Pulmonary Tuberculosis Lesions Research Articles

Triggering Receptor Expressed on Myeloid Cells 2 Mediates the Involvement of M2-Type Macrophages in Pulmonary Tuberculosis Infection.

Macrophage play a significant work in the development of tuberculosis. This study aims to investigate the relationship between TREM2 and macrophage polarization, as well as the related cytokines. This study involved 43 pulmonary tuberculosis patients and 37 healthy controls. Enzyme-linked immunosorbent assay (ELISA) was used to detect the expression levels of M1/M2 macrophage-related cytokines IL-10 and IL-12 in the peripheral blood of pulmonary tuberculosis patients. The relative mRNA expression levels of TREM2, IL-10 and IL-12 were detected using quantitative real-time PCR (qRT-PCR). Additionally, Spearman rank correlation analysis was used to preliminarily assess the correlation between TREM2 and M1 / M2 macrophages. Hematoxylin-eosin (HE) staining was performed to observe the pathological manifestations of pulmonary tuberculosis lesions. Immunohistochemical (IHC) staining was used to observe the localization of the macrophage-specific molecule CD68, the M1 specific molecule iNOS, the M2 specific molecule CD163, and TREM2. The lesions of pulmonary tuberculosis patients showed Langhans multinucleated macrophages and tuberculous granulomas. The ELISA results indicated that the expression levels of IL-10 and IL-12 were significantly increased in peripheral blood of pulmonary tuberculosis patients. Additionally, the relative mRNA expression levels of TREM2, IL-10 and IL-12 were also significantly higher in the pulmonary tuberculosis group. Furthermore, a positive correlation was observed between TREM2 and IL-10, which are secreted by M2 macrophages. IHC revealed significant positivity of TREM2 and macrophage-related markers in tuberculous granuloma. Specifically, TREM2 and M2 macrophage marker CD163 were significantly expressed in the cytoplasm and membrane of Langhans multinucleated macrophages. The role of macrophage polarization in pulmonary tuberculosis is significant, and further investigation is needed to understand relationship between TREM2 and M2 macrophages.

Case-controlled study of tuberculosis in in-vitro fertilisation-embryo transfer and natural pregnancy

ObjectiveTo improve the understanding of the clinical features and imaging characteristics of pregnant women with and without in-vitro fertilisation-embryo transfer combined with pulmonary tuberculosis (TB).MethodsA retrospective analysis was conducted involving 50 patients with pregnancy who had pulmonary TB and were admitted to the Third People’s Hospital of Kunming (China) between 1 January 2017 and 31 December 2021. These patients were divided into an in-vitro fertilisation and embryo transfer (IVF-ET) conception group and a natural conception group according to the conception method. The clinical and imaging data were then collected and compared.ResultsThe mean age of the IVF-ET group (n = 13, 31.85 ± 5.84 years) was higher than in the natural conception group (n = 37, 27.05 ± 5.5 years). The proportions of fever, haematogenous TB and extrapulmonary TB in the IVF-ET group (92.31%, 84.62% and 76.92%, respectively) were higher than those in the natural conception group (40.54%,16.22%,27.03%,respectively). The percentage of patients with pregnancy who had intracranial TB (76.9%) in the IVF-ET group was higher than in the natural conception group (10.8%). The percentage of pregnancy terminations in the IVF-ET conception group (84.62%) was higher than in the natural conception group (48.65%). All the above results had statistically significant differences (p < 0.05).ConclusionOverall, IVF-ET conception combined with extensive pulmonary TB lesions lead to heavy systemic toxic symptoms, severe disease and poor pregnancy outcomes. Therefore, screening for TB prior to performing IVF-ET is recommended.

PtbNet: Based on Local Few-Shot Classes and Small Objects to accurately detect PTB.

Pulmonary Tuberculosis (PTB) is one of the world's most infectious illnesses, and its early detection is critical for preventing PTB. Digital Radiography (DR) has been the most common and effective technique to examine PTB. However, due to the variety and weak specificity of phenotypes on DR chest X-ray (DCR), it is difficult to make reliable diagnoses for radiologists. Although artificial intelligence technology has made considerable gains in assisting the diagnosis of PTB, it lacks methods to identify the lesions of PTB with few-shot classes and small objects. To solve these problems, geometric data augmentation was used to increase the size of the DCRs. For this purpose, a diffusion probability model was implemented for six few-shot classes. Importantly, we propose a new multi-lesion detector PtbNet based on RetinaNet, which was constructed to detect small objects of PTB lesions. The results showed that by two data augmentations, the number of DCRs increased by 80% from 570 to 2,859. In the pre-evaluation experiments with the baseline, RetinaNet, the AP improved by 9.9 for six few-shot classes. Our extensive empirical evaluation showed that the AP of PtbNet achieved 28.2, outperforming the other 9 state-of-the-art methods. In the ablation study, combined with BiFPN+ and PSPD-Conv, the AP increased by 2.1, APs increased by 5.0, and grew by an average of 9.8 in APm and APl. In summary, PtbNet not only improves the detection of small-object lesions but also enhances the ability to detect different types of PTB uniformly, which helps physicians diagnose PTB lesions accurately. The code is available at https://github.com/Wenhui-person/PtbNet/tree/master.

