Search Results (424)

Tuberculosis (TB) remains a leading cause of infectious-disease-related morbidity and mortality worldwide, including in low-incidence, high-income countries, where cases increasingly cluster among vulnerable populations. In these settings, persistent diagnostic and treatment delays, rather than a lack of therapeutic options, drive preventable morbidity, ongoing transmission, and inappropriate antimicrobial use. We argue that TB antimicrobial stewardship must extend beyond treatment adherence and resistance containment to encompass the entire diagnostic continuum. Emerging evidence demonstrating a substantial burden of subclinical and asymptomatic TB challenges symptom-based diagnostic paradigms and reveals an underrecognized “asymptomatic delay”, during which radiologic or microbiologic disease is present but undetected. Failure to identify TB during this interval represents a critical stewardship failure, perpetuating empirical broad-spectrum antibiotic exposure while allowing disease progression and transmission. We review diagnostic challenges across the early clinical spectrum of pulmonary and extrapulmonary TB in low-incidence settings, with particular emphasis on migrants and other high-risk populations disproportionately affected by structural and healthcare system barriers. We propose a stewardship-oriented framework integrating targeted screening, enhanced clinical vigilance, front-loaded and parallel diagnostic pathways, and early referral to specialized TB centers. Explicit incorporation of asymptomatic delay into TB diagnostic frameworks can strengthen system accountability, reduce inappropriate antibiotic use, improve patient outcomes, and accelerate progress toward TB elimination in high-income, low-incidence countries. Full article

In recent decades, the burden of TB has been gradually declining; however, with the emergence of COVID-19 and ongoing political conflicts, including the war in Ukraine, the proper functioning of healthcare services and TB control programs has been jeopardized. Recently, research has emphasized the importance of hematological parameters associated with inflammation, which can be easily analyzed through routine blood tests. Combining these parameters may have predictive value for various diseases, including pulmonary tuberculosis and even help monitor the effectiveness of treatment. Since there is no single hematological or inflammatory biomarker that provides precise and dynamic information about the success or failure of treatment, identifying individual markers or sets of biomarkers with higher sensitivity and specificity is essential. This is particularly important since sputum culture conversion at two months remains insufficiently sensitive and microscopy conversion has limited sensitivity and specificity in detecting treatment failure. Also, the analysis of the impact of the standard directly observed treatment, short-course regimen on pathogenic mechanisms also focuses on how it influences the interaction between inflammation and oxidative tissue degradation, by measuring plasma levels of glutathione. Utilizing a combination of hematological, inflammatory, and antioxidant biomarkers offers significant insights into systemic inflammatory responses in pulmonary tuberculosis patients, both before commencing treatment and during the entire duration of antituberculosis therapy. Combining different inflammatory parameters into a multiple biomarker can significantly enhance the accuracy of predicting prognosis and response to antibiotic chemotherapy. Identifying an optimal combination of biomarkers with predictive value is crucial for assessing treatment response and evaluating the effectiveness of anti-TB medication. Rather than developing or testing a composite prediction model, this review summarizes reported performance metrics from individual studies and highlights priorities for future prospective validation of integrated biomarker panels. Full article

Tuberculosis (TB) remains a leading infectious killer, increasingly complicated by multidrug-resistant (MDR) and extensively drug-resistant (XDR) disease; current regimens, although effective, are prolonged, toxic, and often fail to reach intracellular bacilli in heterogeneous lung lesions. This narrative review synthesizes how next-generation antimycobacterial strategies can be translated “from molecule to patient” by coupling potent therapeutics with delivery platforms tailored to the lesion microenvironment. We survey emerging small-molecule classes, including decaprenylphosphoryl-β-D-ribose 2′-epimerase (DprE1) inhibitors, mycobacterial membrane protein large 3 (MmpL3) inhibitors, and respiratory chain blockers, alongside optimized uses of established agents and host-directed therapies (HDTs). These are mapped to inhalable and nanocarrier systems that improve intralesional exposure, macrophage uptake, and targeted release while reducing systemic toxicity. Particular emphasis is placed on pulmonary dry powder inhalers (DPIs) and aerosols for direct lung targeting, stimuli-responsive carriers that trigger release through pH, redox, or enzymatic cues, and long-acting depots or implants that shift daily dosing to monthly or quarterly schedules to enhance adherence, safety, and access. We also outline translational enablers, including model-informed pharmacokinetic/pharmacodynamic (PK/PD) integration, device formulation co-design, manufacturability, regulatory quality frameworks, and patient-centered implementation. Overall, aligning stronger drugs with smart delivery platforms offers a practical pathway to shorter, safer, and more easily completed TB therapy, improving both individual outcomes and public health impact. Full article

