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Objective: To conduct a systematic review of the computer vision applications that detect, diagnose, or analyse tuberculosis (TB) pathology or bacilli using digitised human lung tissue images either through automatic or semi-automatic methods. We categorised the computer vision platform into four technologies: image processing, object/pattern recognition, computer graphics, and deep learning. In this paper, the focus is on image processing and deep learning (DL) applications for either 2D or 3D digitised human lung tissue images. This review is useful for establishing a common practice in TB analysis using human lung tissue as well as identifying opportunities for further research in this space. The review brings attention to the state-of-art techniques for detecting TB, with emphasis on the challenges and limitations of the current techniques. The ultimate goal is to promote the development of more efficient and accurate algorithms for the detection or analysis of TB, and raise awareness about the importance of early detection., Design: We searched five databases and Google Scholar for articles published between January 2017 and December 2022 that focus on Mycobacterium tuberculosis detection, or tuberculosis pathology using digitised human lung tissue images. Details regarding design, image processing and computer-aided techniques, deep learning models, and datasets were collected and summarised. Discussions, analysis, and comparisons of state-of-the-art methods are provided to help guide future research. Further, a brief update on the relevant techniques and their performance is provided., Results: Several studies have been conducted to develop automated and AI-assisted methods for diagnosing Mtb and TB pathology from digitised human lung tissue images. Some studies presented a completely automated method of diagnosis, while other studies developed AI-assisted diagnostic methods. Low-level focus areas included the development of a novel μ CT scanner for soft tissue image contract, and use of multiresolution computed tomography to analyse the 3D structure of the human lung. High-level focus areas included the investigation the effects of aging on the number and size of small airways in the lungs using CT and whole lung high-resolution μ CT, and the 3D microanatomy characterisation of human tuberculosis lung using μ CT in conjunction with histology and immunohistochemistry. Additionally, a novel method for acquiring high-resolution 3D images of human lung structure and topology is also presented., Conclusion: The literature indicates that post 1950s, TB was predominantly studied using animal models even though no animal model reflects the full spectrum of human pulmonary TB disease and does not reproducibly transmit Mtb infection to other animals (Hunter, 2011). This explains why there are very few studies that used human lung tissue for detection or analysis of Mtb. Nonetheless, we found 10 studies that used human tissues (predominately lung) of which five studies proposed machine learning (ML) models for the detection of bacilli and the other five used CT on human lung tissue scanned ex-vivo., (© 2024. The Author(s).)

Aims: The aim is to describe lung ultrasound (LUS) findings in a cohort of patients with suspected pulmonary tuberculosis (PTB) and compare them with computed tomography (CT) and chest x-ray (CXR) findings in order to evaluate the potentiality of LUS in TB diagnosis., Methods: In this prospective study, 82 subjects with suspected TB were enrolled after being evaluated with CXR and chest CT. LUS was performed by blinded radiologists within 3 days after admission. A semiquantitative index was used: score 1 (lesions that extend for about 1-15% of the affected zone), score 2 (15-40%) and score 3 (40-100%)., Results: Microbiological analysis confirmed TB diagnosis in 58/82 (70.7%). CT was positive in all patients, LUS in 79/82 (96.3%) CXR in 78/82 (95.1%) and adding LUS and CXR in 100%. In PTB patients we found a great number of lungs zones with micronodules and with total findings than non-TPB patients (p < 0.05). Overall LUS sensitivity was 80%, greater for micronodules (82%) and nodules (95%), lower for consolidation with air bronchogram (72%) and cavitations (33%). We reported 5 complicated pleural effusion at LUS, only 1 in CT. CXR overall sensitivity was 81%. Adding CXR and LUS findings we reported a sensitivity of 90%., Conclusions: LUS could be considered a valid, non-invasive and cost-effective diagnostic tool especially in world regions where CT were not available, also in addiction with CXR., Trial Registration: This study was approved by the Ethics Committee of our University Hospital (rif. CEAVC 14,816)., (© 2021. Società Italiana di Ultrasonologia in Medicina e Biologia (SIUMB).)

Rationale: Our current understanding of tuberculosis (TB) pathophysiology is limited by a reliance on animal models, the paucity of human TB lung tissue, and traditional histopathological analysis, a destructive two-dimensional approach that provides limited spatial insight. Determining the three-dimensional (3D) structure of the necrotic granuloma, a characteristic feature of TB, will more accurately inform preventive TB strategies. Objectives: To ascertain the 3D shape of the human tuberculous granuloma and its spatial relationship with airways and vasculature within large lung tissues. Methods: We characterized the 3D microanatomical environment of human tuberculous lungs by using micro computed tomography, histopathology, and immunohistochemistry. By using 3D segmentation software, we accurately reconstructed TB granulomas, vasculature, and airways in three dimensions and confirmed our findings by using histopathology and immunohistochemistry. Measurements and Main Results: We observed marked heterogeneity in the morphology, volume, and number of TB granulomas in human lung sections. Unlike depictions of granulomas as simple spherical structures, human necrotic granulomas exhibit complex, cylindrical, branched morphologies that are connected to the airways and shaped by the bronchi. The use of 3D imaging of human TB lung sections provides unanticipated insight into the spatial organization of TB granulomas in relation to the airways and vasculature. Conclusions: Our findings highlight the likelihood that a single, structurally complex lesion could be mistakenly viewed as multiple independent lesions when evaluated in two dimensions. In addition, the lack of vascularization within obstructed bronchi establishes a paradigm for antimycobacterial drug tolerance. Lastly, our results suggest that bronchogenic spread of Mycobacterium tuberculosis reseeds the lung.

Recently, the number of artificial intelligence powered computer-aided detection (CAD) products that detect tuberculosis (TB)-related abnormalities from chest X-rays (CXR) available on the market has increased. Although CXR is a relatively effective and inexpensive method for TB screening and triaging, a shortage of skilled radiologists in many high TB-burden countries limits its use. CAD technology offers a solution to this problem. Before adopting a CAD product, TB programmes need to consider not only the diagnostic accuracy but also implementation-relevant features including operational characteristics, deployment mechanism, input and machine compatibility, output format, options for integration into the legacy system, costs, data sharing and privacy aspects, and certification. A landscaping analysis was conducted to collect this information among CAD developers known to have or soon to have a TB product. The responses were reviewed and finalized with the developers, and are published on an open-access website: www.ai4hlth.org. CAD products are constantly being improved and the site will continuously be updated to account for updates and new products. This unique online resource aims to inform the TB community about available CAD tools, their features and set-up procedures, to enable TB programmes to identify the most suitable product to incorporate in interventions., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Bronchoscopy using radial probe endobronchial ultrasound (EBUS) is performed when a peripheral lung lesion (PLL) is suspected to be malignant. However, pulmonary tuberculosis is diagnosed in some patients, and healthcare workers could therefore be exposed to tuberculosis if sufficient precautions are not taken. In this study, we examined the proportion of and factors associated with unexpected exposure to Mycobacterium tuberculosis during bronchoscopy using radial probe EBUS., Methods: This retrospective study included 970 patients who received bronchoscopy using radial probe EBUS between December 2015 and November 2018. Clinical, histological, radiological, and microbiological data were reviewed., Results: Pulmonary tuberculosis was diagnosed in 31 patients (3.2%) during bronchoscopy using radial probe EBUS. Patients with a lower age were significantly more likely to be diagnosed with tuberculosis than elderly patients (odds ratio [OR], 0.951; 95% confidence interval [CI], 0.924-0.978; P = 0.001). Among the various CT findings, a low HUs difference between pre- and post-enhanced CT (OR, 0.976; 95% CI, 0.955-0.996; P = 0.022), the presence of concentric cavitation (OR, 5.211; 95% CI, 1.447-18.759; P = 0.012), and the presence of satellite centrilobular nodules (OR, 22.925; 95% CI, 10.556-49.785; P < 0.001) were independently associated with diagnosis of tuberculosis., Conclusions: The proportion of unexpected exposure to Mycobacterium tuberculosis during bronchoscopy using radial probe EBUS was 3.2%. A higher risk was independently associated with a younger age and CT findings of a small difference in HUs between pre- and post-enhancement images, concentric cavitation, and the presence of a satellite centrilobular nodule., Competing Interests: The authors have declared that no competing interests exist.

