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Objectives: This study aims to develop a novel diagnostic approach using the recombinase aided amplification-lateral flow dipstick(RAA-LFD) assay for the distinction of Mycobacterium tuberculosis (MTB) and Mycobacterium avium complex (MAC), enabling rapid and convenient as well as accurate identification of them in clinical samples. Methods: Our study established a duplex RAA-LFD assay capable of discriminating between MTB and MAC. Based on the principles of RAA primer and probe design, specific primers and probes were developed targeting the MTB IS6110 and the MAC DT1 separately. Optimization of reaction time points and temperatures was conducted, followed by an evaluation of specificity, sensitivity, and reproducibility. The established detection method was then applied to clinical samples and compared with smear microscopy, liquid culture, LAMP, and Xpert/MTB RIF in terms of diagnostic performance. Results: The complete workflow allows for the effective amplification of the MTB IS6110 and MAC DT1 target sequences at constant 37°C within 20min, and the amplification products can be visually observed on the LFD test strip. This method exhibits high specificity, showing no cross-reactivity with nucleic acids from M. kansassi, M. abscessus, M. gordonae, M. chelonae, M. fortuitum, M. scrofulaceum, M. malmoense, M. chimaera, M. szulgai and common respiratory pathogens. It also demonstrates high sensitivity, with a detection limit as low as 102 CFU/mL. Additionally, the method's Coefficient of Variation (CV) is less than 5%, ensuring excellent repeatability and reliability. Furthermore, clinical performance evaluations, using Xpert/MTB RIF as the gold standard, demonstrated that the duplex RAA-LFD assay achieves a sensitivity of 92.86% and a specificity of 93.75%. It is also noteworthy that the assay exhibits considerable diagnostic efficacy in smear-negative patients. Conclusions: Our study introduces a rapid, specific, and sensitive duplex RAA-LFD assay for the discriminatory diagnosis of MTB and MAC. This method represents a significant advancement in the field of infectious disease diagnostics, offering a valuable tool for rapid detection and management of MTB and MAC infections. The implementation of this approach in point-of-care settings could greatly enhance TB control and prevention efforts, especially in resource-limited environments.
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Complexo Mycobacterium avium , Mycobacterium tuberculosis , Técnicas de Amplificação de Ácido Nucleico , Sensibilidade e Especificidade , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/isolamento & purificação , Técnicas de Amplificação de Ácido Nucleico/métodos , Complexo Mycobacterium avium/genética , Complexo Mycobacterium avium/isolamento & purificação , Humanos , Reprodutibilidade dos Testes , Técnicas de Diagnóstico Molecular/métodos , Tuberculose/diagnóstico , Tuberculose/microbiologia , Recombinases/metabolismo , DNA Bacteriano/genética , Infecção por Mycobacterium avium-intracellulare/diagnóstico , Infecção por Mycobacterium avium-intracellulare/microbiologia , Primers do DNA/genéticaRESUMO
Tuberculosis (TB) remains a major global health problem, and there is an urgent need for rapid, sensitive, and easy-to-use diagnostic technologies to improve TB diagnosis. In this study, we developed the nested multi-enzyme isothermal rapid amplification (nestMIRA) assay for TB. We designed several pairs of primers and probes targeting the IS6110 sequence of Mycobacterium tuberculosis (Mtb) and performed combinatorial testing to optimize the performance of the TB nestMIRA assay. The reaction can be performed at a constant temperature of approximately 40°C and completed within 30 minutes in the same tube without opening the central cap. There has been no cross-reactivity with common non-tuberculous mycobacteria (NTB) and respiratory pathogens. The TB nestMIRA assay has a minimum detection limit of 5 copies/µL for H37Rv genomic DNA and a limit of quantification of 100 CFU/ml. To test the diagnostic performance of the TB nestMIRA assay, we conducted a 163-person clinical cohort study using comprehensive reference standards as the gold standard for clinical diagnosis. Our study showed that TB nestMIRA performed slightly better than GeneXpert MTB/RIF (Xpert) (85.27% vs. 82.17%) and significantly better than culture (55.81%) and acid-fast bacillus (AFB) smear (38.76%). The TB nestMIRA assay offers speed, specificity, sensitivity, and convenience. We believe that it has the potential to be a rapid alternative for TB diagnosis, particularly in resource-limited settings. IMPORTANCE: In this study, we have successfully developed a method called nested multi-enzyme isothermal rapid amplification (nestMIRA) for the detection of Mycobacterium tuberculosis (Mtb). This method involves a two-step thermostatic amplification process in the same tube and can be read using fluorescence and lateral flow dipstick (LFD) assays. It is known to be rapid, specific, and highly sensitive. Our method has shown promising results in the detection of clinical specimens, and we believe that it can be a valuable tool for the rapid detection of Mtb in a clinical setting.