Comparative pathology of experimental pulmonary tuberculosis in animal models.

Research in human tuberculosis (TB) is limited by the availability of human tissues from patients, which is often altered by therapy and treatment. Thus, the use of animal models is a key tool in increasing our understanding of the pathogenesis, disease progression and preclinical evaluation of new therapies and vaccines. The granuloma is the hallmark lesion of pulmonary tuberculosis, regardless of the species or animal model used. Although animal models may not fully replicate all the histopathological characteristics observed in natural, human TB disease, each one brings its own attributes which enable researchers to answer specific questions regarding TB immunopathogenesis. This review delves into the pulmonary pathology induced by Mycobacterium tuberculosis complex (MTBC) bacteria in different animal models (non-human primates, rodents, guinea pigs, rabbits, cattle, goats, and others) and compares how they relate to the pulmonary disease described in humans. Although the described models have demonstrated some histopathological features in common with human pulmonary TB, these data should be considered carefully in the context of this disease. Further research is necessary to establish the most appropriate model for the study of TB, and to carry out a standard characterisation and score of pulmonary lesions.

Comparison of the pathological outcome and disease progression of two Mycobacterium caprae experimental challenge models in goats: endobronchial inoculation vs. intranasal nebulization.

Goats are natural hosts of tuberculosis (TB) and are a valid animal model to test new vaccines and treatments to control this disease. In this study, a new experimental model of TB in goats based on the intranasal nebulization of Mycobacterium caprae was assessed in comparison with the endobronchial route of infection. Fourteen animals were divided into two groups of seven and challenged through the endobronchial (EB) and intranasal (IN) routes, respectively. Clinical signs, rectal temperature, body weight, and immunological responses from blood samples were followed up throughout the experiment. All goats were euthanized at 9 weeks post-challenge. Gross pathological examination, analysis of lung lesions using computed tomography, and bacterial load quantification in pulmonary lymph nodes (LNs) by qPCR were carried out. The IN-challenged group showed a slower progression of the infection: delayed clinical signs (body weight gain reduction, peak of temperature, and apparition of other TB signs) and delayed immunological responses (IFN-γ peak response and seroconversion). At the end of the experiment, the IN group also showed significantly lower severity and dissemination of lung lesions, lower mycobacterial DNA load and volume of lesions in pulmonary LN, and higher involvement of the nasopharyngeal cavity and volume of the lesions in the retropharyngeal LN. The results indicated that the IN challenge with M. caprae induced pathological features of natural TB in the lungs, respiratory LN, and extrapulmonary organs but extremely exaggerating the nasopharyngeal TB pathological features. On the other hand, the EB route oversized and accelerated the pulmonary TB lesion progression. Our results highlight the need to refine the inoculation routes in the interest of faithfully reproducing the natural TB infection when evaluating new vaccines or treatments against the disease.

Computed Tomography in Diagnosis of Lesions of Pulmonary Tuberculosis

Pulmonary tuberculosis (MTB) is dangerous bacterial infection primarily affecting lungs and is capable of infecting everyone exposed to Mycobacterium tuberculosis. AFB and CXR are useful preliminary investigative tools, but CT scan are invaluable diagnostic tool for establishing a diagnosis and monitoring disease activity. Objectives: To diagnose the lesions of PTB and assess the CT scan findings in AFB-positive patients. Methods: The AFB-positive patients were examined using CT scan to reveal their mediastinal and pulmonary pathological conditions and activities and disease propagation using imaging technology of CT scan. In cases of PTB with lymphadenopathy, 50cc of non-ionic contrast was administered intravenously to examine the low attenuation area. Results: The findings of CT scan regarding micronodules, nodular masses and other foci and lymphadenopathy were scrutinized, and major diagnostic CT scan findings were Centrilobular nodules (97.40%), Parenchymal nodules (84.43%), Paratracheal and mediastinal lymphadenopathy (74.85%), air space consolidation and paucity (62.07%), Pulmonary calcification (31.73%), Pleural effusion (29.34%) and Bronchiectasis (12.77%). Conclusions: CT scan is the most sensitive and accurate tool for diagnosis confirmation and disease activity evaluation. In addition, it details the abnormalities and prognosis of organ deformity in PTB patients.

