitter is correlated with large numbers of people having certain diseases. In this study, we focus on tuberculosis, human immunodeficiency virus (HIV), and malaria, since the World Health Organization ranks these diseases as the top three causes of death worldwide by a single infectious agent. The results of the social-spatial Twitter maps (and additionally performed regression models) reveal the usefulness of the proposed sensor approach. One receives an impression of how research papers on the diseases have been perceived by people in regions that are especially concerned by these diseases. Our study demonstrates a promising approach for using Twitter data for research evaluation purposes beyond simple counting of tweets., Competing Interests: The authors have declared that no competing interests exist.

Purpose: To evaluate the accuracy of a deep learning-based computer-aided detection (CAD) system in identifying active pulmonary tuberculosis on chest radiographs (CRs) of patients with positive interferon-gamma release assay (IGRA) results in different scenarios of clinical implementation., Materials and Methods: We collected the CRs of consecutive patients with positive IGRA results. Findings of active pulmonary tuberculosis on CRs were independently evaluated by the CAD and a thoracic radiologist, followed by interpretation using the CAD. Sensitivity and specificity were evaluated in different scenarios: (a) radiologists' interpretation, (b) radiologists' CAD-assisted interpretation, and (c) CAD-based prescreening (radiologists' interpretation for positive CAD results only). We conducted a reader test to compare the accuracy of the CAD with those of 5 radiologists., Results: Among 1780 patients (men, 53.8%; median age, 56 y), 44 (2.5%) were diagnosed with active pulmonary tuberculosis. The CAD-assisted interpretation exhibited a higher sensitivity (81.8% vs. 72.7%; P =0.046) but lower specificity than the radiologists' interpretation (84.1% vs. 85.7%; P <0.001). The CAD-based prescreening exhibited a higher specificity than the radiologists' interpretation (88.8% vs. 85.7%; P <0.001) at the same sensitivity, with a workload reduction of 85.2% (1780 to 263). In the reader test, the CAD exhibited a higher sensitivity than radiologists (72.7% vs. 59.5%; P =0.005) at the same specificity (88.0%), and CAD-assisted interpretation significantly improved the sensitivity of radiologists' interpretation (72.3%; P <0.001)., Conclusions: For identifying active pulmonary tuberculosis among patients with positive IGRA results, deep learning-based CAD can enhance the sensitivity of interpretation. CAD-based prescreening may reduce the radiologists' workload at an improved specificity., Competing Interests: E.J.H. received a research grant from Lunit Inc. outside the present study. J.G.N. received a research grant from Vuno, outside the present study. C.M.P. received a research grant from Lunit Inc. outside the present study, and holds stock of Promedius and stock options of Lunit Inc. and Coreline Soft. The remaining authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Three facts made new guidelines for tuberkulin skin-testing in Austria necessary: the low incidence of tuberculosis, the stop of routinously performed BCG-vaccination in neonates and the increasing importance of infections with atypical mycobacterials. According to analogous guidelines in Germany, Switzerland, the USA, and other countries and related to the Austrian specifities in tuberculosis situation the authors present guidelines thought as a consensus-paper of the Austrian Societies for Lung Diseases and Tuberculosis and for Pediatrics. The most essential guideline include that tuberkulin skin testing as a screening method with multiple puncture tests cannot further be recommended, and that the Mendel-Mantoux-test is the gold standard test. Only this test is sensitive and specific enough for case-finding and for giving indication to start a preventive or curative chemotherapy. The cut-off size of reactive areas for positive Mendel-Mantoux tuberculin-reaction are presented in this paper and also the consequences what is to decide in relationship to the test result.