Background: Deep learning-based radiological image analysis could facilitate use of chest x-rays as triage tests for pulmonary tuberculosis in resource-limited settings. We sought to determine whether commercially available chest x-ray analysis software meet WHO recommendations for minimal sensitivity and specificity as pulmonary tuberculosis triage tests., Methods: We recruited symptomatic adults at the Indus Hospital, Karachi, Pakistan. We compared two software, qXR version 2.0 (qXRv2) and CAD4TB version 6.0 (CAD4TBv6), with a reference of mycobacterial culture of two sputa. We assessed qXRv2 using its manufacturer prespecified threshold score for chest x-ray classification as tuberculosis present versus not present. For CAD4TBv6, we used a data-derived threshold, because it does not have a prespecified one. We tested for non-inferiority to preset WHO recommendations (0·90 for sensitivity, 0·70 for specificity) using a non-inferiority limit of 0·05. We identified factors associated with accuracy by stratification and logistic regression., Findings: We included 2198 (92·7%) of 2370 enrolled participants. 2187 (99·5%) of 2198 were HIV-negative, and 272 (12·4%) had culture-confirmed pulmonary tuberculosis. For both software, accuracy was non-inferior to WHO-recommended minimum values (qXRv2 sensitivity 0·93 [95% CI 0·89-0·95], non-inferiority p=0·0002; CAD4TBv6 sensitivity 0·93 [0·90-0·96], p<0·0001; qXRv2 specificity 0·75 [0·73-0·77], p<0·0001; CAD4TBv6 specificity 0·69 [0·67-0·71], p=0·0003). Sensitivity was lower in smear-negative pulmonary tuberculosis for both software, and in women for CAD4TBv6. Specificity was lower in men and in those with previous tuberculosis, and reduced with increasing age and decreasing body mass index. Smoking and diabetes did not affect accuracy., Interpretation: In an HIV-negative population, these software met WHO-recommended minimal accuracy for pulmonary tuberculosis triage tests. Sensitivity will be lower when smear-negative pulmonary tuberculosis is more prevalent., Funding: Canadian Institutes of Health Research., (Copyright © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Objective of Study: This study is designed to assess risk factors & magnitude of residual radiological lesion in patients treated for pulmonary tuberculosis., Methods: This is a retrospective observational cohort study which included patients who were newly diagnosed as pulmonary tuberculosis and have completed 6 months of treatment., Statistical Analysis: Categorical data were expressed as proportion and continuous data were expressed as mean ± SD. The obtained data were analysed by means of frequency distribution table and descriptive statistics using SPSS version 20 for Windows (SPSS Inc., Chicago, Ill, USA) and Chi-square test and student t test were used for statistical analysis. We assessed association between risk factors and development of radiological sequelae, using univariate statistical analysis and odds ratio. P-values less than 0.05 were considered statistically significant., Results: Data from 128 patients was used for analysis. The average age in this cohort was 32.84 ± 17.47 years and 68.75% patients were male. Residual x-ray lesions were observed in 92 (71.87%) cases out of 128 study patients. 72.82% of residual lesions appeared as parenchymal fibrosis, 13.04% as bronchiectasis, 2.17% as cavity & 3.26% appeared as calcification. Patients with advanced lesions (34.78% vs 16.66%), bilateral lesions (29.34% vs 11.11%) or cavity (18.47% vs 2.77%) in chest x-ray or Sputum smear positivity for AFB were found to have significant radiological sequelae. Among the variables associated with the risk of having pulmonary tuberculosis sequelae were cavity (OR: 7.03), sputum smear positive for AFB (OR: 4.03), Advanced lesions (OR: 3.38) & bilateral lesions (OR: 2.90) in chest x-ray., Conclusion: This study concluded that a large number of patients remain with residual radiological sequelae despite good clinical response. Patients with extensive lesions, presence of cavity or bilateral involvement in chest x-ray and sputum smear positive for acid fast bacilli were often associated with residual radiological opacity., Competing Interests: Declaration of competing interest The authors have none to declare., (Copyright © 2020 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.)

Statistical shape analysis of lung is a reliable alternative method for diagnosing pulmonary diseases such as tuberculosis (TB). The 2D contour-based lung shape analysis is investigated and developed using Fourier descriptors (FDs). The proposed 2D lung shape analysis is carried out in threefold: (1) represent the normal and the abnormal (i.e. pulmonary tuberculosis (PTB)) lung shape models using Fourier descriptors modeling (FDM) framework from chest X-ray (CXR) images, (2) estimate and compare the 2D inter-patient lung shape variations for the normal and abnormal lungs by applying principal component analysis (PCA) techniques, and (3) describe the optimal type of contour-based feature vectors to train a classifier in order to detect TB using one publicly available dataset-namely the Montgomery dataset. Since almost all of the previous works in lung shape analysis are content-based analysis, we proposed contour-based lung shape analysis for statistical modeling and feature description of PTB cases. The results show that the proposed approach is able to explain more than 95% of total variations in both of the normal and PTB cases using only 6 and 7 principal component modes for the right and the left lungs, respectively. In case of PTB detection, using 138 lung cases (80 normal and 58 PTB cases), we achieved the accuracy (ACC) and the area under the curve (AUC) of 82.03% and 88.75%, respectively. In comparison with existing state-of-art studies in the same dataset, the proposed approach is a very promising supplement for diagnosis of PTB disease. The method is robust and valuable for application in 2D automatic segmentation, classification, and atlas registration. Moreover, the approach could be used for any kind of pulmonary diseases. Graphical abstract Contour-based lung shape analysis in order to detect tuberculosis: modeling and feature description.

Introduction: Non-tuberculous mycobacteria pulmonary disease (NTM-pd) commonly complicates bronchiectasis. However, clinical and radiological features of NTM-pd and bronchiectasis are very similar. We aimed to develop a radiologic prediction tool for bronchiectasis to identify NTM-pd., Methods: We reviewed clinical, laboratory and radiological data in patients with bronchiectasis. Radiologic features on CT scans and the individual components of the Bhalla scoring system were compared between people with and without NTM-pd. Logistic regression and receiver-operating curve (ROC) analysis were performed to predict NTM-pd., Results: People with NTM-pd had more pulmonary segments with bronchiectasis (13 ± 5 vs. 11 ± 5, p = 0.03), presence of mucus plugging (47% vs. 19%, p < 0.0001) and tree in bud infiltrates (53% vs. 28%, p = 0.004). The total modified- Bhalla score was worse among people with NTM-pd (median [IQR] 11[9,13] vs. 9[8,12], p = 0.03). Logistic regression identified the number of pulmonary segments involved, presence of bullae, consolidations, and a total score of 10 or more to be independently associated with presence of NTM-pd. ROC analysis with radiographic variables only identified an AUC of 0.706 (95% CI 0.644-0.762). When people with chronic Pseudomonas infection were excluded from the ROC analysis, prediction for NTM was improved: AUC = 0.87 (95% CI 0.796-0.945)., Discussion and Conclusions: Radiological features together with advanced age and female gender may predict NTM-pd among people with bronchiectasis. Infection with Pseudomonas aeruginosa may resemble NTM radiographically, and this prediction rule may better differentiate people with and without NTM-pd when Pseudomonas infection is not present.

