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Keywords = tuberculosis diagnosis

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18 pages, 3212 KB  
Article
Artificial Intelligence-Assisted Quantification of Longitudinal HRCT Changes During Treatment of Pulmonary Tuberculosis: An Exploratory Proof-of-Concept Study
by Anna Russo, Vittorio Patanè, Francesco Ruotolo, Maria Chiara Brunese, Maria Teresa Del Canto, Loredana Alessio, Caterina Monari, Nicola Coppola and Alfonso Reginelli
Diagnostics 2026, 16(12), 1822; https://doi.org/10.3390/diagnostics16121822 (registering DOI) - 12 Jun 2026
Abstract
Background: Treatment monitoring in pulmonary tuberculosis increasingly requires assessment of residual inflammatory burden and structural lung damage beyond microbiologic response alone. High-resolution computed tomography (HRCT) can provide this information, but interpretation of serial examinations is time-consuming and partly subjective. This study did not [...] Read more.
Background: Treatment monitoring in pulmonary tuberculosis increasingly requires assessment of residual inflammatory burden and structural lung damage beyond microbiologic response alone. High-resolution computed tomography (HRCT) can provide this information, but interpretation of serial examinations is time-consuming and partly subjective. This study did not aim to evaluate AI for the diagnosis of pulmonary tuberculosis. Instead, it explored whether artificial intelligence (AI)-assisted quantitative HRCT analysis could support longitudinal assessment of treatment-related imaging changes in patients with microbiologically confirmed pulmonary tuberculosis. Methods: We conducted a retrospective, single-center, exploratory longitudinal study of patients receiving treatment for pulmonary tuberculosis. HRCT examinations acquired at diagnosis and during follow-up were anonymized, reviewed by an expert thoracic radiologist, and processed using AVIEW Lung Texture (Coreline Soft v2.0). The software quantified total lung volume and six predefined parenchymal categories: normal lung, ground-glass opacity, consolidation, reticulation, honeycombing, and emphysema. Results: Ninety-six patients contributed 256 HRCT examinations. The most frequent software-detected abnormalities were ground-glass opacity, consolidation, and emphysema-labeled low-attenuation areas. Ground-glass opacity and consolidation showed the clearest decline across serial examinations, consistent with regression of active inflammatory disease during treatment. Reticulation showed a heterogeneous course, likely reflecting both inflammatory resolution and residual structural remodeling. Honeycombing was infrequent and quantitatively limited. Lung volume changed variably and did not consistently parallel visual improvement. A key methodological limitation was the absence of a dedicated cavity class. As a result, emphysema-labeled low-attenuation areas should not be interpreted as conventional emphysema alone, because tuberculous cavities and post-destructive abnormalities were frequently included in this category. Conclusions: AI-assisted HRCT quantification may support longitudinal assessment of pulmonary tuberculosis by providing structured and reproducible measures of interval change. However, tuberculosis-specific interpretation remains dependent on expert radiologic oversight, particularly in cavitary disease. Full article
(This article belongs to the Special Issue Artificial Intelligence for Health and Medicine—2nd Edition)
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14 pages, 387 KB  
Article
Distribution of Non-Tuberculous Mycobacterium Species in Pulmonary and Extrapulmonary Infections in South India–A Retrospective Analysis
by Priya Rajendran, Radha Gopalaswamy, Gowsalya Saminathan, Bershila Prey, Hannah Stanley, Adhin Bhaskar, Sudha Solayappan, Dinesh Viswanathan, Radhakrishnan Ramalingam, Asha Frederick and Sivakumar Shanmugam
Microorganisms 2026, 14(6), 1319; https://doi.org/10.3390/microorganisms14061319 - 12 Jun 2026
Abstract
Differential diagnosis of tuberculosis (TB) and non-tuberculous mycobacteria (NTM) is extremely challenging, especially in a high TB burden setting like India. A definitive diagnosis of NTM, along with additional speciation, is warranted to improve NTM management. Beyond the diagnosis of NTM and its [...] Read more.