Nanotechnology based diagnostics has provided improved tools for pathogen detection and sensitive and specific characterization of antibiotic resistance signatures. Tuberculosis (TB) is caused by members of the Mycobacterium tuberculosis Complex (MTBC) and, according to the World Health Organization, is one of the most serious infectious diseases in the world. Recent advances in molecular diagnostics of TB have improved both the detection time and sensitivity but they still require specialized technical personnel and cumbersome laboratory equipment. Diagnostics at point-of-need is crucial to TB control as it may provide rapid identification of pathogen together with the resistance profile of TB strains, originated from single nucleotide polymorphisms (SNPs) in different loci, allowing for a more accurate indication of the adequate therapy.Gold nanoparticles have been widely used in molecular diagnostics platforms. Here, we describe the use of gold nanoprobes (oligonucleotide functionalized gold nanoparticles) to be used in a non-cross-linking colorimetric method for the direct detection of specific DNA targets. Due to the remarkable optical properties of gold nanoparticles, this detection system provides colorimetric detection of the pathogen together with the potential of identification of several single nucleotide polymorphisms (SNPs) involved in TB resistance to antibiotics. For point-of-need use, we adapted this strategy to a low-cost mobile scheme using a paper based revelation platform and where the spectral signature is transposed to RGB data via a smartphone device. This way, identification of pathogen and characterization of resistance signatures is achieved at point-of-need.

This case-control study sought to confirm and investigate in more depth protective associations previously found of bovine (cattle and water buffalo) ownership with reduced risk of both pulmonary tuberculosis (PTB) and latent tuberculosis infection (LTBI) in humans. The study recruited male and female PTB cases from a diagnostic centre and a frequency-matched community-based control group in Kaski District, Nepal. Controls were tested for LTBI status and a separate nested case-control study was conducted based on LTBI status. Data were collected on participant household animal ownership. Using logistic regression, animal ownership was investigated for associations with both PTB and LTBI. Data were obtained from 570 PTB cases and 1,224 controls, the latter group providing 396 LTBI-positive and 692 LTBI-negative subjects. Results provided evidence of decreased odds of both PTB and LTBI positivity associated with owning bovines. The evidence was strongest for protection against infection, rather than activation of infection to PTB. Effects were strongest in women, who usually manage the animals in Nepal, and there were exposure-response relationships with numbers of bovines owned. Results suggest that exposure to bovines is protective against LTBI and PTB. A possible mechanism involves boosting the effect of BCG (Bacillus Calmette-Guerin) vaccination, particularly in protecting against tuberculous infection. Additional studies with more extensive data collection are needed to confirm the observed associations., (© 2021 Wiley-VCH GmbH.)

World Health Organisation recommends the practice of BCG vaccination at birth in countries which have a high incidence of tuberculosis and/or high leprosy burden. The BCG vaccination is considered safe for a competent immune system. However, in children with weakened immune systems cause of which can be primary or secondary, the vaccine may lead to side effects which can be localized or disseminated. In this study, we report a spectrum of inborn errors of immunity (IEI) commonly referred to as primary immunodeficiency disorders (PIDs) diagnosed in a large cohort of patients presenting with complications to BCG vaccination from India. Retrospective data analysis of patients referred to ICMR- National Institute of Immunohematology (ICMR-NIIH) for IEI workup between 2007 and 2019 was done. IEI was identified in n = 52/90 (57.7%) patients presenting with BCG complications. Of these, n = 13(14.4%) patients were diagnosed with severe combined immune deficiency, n = 15(16.7%) with chronic granulomatous disease, n = 19(21.1%) with Inborn errors of IFN-γ immunity, n = 4(4.4%) with Combined immunodeficiency and n = 1(1.1%) with Leucocyte Adhesion Deficiency type1. Majority of cases with BCGosis (88%) had an underlying IEI. This study strongly highlights the need for evaluation of patients with BCG complications for underlying IEI. While disseminated BCGosis strongly predicts underlying IEI, even localized persistent adenitis may be a warning sign of underlying IEI. It is also strongly recommended to record a family history of previous sibling death prior to administration of this live vaccine and deferring live vaccine till the diagnosis of IEI is ruled out in cases with a positive family history., (© 2020 The Scandinavian Foundation for Immunology.)