Although smoking is the main risk factor for chronic obstructive pulmonary disease (COPD), about one-third of patients have never smoked. This phenomenon supports the idea of a distinct phenotype of the disease in never-smokers, influenced by genetic, infectious, socioeconomic, environmental, and occupational factors. The paper is based on a narrative review of recent literature on the etiology, clinical features, evolution, and therapeutic strategies of COPD in never-smokers, mainly through the analysis of published studies over the last 3 years. COPD in never-smokers occurs predominantly in women, the elderly, and individuals from rural areas or with poor socioeconomic status. Key risk factors include exposure to occupational or environmental pollutants, air pollution, previous respiratory infections, particularly due to pulmonary tuberculosis, and genetic predisposition, mainly through alpha-1 antitrypsin deficiency (A1ATD). Clinically, COPD in never-smokers is characterized by chronic cough and dyspnea, with less severe pulmonary functional impairment, slow progression, and lower prevalence of emphysema compared to smokers. Imaging often highlights bronchiectasis or post-infectious sequelae, and biological markers indicate a significant eosinophilic component. Thus, COPD in never-smokers is a distinct clinical entity with multifactorial pathogenesis and distinct clinical-functional characteristics. Prompt recognition of this form of disease is essential for prevention and adaptation of therapeutic strategies. A personalized multidisciplinary approach can improve disease prognosis and the quality of life for these patients. Full article

Clinical indicators for pulmonary tuberculosis (PTB) among patients with community-acquired pneumonia (CAP) have been derived from studies on younger or middle-aged populations in high TB-burden countries. However, diagnostic clues specific to older adults remain insufficiently validated. This multicenter prospective observational study aimed to identify the clinical features that can help differentiate PTB from CAP among older patients. We enrolled patients aged ≥ 65 years who were diagnosed with PTB or non-TB CAP between September 2023 and September 2025. Clinical data—including demographics, symptoms, and laboratory findings, previously reported as potential discriminators of PTB—were compared between the two groups. Of 233 patients included, 57 (24%) were diagnosed with PTB. No significant difference in sex was observed between the PTB and non-TB CAP groups. The PTB group was older and had a poorer performance status than the CAP group. On multivariate logistic regression analysis, PTB was significantly and independently associated with weight loss (aOR 8.17, p < 0.001); symptoms lasting ≥ 2 weeks (aOR 5.79, p < 0.001); and absence of general fatigue (aOR 0.19, p < 0.001) and dyspnea (aOR 0.19, p = 0.002) but not with night sweats and hemoptysis. These clinical features may be valuable indicators of PTB in older adults and inform tuberculosis control strategies in regions expected to have accelerated population aging. Full article

Tuberculosis (TB) has various clinical presentations; pulmonary TB (PTB) affects only the lungs, whereas extrapulmonary TB involves other organs, including pleural TB (PLTB). Immunological studies of patients with extrapulmonary TB primarily focus on the cellular Th1 response, which produces key cytokines, including IFN-γ, TNF, IL-12, and IL-6. TNF and IL-6 play functional roles in host resistance to Mycobacterium tuberculosis (Mtb) infection. Findings suggest that TNF facilitates macrophage containment of Mtb, whereas IL-6 increases macrophage apoptosis induced by Mtb. Studies of the human genome have identified single-nucleotide polymorphisms (SNPs) in genes encoding cytokines associated with TB susceptibility. This study aimed to assess the potential of the IL6-174G/C (rs1800795), TNF-308G/A (rs1800629), and TNF-238G/A (rs361525) SNPs as genetic biomarkers of susceptibility to PLTB in the Venezuelan mestizo population. A total of 269 individuals were included: 69 patients with PLTB and 200 healthy individuals. The IL6-174G/C, TNF-308G/A, and TNF-238G/A polymorphisms were determined by sequence-specific primer polymerase chain reaction (SSP-PCR). Results showed significantly higher frequencies of the G/C, G/A, and G/A genotypes in patients with PLTB (94.0%, 94.2%, and 83.3%) than in controls (40.0%, 19.0%, and 13.4%) for the IL6-174G/C, TNF-308G/A, and TNF-238G/A polymorphisms, respectively. Logistic regression analysis showed significant associations between the G/C, G/A, and G/A genotypes and susceptibility to PLTB. The IL6-174G/C, TNF-308G/A, and TNF-238G/A gene polymorphisms may serve as genetic biomarkers of susceptibility to PLTB in the Venezuelan mestizo population. Full article