Differential diagnosis of tuberculosis (TB) and non-tuberculous mycobacteria (NTM) is extremely challenging, especially in a high TB burden setting like India. A definitive diagnosis of NTM, along with additional speciation, is warranted to improve NTM management. Beyond the diagnosis of NTM and its speciation, clinical correlation is vital for differentiating NTM colonisation or contamination from disease. In this cross-sectional, retrospective analysis, both pulmonary and extrapulmonary samples from 1121 presumptive NTM patients from Tuberculosis Units across the country and from other private hospitals were included. Composite diagnosis were performed using X-rays, nucleic acid amplification tests, smear microscopy, and mycobacterial growth indicator tube cultures, with speciation of NTM isolates confirmed by line probe assay. Of the 1121 presumptive NTM patients, 66.0% were smear-negative, 44.7% had X-ray changes, and 98.0% were M. tuberculosis-negative according to the nucleic acid amplification test. Cultures identified 310 patients as NTM-positive, including 22 extrapulmonary cases. Speciation was performed for 135 NTM-positive isolates, where M. abscessus was identified as the predominant species in 30.4%, followed by M. kansasii in 25.1%. Our study demonstrated that although the composite diagnosis of NTM holds promise for identifying pulmonary and extrapulmonary NTM, culture (mean confirmation rate of 30–40% over 5 years) remains the gold standard, with NTM speciation by line probe assay completing the diagnosis. Full article
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17 pages, 6426 KB  
Article
Metagenomic Next-Generation Sequencing for Pulmonary Tuberculosis Diagnosis and Infection Risk Factor Analysis in AECOPD Patients: A Single-Center Retrospective Study
by Chao He, Hua Zou, Ziyang Jiang, Yi Zhou and Binwu Ying
J. Clin. Med. 2026, 15(12), 4507; https://doi.org/10.3390/jcm15124507 - 10 Jun 2026
Viewed by 171
Abstract
Background: Pulmonary tuberculosis (TB) is a significant trigger of acute exacerbations of chronic obstructive pulmonary disease (AECOPD), so its timely and accurate diagnosis is essential. Also, the risk factors for TB occurrence in this population remain unclear. This study aimed to evaluate [...] Read more.
Background: Pulmonary tuberculosis (TB) is a significant trigger of acute exacerbations of chronic obstructive pulmonary disease (AECOPD), so its timely and accurate diagnosis is essential. Also, the risk factors for TB occurrence in this population remain unclear. This study aimed to evaluate the performance of metagenomic next-generation sequencing (mNGS) for TB diagnosis in AECOPD patients, as well as to identify the associated risk factors. Methods: A retrospective observational cohort of 659 AECOPD patients with suspected pulmonary infection was enrolled. The microbial cell-free nucleic acids in bronchoalveolar lavage fluid samples were extracted and subjected to mNGS detection. The clinical data for each patient were collected from the hospital information system. The statistical analyses were performed with SPSS version 25.0. Results: A total of 170 cases, included for final analyses, were categorized into TB (n = 41), bacterial infection (n = 73), and non-infective control (n = 56) groups. Among these groups, the TB group had the highest intensive care unit (ICU) admission rate (46.34%) and longest median hospital stay (19.50 days) (p < 0.01). For TB diagnosis, mNGS demonstrated a greater sensitivity (86.00%), a lower specificity (93.30%), and a higher area under the curve (AUC, 0.877) than TB-DNA detection (70.21%, 100%, 0.848, respectively) and Xpert Mycobacterium tuberculosis/rifampicin (MTB/RIF) assay (63.83%, 100.00%, 0.870, respectively). Notably, mNGS identified the bacterial or viral co-infections in 18.00% of TB cases. Furthermore, the stringently mapped read number determined by mNGS showed a positive correlation with ICU admission rate (r = 0.76) and in-hospital mortality (r = 0.77). The lower body mass index (BMI) and reduced natural killer (NK) cell count were identified as the independent risk factors in the TB group (both p < 0.05). Conclusions: For the diagnosis of pulmonary TB in AECOPD patients, mNGS demonstrated comparable performance to TB-DNA detection and Xpert MTB/RIF assay, and also mNGS identified co-infections. In addition, a lower BMI and reduced NK cell count were identified as the independent risk factors for TB occurrence in this cohort. Full article
(This article belongs to the Section Clinical Laboratory Medicine)
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22 pages, 3482 KB  
Review
Advanced Multimodal Imaging in Granulomatous Uveitis: From Differential Diagnosis to Treatment Monitoring and Surgical Integration
by Matteo Capobianco, Francesco Bandello, Elisabetta Miserocchi and Federico Rissotto
J. Clin. Med. 2026, 15(11), 4222; https://doi.org/10.3390/jcm15114222 - 29 May 2026
Viewed by 154
Abstract
Background/Objectives: Granulomatous uveitis comprises a clinically heterogeneous group of inflammatory disorders, including ocular sarcoidosis, Vogt–Koyanagi–Harada disease, sympathetic ophthalmia, tuberculosis-associated uveitis, and syphilitic uveitis. Because these entities may share overlapping posterior segment findings, clinical examination alone is often insufficient for differential diagnosis, particularly [...] Read more.