Purpose: We aim to accurately differentiate between active pulmonary tuberculosis (TB) and lung cancer (LC) based on radiomics and semantic features as extracted from pre-treatment positron emission tomography/X-ray computed tomography (PET/CT) images., Procedures: A total of 174 patients (77/97 pulmonary TB/LC as confirmed by pathology) were retrospectively selected, with 122 in the training cohort and 52 in the validation cohort. Four hundred eighty-seven radiomics features were initially extracted to quantify phenotypic characteristics of the lesion region in both PET and CT images. Eleven semantic features were additionally defined by two experienced nuclear medicine physicians. Feature selection was performed in 5 steps to enable derivation of robust and effective signatures. Multivariable logistic regression analysis was subsequently used to develop a radiomics nomogram. The calibration, discrimination, and clinical usefulness of the nomogram were evaluated in both the training and independent validation cohorts., Results: The individualized radiomics nomogram, which combined PET/CT radiomics signature with semantic features, demonstrated good calibration and significantly improved the diagnostic performance with respect to the semantic model alone or PET/CT signature alone in training cohort (AUC 0.97 vs. 0.94 or 0.91, p = 0.0392 or 0.0056), whereas did not significantly improve the performance in validation cohort (AUC 0.93 vs. 0.89 or 0.91, p = 0.3098 or 0.3323)., Conclusion: The radiomics nomogram showed potential for individualized differential diagnosis between solid active pulmonary TB and solid LC, although the improvement of performance was not significant relative to semantic model.

This paper presents a novel multi-scale attention residual network (MAResNet) for diagnosing patients with pulmonary tuberculosis (PTB) by computed tomography (CT) images. First, a three-dimensional (3D) network structure is applied in MAResNet based on the continuity and correlation of nodal features on different slices of CT images. Secondly, MAResNet incorporates the residual module and Convolutional Block Attention Module (CBAM) to reuse the shallow features of CT images and focus on key features to enhance the feature distinguishability of images. In addition, multi-scale inputs can increase the global receptive field of the network, extract the location information of PTB, and capture the local details of nodules. The expression ability of both high-level and low-level semantic information in the network can also be enhanced. The proposed MAResNet shows excellent results, with overall 94% accuracy in PTB classification. MAResNet based on 3D CT images can assist doctors make more accurate diagnosis of PTB and alleviate the burden of manual screening. In the experiment, a called Grad-CAM was employed to enhance the class activation mapping (CAM) technique for analyzing the model's output, which can identify lesions in important parts of the lungs and make transparent decisions., (© 2024. International Federation for Medical and Biological Engineering.)

Pulmonary tuberculosis (PTB) stands as a significant and prevalent infectious disease in China. Integrating 13 natural and socioeconomic factors, we conduct nine machine learning (ML) models alongside the Tree-Structured Parzen Estimator to predict the monthly PTB incidence rate from 2013 to 2019 in mainland China. With explainable ML techniques, our research highlights that population size, per capita GDP, and PM 10 concentration emerge as the primary determinants influencing the PTB incidence rate. We delineate both the independent and interactive impacts of these factors on the PTB incidence rate. Furthermore, crucial thresholds associated with factors influencing the PTB incidence rate are identified. Taking factors that have a positive effect on reducing the incidence rate of PTB as an example, the thresholds at which the effects of factors PM 2.5 , PM 10 , O 3 , and RH on the incidence rate change from increase to decrease are 105.5 µg/m3, 75.5 µg/m3, 90.8 µg/m3, and 72.3 % respectively. Our work will contribute valuable insights for public health interventions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Tuberculosis (TB) is a serious health issue that contributes to millions of deaths throughout the world and increases the threat of serious pulmonary infections in patients with respiratory illness. Delamanid is a novel drug approved in 2014 to deal with multi-drug resistant TB (MDR-TB). Despite its high efficiency in TB treatment, delamanid poses delivery challenges due to poor water solubility leading to inadequate absorption upon oral administration. This study involves the development of novel formulation-based pressurized metered dose inhalers (pMDIs) containing self-microemulsifying mixtures of delamanid for efficient delivery to the lungs. To identify the appropriate self-microemulsifying formulations, ternary diagrams were plotted using different combinations of surfactant to co-surfactant