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The development of an affordable chemiresistive biosensor enhanced with a multi-walled carbon nanotube-zinc oxide (MWCNT-ZnO) nanofiber composite is presented. The sensor leverages the precise interaction between lipoarabinomannan (LAM) tuberculosis (TB) antigens and antibodies to achieve high sensitivity and specificity. The MWCNT-ZnO nanofibers have a larger surface area and better electrical conductivity, which makes it easier for TB antibodies to stick to them. The binding of LAM TB antigens to the fixed Monoclonal Antibody-MBS320597 induces significant resistance changes in the chemiresistive sensor, enabling accurate TB detection. Performance evaluation reveals a linear detection range from 1.0 to 100.0 pg/mL in the lower concentration range and up to 6.0 ng/mL in the higher concentration range, with a sensitivity of 79.750 mA pg mL-1 cm-2 and a lower limit of detection of 40.54 fg/mL. The sensor exhibits a response time of 102 s. Featuring rapid response time and high sensitivity, this biosensor is ideally suited for point-of-care (PoC) applications. The incorporation of MWCNT-ZnO nanofibers shows great potential for enhancing the development of sensitive and cost-effective TB diagnostic tools, which could play a crucial role in advancing global TB control and management efforts.
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Técnicas Biossensoriais , Lipopolissacarídeos , Nanofibras , Nanotubos de Carbono , Tuberculose , Óxido de Zinco , Óxido de Zinco/química , Técnicas Biossensoriais/métodos , Nanofibras/química , Lipopolissacarídeos/análise , Lipopolissacarídeos/química , Humanos , Nanotubos de Carbono/química , Tuberculose/diagnóstico , Antígenos de Bactérias/imunologia , Antígenos de Bactérias/análise , Limite de Detecção , Mycobacterium tuberculosis/imunologia , Anticorpos Imobilizados/imunologiaRESUMO
Host-directed therapies (HDT) via modulation of specific host responses like inflammation can limit mycobacterial infection. HDTs could be included in current TB therapy as an adjunct to increase bacterial clearance and limit tissue damage to control spread. Individually, Mycobacterium indicus pranii (MIP) and human beta defensin-2 (hBD-2) are promising therapies for tuberculosis (TB). They can directly target the TB bacilli and enhance cell-mediated immune responses, which is limiting with conventional drugs. Therefore, our study investigated the combined application of MIP and hBD-2 to evaluate their efficacy in clearing infections caused by Mycobacterium smegmatis (M.smeg) and Mycobacterium tuberculosis (M.tb) (both avirulent; H37Ra and virulent strain; H37Rv) in THP-1 cells and human monocyte-derived macrophages (MDMs). A strong pro-inflammatory response was observed against the combination of MIP and hBD-2 which also correlated with a significant reduction in the bacterial load. This combination further showed protection against M.tb by enhancing pyroptosis in the infected cells. The study suggests the combined use of these potent immunomodulators, which could be employed as an effective mode of therapy as adjuvants against mycobacterial infections after validation in a suitable animal model.