Background/Objectives: Granulomatous uveitis comprises a clinically heterogeneous group of inflammatory disorders, including ocular sarcoidosis, Vogt–Koyanagi–Harada disease, sympathetic ophthalmia, tuberculosis-associated uveitis, and syphilitic uveitis. Because these entities may share overlapping posterior segment findings, clinical examination alone is often insufficient for differential diagnosis, particularly when choroidal, retinal, or retinal vascular involvement predominates. Methods: This review provides a clinically oriented overview of multimodal imaging in granulomatous uveitis, including optical coherence tomography (OCT), enhanced-depth imaging OCT, swept-source OCT, OCT angiography, fundus autofluorescence, fluorescein angiography, indocyanine green angiography, and ultrawidefield imaging. Results: Emphasis is placed on imaging patterns that help localize the predominant anatomic compartment of inflammation, distinguish major etiologies, identify diagnostic pitfalls, and assess disease activity over time. By integrating current evidence with representative multimodal imaging findings, we propose an anatomic and decision-oriented framework for interpreting granulomatous posterior segment inflammation. Conclusions: Particular attention is given to the distinction between active inflammation and irreversible structural damage, as this distinction may influence treatment escalation or tapering, timing of elective surgery, local corticosteroid therapy, and the need for diagnostic sampling in infectious or masquerade-like presentations. Full article
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12 pages, 1195 KB  
Article
A Case of Transmission of Bedaquiline- and Linezolid-Resistant Tuberculosis
by Anastasia Ushtanit, Irina Peretokina, Ludmila Krylova, Svetlana Safonova, Alexey Filippov and Danila Zimenkov
Int. J. Mol. Sci. 2026, 27(11), 4912; https://doi.org/10.3390/ijms27114912 - 29 May 2026
Viewed by 250
Abstract
Tuberculosis is one of the hardest-to-treat bacterial diseases with a high capacity to develop antibiotic resistance. The treatment scheme based on bedaquiline and linezolid was introduced in Russia in 2014 and, since 2018, has been widely used for the treatment of resistant tuberculosis. [...] Read more.
Tuberculosis is one of the hardest-to-treat bacterial diseases with a high capacity to develop antibiotic resistance. The treatment scheme based on bedaquiline and linezolid was introduced in Russia in 2014 and, since 2018, has been widely used for the treatment of resistant tuberculosis. In our study of clinical M. tuberculosis isolates, we identified a case of a recent transmission of a strain with mutations in the genes rv0678 and rplC, associated with resistance to bedaquiline and linezolid. We analyzed five isolates obtained from patient A between 2015 and 2019 after unsuccessful treatment and three isolates from patient B obtained between diagnosis in 2019 and death in mid-2020 via whole-genome sequencing and 24-loci MIRU-VNTR genotyping. During the treatment of patient A, a large spectrum of different mutations in rv0678 developed, accompanied by an increase in bedaquiline MIC from 0.06 to 0.5 mg/L. Simultaneously, rplC C154R substitution emerged, leading to linezolid resistance. The isolates from patient B contained nearly the same mutation spectra as the isolates from patient A, differing in only four variants that emerged during transmission. The possible transmission event must have occurred in a public place in Moscow, since there was no evidence of direct contact between the patients. This finding confirms the worrying trend of untreatable M. tuberculosis strains circulating in the general population. Full article
(This article belongs to the Special Issue Research Advances in Antibiotic Resistance)
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24 pages, 6565 KB  
Review
Bacterial Granulomatous Lung Diseases: Radiological Findings and Differential Diagnosis
by Picchi Stefano Giusto, Minieri Augusto, Lassandro Francesco, Russo Giuseppe and Lassandro Giulia
Infect. Dis. Rep. 2026, 18(3), 53; https://doi.org/10.3390/idr18030053 - 28 May 2026
Viewed by 148
Abstract
Background Granulomatous lung diseases include a spectrum of disorders, both infectious and noninfectious, unified by the presence of granulomas in the lung parenchyma. Granulomas are microscopic, organized collections of immune cells that arise as a response to persistent antigenic stimulation. Infectious granulomatous lung [...] Read more.