ratios (1:1, 2:1, and 3:1). The combinations used Cremophor RH40, Poly Ethylene Glycol 400 (PEG 400), and peppermint oil, and those that showed the maximum microemulsion region and rapid and stable emulsification were selected for further characterization. The diluted self-microemulsifying mixtures underwent evaluation of dose uniformity, droplet size, zeta potential, and transmission electron microscopy. The selected formulations exhibited uniform delivery of the dose throughout the canister life, along with droplet sizes and zeta potentials that ranged from 24.74 to 88.99 nm and - 19.27 to - 10.00 mV, respectively. The aerosol performance of each self-microemulsifying drug delivery system (SMEDDS)-pMDI was assessed using the Next Generation Impactor, which indicated their capability to deliver the drug to the deeper areas of the lungs. In vitro cytotoxicity testing on A549 and NCI-H358 cells revealed no significant signs of toxicity up to a concentration of 1.56 µg/mL. The antimycobacterial activity of the formulations was evaluated against Mycobacterium bovis using flow cytometry analysis, which showed complete inhibition by day 5 with a minimum bactericidal concentration of 0.313 µg/mL. Moreover, the cellular uptake studies showed efficient delivery of the formulations inside macrophage cells, which indicated the potential for intracellular antimycobacterial activity. These findings demonstrated the potential of the Delamanid-SMEDDS-pMDI for efficient pulmonary delivery of delamanid to improve its effectiveness in the treatment of multi-drug resistant pulmonary TB., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Tuberculosis (TB) remains a major global public health problem worldwide. Though Pulmonary TB (PTB) is mostly discussed, one in five cases of TB present are extrapulmonary TB (EPTB) that manifests conspicuous diagnostic and management challenges with respect to the site of infection. The diagnosis of EPTB is often delayed or even missed due to insidious clinical presentation, pauci-bacillary nature of the disease, and lack of laboratory facilities in the resource limited settings. Culture, the classical gold standard for the diagnosis of tuberculosis, suffers from increased technical and logistical constraints in EPTB cases. Other than culture, several other tests are available but their feasibility and effciacy for the detection of EPTB is still the matter of interest. We need more specific and precise test/s for the various forms of EPTB diagnosis which can easily be applied in the routine TB control program is required. A test that can contribute remarkably towards improving EPTB case detection reducing the morbidity and mortality is the utmost requirement. In this review we described the scenario of molecular and other noval methods available for laboratory diagnosis of EPTB, and also discussed the challenges linked with each diagnostic method. This review will make the readers aware of new emerging diagnostic techniques in the field of EPTB diagnosis. They can make an informed decision to choose the appropriate one according to the test availability, their clinical settings and financial considerations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

In recent decades, many studies have been published on the use of automatic smear microscopy for diagnosing pulmonary tuberculosis (TB). Most of them deal with a preliminary step of the diagnosis, the bacilli detection, whereas sputum smear microscopy for diagnosis of pulmonary TB comprises detecting and reporting the number of bacilli found in at least 100 microscopic fields, according to the 5 grading scales (negative, scanty, 1+, 2+ and 3+) endorsed by the World Health Organization (WHO). Pulmonary TB diagnosis in bright-field smear microscopy, however, depends upon the attention of a trained and motivated technician, while the automated TB diagnosis requires little or no interpretation by a technician. As far as we know, this work proposes the first automatic method for pulmonary TB diagnosis in bright-field smear microscopy, according to the WHO recommendations. The proposed method comprises a semantic segmentation step, using a deep neural network, followed by a filtering step aiming to reduce the number of false positives (false bacilli): color and shape filtering. In semantic segmentation, different configurations of encoders are evaluated, using depth-wise separable convolution layers and channel attention mechanism. The proposed method was evaluated with a large, robust, and annotated image dataset designed for this purpose, consisting of 250 testing sets, 50 sets for each of the 5 TB diagnostic classes. The following performance metrics were obtained for automatic pulmonary TB diagnosis by smear microscopy: mean precision of 0.894, mean recall of 0.896, and mean F1-score of 0.895., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Cicero Ferreira Fernandes Costa Filho reports financial support was provided by Samsung Electronics of Amazonia Ltda. Marly Guimaraes Fernandes Costa reports financial support was provided by Samsung Electronics of Amazonia Ltda. Mikaela Kalline Serrao reports financial support was provided by Samsung Electronics of Amazonia Ltda. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Traditional methods for monitoring pulmonary tuberculosis (PTB) treatment efficacy lack sensitivity, prompting the exploration of artificial intelligence (AI) to enhance monitoring. This review investigates the application of AI in monitoring anti-tuberculosis (ATTB) treatment, revealing its potential in predicting treatment duration, adverse reactions, outcomes, and drug resistance. It provides important insights into the potential of AI technology to enhance monitoring and management of ATTB treatment. Systematic search across six databases from 2013 to 2023 explored AI in forecasting PTB treatment efficacy. Support vector machine and convolutional neural network excel in treatment duration prediction, while random forest, artificial neural network, and classification and regression tree show promise in forecasting adverse reactions and outcomes. Neural networks and random forest are effective in predicting drug resistance. AI advancements offer improved monitoring strategies, better patient prognosis, and pave the way for future AI research in PTB treatment monitoring., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. Yu Pang reports financial support was provided by Beijing Hospitals Authority Ascent Plan. Liang Li reports financial support was provided by Beijing Hospitals Authority Ascent Plan. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Pulmonary Tuberculosis (PTB) is an infectious disease caused by a bacterium called Mycobacterium tuberculosis. This paper aims to create Symbolic Artificial Intelligence (SAI) system to diagnose PTB using clinical and paraclinical data. Usually, the automatic PTB diagnosis is based on either microbiological tests or lung X-rays. It is challenging to identify PTB accurately due to similarities with other diseases in the lungs. X-ray alone is not sufficient to diagnose PTB. Therefore, it is crucial to implement a system that can diagnose based on all paraclinical data. Thus, we propose in this paper a new PTB ontology that stores all paraclinical tests and clinical symptoms. Our SAI system includes domain ontology and a knowledge base with performance indicators and proposes a solution to diagnose current and future PTB also abnormal patients. Our approach is based on a real database of more than four years from our collaborators at Pondicherry hospital in India.

Increased susceptibility to bacterial infections like tuberculosis (TB) is one of the complications of type 2 diabetes, however the underlying mechanisms remains poorly characterized. To explore how chronic hyperglycemia in diabetes affects progression of active TB, we examined mRNA expression of M1 (proinflammatory) and M2 (anti-inflammatory) cytokines/markers, in monocyte-derived macrophages obtained from patients with PTB + DM (pulmonary TB + diabetes mellitus type 2), patients with DM alone, patients with PTB alone, and healthy individuals (controls). Our findings indicate a dysregulated cytokine response in patients with both PTB and DM, characterized by decreased expression levels of interferon-gamma (IFN-γ) and inducible nitric oxide synthase (iNOS), along with increased expression levels of interleukin-1 beta (IL-1β) and CD206. Furthermore, we observed a positive correlation of IL-1β and CD206 expression with levels of glycosylated hemoglobin (HbA1c) in both PTB + DM and DM groups, while IFN-γ showed a positive correlation with HbA1c levels, specifically in the PTB + DM group. Additionally, M1 cytokines/markers, IL-1β and iNOS were found to be significantly associated with the extent of sputum positivity in both PTB and PTB + DM groups, suggesting it to be a function of increased bacterial load and hence severity of infection. Our data demonstrates that tuberculosis in individuals with PTB + DM is characterized by altered M1/M2 cytokine responses, indicating that chronic inflammation associated with type 2 diabetes may contribute to increased immune pathology and inadequate control of tuberculosis infection., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Introduction: The intensity of exposure to index cases of tuberculosis [TB] may increase the risk of TB in their contacts. The aim was to determine TB risk factors among contacts of TB index cases., Methods: A cohort study was carried out in the contacts of pulmonary TB cases registered by the epidemiological surveillance network from 01/01/2019 to 06/30/2021. The factors associated with the risk of TB in contacts were determined using the adjusted odds ratio [aOR] and its 95% confidence interval [CI]., Results: From 847 TB cases, 7087 contacts were identified. The prevalence of TB was 2.0% [145/7087] and was higher in < 5 years compared to those ≥ 65 years [4.4% versus 1.2%; p < 0.001], in those exposed ≥ 6 h daily [4%], and < 6 h daily [1.6%] with respect