Background and Clinical Significance: Cutaneous lupus erythematosus (CLE) is an autoimmune condition characterized by a wide range of cutaneous manifestations, classified into three major subtypes—chronic (CCLE), subacute (SCLE), and acute (ACLE)—based on clinical morphology and lesion duration. Discoid lupus erythematosus (DLE), the most common form of CCLE, predominantly affects sun-exposed areas and presents as erythematous macules that progress to well-demarcated, disc-shaped plaques. If left untreated, DLE may lead to scarring and permanent alopecia. Diagnosis is primarily clinical, with skin biopsy performed when indicated. Management includes photoprotection and topical corticosteroids, with systemic immunosuppressive therapy reserved for severe cases. Case Presentation: We report a case of a 38-year-old female patient presenting with confluent lesions with indurated borders and multiple pustules, initially raising suspicion of cutaneous infection. A broad differential diagnosis was considered, including fungal and bacterial infections, demodicosis, and cutaneous tuberculosis, all of which were excluded through comprehensive clinical and laboratory investigations. Ultimately, DLE was diagnosed based on serologic and histopathologic findings. During the course of immunosuppressive therapy, her condition deteriorated, and she developed pulmonary tuberculosis. Conclusions: The presented case underlines the rarity and broad differential diagnosis of DLE as well as the possibility of complications. Full article

Pulmonary diseases caused by nontuberculous mycobacteria are increasingly becoming common worldwide and are occurring more frequently alongside pulmonary tuberculosis. Given that pulmonary diseases resulting from nontuberculous mycobacteria and pulmonary tuberculosis display similar features—such as clinical manifestations, imaging findings, and laboratory results—the accurate differentiation of each disease type is highly challenging. Mycobacterial culture, as a gold standard method, cannot be considered completely trustworthy because of low bacterioexcretion rates among nontuberculous mycobacterial pulmonary patients. Additional problems result from poor diagnosis. The treatment of lung diseases caused by nontuberculous mycobacteria is also difficult. This could be due to the wide spectrum of bacteria belonging to nontuberculous mycobacteria, as well as low bacterioexcretion. Therefore, bacterial sensitivity to drugs is insufficient. As a result, in this article, our intention is to explain the diagnostic difficulties of pulmonary diseases caused by nontuberculous mycobacteria and the Mycobacterium tuberculosis complex. The review seeks to outline promising directions for the development of novel diagnostic approaches in order to improve clinical decision-making and ultimately treatment outcomes. Full article

Background/Objectives: Treatment adherence challenges affect 10–20% of tuberculosis patients globally, contributing to drug resistance and continued transmission. While artificial intelligence approaches show promise for identifying patients who may benefit from additional treatment support, most models lack the interpretability necessary for clinical implementation. We aimed to develop and validate an integrated artificial intelligence framework combining traditional machine learning (interpretable algorithms like logistic regression and decision trees), explainable AI (methods showing which patient characteristics influence predictions), deep reinforcement learning (algorithms learning optimal intervention strategies), and natural language processing (clinical text analysis) to identify tuberculosis patients who would benefit from enhanced treatment support services. Methods: We analyzed 103,846 pulmonary tuberculosis cases from São Paulo state surveillance data (2006–2016). We evaluated models using precision (accuracy of positive predictions), recall (ability to identify all patients requiring support), F1-score (balanced performance measure), and AUC-ROC (overall discrimination ability) while maintaining interpretability scores above 0.90 for clinical transparency. Results: Our integrated framework demonstrated that explainable AI matched traditional machine learning performance (both F1-score: 0.77) while maintaining maximum interpretability (score: 0.95). The combined ensemble delivered superior results (F1-score: 0.82, 95% CI: 0.79–0.85), representing a 6.5% improvement over individual approaches (p < 0.001). Key predictors included substance use disorders, HIV co-infection, and treatment supervision factors rather than demographic characteristics. Conclusions: This multi-paradigm AI system provides a methodologically sound foundation for identifying tuberculosis patients who would benefit from enhanced treatment support services. The approach delivers excellent predictive accuracy while preserving full clinical transparency, demonstrating that the accuracy–interpretability trade-off in medical AI can be resolved through the systematic integration of complementary methodologies. Full article