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Silico-Tuberculosis (silico-TB) is a severe combination of tuberculosis and silicosis, caused by occupational exposure to fine crystalline silica dust, which has become a global health concern. This comprehensive review compiles the updated knowledge regarding pathophysiology, clinical manifestations, important diagnostic techniques, treatment aspects, and challenges in understanding silico-TB. The review compiles the disease's history and epidemiology, highlighting a lack of data owing to poor monitoring and healthcare particularly in low- and middle-income countries like India. Further weak safety regulations, lack of preventative measures, and inadequate education increase the rates of silico-TB. The pathophysiology shows how silica particles impair the immune system and stimulate Th2 cells and M2 macrophages, which exacerbate TB, while inhibiting Th1 cells and M1 macrophages, which fight against the disease. Subsequently, it can be difficult to distinguish current TB from pre-existing silicosis. In cases where sputum and X-ray results are negative, chest CT scans may be helpful since radiographic screening identifies TB earlier than sputum assessment. Isoniazid, rifampicin, or both minimize the risk of active tuberculosis in people with silicosis. Consistent anti-tuberculosis drug therapy is recommended for 8-9 months to stop recurrence. The assessment recommends integrating silicosis and TB control initiatives to fight this combined health issue.
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Silicose , Humanos , Silicose/diagnóstico , Antituberculosos/uso terapêutico , Antituberculosos/efeitos adversos , Exposição Ocupacional/efeitos adversos , Índia/epidemiologia , Silicotuberculose/diagnósticoRESUMO
Background: To effectively control tuberculosis (TB), it is crucial to distinguish between active TB disease and latent TB infection (LTBI) to provide appropriate treatment. However, no such tests are currently available. Immune responses associated with active TB and LTBI are dynamic and exhibit distinct patterns. Comparing these differences is crucial for developing new diagnostic methods and understanding the etiology of TB. This study aimed to investigate the relationship between pro- and anti-inflammatory CD4+ cytokine production following stimulation with two types of latency-associated Mycobacterium tuberculosis (M.tb) antigens to allow differentiation between active TB and LTBI. Methods: Cryopreserved PBMCs from patients with active TB disease or LTBI were stimulated overnight with replication-related antigen [ESAT-6/CFP-10 (E/C)] or two latency-associated antigens [heparin-binding hemagglutinin (HBHA) and alpha-crystallin-like protein (Acr)]. Responses were analyzed using multiparameter flow cytometry: active TB disease (n=15), LTBI (n=15) and ELISA: active TB disease (n=26) or LTBI (n=27). Results: CD4+ central memory T cells (Tcm) specific to E/C and CD4+ effector memory T cells specific to Acr and HBHA were higher in LTBI than in TB patients. IFN-γ+Tcm and IL-17+ Tem cells was higher in the LTBI group (p= 0.012 and p=0.029 respectively), but IL-10+ Tcm was higher in the active TB group (p= 0.029) following HBHA stimulation. Additionally, following stimulation with HBHA, IL-10 production from CD4+ T cells was significantly elevated in patients with active TB compared to those with LTBI (p= 0.0038), while CD4+ T cell production of IL-17 and IFN-γ was significantly elevated in LTBI compared to active TB (p= 0.0076, p< 0.0001, respectively). HBHA also induced more CCR6+IL-17+CD4Tcells and IL-17+FoxP3+CD25+CD4Tcells in LTBI than in TB patients (P=0.026 and P=0.04, respectively). HBHA also induced higher levels of IFN-γ+IL-10+CD4+ T cells in patients with active TB (Pp=0.03) and higher levels of IFN-γ+IL-17+ CD4+ T cells in those with LTBI (p=0.04). HBHA-specific cytokine production measured using ELISA showed higher levels of IFN-γ in participants with LTBI (P=0.004) and higher levels of IL-10 in those with active TB (P=0.04). Conclusion: Stimulation with HBHA and measurement of CD4+ T cell production of IFN-γ, IL-10, and IL-17 could potentially differentiate active TB from LTBI. The characteristics of cytokine-expressing cells induced by HBHA also differed between participants with active TB and LTBI.