Objective: To investigate the prevalence, patient characteristics, and natural history of clustered micronodules (CMs) in active pulmonary tuberculosis., Materials and Methods: From January 2013 through July 2018, 833 consecutive patients with bacteriologically or polymerase chain reaction-proven active pulmonary tuberculosis were retrospectively evaluated. CMs were defined as a localized aggregation of multiple dense discrete micronodules, which primarily distributed around small airways distal to the level of the segmental bronchus: small airways surrounded by CMs maintained luminal patency and the CMs might coalesce into a larger nodule. The patients were dichotomized according to whether the predominant computed tomography (CT) abnormalities were CMs. We analyzed radiologic and pathologic findings in patients whose predominant diagnostic CT abnormalities were CMs, along with those of incidental pre-diagnostic CT scans, if available. Chi-square, McNemar, Student t-test and Wilcoxon-signed rank test were performed., Results: CMs were the predominant CT abnormality in 2.6% of the patients (22/833, 95% CI, 1.8-4.0%) with less sputum smear-positivity (4.8% vs 31.0%; p = .010) and a similar proportion of immunocompromised status (40.9% vs 46.0%; p = .637) than those without having CMs as the predominant CT abnormality. The time interval for minimal radiologic progression was 6.4 months. The extent of CMs increased with disease progression, frequently accompanied by consolidation and small airway wall thickening. Pathologically, smaller CMs were non-caseating granulomas confined to the peribronchiolar interstitium, whereas larger CMs were caseating granulomas involving lung parenchyma. Two of the five patients with a pre-diagnostic CT scan obtained more than 50 months pre-diagnosis showed an incipient stage of CMs, in which they were small peribronchiolar nodules., Conclusion: Active pulmonary tuberculosis manifested predominantly as CMs in 2.6% of patients, with scarce of acid-fast bacilli smear-positivity and no association with impaired host immunity. CMs indolently progressed, accompanied by consolidation and small airway wall thickening, and originated from small nodules., Competing Interests: NO authors have competing interests.

Efforts to develop effective and safe drugs for treatment of tuberculosis require preclinical evaluation in animal models. Alongside efficacy testing of novel therapies, effects on pulmonary pathology and disease progression are monitored by using histopathology images from these infected animals. To compare the severity of disease across treatment cohorts, pathologists have historically assigned a semi-quantitative histopathology score that may be subjective in terms of their training, experience, and personal bias. Manual histopathology therefore has limitations regarding reproducibility between studies and pathologists, potentially masking successful treatments. This report describes a pathologist-assistive software tool that reduces these user limitations, while providing a rapid, quantitative scoring system for digital histopathology image analysis. The software, called 'Lesion Image Recognition and Analysis' (LIRA), employs convolutional neural networks to classify seven different pathology features, including three different lesion types from pulmonary tissues of the C3HeB/FeJ tuberculosis mouse model. LIRA was developed to improve the efficiency of histopathology analysis for mouse tuberculosis infection models, this approach has also broader applications to other disease models and tissues. The full source code and documentation is available from https://Github.com/TB-imaging/LIRA.

Context: Chest radiographs have been used worldwide as a screening tool before employment and training, by various healthcare and other government and nongovernment institutions. Many studies done in the past have demonstrated a relatively low yield for tuberculosis detection and therefore, the authors have questioned this practice., Aims: To compare the value of the preadmission/employment chest radiograph in two groups, namely, those who have been previously exposed to a healthcare setting (post-exposure group) and those who have not been exposed (pre-exposure group) and to determine if there is a significant difference in tuberculosis detection between these two groups., Settings and Design: A retrospective review of the reports of the chest radiographs of all candidates appearing for admission to various undergraduate and postgraduate courses in our institute between 2014 and 2017 was performed., Materials and Methods: The various abnormalities detected were recorded and the findings in the two groups were compared., Statistical Analysis Used: Chi-square test was used to compare between two group proportions., Results: Thirty out of 4333 (0.69%) candidates in the pre-exposure group and 53 out of 3379 (1.57%) candidates in the post-exposure group showed abnormalities on chest radiographs involving the lung parenchyma, mediastinum, heart, or pleura. In the pre-exposure group, six (0.14%) were found to have underlying cardiac disease and one (0.02%) had tuberculosis. Among the six candidates in the post-exposure group who underwent further investigations in our institute, five (0.15%) were diagnosed to have tuberculosis. Although there was no statistically significant difference in tuberculosis detection between the groups (P = 0.051), there is a trend towards higher detection of tuberculosis in the post-exposure group., Conclusions: In a country where the prevalence of tuberculosis is high, the pre-employment chest radiograph may still have a role in detecting tuberculosis in the post-exposure group., Competing Interests: None

Objective: To compare patients with and without previous lung disease, in terms of the spirometry results after they had been treated for pulmonary tuberculosis (PTB) and cured, as well as to analyze risk factors related to functional severity., Methods: This was a cross-sectional, multicenter study conducted at four referral centers in Brazil. Patients were divided into two groups: those with a history of lung disease or smoking (LDS+ group); and those with no such history (LDS- group). Patients underwent spirometry (at least six months after being cured). Sociodemographic and clinical data were collected., Results: A total of 378 patients were included: 174 (46.1%) in the LDS+ group and 204 (53.9%) in the LDS- group. In the sample as a whole, 238 patients (62.7%) had spirometric changes. In the LDS+ group, there was a predominance of obstructive lung disease (in 33.3%), whereas restrictive lung disease predominated in the LDS- group (in 24.7%). Radiological changes were less common in the LDS- group than in the LDS+ group (p < 0.01), as were functional changes (p < 0.05). However, of the 140 (79.1%) LDS- group patients with a normal or minimally altered chest X-ray, 76 (54%) had functional changes (p < 0.01). The risk factors associated with functional severity in the LDS- group were degree of dyspnea (p = 0.03) and moderate or severe radiological changes (p = 0.01)., Conclusions: Impaired pulmonary function is common after treatment for PTB, regardless of the history of lung disease or smoking. Spirometry should be suggested for patients who develop moderate/severe dyspnea or relevant radiological changes after treatment for PTB.

Objective: To evaluate the radiological presentation of patients with pulmonary tuberculosis diagnosed in the emergency department and to investigate its association with the time to diagnosis., Methods: This was a prospective observational study involving patients diagnosed with pulmonary tuberculosis in the emergency department of a tertiary university hospital in southern Brazil. Chest X-rays taken on admission were evaluated by a radiologist. The various patterns of radiological findings and locations of the lesions were described. The main study outcome was the total time elapsed between the initial radiological examination and the diagnosis of tuberculosis., Results: A total of 78 patients were included in the study. The median time from chest X-ray to diagnosis was 2 days, early and delayed diagnosis being defined as a time to diagnosis < 2 days and ≥ 2 days, respectively. Sputum smear positivity was associated with early diagnosis (p = 0.005), and positive culture was associated with delayed diagnosis (p = 0.005). Early diagnosis was associated with the presence of sputum (p = 0.03), weight loss (p = 0.047), cavitation (p = 0.001), and consolidation (p = 0.003). Pulmonary cavitation was found to be an independent predictor of early diagnosis (OR = 3.50; p = 0.028)., Conclusions: There is a need for tuberculosis-specific protocols in emergency departments, not only to avoid delays in diagnosis and treatment but also to modify the transmission dynamics of the disease.

The sensitivity of in vivo low-dose high-resolution micro-computed tomography imaging enables monitoring the lung damage caused by tuberculosis. Here, we propose a radiological score integrated in the experimental workflow that enables longitudinal monitoring for prospective efficacy studies in drug development programs. The score is based on an automatic measurement of total unaffected lung volume in vivo normalized for inter-subject comparison. It was validated on well-characterized progression of chronic tuberculosis in Erdman and H37Rv strains in C3HeB/FeJ-based models. We demonstrated that a decrease in the score value indicates increasing adverse effects and vice versa. The colony-forming units count confirmed the variability in the host response suggested by the score values. The correlation between changes in the mice's weight and the score is consistent with disease progression. The classification of disease extent by k-means clustering of the score values provided the definition of the lung damage severity according to the bacillus strain. The proposed score will reduce sources of bias and improve the statistical robustness of studies by the attrition of non-infected subjects or subjects with a weak immune response. Readily available quantifications allow for a fast assessment of the therapeutic potential in drug-resistant tuberculosis strains., (Copyright © 2020. Published by Elsevier Ltd.)