Background Granulomatous lung diseases include a spectrum of disorders, both infectious and noninfectious, unified by the presence of granulomas in the lung parenchyma. Granulomas are microscopic, organized collections of immune cells that arise as a response to persistent antigenic stimulation. Infectious granulomatous lung diseases arise from a variety of microbial agents, that include most frequently Mycobacterium tuberculosis, non-tuberculous mycobacteria, Nocardia, and Borrelia, as well as a wide range of fungal pathogens including Histoplasma, Cryptococcus, Pneumocystis, and Aspergillus species. Methods and Results: Definitive diagnosis is achieved through direct identification and subsequent culture of the causative pathogen in appropriate clinical specimens, including sputum, bronchoscopic samples, gastric aspirates, or pleural fluid. Imaging is fundamental for the detection and characterization of pulmonary granulomas. HRCT allows precise assessment of the number, size, and distribution of granulomatous lesions, can suggest an infectious etiology based on specific imaging patterns, and is essential for monitoring response to therapy over time. Differential diagnosis is challenging due to the numerous different imaging appearances with whom granulomatous lung diseases may manifest. Conclusions: The purpose of our review is to describe the spectrum of infectious granulomatous lung diseases caused by bacterial pathogens, highlighting their diverse radiologic presentations in order to assist radiologists in recognizing these entities and improving diagnostic accuracy. Full article
(This article belongs to the Section Bacterial Diseases)
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31 pages, 4069 KB  
Review
Tuberculosis in Pregnancy: An Updated Narrative Review
by Carolina Longo, Karina Felippe Monezi Pontes, Marina Matos de Moura Faíco, Mayra Martins Melo, Gustavo Yano Callado, Célio de Barros Barbosa, Edward Araujo Júnior and Antonio Braga
Diagnostics 2026, 16(11), 1576; https://doi.org/10.3390/diagnostics16111576 - 22 May 2026
Viewed by 292
Abstract
Tuberculosis remains one of the leading infectious causes of morbidity and mortality worldwide, disproportionately affecting women of reproductive age, particularly in low- and middle-income countries. Tuberculosis during pregnancy represents a major clinical challenge, as physiological and immunological changes associated with pregnancy may obscure [...] Read more.
Tuberculosis remains one of the leading infectious causes of morbidity and mortality worldwide, disproportionately affecting women of reproductive age, particularly in low- and middle-income countries. Tuberculosis during pregnancy represents a major clinical challenge, as physiological and immunological changes associated with pregnancy may obscure symptoms, delay diagnosis, and contribute to adverse maternal and perinatal outcomes. This narrative review provides an updated and clinically oriented overview of tuberculosis during pregnancy, with particular emphasis on diagnostic challenges, imaging strategies, microbiological testing, maternal–fetal complications, and therapeutic management. Key topics include symptom-based screening, tuberculin skin test and interferon gamma release assays, as well as molecular diagnostic methods such as GeneXpert Mycobacterium tuberculosis/Rifampicin (MTB/RIF) and Xpert MTB/RIF Ultra, chest radiography, computed tomography, and emerging biomarkers. We also discuss the impact of tuberculosis on pregnancy outcomes, including prematurity, low birth weight, maternal morbidity, and neonatal complications, as well as the particular challenges posed by human immunodeficiency virus HIV coinfection and multidrug-resistant tuberculosis. Current treatment strategies, preventive approaches, postpartum care, neonatal management, and Bacille Calmette–Guérin vaccination are reviewed in light of contemporary evidence and international recommendations. Finally, we highlight practical diagnostic algorithms, current evidence gaps, and priorities for future research aimed at improving maternal and neonatal outcomes in both high- and low-resource settings. Full article
(This article belongs to the Section Diagnostic Microbiology and Infectious Disease)
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38 pages, 9446 KB  
Article
Metaheuristic-Optimized Convolutional Neural Network for Automated Diagnosis of Viral Pneumonia and Tuberculosis from Chest X-Rays
by Pamela Hermosilla, Emanuel Vega, Eric Monfroy, Lucas Erazo, Valentina Guzmán and Ricardo Soto
Diagnostics 2026, 16(10), 1529; https://doi.org/10.3390/diagnostics16101529 - 18 May 2026
Viewed by 245
Abstract
Background: Viral Pneumonia and Tuberculosis continue to represent a significant burden on global public health, relying heavily on chest X-rays for screening and diagnosis. Although deep learning systems offer promising diagnostic support, the traditional manual tuning of hyperparameters for Convolutional Neural Networks is [...] Read more.