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Antígenos de Bactérias , Linfócitos T CD4-Positivos , Interferon gama , Interleucina-10 , Interleucina-17 , Tuberculose Latente , Mycobacterium tuberculosis , Tuberculose , Humanos , Masculino , Feminino , Linfócitos T CD4-Positivos/imunologia , Adulto , Interleucina-17/imunologia , Interleucina-17/metabolismo , Mycobacterium tuberculosis/imunologia , Interleucina-10/imunologia , Interferon gama/metabolismo , Interferon gama/imunologia , Pessoa de Meia-Idade , Tuberculose Latente/imunologia , Tuberculose/imunologia , Antígenos de Bactérias/imunologia , Idoso , Adulto Jovem , LectinasRESUMO
Tuberculous infection of the extrapulmonary sites, especially the small bones, is a seldom reported entity even in endemic countries. Moreover, simultaneous involvement of the forearm muscles is a very rare presentation with no such case reported showing concurrent involvement of the two sites. The diagnosis is challenging due to the paucibacillary nature of the disease, a lack of awareness among primary clinicians, and ambiguity in clinical features with other musculoskeletal disorders, especially when there is no pulmonary involvement. Herein, we present a first-of-its-type case of spina ventosa of the left ring finger with a tuberculous abscess in the forearm in a 15-year-old Indian male with no pulmonary seeding. The diagnosis was achieved through a detailed diagnostic workup, which resulted in the detection of Mycobacterium tuberculosis. He was initiated on antituberculous treatment with a remarkable improvement.
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Tuberculosis (T.B.) remains a prominent global cause of health challenges and death, exacerbated by drug-resistant strains such as multidrug-resistant tuberculosis MDR-TB and extensively drug-resistant tuberculosis XDR-TB. For an effective disease management strategy, it is crucial to understand the dynamics of T.B. infection and the impacts of treatment. In the present article, we employ AI-based machine learning techniques to investigate the immunity impact of medications. SEIPR epidemiological model is incorporated with MDR-TB for compartments susceptible to disease, exposed to risk, infected ones, preventive or resistant to initial treatment, and recovered or healed population. These masses' natural trends, effects, and interactions are formulated and described in the present study. Computations and stability analysis are conducted upon endemic and disease-free equilibria in the present model for their global scenario. Both numerical and AI-based nonlinear autoregressive exogenous NARX analyses are presented with incorporating immediate treatment and delay in treatment. This study shows that the active patients and MDR-TB, both strains, exist because of the absence of permanent immunity to T.B. Furthermore, patients who have recovered from tuberculosis may become susceptible again by losing their immunity and contributing to transmission again. This article aims to identify patterns and predictors of treatment success. The findings from this research can contribute to developing more effective tuberculosis interventions.
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Antituberculosos , Aprendizado de Máquina , Tuberculose Resistente a Múltiplos Medicamentos , Humanos , Antituberculosos/uso terapêutico , Antituberculosos/farmacologia , Tuberculose Resistente a Múltiplos Medicamentos/imunologia , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose/imunologia , Tuberculose/microbiologia , Tuberculose/tratamento farmacológico , Mycobacterium tuberculosis/imunologia , Tuberculose Extensivamente Resistente a Medicamentos/imunologiaRESUMO
Tuberculosis (TB) is a grave public health concern and is considered the foremost contributor to human mortality resulting from infectious disease. Due to the stringent clonality and extremely restricted genomic diversity, conventional methods prove inefficient for in-depth exploration of minor genomic variations and the evolutionary dynamics operating in Mycobacterium tuberculosis (M.tb) populations. Until now, the majority of reviews have primarily focused on delineating the application of whole-genome sequencing (WGS) in predicting antibiotic resistant genes, surveillance of drug resistance strains, and M.tb lineage classifications. Despite the growing use of next generation sequencing (NGS) and WGS analysis in TB research, there are limited studies that provide a comprehensive summary of there role in studying macroevolution, minor genetic variations, assessing mixed TB infections, and tracking transmission networks at an individual level. This highlights the need for systematic effort to fully explore the potential of WGS and its associated tools in advancing our understanding of TB epidemiology and disease transmission. We delve into the recent bioinformatics pipelines and NGS strategies that leverage various genetic features and simultaneous exploration of host-pathogen protein expression profile to decipher the genetic heterogeneity and host-pathogen interaction dynamics of the M.tb infections. This review highlights the potential benefits and limitations of NGS and bioinformatics tools and discusses their role in TB detection and epidemiology. Overall, this review could be a valuable resource for researchers and clinicians interested in NGS-based approaches in TB research.