Background: Diabetes mellitus (DM) is thought to affect tuberculosis (TB) clinical presentation and treatment response. Whether DM impacts radiological manifestations of pulmonary TB is still not clear. This study investigated the impact of glycemic status on radiological manifestations of pulmonary TB cases and its relationship with concentration of biochemical parameters in peripheral blood., Methods: A retrospective cross-sectional study used data from 132 microbiologically confirmed pulmonary TB patients from Lima, Peru, evaluated in a previous investigation performed between February and December 2017. Chest radiographs were analyzed by a radiologist and a pulmonologist. Radiographic lesions were identified as cavities, alveolar infiltrates and fibrous tracts. Hyperglycemia in TB patients was identified by use of fasting plasma glucose, HbA1c and oral glucose tolerance test. Clinical, biochemical and hematological parameters were also analyzed., Results: TB patients with hyperglycemia presented more frequently with cavities, alveolar infiltrates and fibrous tracts than those with normoglycemia. Hierarchical clustering analysis indicated that patients with more diverse and higher number of lung lesions exhibited a distinct laboratorial profile characterized by heightened white blood cell counts and circulating levels of total cholesterol, triglycerides and transaminases and simultaneously low levels of albumin and hemoglobin. Multivariable regression analyses adjusted for age, sex, prior TB, hemoglobin levels and acid-fast bacilli ≥2+ in sputum smears, demonstrated that presence of prediabetes or diabetes in TB patients was associated with increased odds of having 3 pulmonary lesion types (p = 0.003 and p < 0.01 respectively) or ≥ 4 lesions (p = 0.001 and p = 0.01 respectively)., Conclusion: Hyperglycemia (both DM and prediabetes) significantly affected the presentation of radiographic manifestations and the number of lesions in pulmonary TB patients as well as the biochemical profile in peripheral blood.

The main surgical approaches to the treatment of pulmonary tuberculosis were developed and introduced into surgical practice in the 60s of the last century. However, epidemiological changes and new medical technologies justify advisability of further improvement of surgical management of pulmonary tuberculosis. Computed tomography with 3D-nodeling and preoperative planning are valuable to analyze spread of pathological process and visualize pulmonary structures for improvement of surgical treatment.

Hollow organs such as the lungs pose a considerable challenge for post-mortem imaging in preclinical research owing to their extremely low contrast and high structural complexity. The aim of our study was to enhance the contrast of tuberculosis lesions for their stratification by 3D x-ray-based virtual slicing. Organ samples were taken from five control and five tuberculosis-infected mice. Micro-Computed Tomography (CT) scans of the subjects were acquired in vivo (without contrast agent) and post-mortem (with contrast agent). The proposed contrast-enhancing technique consists of x-ray contrast agent uptake (silver nitrate and iodine) by immersion. To create the histology ground-truth, the CT scan of the paraffin block guided the sectioning towards specific planes of interest. The digitalized histological slides reveal the presence, extent, and appearance of the contrast agents in lung structures and organized aggregates of immune cells. These findings correlate with the contrast-enhanced micro-CT slice. The abnormal densities in the lungs due to tuberculosis disease are concentrated in the right tail of the lung intensity histograms. The increase in the width of the right tail (~376%) indicates a contrast enhancement of the details of the abnormal densities. Postmortem contrast agents enhance the x-ray attenuation in tuberculosis lesions to allow 3D visualization by polychromatic x-ray CT, providing an advantageous tool for virtual slicing of whole lungs. The proposed contrast-enhancing technique combined with computational methods and the diverse micro-CT modalities will open the doors to the stratification of lesion types associated with infectious diseases.

Purpose: To fast and accurately reconstruct human lung gas MRI from highly undersampled k-space using deep learning., Methods: The scheme was comprised of coarse-to-fine nets (C-net and F-net). Zero-filling images from retrospectively undersampled k-space at an acceleration factor of 4 were used as input for C-net, and then output intermediate results which were fed into F-net. During training, a L2 loss function was adopted in C-net, while a function that united L2 loss with proton prior knowledge was used in F-net. The 871 hyperpolarized 129 Xe pulmonary ventilation images from 72 volunteers were randomly arranged as training (90%) and testing (10%) data. Ventilation defect percentage comparisons were implemented using a paired 2-tailed Student's t-test and correlation analysis. Furthermore, prospective acquisitions were demonstrated in 5 healthy subjects and 5 asymptomatic smokers., Results: Each image with size of 96 × 84 could be reconstructed within 31 ms (mean absolute error was 4.35% and structural similarity was 0.7558). Compared with conventional compressed sensing MRI, the mean absolute error decreased by 17.92%, but the structural similarity increased by 6.33%. For ventilation defect percentage, there were no significant differences between the fully sampled and reconstructed images through the proposed algorithm (P = 0.932), but had significant correlations (r = 0.975; P < 0.001). The prospectively undersampled results validated a good agreement with fully sampled images, with no significant differences in ventilation defect percentage but significantly higher signal-to-noise ratio values., Conclusion: The proposed algorithm outperformed classical undersampling methods, paving the way for future use of deep learning in real-time and accurate reconstruction of gas MRI., (© 2019 International Society for Magnetic Resonance in Medicine.)

SETTING: The Korea National Health and Nutrition Examination Survey is a national, population-based, cross-sectional surveillance programme. OBJECTIVE: 1) To investigate the prevalence of spontaneously healed pulmonary tuberculosis (SHPTB) on chest radiographs (CXRs) in South Korea, as well as its demographic and clinical associations, and 2) to determine the relationship between SHPTB and smoking. DESIGN: People with normal findings on CXRs ( n = 24 190) and those with SHPTB ( n = 1863) were compared in univariate, bivariate and multivariate analyses with respect to smoking and demographic and clinical factors. RESULTS: The prevalence of SHPTB was 7.2%. The proportion of patients with SHPTB tended to be higher in males, people of older age, ever smokers, as well as people with low body mass index and low education level. In bivariate analysis, after adjustments for age and sex, SHPTB was found more often among ex-smokers ( P = 0.005) and current smokers ( P = 0.024) than in non-smokers. Multivariate analyses revealed increased relative odds for SHPTB with increased age ( P < 0.001), male sex ( P < 0.001) and ex-smoker status ( P = 0.016). Passive smoking was also significantly associated with SHPTB ( P = 0.022). CONCLUSION: In addition to increasing the risk of active TB and negatively affecting the outcome of TB treatment, smoking is also associated with SHPTB, as detected on CXRs.

Objectives: The validity of lung ultrasound (LUS) in the diagnosis of interstitial or focal lung pathologies is well documented, we assessed its accuracy in the diagnosis of pulmonary tuberculosis (PTB)., Methods: Sonographic signs suggestive of PTB and their diagnostic accuracy were evaluated in patients admitted with clinical suspicion of PTB. Consolidations, subpleural nodules, pleural thickenings or irregularities and pleural effusion were assessed. LUS signs significantly associated with PTB in the univariate analysis (p < .05) were entered in a multivariate logistic regression model., Results: PTB was confirmed in 51 out of 102 patients. Multiple consolidations (OR 3.54, 95%CI 1.43-8.78), apical consolidations (OR 9.65, 95%CI 3.02-30.78), superior quadrant consolidations (OR 4.01, 95%CI 1.76-9.14), and subpleural nodules (OR 5.29, 95%CI 2.27-12.33) were significantly associated with PTB diagnosis. Apical consolidation (OR 9.67, 95%CI 2.81-33.25, p 0.003) and subpleural nodules (OR 5.30, 95%CI 2.08-13.52, p 0.005) retained a significant association in a multivariate model, with an overall accuracy of 0.799., Conclusions: Our data suggest a possible role of LUS in the diagnosis of PTB, a high burden pathological condition for which the delay in diagnosis still represents a critical point in the control of the disease., (Copyright © 2019 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Background and Objective: Chest X-ray (CXR) is one of the most used imaging techniques for detection and diagnosis of pulmonary diseases. A critical component in any computer-aided system, for either detection or diagnosis in digital CXR, is the automatic segmentation of the lung field. One of the main challenges inherent to this task is to include in the segmentation the lung regions overlapped by dense abnormalities, also known as opacities, which can be caused by diseases such as tuberculosis and pneumonia. This specific task is difficult because opacities frequently reach high intensity values which can be incorrectly interpreted by an automatic method as the lung boundary, and as a consequence, this creates a challenge in the segmentation process, because the chances of incomplete segmentations are increased considerably. The purpose of this work is to propose a method for automatic segmentation of lungs in CXR that addresses this problem by reconstructing the lung regions "lost" due to pulmonary abnormalities., Methods: The proposed method, which features two deep convolutional neural network models, consists of four steps main steps: (1) image acquisition, (2) initial segmentation, (3) reconstruction and (4) final segmentation., Results: The proposed method was experimented on 138 Chest X-ray images from Montgomery County's Tuberculosis Control Program, and has achieved as best result an average sensitivity of 97.54%, an average specificity of 96.79%, an average accuracy of 96.97%, an average Dice coefficient of 94%, and an average Jaccard index of 88.07%., Conclusions: We demonstrate in our lung segmentation method that the problem of dense abnormalities in Chest X-rays can be efficiently addressed by performing a reconstruction step based on a deep convolutional neural network model., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The lung acinus is the most distal portion of the airway responsible for the gas exchange. The normal acini are not visible on conventional computed tomography (CT), but the advent of micro-CT improved the understanding of the microarchitecture of healthy acini. The comprehension of the acinar architecture is pivotal for the understanding of CT findings of diseases that involve the acini. Centriacinar emphysema, for example, presents as round areas of low attenuation due to the destruction of the most central acini with compensatory enlargement of proximal acini due to alveolar wall destruction. In pulmonary fibrosis, intralobular septal fibrosis manifests as acinar wall thickening with an overlap of acinar collapse and compensatory dilation of surrounding acini constituting the cystic disease typical of the usual interstitial pneumonia pattern. This is a state-of-the-art review to describe the acinar structure from the micro-CT perspective and display how the comprehension of the acinar structure can aid in the interpretation of its microarchitecture disruption on conventional CT.

Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Background: The role of cytomorphology in differentiating sarcoidosis from tuberculosis is not fully elucidated. Herein, we evaluate the utility of cytological features in differentiating between these two diseases in subjects undergoing endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA)., Methods: Retrospective analysis of subjects who underwent EBUS-TBNA and had a final diagnosis of sarcoidosis or tuberculosis. The final diagnosis was based on the clinicoradiological features, microbiology and clinical course during follow-up (including response to treatment) at six months. A cytologist blinded to the clinical details and microbiology examined the aspirates. The primary outcome was the diagnostic accuracy of cytologist's impression to diagnose sarcoidosis as compared to the final diagnosis., Results: 179 (145 sarcoidosis, 34 tuberculosis) subjects were included. Granuloma was identified in 135 (75.4%) subjects; amongst these, the cytologist made a correct diagnosis in 62.2% cases, misdiagnosed 28.9% cases, and in 8.9% cases differentiating sarcoidosis from tuberculosis was not possible. The sensitivity, specificity, positive and negative predictive values (PPV and NPV) of the cytologist in diagnosing sarcoidosis was 62%, 64%, 90%, and 25%, respectively. The identification of a non-necrotic granuloma, along with a negative TST and the lack of endosonographic features favouring tuberculosis (heterogeneous echotexture and coagulation necrosis sign), provided the best specificity (97%) and PPV (99%) to diagnose sarcoidosis., Conclusion: Sarcoidosis cannot be reliably differentiated from tuberculosis based on cytomorphology alone. A combination of clinical features, endosonography, cytology and microbiology is required for accurate diagnosis., (Copyright: © 2020.)

Objectives: To describe the residual broncho-pulmonary lesions and evaluate the role of CT scanning at the end of treatment of pulmonary tuberculosis., Materials and Methods: Analysis of the initial and end of treatment CT scans of 56 patients with pulmonary tuberculosis according to a reading grid including parenchymatous and airways lesions. The CT data at the end of treatment were analysed in relation to the clinical and microbiological data, and the original CT scan., Results: Active lesions (thick walled cavities and/or centrilobular micronodules) persisted in 24 patients (43%) after a mean treatment period of 7 months. The persistence of these signs of activity was correlated with the initial presence of a cavitary syndrome (p=0.027), with predominant sub-segmentary bronchial involvement, with extensive micronodular spread (p=0.024) and with bronchiectasis (p=0.04). These residual lesions were not associated with an increased risk of relapse., Conclusion: The persistence of signs of activity on the CT scan at the end of treatment of tuberculosis do not necessarily correspond to an absence of cure but to a radiological delay. This imaging is nevertheless useful to make an assessment of any subsequent changes in the bronchial tree and to estimate the risk of later complications., (Copyright © 2018 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

Antibiotic treatment of tuberculosis takes ≥6 months, putting a major burden on patients and health systems in large parts of the world. Treatment beyond 2 months is needed to prevent tuberculosis relapse by clearing remaining, drug-tolerant Mycobacterium tuberculosis bacilli. However, the majority of patients treated for only 2-3 months will cure without relapse and do not need prolonged treatment. Assays that can identify these patients at an early stage of treatment may significantly help reduce the treatment burden, while a test to identify those patients who will fail treatment may help target host-directed therapies.In this review we summarise the state of the art with regard to discovery of biomarkers that predict relapse-free cure for pulmonary tuberculosis. Positron emission tomography/computed tomography scanning to measure pulmonary inflammation enhances our understanding of "cure". Several microbiological and immunological markers seem promising; however, they still need a formal validation. In parallel, new research strategies are needed to generate reliable tests., Competing Interests: Conflict of interest: D. Goletti reports personal fees from Qiagen, Quidel and Janssen, outside the submitted work. Conflict of interest: C.S. Lindestam Arlehamn has nothing to disclose. Conflict of interest: T.J. Scriba reports two pending patents of blood transcriptomic signatures of risk. Conflict of interest: R. Anthony reports grants from FIND to study the utility of IP-10 for treatment monitoring, outside the submitted work. Conflict of interest: D.M. Cirillo reports an unrestricted grant from QIAGEN to research the use of Quantiferon plus to predict outcome, and grants from JANSSEN on the establishment of Bedaquiline DST as SRL, outside the submitted work. Conflict of interest: T. Alonzi has nothing to disclose. Conflict of interest: C.M. Denkinger reports that FIND is a non-for-profit foundation, whose mission is to find diagnostic solutions to overcome diseases of poverty in LMICs. It works closely with the private and public sectors and receives funding from some of its industry partners. It has organisational firewalls to protect it against any undue influences in its work or the publication of its findings. All industry partnerships are subject to review by an independent scientific advisory committee or another independent review body, based on due diligence, TTPs and public sector requirements. FIND catalyses product development, leads evaluations, takes positions, and accelerates access to tools identified as serving its mission. It provides indirect support to industry (e.g. access to open specimen banks, a clinical trial platform, technical support, expertise, laboratory capacity strengthening in LMICs) to facilitate the development and use of products in these areas. FIND also supports the evaluation of prioritised assays and the early stages of implementation of WHO-approved (guidance and PQ) assays using donor grants. In order to carry out test validations and evaluations, has product evaluation agreements with several private sector companies for the diseases FIND works in which strictly define its independence and neutrality vis-a-vis the companies whose products get evaluated, and describes roles and responsibilities. Conflict of interest: F. Cobelens has nothing to disclose., (Copyright ©ERS 2018.)

Background: Little is known about the correlation between microbiological yield and radiographic activity, on chest computed tomography (CT), in suspected pulmonary tuberculosis (PTB) cases, despite CT being widely used, clinically., Methods: We used multicenter retrospective data, obtained from medical records, focusing on the diagnostic performance for definite PTB. We categorized patients into four groups, by radiographic activity: definitely active, probably active, indeterminate activity, and probably inactive., Results: Of the 650 patients included, 316 had culture-confirmed PTB; 190 (29.2%), 323 (49.7%), 70 (10.8%), and 67 (10.3%) were classified into the definitely active, probably active, indeterminate activity, and probably inactive groups, respectively. The corresponding observed culture rates for CT radiographic activity were 61.6%, 60.7%, 4.3% and 0%, respectively. When not only culture rates but TB-PCR and histological results were taken into consideration as definite PTB, it showed 66.6%, 67.2%, 14.3%, and 0% of each CT radiographic activity, respectively. Regarding the diagnostic performance for definite PTB, radiographic activity displayed high sensitivity (97.1%, 95% confidence interval (CI), 94.6-98.5) and negative predictive values (92.7%, 95% CI, 86.6-96.2), considered definitely and probably active PTB. Apart from PTB, other etiologies, according to radiographic activity, were predominantly respiratory infections such as bacterial pneumonia and non-tuberculous mycobacterial infection., Conclusions: Radiographic activity showed good diagnostic performance, and can be used easily in clinical practice. However, clinicians should consider other possibilities, because radiologic images do not confirm microbiological PTB., Competing Interests: The authors have declared that no competing interests exist.