Background: Viral Pneumonia and Tuberculosis continue to represent a significant burden on global public health, relying heavily on chest X-rays for screening and diagnosis. Although deep learning systems offer promising diagnostic support, the traditional manual tuning of hyperparameters for Convolutional Neural Networks is often inefficient and computationally expensive, frequently resulting in suboptimal or overly heavy architectures. Methods: To address these challenges, this study proposes a hybrid framework that employs metaheuristic algorithms, specifically the Whale Optimization Algorithm, Grey Wolf Optimizer, and Cuckoo Search to automatically optimize the architecture and training parameters of a custom neural network for the multi-class classification of Normal, Viral Pneumonia, and Tuberculosis cases. The proposed approach was evaluated using a rigorous stratified k-fold cross-validation protocol on a balanced, multi-source dataset. Results: The experimental results demonstrate that the model optimized by the Whale Optimization Algorithm statistically outperforms manually configured baselines, achieving the highest diagnostic accuracy and specificity. Furthermore, a critical finding of this research is the substantial improvement in computational efficiency; the automated optimization reduced the computational load by approximately 74% and the storage requirements by 63%, making the model viable for deployment in resource-constrained environments. Conclusions: Finally, to ensure clinical reliability, the decision-making process was validated using Gradient-weighted Class Activation Mapping, which confirmed that the network successfully learns to identify clinically relevant pulmonary structures while ignoring confounding artifacts. Full article
(This article belongs to the Section Machine Learning and Artificial Intelligence in Diagnostics)
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42 pages, 9695 KB  
Review
Beyond the Scan: Adapting Multimodal Lung Cancer Screening for Central and Eastern Europe—Overcoming Systemic Barriers and Epidemiological Confounders
by Rodica Anghel, Antonia-Ruxandra Folea, Vlad-Luca Moga, Cristian Pavel, Diana Troncotă, Matei Celea, Corneliu-Octavian Dumitru, Andreea-Iren Șerban and Liviu Bîlteanu
Med. Sci. 2026, 14(2), 259; https://doi.org/10.3390/medsci14020259 - 18 May 2026
Viewed by 622
Abstract
Background/Objectives: Lung cancer remains the leading cause of cancer-related mortality in Central and Eastern Europe (CEE), where late-stage diagnosis, structural healthcare limitations, and regional epidemiological confounders complicate early detection. This review aimed to synthesize the evidence from Romania, Poland, Hungary, and Bulgaria and [...] Read more.
Background/Objectives: Lung cancer remains the leading cause of cancer-related mortality in Central and Eastern Europe (CEE), where late-stage diagnosis, structural healthcare limitations, and regional epidemiological confounders complicate early detection. This review aimed to synthesize the evidence from Romania, Poland, Hungary, and Bulgaria and to outline a context-adapted multimodal screening strategy for CEE settings. Methods: A structured review of PubMed-, Scopus-, and Web of Science-indexed literature published from 2010 through 27 December 2025 was performed, focusing on lung cancer epidemiology, screening, implementation barriers, risk stratification, and adjunctive diagnostic approaches in the four selected CEE countries. A total of 297 articles were included. Results: The evidence confirms a persistently high burden of late-stage lung cancer across CEE, driven by tobacco exposure, air pollution, radon, comorbidities, diagnostic delays, fragmented registries, workforce shortages, and marked socioeconomic and geographic inequalities. In addition, tuberculosis-related granulomatous lesions and chronic inflammatory lung disease complicate nodule interpretation and reduce screening specificity in parts of the region. Screening experience from Poland and Hungary supports the feasibility of low-dose computed tomography (LDCT) when paired with volumetric assessment and structured follow-up. Risk-prediction models may improve participant selection, while biological triage may help reduce unnecessary invasive procedures, although prospective validation remains limited. Conclusions: In CEE, lung cancer screening should be implemented as a multimodal, context-adapted program combining risk-based enrollment, volumetric LDCT, selective biological triage, smoking-cessation support, and centralized multidisciplinary delivery. Full article
(This article belongs to the Special Issue Feature Papers in Section “Cancer and Cancer-Related Research”)
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47 pages, 5667 KB  
Review
Infectious Spondylodiscitis of Bacterial Causes in Adults: Epidemiology, Pathophysiology, Diagnostic and Treatment Challenges
by Bogdan Sendrea, Argyrios Periferakis, Aristodemos-Theodoros Periferakis, Ioannis Xefteris, Lamprini Troumpata, Konstantinos Periferakis, Andreea-Elena Scheau, Emi Marinela Preda, Dana-Georgiana Nedelea, Diana-Elena Vulpe, Rares-Mircea Birlutiu, Cristian Scheau and Romica Cergan
Microorganisms 2026, 14(5), 1110; https://doi.org/10.3390/microorganisms14051110 - 13 May 2026
Viewed by 657
Abstract
Spinal infections in general, and infectious spondylodiscitis in particular, are increasingly diagnosed in the Western world, in recent decades. This rise in incidence is associated with an ageing population and with an increased availability of accurate diagnostic modalities. Even so, due to the [...] Read more.