Background: Tuberculosis (TB) remains a leading cause of global mortality, with 1.25 million deaths reported in 2023. Extended treatment duration contributes to poor patient adherence and treatment failure. Innovative drug delivery platforms are needed to improve therapeutic outcomes. Objective: This study aimed to develop nanoemulsions co-encapsulating quercetin and rifampicin and evaluate their physicochemical properties and in vitro biological activity relevant to TB therapy. Methods: Nanoemulsions (NEs) were prepared via hot solvent diffusion and phase inversion temperature techniques. Physicochemical characterization, stability, anti-inflammatory effects in BEAS-2B cells, and antimycobacterial activity against Mycobacterium tuberculosis H37Rv and resistant strains were assessed in vitro. Results: The quercetin-rifampicin nanoemulsion (QUE-RIF-NE) showed an average size of 24 nm, zeta potential of −27 mV, and drug recovery rates of 77% (quercetin) and 75% (rifampicin). The formulation was stable and non-cytotoxic at 10⁻⁸ M, reducing IFN-γ production by half and reactive oxygen species production by almost 75% in BEAS-2B cells. It also exhibited antimycobacterial activity against both susceptible and resistant M. tuberculosis strains (MIC ≤ 0.015 µg/mL). Conclusions: QUE-RIF-NE exhibits promising physicochemical stability and dual anti-inflammatory and antimicrobial activity in vitro, demonstrating potential for optimized pulmonary or systemic TB therapy that integrates both anti-inflammatory and antimicrobial effects. Full article

Background: Tuberculosis (TB) remains a leading cause of morbidity and mortality, with South Africa among the highest-burden countries. The Eastern Cape is particularly affected due to poverty, HIV co-infection, and weak health systems. Understanding treatment outcomes and their determinants is required to achieve the WHO End TB Strategy targets. The objective of this study was to examine treatment outcomes for tuberculosis (TB) in both rural and urban clinics within the Eastern Cape Province. We aimed to identify the socio-demographic, clinical, and geographic factors that influence treatment success or failure. We included simple geographic visualisations comparing treatment outcomes between the two participating clinics to inform the development of targeted interventions aimed at enhancing TB control efforts. Methods: A retrospective cohort study of 385 TB patients treated at two public clinics in the Eastern Cape (2020–2024) was conducted. Socio-demographic, clinical, and geographical data were extracted from records. Outcomes were classified using WHO and South African National TB Programme guidelines. Logistic regression identified predictors of success, and spatial analysis mapped treatment outcomes. Results: The mean patient age was 40.6 years; 69.1% were HIV-positive, and 89.9% had pulmonary TB. The overall treatment success rate was 63.8%, below the WHO target of ≥85%. Pulmonary TB was independently associated with greater odds of success (aOR = 2.86, 95% CI: 1.23–6.65), while older age predicted poorer outcomes (aOR = 0.98, 95% CI: 0.963–0.998). HIV status and socioeconomic variables were not independently associated after adjustment, although poverty and unemployment were widespread. Spatial mapping showed clustering of poor outcomes in specific clinics, highlighting geographic and health system disparities. Conclusions: TB treatment outcomes in the Eastern Cape remain unsatisfactory. Older patients and those with extrapulmonary TB face higher risks of unfavourable outcomes, underscoring the need for closer monitoring and adherence support. Integrated TB/HIV care, social protection, and geographically targeted interventions are essential to strengthen health systems and reduce inequalities. Full article

Sarcoidosis is a chronic, idiopathic, multisystemic inflammatory disease characterized by non-caseating granulomas, most commonly affecting the lungs and mediastinal lymph nodes. Radiological imaging plays a fundamental role in the diagnosis, assessment of disease extent, and differentiation from other pulmonary conditions. This narrative review offers a comprehensive overview of the imaging features of pulmonary sarcoidosis, focusing on both typical patterns—such as bilateral hilar lymphadenopathy, perilymphatic nodules, and upper lobe-predominant infiltrates—and atypical manifestations—including alveolar opacities, miliary nodules, fibrocystic changes, and lower lobe involvement. Emphasis is placed on the utility of high-resolution computed tomography (HRCT) in detecting early parenchymal changes and complications such as fibrosis, bronchiectasis, and pulmonary hypertension. Differential diagnosis, including tuberculosis, silicosis, metastatic disease, organizing pneumonia, and hypersensitivity pneumonitis, are discussed to aid interpretation. Recognizing the spectrum of radiological presentations is essential for distinguishing sarcoidosis from other interstitial and granulomatous lung diseases. Radiologists play a pivotal role in the multidisciplinary diagnostic process, contributing to timely diagnosis, risk stratification, and optimized patient management. Full article