Objectives: We retrospectively reviewed the evolution of segmentectomy for pulmonary tuberculosis (TB) and the feasibility of multi- and single-incision video-assisted thoracoscopic segmentectomy., Methods: Of 348 patients undergoing surgery for TB, the medical records of 121 patients undergoing segmentectomy between January 1996 and November 2015 were reviewed. Clinical information and computed tomography (CT) image characteristics were investigated and analyzed., Results: Eighteen patients underwent direct or intended thoracotomy. Sixty-four underwent video-assisted thoracoscopic segmentectomy (VATS), including 53 multi-incision thoracoscopic segmentectomy (MITS), and 11 single-incision thoracoscopic segmentectomy (SITS). Thirty-nine were converted to thoracotomy. The intended thoracotomy group had more operative blood loss (p = 0.005) and hospital stay (p = 0.001) than the VATS group although the VATS group had higher grade of cavity (p = 0.007). The intended thoracotomy group did not differ from converted thoracotomy in operative time, blood loss, or hospital stay, and the grade of pleural thickening was higher in the converted thoracotomy group (p = 0.001). The converted thoracotomy group had more operative blood loss, hospital stay, and complication rate than the MITS group (p = 0.001, p<0.001, and p = 0.009, respectively). The MITS group had lower pleural thickening, peribronchial lymph node calcification, cavity, and tuberculoma grading than the converted thoracotomy group (p<0.001, p = 0.001, 0.001, and 0.017, respectively). The SITS group had lower grading in pleural thickening, peribronchial lymph node calcification, and aspergilloma grading than the converted thoracotomy group (p = 0.002, 0.010, and 0.031, respectively). Four patients in the intended thoracotomy group and seven in the converted thoracotomy group had complications compared with three patients in the MITS and two in the SITS group. Risk factors of conversion were pleural thickening and peribronchial lymph node calcification., Conclusion: Although segmentectomy is technically challenging in patients with pulmonary TB, it could be safely performed using MITS or SITS and should be attempted in selected patients. Its efficacy for medical treatment failure needs investigation.

Background: Continuing use of analog film and digital chest radiography for screening and surveillance for pneumoconiosis and tuberculosis in lower and middle income countries raises questions of equivalence of disease detection. This study compared analog to digital images for intra-rater agreement across formats and prevalence of changes related to silicosis and tuberculosis among South African gold miners using the International Labour Organization classification system., Methods: Miners with diverse radiological presentations of silicosis and tuberculosis were recruited. Digital and film chest images on each subject were classified by four expert readers., Results: Readings of film and soft copy digital images showed no significant differences in prevalence of tuberculosis or silicosis, and intra-rater agreement across formats was fair to good. Hard copy images yielded higher prevalences., Conclusion: Film and digital soft copy images show consistent prevalence of findings, and generally fair to good intra-rater agreement for findings related to silicosis and tuberculosis., (© 2017 Wiley Periodicals, Inc.)

Background: Pulmonary tuberculosis (PTB) is a risk factor for COPD, but the clinical characteristics and the chest imaging features (emphysema and bronchiectasis) of COPD with previous PTB have not been studied well., Methods: The presence, distribution, and severity of emphysema and bronchiectasis in COPD patients with and without previous PTB were evaluated by high-resolution computed tomography (HRCT) and compared. Demographic data, respiratory symptoms, lung function, and sputum culture of Pseudomonas aeruginosa were also compared between patients with and without previous PTB., Results: A total of 231 COPD patients (82.2% ex- or current smokers, 67.5% male) were consecutively enrolled. Patients with previous PTB (45.0%) had more severe ( p =0.045) and longer history ( p =0.008) of dyspnea, more exacerbations in the previous year ( p =0.011), and more positive culture of P. aeruginosa ( p =0.001), compared with those without PTB. Patients with previous PTB showed a higher prevalence of bronchiectasis ( p <0.001), which was more significant in lungs with tuberculosis (TB) lesions, and a higher percentage of more severe bronchiectasis (Bhalla score ≥2, p =0.031), compared with those without previous PTB. The overall prevalence of emphysema was not different between patients with and without previous PTB, but in those with previous PTB, a higher number of subjects with middle ( p =0.001) and lower ( p =0.019) lobe emphysema, higher severity score ( p =0.028), higher prevalence of panlobular emphysema ( p =0.013), and more extensive centrilobular emphysema ( p =0.039) were observed. Notably, in patients with TB lesions localized in a single lung, no difference was found in the occurrence and severity of emphysema between the 2 lungs., Conclusion: COPD patients with previous PTB had unique features of bronchiectasis and emphysema on HRCT, which were associated with significant dyspnea and higher frequency of severe exacerbations. While PTB may have a local effect on bronchiectasis, its involvement in airspace damage in COPD may be extensive, probably through interactions with cigarette smoke., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Granulomas are the histopathologic hallmark of tuberculosis (TB), both in latency and active disease. Diagnostic and therapeutic strategies that specifically target granulomas have not been developed. Our objective is to develop a probe for imaging relevant immune cell populations infiltrating the granuloma. We report the binding specificity of Cyanine 3 (Cy3)-labeled cFLFLFK-PEG 12 to human leukocytes and cellular constituents within a human in vitro granuloma model. We also report use of the probe in in vivo studies using a mouse model of lung granulomatous inflammation. We found that the probe preferentially binds human neutrophils and macrophages in human granuloma structures. Inhibition studies showed that peptide binding to human neutrophils is mediated by the receptor formyl peptide receptor 1 (FPR1). Imaging the distribution of intravenously administered cFLFLFK-PEG 12 -Cy3 in the mouse model revealed probe accumulation within granulomatous inflammatory responses in the lung. Further characterization revealed that the probe preferentially associated with neutrophils and cells of the monocyte/macrophage lineage. As there is no current clinical diagnostic imaging tool that specifically targets granulomas, the use of this probe in the context of latent and active TB may provide a unique advantage over current clinical imaging probes. We anticipate that utilizing a FPR1-targeted radiopharmaceutical analog of cFLFLFK in preclinical imaging studies may greatly contribute to our understanding of granuloma influx patterns and the biological roles and consequences of FPR1-expressing cells in contributing to disease pathogenesis., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Rationale and Objectives: The purpose of this study was to assess the frequency and spectrum of abnormalities on routine screening chest radiographs among inpatients and outpatients with "positive purified protein derivative (PPD)" in a large tertiary care academic medical center in a country with low prevalence of tuberculosis (TB)., Materials and Methods: The reports of all chest radiographs of general inpatients and outpatients referred for positive PPD (2010-2014) were evaluated for the frequency of evidence of active or latent TB and the spectrum of imaging findings. The results of additional chest radiographs and computed tomography scans were recorded, as were additional relevant clinical histories and symptoms., Results: Of the 2518 patients who underwent chest radiography for positive PPD, the radiographs were normal in 91.3%. The vast majority of the abnormal radiographs demonstrated findings consistent with old tuberculous disease. There were three cases (0.1%) of active TB, all of which were either recent immigrants from an endemic area or had other relevant histories or clinical symptoms suggestive of the disease., Conclusions: Universal chest radiography in general inpatient and outpatient populations referred for positive PPD is of low yield for detecting active disease in a country with low prevalence of TB., (Copyright © 2017 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Objectives. To evaluate tomographic changes in pulmonary tuberculosis (TB), degree of agreement among three radiologists regarding tomographic diagnoses, and sequelae following treatment. Methods. Cross-sectional and descriptive study of 74 TB patients confirmed by sputum culture and chest computed tomography before (CT1) and 6 months after (CT2) drug therapy. Results were performed by three radiologists blinded to clinical and laboratory results. Results. Main findings in CT1 included nodules indicating the presence of a tree-in-bud pattern in 93% of cases, ill-defined nodules in 84% of cases, consolidation in 77% of cases, architectural distortion in 71% of cases, cavitary lesions in 62% of cases, and ground glass opacities in 37% of cases. Airway involvement, characterized by increased thickness and dilatation of the bronchial walls, occurred in 93% of cases. Pleural involvement occurred in 54%. There was an agreement on active TB among the three radiologists in 85% of cases. The results in CT2 indicated the presence of architectural distortion in 91% of cases and cylindrical bronchiectasis in 86%. Conclusions. The study established a tomographic pattern for diagnosis of active TB characterized by the presence of airway nodules, consolidation, architectural distortion, and cavitary lesions, and an almost complete degree of agreement (Kappa) was observed among the radiologists (0.85). CT after treatment assists in defining the cure., Competing Interests: The authors declare that they have no competing interests.