to weekly exposure of < 6 h [0.7%; p < 0.001]. Those contacts exposed ≥ 6 h daily [aOR= 6.9; 95%CI:2.1-22.1], < 5 years [aOR= 8.3; 95%CI:1.8-37.8] and immigrants [aOR= 1.7; 95%CI:1.1-2.7] had a higher risk of TB., Conclusions: The risk of TB increases with the time of exposure to the index case and this risk is also higher in < 5 years and immigrants. Contact tracing has a high yield for detecting new cases of TB., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Mycobacterium microti is a member of the Mycobacterium tuberculosis complex that seldom causes disease in livestock and humans. This study evaluated the effects on immunodiagnosis and the pathological findings in goats after experimental exposure by different routes and doses to M. microti. In a first experiment goats were challenged orally (PO, n = 7) or intranasally (IN, n = 7) with 10 4 CFU. In a second experiment, the endobronchial route was assessed, with a low dose of 10 2 CFU (EB-LD, n = 7) and a high dose of 10 5 CFU (EB-HD, n = 7) as well as the subcutaneous route (SC, n = 5). Temperature, body weight, clinical signs and immunological responses were monitored. Pathological evaluation was carried out and samples were processed for mycobacterial detection. RESULTS: demonstrated the induction of a subclinical pulmonary infection in all the EB-HD challenged animals. Infection was also confirmed in one animal of the SC group, but not in the EB-LD, PO or IN groups. Two animals belonging to the EB-HD and SC groups, respectively, showed positive results to the single intradermal tuberculin test, and another two animals of the EB-HD and EB-LD groups showed doubtful (inconclusive) results, indicating that M. microti can induce mild responses to tuberculin skin testing. No positive results were observed when defined antigens absent in M. microti (ESAT-6 and CPF-10) were used. Our results indicate that animals exposed to M. microti can yield positive results to the skin tests currently performed in livestock tuberculosis eradication campaigns and reinforce the need to use specific antigens in antemortem tests to avoid interference with M. bovis/M. caprae diagnosis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction and Objectives: Excessive delay in the diagnosis of Tuberculosis may have a negative impact on the epidemiological control and elimination of this disease. An accurate determination and analysis of delay times may help identify where and how to improve Tuberculosis diagnosis according to local needs. The Portuguese Tuberculosis Surveillance System - SVIG-TB - is the main source of data regarding diagnosis delay. However, to our knowledge, there has been no recent evaluation of its data. This study's primary aim was to conduct a thorough quantitative and qualitative evaluation of data obtained from the SVIG-TB registry concerning the delay in Tuberculosis diagnosis in Matosinhos, a Portuguese municipality., Methods: All patients living in the Matosinhos municipality diagnosed with Tuberculosis between January 1 st 2012 and December 31 st 2019 were identified and individual SVIG-TB records retrieved. Patient-related, Healthcare-related and Total delay in Tuberculosis diagnosis were determined based on data obtained from this source and compared to data recovered from patient record review. Missing data, registering errors and differences in diagnosis delay between these two sources were analysed and compared. Subsequently, diagnosis delay data from a recent Portuguese nationwide SVIG-TB paper, covering years 2010 to 2014, was compared to local SVIG-TB and patient record review data., Results: This study identified a significantly greater percentage of cases with missing data on delay in SVIG-TB records when compared to Patient Record Review (57.2% versus 1.11%). The median patient-related, healthcare-related and Total delay in Tuberculosis diagnosis were of 17, 30 and 68 days, respectively, in the SVIG-TB based data. A significant underestimation of healthcare-related and total Tuberculosis diagnosis delay was identified in SVIG-TB data when compared to Patient Record Review. There was no significant difference between Patient-related delays determined from these two sources. Compared to the national study results, missing values were more common in this data set (57.2 vs 44.6%), mainly due to the absence of patient-related delay data. Median Total and Healthcare-related delays were significantly greater in Matosinhos Municipality, regardless of the data source (SVIG-TB or Patient Record Review). The patient-related delay was, conversely, shorter., Conclusions: SVIG-TB has been crucial in guiding National Public Health policies on the path towards Tuberculosis elimination in Portugal. However, there is still room for improvement. These results provide a basis for further reflection on the shortcomings and potential of SVIG-TB in guiding the national Tuberculosis program., (Copyright © 2021 Sociedade Portuguesa de Pneumologia. Published by Elsevier España, S.L.U. All rights reserved.)