Accurate normalization of qRT-PCR data in pulmonary tuberculosis (TB) research requires reference genes whose expression is invariant across clinically relevant matrices, yet no studies have addressed this in lesion tissue and blood concurrently. We assessed the expression stability of eight popular housekeeping genes—ACTB, B2M, GAPDH, HPRT1, PPIA, RPL13A, UBC and YWHAZ—in lung tuberculomas and peripheral blood mononuclear cells (PBMCs) from TB patients. Standardized extraction and amplification yielded Cq values that were ranked by geNorm, NormFinder, BestKeeper and comparative Delta CT, with consensus scores generated in RefFinder; and correlation analysis was conducted in order to select the most suitable genes to work collectively for future normalization. The consensus analysis placed PPIA, YWHAZ and HPRT1 at the top, while GAPDH and UBC were the least stable. Our findings endorse a three-gene panel (PPIA, YWHAZ, HPRT1) for robust normalization of host gene-expression studies in both lesion tissue and PBMCs in pulmonary TB and highlight the necessity of context-specific reference-gene validation. Full article

Background: The diagnosis of abdominal tuberculous lymphadenopathy (ATBL) remains challenging in clinical practice. Patients with ATBL and HIV infection may have atypical clinical and computed tomography (CT) features. The aim of this study was to investigate the impact of HIV infection on the clinical and CT features of ATBL patients. Methods: From January 2012 to March 2023, 178 patients with untreated ATBL were retrospectively analyzed. Patients with ATBL were classified into HIV-negative group (n = 152) and HIV-positive group (n = 26). In addition to the clinical characteristics of the patients, the features of ATBL (e.g., size and location) were evaluated via CT. The Mann–Whitney U test (for continuous variables) and Fisher’s exact test (for categorical variables) were used to compare clinical data and CT imaging features between the two groups. Missing values were handled using multiple imputation, and the Benjamini–Hochberg procedure was applied to control the false discovery rate (FDR) in multiple comparisons. Post hoc power analysis for key variables was performed. Results: Compared with the HIV-negative group, the HIV-positive group had older age, lower CD4⁺ T-cell counts, and larger ATBL diameter. The HIV-positive group also showed a stronger tendency for disease dissemination, with significantly higher rates of smear positivity, miliary pulmonary tuberculosis (PTB), and disseminated tuberculosis (TB). On CT imaging, the HIV-positive group had a higher frequency of ATBL involvement in the upper para-aortic region, portacaval space, and hepatogastric ligament. In contrast, abdominal distension was more common in the HIV-negative group. post hoc power analysis confirmed that most key variables had adequate statistical power (≥0.8), except for age (power = 0.597) and ATBL diameter (Power = 0.769). Conclusions: The clinical and CT features of ATBL differ significantly between HIV-negative and HIV-positive patients. Full article

This review focuses on the diverse etiologies of secondary spontaneous pneumothorax (SSP) and the crucial role of imaging in their diagnosis. Unlike primary spontaneous pneumothorax (PSP), which is typically due to ruptured blebs, SSP results from a wide array of underlying pulmonary conditions that can pose significant diagnostic challenges. These include infections like tuberculosis, airway diseases such as chronic obstructive pulmonary disease, malignancies (primary and metastatic), interstitial lung diseases like sarcoidosis, cystic lung diseases such as lymphangioleiomyomatosis, and connective tissue disorders. In women, catamenial pneumothorax secondary to endometriosis should be considered. The role of radiologists is crucial in uncovering these underlying conditions. While chest radiography is the initial imaging modality, computed tomography (CT) provides superior sensitivity for detecting subtle parenchymal abnormalities. Advanced techniques like photon-counting detector CT offer further benefits, including enhanced spatial resolution, reduced noise, and lower radiation dose, potentially revealing underlying causes that might be missed with conventional CT. This enhanced visualization of subtle parenchymal changes, small airways, and vascular structures can be the key to diagnosing the underlying cause of pneumothorax. Recognizing the diverse etiologies of SSP and utilizing advanced imaging techniques is paramount for accurate diagnosis, appropriate management, and improved patient outcomes. Full article