The authors report a case of coinfection of pulmonary paragonimiasis and pulmonary tuberculosis which is an uncommon coinfection. The patient presented with a one-week history of nonmassive hemoptysis about 1 month after completion of treatment for smear-negative pulmonary tuberculosis (sputum polymerase chain reaction positive for Mycobacterium tuberculosis). She lived in Nakhon Nayok province and reported taking raw crabs from time to time. The complete blood count revealed eosinophilia and her chest radiograph showed patchy infiltration at right lower lung field. Computed tomography scan of the chest revealed consolidation with internal air bubbles at anterobasal segment of right lower lobe. The diagnosis of pulmonary paragonimiasis was confirmed by detecting eggs of the genus Paragonimus in her wet-mount sputum. She was treated with oral praziquantel for 3 consecutive days with improvement. To our knowledge, although coinfection of pulmonary paragonimiasis and pulmonary tuberculosis is rare, it should be considered as the differential diagnosis in patients who live in the endemic area presenting with hemoptysis and eosinophilia.

Pulmonary cavitation is one of the most frequently observed clinical characteristics in tuberculosis (TB). The objective of this study was to investigate the potential risk factors associated with cavitary TB in China. A total of 385 smear-positive patients were enrolled in the study, including 192 (49.9%) patients with cavitation as determined by radiographic findings. Statistical analysis revealed that the distribution of patients with diabetes in the cavitary group was significantly higher than that in the non-cavitary group (adjusted odds ratio (OR) (95% confidence interval (CI)):12.08 (5.75-25.35), P<0.001). Similarly, we also found that the proportion of individuals with multidrug-resistant TB in the cavitary group was also higher than that in the non-cavitary group (adjusted OR (95% CI): 2.48 (1.52-4.07), P<0.001). Of the 385 Mycobacterium tuberculosis strains, 330 strains (85.7%) were classified as the Beijing genotype, which included 260 strains that belonged to the modern Beijing sublineage and 70 to the ancient Beijing sublineage. In addition, there were 80 and 31 strains belonging to large and small clusters, respectively. Statistical analysis revealed that cavitary disease was observed more frequently among the large clusters than the small clusters (P=0.037). In conclusion, our findings demonstrate that diabetes and multidrug resistance are risk factors associated with cavitary TB. In addition, there was no significant difference in the cavitary presentation between patients infected with the Beijing genotype strains and those infected with the non-Beijing genotype strains.

Background: The galaxy sign is an irregularly marginated pulmonary nodule formed by a confluence of multiple small nodules, and it is a diagnostic radiological finding for pulmonary sarcoidosis. However, the clinical significance of the galaxy sign for sarcoidosis has been poorly investigated., Objective: This study aimed to investigate the clinical significance and detailed radiological features of the galaxy sign in patients with pulmonary sarcoidosis., Methods: We retrospectively reviewed 87 patients with biopsy-proven sarcoidosis and 108 patients with pulmonary tuberculosis. Galaxy sign incidence was assessed on thoracic high-resolution computed tomography (HRCT) images from each group. Correlations of galaxy sign with clinical characteristics and disease outcomes were evaluated for patients with sarcoidosis., Results: HRCT findings were available for 65 of 87 patients with pulmonary sarcoidosis and all 108 patients with pulmonary tuberculosis. Galaxy sign incidence was significantly higher in patients with pulmonary sarcoidosis (n=15, 23.1%) than in those with pulmonary tuberculosis (n=2, 1.9%, p<0.001). Among the 65 patients with pulmonary sarcoidosis, those with galaxy signs (n=15) were significantly younger (median: 32 years, interquartile range [IQR] 28-38 years) than those without (n=50) (median: 62 years, IQR 37.7-73 years). The CD4/CD8 ratio in bronchoalveolar lavage fluid (BALF) was also significantly lower in the former group (median: 2.6, IQR 2.0-3.9 vs. median 5.8, IQR 3.7-8.6, p<0.001)., Conclusion: Galaxy signs are associated with younger age and low BALF CD4/CD8 ratio but not disease severity.

The absence of a gold standard to determine when antibiotics induce a sterilizing cure has confounded the development of new approaches to treat pulmonary tuberculosis (PTB). We detected positron emission tomography and computerized tomography (PET-CT) imaging response patterns consistent with active disease, along with the presence of Mycobacterium tuberculosis (MTB) mRNA in sputum and bronchoalveolar lavage samples, in a substantial proportion of adult, HIV-negative patients with PTB after a standard 6-month treatment plus 1 year follow-up, including patients with a durable cure and others who later developed recurrent disease. The presence of MTB mRNA in the context of nonresolving and intensifying lesions on PET-CT images might indicate ongoing transcription, suggesting that even apparently curative treatment for PTB may not eradicate all of the MTB bacteria in most patients. This suggests an important complementary role for the immune response in maintaining a disease-free state. Sterilizing drugs or host-directed therapies, and better treatment response markers, are probably needed for the successful development of improved and shortened PTB-treatment strategies., Competing Interests: statement. We have no competing financial interest to declare.

Introduction: Tuberculosis is a major public health problem in Morocco. Tuberculosis of the lung bases is a rare and atypical form and raises real diagnostic problems., Patients and Methods: We report a retrospective study of 21 cases of basal pulmonary tuberculosis, collected at the service of respiratory diseases in Ibn Rushd hospital in Casablanca between 2004 and 2015 (11 years)., Results: From a total of 21 patients having basal pulmonary tuberculosis, 13 (62%) were women versus eight men (48%), the average age was 33 years. The average time of diagnosis was 25 days. The disease was unilateral in 20 cases (95%). The right lower lobe was the most frequently affected (71%). Inhomogeneous opacities (66%) and consolidation (28%) were the main radiological findings. Associated comorbidities were dominated by diabetes in six cases (28%). Bronchoscopy had recovered thickening spurs in eight cases, endobronchial granules in seven cases and bronchial inflammation in six cases. Bronchial biopsies had found a necrotizing granulomatous inflammation tuberculoide in seven cases (33%). The smear was positive in sputum in three cases (14%), in the bronchial aspirate in four cases (19%), in induced sputum in one case (4.7%) and in post-bronchoscopic sputum in six cases (28%). The antituberculous treatment was started in all patients with good clinical and radiological evolution., Conclusion: The basal localization of the pulmonary tuberculosis is misleading; source of diagnostic delay, hence the need to think about it especially in patients with comorbidities., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Lack of access to human tissues with untreated tuberculosis (TB) has forced generations of researchers to use animal models and to adopt a paradigm that granulomas are the characteristic lesion of both primary and post primary TB. An extended search of studies of human lung tissues failed to find any reports that support this paradigm. We found scores of publications from gross pathology in 1804 through high resolution CT scans in 2015 that identify obstructive lobular pneumonia, not granulomas, as the characteristic lesion of developing post-primary TB. This paper reviews this literature together with other relevant observations to formulate a new paradigm of TB with three distinct stages: a three-act play. First, primary TB, a war of attrition, begins with infection that spreads via lymphatics and blood stream before inducing systemic immunity that contains and controls the organisms within granulomas. Second, post-primary TB, a sneak attack, develops during latent TB as an asymptomatic obstructive lobular pneumonia in persons with effective systemic immunity. It is a paucibacillary process with no granulomas that spreads via bronchi and accumulates mycobacterial antigens and host lipids for 1-2 years before suddenly undergoing caseous necrosis. Third, the fallout, is responsible for nearly all clinical post primary disease. It begins with caseous necrotic pneumonia that is either retained to become the focus of fibrocaseous disease or is coughed out to leave a cavity. This three-stage paradigm suggests testable hypotheses and plausible answers to long standing questions of immunity to TB., (Copyright © 2015 The Author. Published by Elsevier Ltd.. All rights reserved.)