The purposes of this study were to construct a comprehensive nomogram for providing a simple, precise and personalized prediction of incident multidrug-resistant tuberculosis (MDR-TB) after completing pulmonary tuberculosis treatment (CPTBT). A matched case-control study (1:2 ratios) was performed between 2005 and 2018. A multivariable Cox regression analysis was used to evaluate independent predictors of incident MDR-TB after the CPTBT. A comprehensive nomogram was developed based on the multivariable Cox model. Overall, 1, 836 participants were included in this study. We developed and validated a simple-to-use nomogram that predicted the individualized risk of incident MDR-TB by using 10 parameters after the CPTBT. The concordance index of this nomogram was 0.833 [95% confidence interval (CI) 0.807-0.859] and 0.871 (95% CI 0.773-0.969) for the training and validation sets, respectively, which indicated adequate discriminatory power. The calibration curves for the risk of incident MDR-TB showed an optimal agreement between nomogram prediction and actual observation in the training and validation sets, respectively. The high sensitivity and specificity of nomogram was indicated by using a receiver operating characteristic curve analysis. Through this clinic tool, TB control executives could more precisely monitor, estimate and intervene the risk of incident MDR-TB among individuals with CPTBT.

Introduction: In sub-Saharan African (SSA) countries endemic for tuberculosis (TB), previous TB is a significant risk factor for non-tuberculous mycobacterial pulmonary disease (NTM-PD). The deployment of GeneXpert MTB/RIF in pulmonary TB diagnostic work-up regularly identifies symptomatic patients with a positive smear microscopy but negative GeneXpert, indicative of NTM presence. This scoping review outlines recent evidence for NTM-PD diagnosis and management in SSA., Objective: The review's objective was to outline the risk factors, available diagnostics, management options and outcomes of NTM-PD in high-burden TB settings in SSA using the population-concept-context framework., Design and Data Sources: We searched existing literature from PubMed, Web of Science, African Journals Online, Google Scholar and grey literature. Studies published between January 2005 and December 2022 were retained. Data were extracted into Rayyan software and Mendeley and summarised using Excel., Results: We identified 785 potential articles, of which 105 were included in the full-text review, with 7 papers retained. Included articles used international criteria for diagnosing NTM-PD. Multiple papers were excluded due to non-application of the criteria, suggesting challenging application in the SSA setting. Identified risk factors include previous TB, smoking and mining. Most commonly, chest radiography and not CT was used for the radiological diagnosis of PD, which may miss early changes related to NTM-PD. Molecular methods for NTM species identification were employed in research settings, usually at referral centres, but were unavailable for routine care. Most studies did not report a standardised approach to treatment and they were not offered treatment for the specific disease, marking a lack of guidance in treatment decision-making. When treatment was provided, the outcome was often not reported due to the lack of implementation of standardised outcome definitions., Conclusions: These outlined challenges present a unique opportunity for researchers to undertake further studies in NTM-PD and proffer solutions more applicable to SSA., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To characterise tuberculosis deaths in a region of northeast Brazil during the period from 2006 to 2017 and to identify determinants associated with areas with higher tuberculosis mortality rates., Methods: Ecological descriptive study of deaths from tuberculosis with multivariate mapping and logistic regression, carried out from 2006 to 2017 in the 75 municipalities of Sergipe, Brazil. The focus of the analysis was the mean mortality rate from tuberculosis, dichotomised according to the median. The independent variables were selected based on the conceptual model of the social determinants of health., Results: Mortality due to tuberculosis in Sergipe, Brazil, was most prevalent among males, mixed-race people, and people over 40 years old and with a low level of education. Multivariate logistic regression identified the mean incidence rate for tuberculosis (aOR: 1.06), the proportion of HIV testing (aOR: 7.10), people without primary education and with informal occupation (aOR: 1.26) and people living in urban households without waste collection service (aOR: 0.10) as determinants associated to municipalities with higher tuberculosis mortality rates, with area under the ROC curve of 84% (P-value 0.000). Mapping revealed evident spatial variability., Conclusions: The tuberculosis epidemic in Brazil is determined by access to health services, especially the provision of HIV testing among those diagnosed with tuberculosis, accelerated urbanisation with large pockets of poverty and unsanitary housing conditions, corroborating global trends., (© 2019 John Wiley & Sons Ltd.)