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Genômica , Sequenciamento de Nucleotídeos em Larga Escala , Mycobacterium tuberculosis , Tuberculose , Mycobacterium tuberculosis/genética , Humanos , Tuberculose/microbiologia , Sequenciamento Completo do Genoma , Genoma Bacteriano , Biologia Computacional/métodos , Interações Hospedeiro-PatógenoRESUMO
The final step of epigenetic processes is changing the gene expression in a new microenvironment in the body, such as neuroendocrine changes, active infections, oncogenes, or chemical agents. The case of tuberculosis (TB) is an outcome of Mycobacterium tuberculosis (M.tb) and host interaction in the manifestation of active and latent TB or clearance. This comprehensive review explains and interprets the epigenetics findings regarding gene expressions on the host-pathogen interactions in the development and progression of tuberculosis. This review introduces novel insights into the complicated host-pathogen interactions, discusses the challengeable results, and shows the gaps in the clear understanding of M.tb behavior. Focusing on the biological phenomena of host-pathogen interactions, the epigenetic changes, and their outcomes provides a promising future for developing effective TB immunotherapies when converting gene expression toward appropriate host immune responses gradually becomes attainable. Overall, this review may shed light on the dark sides of TB pathogenesis as a life-threatening disease. Therefore, it may support effective planning and implementation of epigenetics approaches for introducing proper therapies or effective vaccines.
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Tuberculosis of the long bones/femur, especially in an immunocompetent person, is a challenging diagnosis. It is a rare entity, even in endemic settings. The non-specific clinical features, backed by a low suspicion about such presentations even in endemic settings, may result in delayed diagnosis and often unfavorable treatment outcomes. The situation becomes even more challenging in the absence of pulmonary foci and a contact history of tuberculosis. Here is a case of a young adult male who presented with complaints of pain over his left leg for three months. A diagnosis was achieved with magnetic resonance imaging and the isolation of the bacteria from a bone biopsy using a cartridge-based nucleic acid amplification test. Antituberculous treatment was promptly initiated.
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INTRODUCTION: 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. CONCLUSION: 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.
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Hospitais de Ensino , Microscopia , Mycobacterium tuberculosis , Escarro , Tuberculose Pulmonar , Humanos , Mycobacterium tuberculosis/isolamento & purificação , Mycobacterium tuberculosis/genética , Estudos Retrospectivos , Escarro/microbiologia , Gana/epidemiologia , Feminino , Adulto , Masculino , Microscopia/métodos , Pessoa de Meia-Idade , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/microbiologia , Adulto Jovem , Adolescente , Sensibilidade e Especificidade , Idoso , Técnicas de Diagnóstico Molecular/métodos , Criança , Pré-EscolarRESUMO
Chronic infections, including Mycobacterium tuberculosis (Mtb)-caused tuberculosis (TB), can induce host immune exhaustion. However, the key checkpoint molecules involved in this process and the underlying regulatory mechanisms remain largely undefined, which impede the application of checkpoint-based immunotherapy in infectious diseases. Here, through adopting time-of-flight mass cytometry and transcriptional profiling to systematically analyze natural killer (NK) cell surface receptors, we identify leukocyte immunoglobulin like receptor B1 (LILRB1) as a critical checkpoint receptor that defines a TB-associated cell subset (LILRB1+ NK cells) and drives NK cell exhaustion in TB. Mechanistically, Mtb-infected macrophages display high expression of human leukocyte antigen-G (HLA-G), which upregulates and activates LILRB1 on NK cells to impair their functions by inhibiting mitogen-activated protein kinase (MAPK) signaling via tyrosine phosphatases SHP1/2. Furthermore, LILRB1 blockade restores NK cell-dependent anti-Mtb immunity in immuno-humanized mice. Thus, LILRB1-HLA-G axis constitutes a NK cell immune checkpoint in TB and serves as a promising immunotherapy target.