Spinal infections in general, and infectious spondylodiscitis in particular, are increasingly diagnosed in the Western world, in recent decades. This rise in incidence is associated with an ageing population and with an increased availability of accurate diagnostic modalities. Even so, due to the non-specific nature of clinical manifestations, and of the implicated blood and serum markers, there is a risk of underdiagnosis or misdiagnosis of the disease in its initial stages. Ionizing radiation methods, such as plain radiography (X-ray) and computed tomography (CT), are also not reliable in the early stages of the diseases, and the golden standard of imagistic diagnosis, magnetic resonance imaging (MRI), is not always available or requested. Still, MRI remains the most reliable method in most cases where there is a need for differential diagnosis with other pathologies, namely Andersson lesions, destructive spondyloarthropathy, erosive osteochondritis, micro-crystalline spondylitis, Modic 1 lesion, Charcot spinal arthropathy, osteoporotic fractures, SAPHO syndrome with spinal involvement, and Schmorl’s nodes. Infectious spondylodiscitis is caused by bacteria, and, less frequently, by fungi. Rare cases of parasitic causes have also been reported in the literature. Infectious spondylodiscitis of bacterial causes may be pyogenic, more frequently caused by Staphylococcus spp. or Streptococcus spp., or granulomatous, usually caused by Mycobacterium tuberculosis complex (MTBC) or from classical brucellosis. In all these cases, therapy may be conservative, with antibiotics, or surgical, when the former fails or in patients with significant spinal instability or other neurological manifestations. There are various surgical approaches, each with its own drawbacks, and usually used according to the preference of the attending physician. Even in cases of surgical treatment, antibiotic administration is prolonged, and it is important for a proper scheme to be selected based on antimicrobial susceptibility testing. However, given that in many cases, the causative agent cannot be identified, empirical treatment must be initiated. Finally, newer approaches, including the incorporation of antimicrobial substances, may offer better solutions for improving treatment and rehabilitation outcomes. Full article
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16 pages, 5602 KB  
Article
Tailoring Prevention and Control Strategies for Childhood Tuberculosis: From a Global Analysis of Burden Trends and Inequalities Across Three Age Groups (1990–2021) to Prevention and Control Strategies
by Xiaoming Liu, Howard Takiff, Hui Jiang and Weimin Li
Trop. Med. Infect. Dis. 2026, 11(5), 129; https://doi.org/10.3390/tropicalmed11050129 - 9 May 2026
Viewed by 486
Abstract
Background: Childhood tuberculosis (TB) is a major but underappreciated threat to human health. Because diagnosis of tuberculosis in children is difficult, there are a lack of accurate global statistics. This study aimed to comprehensively assess the long-term global, regional, and age-specific burden [...] Read more.
Background: Childhood tuberculosis (TB) is a major but underappreciated threat to human health. Because diagnosis of tuberculosis in children is difficult, there are a lack of accurate global statistics. This study aimed to comprehensively assess the long-term global, regional, and age-specific burden of childhood TB from 1990 to 2021, to examine its temporal trends and socioeconomic inequalities, and to project future patterns through 2045. Methods: We used incidence and mortality data from the GBD 2021 database for TB in children ages 0–14 years from 1990 to 2021. Children were stratified into three age groups—<5, 5–9 and 10–14 years—and classified by region and Socio-Demographic Index (SDI). Multiple statistical approaches were employed, including average annual percentage change and Bayesian age-period-cohort models, to analyze spatiotemporal trends in disease burden and generate projections for the next 20 years. We used decomposition analysis to separate demographic from epidemiological drivers and concentration indices to quantify socioeconomic inequalities. Results: In 2021 there were, globally, an estimated 759,300 incident cases of childhood TB and 70,659 deaths. Since 1990, childhood TB incidence and mortality rates have declined at average annual rates of 2.61% and 4.48%, respectively. The SDI showed a significant negative correlation with both incidence and mortality of childhood TB (p < 0.05). In 2021, 78.01% of childhood TB deaths were in children under 5 years of age, and over 80% of global childhood TB deaths occurred in Sub-Saharan Africa. Epidemiological interventions were partly offset by rapid population growth in low-SDI regions. The trends show that the incidence and mortality will continue to decline through 2045, but not enough to meet the goal of eliminating childhood TB by 2035. Conclusions: Global efforts should adopt an age-specific framework that prioritizes universal preventive treatment to eliminate mortality in children under 5 years, and implements active case finding to reduce transmission chains among children 5–14 years. Sustaining the decrease in the TB burdens of low-SDI regions requires international financing strategies attuned to expanding populations to ensure epidemiological success is not erased by demographic growth. Full article
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13 pages, 518 KB  
Article
Molecular Epidemiology of Drug-Resistant Mycobacterium tuberculosis: Mutation Profiles and Resistance Associations
by Mandlenkosi Manika, Lindiwe Modest Faye, Ntandazo Dlatu and Mojisola Clara Hosu
Microbiol. Res. 2026, 17(5), 93; https://doi.org/10.3390/microbiolres17050093 - 8 May 2026
Viewed by 396
Abstract
Background: The global burden of drug-resistant Mycobacterium tuberculosis continues to threaten tuberculosis control efforts, largely due to the emergence and transmission of resistance-associated genetic mutations. Molecular epidemiology provides critical insights into mutation profiles and resistance associations, yet the interplay among key mutations and [...] Read more.