Background: Little attention has been paid to the initial and follow-up computed tomography (CT) features in primary multi-drug resistant tuberculosis (pMDR-TB) setting., Purpose: To describe serial CT findings and clinical course of pMDR-TB with antibiotic treatment., Material and Methods: For the last 10 years, 340 MDR-TB patients were managed in a tertiary referral hospital. Among them, we included 44 (27 men, 17 women; mean age, 40 years; age range, 20-81 years) pMDR-TB patients; 37 treated with chemotherapy only and seven treated with medical therapy plus surgery. CT findings were evaluated regarding tree-in-bud sign, acinar nodule, peribronchial, segmental or lobar consolidation and cavity, and their extent. Sputum negative conversion rates and serial CT scores were assessed. To compare changes in disease extent between initial and follow-up CT studies, paired t-test was performed., Results: Two most frequent patterns of lung abnormality were tree-in-bud sign (37 of 44, 84.1%) and acinar nodule (41 of 44, 93.2%). Among 37 patients treated with chemotherapy only, 36 showed negative sputum conversion within 3 months after second-line drug commencement, maintained for >12 months. The other seven undergoing surgery during medical treatment showed excellent outcome with negative conversion achieved within one month after surgery and maintained for >12 months. CT scores showed significant decrease on serial CT studies (P < 0.001) in all., Conclusion: In pMDR-TB, two most frequent abnormal CT patterns are tree-in-bud sign and acinar nodule. In 98% of patients, negative sputum conversion is achieved, and CT score also shows decrease in extent after TB chemotherapy., (© The Foundation Acta Radiologica 2015.)

Well characterised animal models that can accurately predict efficacy are critical to the development of an improved TB vaccine. The use of high dose challenge for measurement of efficacy in Non-human primate models brings the risk that vaccines with the potential to be efficacious against natural challenge could appear ineffective and thus disregarded. Therefore, there is a need to develop a challenge regimen that is more relevant to natural human infection. This study has established that ultra-low dose infection of macaques via the aerosol route can be reproducibly achieved and provides the first description of the development of TB disease in both rhesus and cynomolgus macaques following exposure to estimated retained doses in the lung of less than 10 CFU of Mycobacterium tuberculosis. CT scanning in vivo and histopathology revealed differences in the progression and burden of disease between the two species. Rhesus macaques exhibited a more progressive disease and cynomolgus macaques showed a reduced disease burden. The ability to deliver reproducible ultra-low dose aerosols to macaques will enable the development of refined models of M. tuberculosis infection for evaluation of the efficacy of novel tuberculosis vaccines that offers increased clinical relevance and improved animal welfare., (Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.)

Chitotriosidase, secreted by activated macrophages, is a biomarker of activated macrophages. In this study, we explored whether chitotriosidase could be adopted as a biomarker to evaluate the curative effect on tuberculosis (TB). Five counties were randomly selected out of 122 counties/cities/districts in Hunan Province, China. Our cases were all TB patients who were newly diagnosed or had been receiving treatment at the Centers for Disease Control (CDCs) of these five counties between April and August in 2009. Healthy controls were selected from a community health facility in the Kaifu district of Changsha City after frequency-matching of gender and age with the cases. Chitotriosidase activity was evaluated by a fluorometric assay. Categorical variables were analysed with the χ 2 test. Measurement data in multiple groups were tested with analysis of variance and least significant difference (LSD). Correlation between chitotriosidase activity and the degree of radiological extent (DRE) was examined by Spearman's rank correlation test. The average chitotriosidase activity levels of new TB cases, TB cases with different periods of treatment (6 months) and the control group were 54·47, 34·77, 21·54, 12·73 and 10·53 nmol/h.ml, respectively. Chitotriosidase activity in TB patients declined along with the continuity of treatment. The chitotriosidase activity of both smear-positive and the smear-negative pulmonary TB patients decreased after 6 months' treatment to normal levels (P < 0·05). Moreover, chitotriosidase activity was positively correlated with DRE (r = 0·607, P < 0·001). Our results indicate that chitotriosidase might be a marker of TB treatment effects. However, further follow-up study of TB patients is needed in the future.

Objectives: Pulmonary tuberculosis (TB) can affect lung function, but studies regarding long-term follow-up in patients with no sequelae on chest X-ray (CXR) have not been performed. We evaluated lung functional impairment and persistent respiratory symptoms in those with prior pulmonary TB and those with prior pulmonary TB with no residual sequelae on CXR, and determined risk factors for airflow obstruction., Methods: We used data from adults aged ≥ 40 years from the annual Korean National Health and Nutrition Examination Surveys conducted between 2008 and 2012. P values for comparisons were adjusted for age, sex, and smoking status., Results: In total of 14,967 adults, 822 subjects (5.5%) had diagnosed and treated pulmonary TB (mean 29.0 years ago). The FVC% (84.9 vs. 92.6), FEV1% (83.4 vs. 92.4), and FEV1/FVC% (73.4 vs. 77.9) were significantly decreased in subjects with prior pulmonary TB compared to those without (p < 0.001, each). In 12,885 subjects with no sequalae on CXR, those with prior pulmonary TB (296, 2.3%) had significantly lower FEV1% (90.9 vs. 93.4, p = 0.001) and FEV1/FVC% (76.6 vs. 78.4, p < 0.001) than those without. Subjects with prior pulmonary TB as well as subjects with no sequalae on CXR were more likely to experience cough and physical activity limitations due to pulmonary symptoms than those without prior pulmonary TB (p < 0.001, each). In total subjects, prior pulmonary TB (OR, 2.314; 95% CI, 1.922-2.785), along with age, male, asthma, and smoking mount was risk factor for airflow obstruction. In subjects with prior pulmonary tuberculosis, inactive TB lesion on chest x-ray (OR, 2.300; 95% CI, 1.606-3.294) were risk factors of airflow obstruction., Conclusion: In addition to subjects with inactive TB lesion on CXR, subjects with no sequelae on CXR can show impaired pulmonary function and respiratory symptoms. Prior TB is a risk factor for airflow obstruction and that the risk is more important when they have inactive lesions on chest X-ray. Hence, the patients with treated TB should need to have regular follow-up of lung function and stop smoking for early detection and prevention of the chronic airway disease.

Purpose: To develop an automated pulmonary image analysis framework for infectious lung diseases in small animal models., Methods: The authors describe a novel pathological lung and airway segmentation method for small animals. The proposed framework includes identification of abnormal imaging patterns pertaining to infectious lung diseases. First, the authors' system estimates an expected lung volume by utilizing a regression function between total lung capacity and approximated rib cage volume. A significant difference between the expected lung volume and the initial lung segmentation indicates the presence of severe pathology, and invokes a machine learning based abnormal imaging pattern detection system next. The final stage of the proposed framework is the automatic extraction of airway tree for which new affinity relationships within the fuzzy connectedness image segmentation framework are proposed by combining Hessian and gray-scale morphological reconstruction filters., Results: 133 CT scans were collected from four different studies encompassing a wide spectrum of pulmonary abnormalities pertaining to two commonly used small animal models (ferret and rabbit). Sensitivity and specificity were greater than 90% for pathological lung segmentation (average dice similarity coefficient > 0.9). While qualitative visual assessments of airway tree extraction were performed by the participating expert radiologists, for quantitative evaluation the authors validated the proposed airway extraction method by using publicly available EXACT'09 data set., Conclusions: The authors developed a comprehensive computer-aided pulmonary image analysis framework for preclinical research applications. The proposed framework consists of automatic pathological lung segmentation and accurate airway tree extraction. The framework has high sensitivity and specificity; therefore, it can contribute advances in preclinical research in pulmonary diseases.