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Antígenos HLA-G , Células Matadoras Naturais , Receptor B1 de Leucócitos Semelhante a Imunoglobulina , Mycobacterium tuberculosis , Tuberculose , Receptor B1 de Leucócitos Semelhante a Imunoglobulina/metabolismo , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Antígenos HLA-G/metabolismo , Antígenos HLA-G/genética , Antígenos HLA-G/imunologia , Humanos , Animais , Tuberculose/imunologia , Tuberculose/microbiologia , Camundongos , Mycobacterium tuberculosis/imunologia , Macrófagos/imunologia , Macrófagos/metabolismo , Receptores Imunológicos/metabolismo , Receptores Imunológicos/genética , Antígenos CDRESUMO
Post-tuberculosis lung disease (PTLD) poses a significant clinical challenge in regions with a high burden of tuberculosis (TB). This review provides a comprehensive overview of PTLD, encompassing its pathogenesis, clinical manifestations, diagnostic modalities, management strategies, long-term outcomes, and public health implications. PTLD arises from residual lung damage following TB treatment and is characterized by a spectrum of pathological changes, including fibrosis, bronchiectasis, and cavitation. Clinical presentation varies widely, from chronic cough and hemoptysis to recurrent respiratory infections, which are oftentimes a diagnostic dilemma. Radiological imaging, pulmonary function tests, and careful consideration of patient history play pivotal roles in diagnosis. Management strategies involve pharmacological interventions to alleviate symptoms and prevent disease progression, which are influenced by the extent of lung damage, comorbidities, and access to healthcare. Rehabilitation programs and surgical options are available for select cases. Prognosis is influenced by the extent of lung damage, comorbidities, and access to healthcare. Prevention efforts through a TB control program and early detection are crucial in reducing the burden of PTLD. This review stresses the importance of understanding and addressing PTLD to mitigate its impact on individuals and public health systems worldwide.
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The PE and PPE family proteins of Mycobacterium tuberculosis (Mtb) is exclusively found in pathogenic Mycobacterium species, comprising approximately 8-10 % of the Mtb genome. These emerging virulent factors have been observed to play pivotal roles in Mtb pathogenesis and immune evasion through various strategies. These immunogenic proteins are known to modulate the host immune response and cell-death pathways by targeting the powerhouse of the cell, the mitochondria to support Mtb survival. In this article, we are focused on how PE/PPE family proteins target host mitochondria to induce mitochondrial perturbations, modulate the levels of cellular ROS (Reactive oxygen species) and control cell death pathways. We observed that the time of expression of these proteins at different stages of infection is crucial for elucidating their impact on the cell death pathways and eventually on the outcome of infection. This article focuses on understanding the contributions of the PE/PPE proteins by unravelling the triad of host mitochondria, oxidative stress and cell death pathways that facilitate the Mtb persistence. Understanding the role of these proteins in host cellular pathways and the intricate mechanisms paves the way for the development of novel therapeutic strategies to combat TB infections.
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Proteínas de Bactérias , Morte Celular , Interações Hospedeiro-Patógeno , Mitocôndrias , Mycobacterium tuberculosis , Espécies Reativas de Oxigênio , Humanos , Antígenos de Bactérias/metabolismo , Antígenos de Bactérias/genética , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Mitocôndrias/metabolismo , Mycobacterium tuberculosis/patogenicidade , Mycobacterium tuberculosis/metabolismo , Mycobacterium tuberculosis/genética , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , Tuberculose/microbiologia , Tuberculose/metabolismo , Fatores de Virulência/metabolismoRESUMO
Tuberculosis (TB) remains a significant global health concern, particularly with the emergence of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB). Traditional methods for diagnosing drug resistance in TB are time-consuming and often lack accuracy, leading to delays in appropriate treatment initiation and exacerbating the spread of drug-resistant strains. In recent years, artificial intelligence (AI) techniques have shown promise in revolutionizing TB diagnosis, offering rapid and accurate identification of drug-resistant strains. This comprehensive review explores the latest advancements in AI applications for the diagnosis of MDR-TB and XDR-TB. We discuss the various AI algorithms and methodologies employed, including machine learning, deep learning, and ensemble techniques, and their comparative performances in TB diagnosis. Furthermore, we examine the integration of AI with novel diagnostic modalities such as whole-genome sequencing, molecular assays, and radiological imaging, enhancing the accuracy and efficiency of TB diagnosis. Challenges and limitations surrounding the implementation of AI in TB diagnosis, such as data availability, algorithm interpretability, and regulatory considerations, are also addressed. Finally, we highlight future directions and opportunities for the integration of AI into routine clinical practice for combating drug-resistant TB, ultimately contributing to improved patient outcomes and enhanced global TB control efforts.