Introduction: Chronic pulmonary aspergillosis (CPA) is a debilitating disease estimated to affect over 3 million people worldwide. Pulmonary tuberculosis (PTB) is the most significant risk factor for CPA. However, the true burden of CPA at the time of PTB diagnosis, during, and after PTB treatment remains unknown. In this paper, we present a protocol for a living systematic review aimed at estimating the current burden of CPA along the continuum of PTB care., Materials and Methods: We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) guidelines to formulate this protocol, which is registered with the International Prospective Register of Systematic Reviews (PROSPERO: CRD42023453900). We will identify primary literature through various electronic databases, including CINAHL, Ovid MEDLINE, MEDLINE (PubMed), EMBASE, Google Scholar, Cochrane Database of Systematic Reviews, and African Journal Online. The search will encompass articles from inception to December 31st, 2023, using medical subject heading search terms "pulmonary tuberculosis" AND "chronic pulmonary aspergillosis". Two reviewers will independently assess titles, abstracts, and full texts for eligibility using the Covidence web-based software. The eligible studies will comprise original observational research that reports on the prevalence of CPA diagnosed in individuals with PTB, based on established criteria, without language or geographic restriction. We intend to exclude single case reports and case series with fewer than 10 participants, as well as review articles, guidelines, and letters to the editors. Cochrane Risk of Bias Tools (ROB2 and ROBINS-I) will used to assess study quality and risk of bias and the quality of the evidence will be rated using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) tool. Our data syntheses will encompass meta-analysis and meta-regression, conducted using STATA version 18 and R- Studio version 4.0.2. This systematic review will be updated every 3-5 years as more data emerges., Conclusions: The findings of this proposed systematic review will summarize the available evidence on the occurrence of CPA, at the time of PTB diagnosis, during and after PTB treatment. The study results have the potential to guide healthcare policies regarding screening for CPA, enhance clinical decision-making, and catalyse further research into understanding the interplay between PTB and CPA. By shedding light on the current burden of CPA along the continuum of PTB care, we aspire to contribute to the betterment of patient care, disease management, and global health outcomes., Prospero Registration: CRD42023453900., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Bongomin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Bacillus Calmette-Guérin (BCG) remains the only licensed vaccine against human tuberculosis (TB). BCG is a live-attenuated strain of Mycobacterium bovis, with limitations in efficacy against respiratory TB, the most common form of the disease responsible for transmission. However, continues to be used in the immunization programmes of different countries in the absence of another alternative. In order to improve BCG efficacy against pulmonary TB, in the current clinical TB vaccine pipeline, there are live-attenuated TB vaccines to replace BCG. This review discusses the current status of the development of live vaccine candidates designed to replace BCG from the rational strategies and immunological challenges to its clinical trial and identify key areas in the next years considered essential to confer improved safety and efficacy over BCG., (© 2019 The Foundation for the Scandinavian Journal of Immunology.)