Background: The global burden of drug-resistant Mycobacterium tuberculosis continues to threaten tuberculosis control efforts, largely due to the emergence and transmission of resistance-associated genetic mutations. Molecular epidemiology provides critical insights into mutation profiles and resistance associations, yet the interplay among key mutations and their contributions to complex resistance patterns remains poorly understood, particularly in high-burden settings. Methods: A retrospective, cross-sectional, laboratory-based design was used to analyze 111 phenotypically confirmed drug-resistant isolates. Molecular drug susceptibility testing (DST) for first- and second-line anti-tuberculosis drugs was performed at the National Health Laboratory Service (NHLS) TB reference laboratory. Drug-resistance profiles were classified according to World Health Organization (WHO) definitions. Descriptive and inferential statistical analyses were conducted to determine mutation frequencies, co-occurrence patterns, and associations with resistance profiles. Results: rpoB (D435V 38.7%; S450L 36.0%) and katG (S315T 80.2%) mutations predominated, forming the core molecular basis of MDR-TB, while 15% harbored inhA promoter mutations associated with low-level isoniazid resistance. The most frequent combinations included rpoB S450L with katG S315T and rpoB D435V with katG S315T, consistent with multidrug-resistant tuberculosis (MDR-TB) profiles. Nearly 48% showed dual resistance to fluoroquinolones and second-line injectables. Conclusion: This study highlights the predominance of resistance-associated mutations and their co-occurrence patterns in shaping MDR-TB profiles in the study setting. The observed burden of second-line drug resistance underscores the importance of comprehensive resistance testing. These findings support the use of mutation profiling for rapid diagnosis and informed treatment decisions, while emphasizing the need for ongoing local surveillance to guide TB control efforts. Full article
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12 pages, 1127 KB  
Article
Predictive Value of Semi-Quantitative GeneXpert Categories for Microbiological Outcomes in Pulmonary Tuberculosis
by Elena Cojocaru, Ioana-Adelina Stoian, Radu-Adrian Crișan-Dabija, Ruxandra Cojocaru, Adriana Ignat and Cristian Cojocaru
Biomedicines 2026, 14(5), 1052; https://doi.org/10.3390/biomedicines14051052 - 6 May 2026
Viewed by 491
Abstract
Background: Molecular testing has improved pulmonary tuberculosis (PTB) diagnosis, but the clinical interpretation of semi-quantitative GeneXpert results—particularly at low bacillary loads—remains uncertain. Methods: This retrospective study included 167 patients with positive GeneXpert results evaluated at a tertiary pneumology hospital between January [...] Read more.