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Tuberculosis can present at various extrapulmonary sites. However, even in endemic countries, concomitant involvement of different sites in the same patient is rarely reported. Further, tuberculous pericarditis represents a fraction of all tuberculosis infections and is an uncommon form of extrapulmonary tuberculosis. In underdeveloped nations, it is the most frequent cause of massive pericardial effusion. Additionally, it is the most common cause of constrictive pericarditis in adults, which has a high death rate and a poor prognosis. Furthermore, concomitant pleural effusion due to Mycobacterium tuberculosis is infrequently reported. Herein, a case of concomitant pericardial and left-sided pleural effusion in an Indian female is reported. She came with complaints of breathlessness, chest pain, night sweats, and loss of appetite. A diagnostic pleural thoracentesis and pericardiocentesis helped establish the diagnosis, and she was commenced on antituberculous treatment for 168 days.
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Tuberculosis can present in various atypical forms. The clinical manifestations could involve sites like bones. Tuberculosis of the scapula, humerus, and posterolateral thoracic wall is extremely rare, and diagnosis is challenging due to similarities with conditions like tumors. A young boy presented with swelling of the right shoulder joint for three months. The diagnosis was challenging due to similarities with Ewing's sarcoma on the initial radiometric workup. A clinical assessment and diagnostic workup with biopsy, a cartridge-based nucleic acid amplification test, and an advanced radiometric investigation resulted in a final diagnosis. He was started on antituberculous drugs for 12 months.
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The recalcitrance of Mycobacterium tuberculosis (MTB) to eradication was related to achieving a nonreplicating (dormant) state and the increasing global burden of HIV coinfection. Consequently, understanding the knowledge and perception of the population at risk of tuberculosis-HIV infection is essential to designing a strategy of intervention embraced by the target population. A cross-sectional study was conducted among Nomads in Adamawa State, Nigeria. A multistage sampling technique was employed to recruit consented participants. Self-administered questionnaires were used to gather the required information from 4 nomadic schoolteachers in each selected school. Data were entered into a Microsoft Excel sheet where trends and tables of collated data were developed. The findings show that only 13.5% of the participants expressed the correct perceptions of the complementary relationship between HIV and TB. More people in government employment (35%) understand the coexisting relationship of TB-HIV infections. At the same time, cattle herders and crop farmers who practice the prevalent occupation lack knowledge of TB-HIV relatedness. Across gender, only a proportion of males (14.8%) than females (10.5%) were more likely to show an understanding of the complementary association of HIV and TB, and this difference showed statistical significance (p = 0.0001). In conclusion, male gender, education at a degree or professional level, and employment with the government are factors associated with positive perceptions of TB/HIV relatedness. Thus, there is a need to intensify communication to educate Nomads on HIV and TB-related issues.
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Infecções por HIV , Conhecimentos, Atitudes e Prática em Saúde , Tuberculose , Humanos , Nigéria/epidemiologia , Masculino , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/psicologia , Estudos Transversais , Adulto , Tuberculose/epidemiologia , Tuberculose/psicologia , Pessoa de Meia-Idade , Adulto Jovem , Inquéritos e Questionários , Comorbidade , Coinfecção/epidemiologia , AdolescenteRESUMO
Tuberculosis is rampant in endemic countries. Extrapulmonary tuberculosis, like pleural effusion, is infrequently reported in outpatient departments. However, diaphragmatic eventration is rare and is not reported in active tuberculosis. Herein, the first-of-its-type case of a diaphragmatic eventration with tuberculous right pleural effusion in an Indian male is presented. The diagnosis was challenging and achieved through radiometric investigations and diagnostic pleural tapping. He was put on an anti-tuberculous treatment based on his weight.