Background: Molecular testing has improved pulmonary tuberculosis (PTB) diagnosis, but the clinical interpretation of semi-quantitative GeneXpert results—particularly at low bacillary loads—remains uncertain. Methods: This retrospective study included 167 patients with positive GeneXpert results evaluated at a tertiary pneumology hospital between January and December 2024. Patients were stratified by culture status. Associations between semi-quantitative GeneXpert categories and smear positivity, culture confirmation, and time to culture positivity were evaluated using logistic regression, ROC analysis, and Cox proportional hazards models. Results: Increasing GeneXpert categories were associated in a graded association with microbiological positivity. Compared with “Very Low”, the odds of smear positivity were higher for “Medium” (OR 36.00, 95% CI 6.49–199.65) and “High” results (OR 328.50, 95% CI 43.29–2492.98). The probability of culture confirmation increased stepwise (0.60 for “Very Low”, 0.79 for “Low”, 0.93 for “Medium”, and 0.92 for “High”; AUC 0.70), indicating that bacillary load is only one of several determinants of culture positivity. Prior tuberculosis and underweight status were associated with “Very Low” results, while cavitary disease was associated with higher categories. Higher GeneXpert categories were also associated with shorter time to culture positivity. Conclusions: Semi-quantitative GeneXpert categories provide clinically relevant information in PTB. “Medium” and “High” results were usually associated with microbiological positivity, whereas “Very Low” results were less reliable and required cautious interpretation. These categories may support early clinical decision-making while culture results are pending. Full article
(This article belongs to the Section Molecular and Translational Medicine)
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26 pages, 1601 KB  
Review
RISK6  as a Translational Host Transcriptomic Signature for Tuberculosis Diagnosis, Treatment Monitoring, and Risk Stratification 
by Chrispian Mamudi, Purnamawati, Panca Andana, Prayudi Santoso, Lidya Chaidir and Arto Soeroto
Pathogens 2026, 15(5), 489; https://doi.org/10.3390/pathogens15050489 - 1 May 2026
Viewed by 415
Abstract
Tuberculosis (TB) remains a leading cause of infectious mortality worldwide, reflecting persistent gaps in diagnosis, risk stratification, and treatment monitoring. Host RNA transcriptomic signatures have emerged as promising tools for capturing dynamic immune responses across the TB disease spectrum. Among these, the six-gene [...] Read more.
Tuberculosis (TB) remains a leading cause of infectious mortality worldwide, reflecting persistent gaps in diagnosis, risk stratification, and treatment monitoring. Host RNA transcriptomic signatures have emerged as promising tools for capturing dynamic immune responses across the TB disease spectrum. Among these, the six-gene RISK6 signature has attracted attention due to its parsimonious design and potential for clinical translation. This review provides a clinically oriented synthesis of current evidence on host transcriptomic biomarkers, with a particular focus on the application of RISK6 in diagnosis, prediction of disease progression, and treatment monitoring. Available data suggest that RISK6 demonstrates promising but context-dependent diagnostic performance and represents a versatile host-response biomarker across multiple clinical applications. However, variability across populations and the limited evidence in multidrug-resistant TB remain important constraints. In practice, RISK6 is unlikely to function optimally as a standalone biomarker. Its clinical value appears greater when interpreted within integrated frameworks that combine transcriptomic, microbiological, and clinical data. Further validation in diverse populations and real-world settings will be essential to support meaningful clinical implementation. Full article
(This article belongs to the Section Bacterial Pathogens)
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Article
Depressive Symptoms in Pediatric Tuberculosis: A Retrospective Two-Time-Point Observational Study
by Oana Mariana Mihailov, Loredana Stavăr Matei, George Țocu, Valerii Luțenco, Cosmin George Popovici and Raul Mihailov
Diseases 2026, 14(5), 157; https://doi.org/10.3390/diseases14050157 - 29 Apr 2026
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Abstract
Background: Tuberculosis (TB) in children is associated not only with infectious burden but also with potential psychological distress, which remains insufficiently explored. The aim of this study was to evaluate the pattern and evolution of depressive symptoms in pediatric TB patients during treatment [...] Read more.
Background: Tuberculosis (TB) in children is associated not only with infectious burden but also with potential psychological distress, which remains insufficiently explored. The aim of this study was to evaluate the pattern and evolution of depressive symptoms in pediatric TB patients during treatment using a structured screening approach. Methods: We conducted a retrospective observational study including 190 pediatric patients aged 7–18 years diagnosed with tuberculosis between 2019 and 2021. Depressive symptoms were assessed at two time points, namely at diagnosis (T0) and at first follow-up (T1), using a 10-item structured clinical screening tool routinely applied in practice. A threshold of ≥50% affirmative responses was used to identify patients with suspected depressive symptoms. The Children’s Depression Inventory (CDI) was administered to patients with positive screening results, according to standard clinical protocols. Descriptive and comparative analyses were performed to evaluate changes over time. Results: A high proportion of patients screened positive for depressive symptoms at baseline (T0). At follow-up (T1), a reduction in the proportion of patients with suspected depressive symptoms was observed; however, a substantial number of patients continued to report symptoms suggestive of emotional distress. Most symptom changes between T0 and T1 were not statistically significant, with the exception of decreased appetite, which showed a modest improvement. The overall pattern suggests persistence of symptoms in a subset of patients over time. Conclusions: These findings suggest that symptoms indicative of psychological distress are common among pediatric TB patients and may persist during treatment. However, given the use of a non-validated screening tool and the retrospective design, the results should be interpreted with caution. The study highlights the potential value of systematic psychological assessment in this population and supports the need for further research using validated instruments. Full article
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