Bacteriomes in lesions of pulmonary tuberculosis and its association with status of Mycobacterium tuberculosis excretion

BackgroundBacteria in lung play an important role in sustaining lung health. Understanding the characteristics of bacteriomes in lesions of pulmonary tuberculosis (TB) patients, who excrete Mycobacterium tuberculosis (MTB), is important for TB prevention and effective treatment. MethodsIn this study, bacteriomes in lesions from TB patients excreting bacteria (TB-E) and those from TB patients not excreting bacteria (TB-NE) with matched normal lung tissues (NT) were compared by 16S rRNA sequencing. Bacterial MetaCyc functions in TB lesions were also predicted by PICRUSt2 tool.ResultsAlpha diversity of bacteria, including Chao 1 and Shannon indexes, for TB-E was significantly higher than those in TB-NE and NT; while for TB-NE group, Chao 1 index was higher than that in NT group. Predominant phyla in TB lesions and NT were Proteobacteria, Actinobacteria, Firmicutes, and Bacteroidetes, but analysis of similarity (ANOSIM, p < 0.001) revealed significantly different bacterial compositions among TB-E, TB-NE and NT samples. As for bacteriomes in TB lesions, a strong association (ANOSIM, p < 0.001) was observed with the status of MTB excretion. Indicator genera identified in TB-E and TB-NE demonstrated distinctive micro-ecological environments of TB lesions from patients with different clinical manifestations. Co-occurrence analysis revealed a densely-linked bacterial community in TB-NE compared to that in TB-E. MetaCyc functions responsible for menaquinone synthesis and chorismate metabolism that could potentially impact the persistent-state and nutrient metabolism of MTB were enriched in TB-E samples. While in TB-NE samples, enrichment of bacterial MetaCyc function responsible for heme b synthesis might contribute to TB pathology through ferroptosis.ConclusionBacteriomes and their MetaCyc functions in TB lesions are elucidated, and they are associated with status of MTB excretion among pulmonary TB patients. These results serve as a basis for designing novel strategies for preventing and treating pulmonary TB disease.

Screening and preliminary validation of biomarkers in sputum-negative pulmonary tuberculosis based on positron emission tomography/computed tomography and transcriptomics

Objective: To screen and perform preliminary clinical validation of biomarkers of activity based on positron emission tomography/computed tomography (PET-CT) and transcriptomics in sputum-negative pulmonary tuberculosis lesion tissue. Methods: Nine patients with sputum-negative pulmonary tuberculosis treated surgically at the Shanghai Public Health Clinical Center for Thoracic Surgery from January 1, 2017 to December 31, 2019 were retrospectively collected as the discovery group, including four males and five females, aged 20-57 years (mean 36 years). All of the patients underwent PET-CT scanning before surgery, and the resected specimens were postoperatively classified according to preoperative PET-CT. The resected specimens were divided into areas with increased fluorodeoxyglucose (FDG) metabolism (SUVmax>3) and areas with normal FDG metabolism (SUVmax ≤ 3) according to the preoperative PET-CT performance. After sample processing, total RNA was extracted from the tissues of different regions, and then whole gene transcriptome sequencing was performed. Bioinformatics analysis of the two sets of data was performed to discover the expression profiles of the differences in whole gene transcriptome data between the two regions and to screen for candidate biomarkers. Eighty patients with sputum-negative pulmonary tuberculosis admitted to Shanghai Public Health Clinical Center from January 1, 2019 to January 1, 2021 were retrospectively collected as the validation group, including 37 males and 43 females, aged 20-62 years, with an average age of 39 years. The validation group was divided into a group with increased SUV (n=40) and a group without lesions on CT imaging (n=40). Enzyme-linked immunosorbent assay (ELISA) was used to determine the protein levels of candidate biomarkers in the peripheral plasma of patients. The effect of biomarkers was assessed using subject operating characteristic (ROC) curves. Student's t-test was used to determine whether the difference in protein levels between the two groups was statistically significant. Results: Bioinformatics analysis revealed that the expression levels of C1QB, CCL19, CCL5 and HLA-DMB correlated with the metabolic activity of sputum-negative tuberculosis lesion tissue. Further screening and validation by the validation group confirmed that the difference in C1QB protein levels in the peripheral plasma of patients was statistically significant between the group with increased SUV and the group without lesions on CT imaging [(3.55±0.34) mg/L vs. (2.75±0.21) mg/L, t=4.12, P<0.001]. And the ROC curve showed that the area under the curve for C1QB protein levels was 0.731, which had potential clinical value. Conclusion: The C1QB protein level can be used to assess the activity of lesions in patients with sputum-negative tuberculosis and is a potential biomarker.

Clinical characteristics of COVID-19 in patients with tuberculosis and factors associated with the disease severity

BackgroundData on patients with COVID-19 who have pulmonary tuberculosis (TB) are limited. In this study, we compared the clinical characteristics of patients with COVID-19/TB and patients with COVID-19 only. In addition, we analyzed the links between the severity of COVID-19 disease and the clinical characteristics of patients with COVID-19/TB. MethodsWe conducted a retrospective, anonymized, cross-sectional study of 111 patients who met inclusion criteria for analysis (75 patients with COVID-19/TB and 36 patients with COVID-19). ResultsPatients in both groups (COVID-19/TB vs COVID-19) mainly suffered from fever (72.0% vs 100%, p < 0.001), fatigue (76.0% vs 94.4%, p = 0.018), chest pain (72.0% vs 36.1%, p < 0.001), followed by cough (60.0% vs 97.2%, p < 0.001) and dyspnea (44.0% vs 63.9%, p = 0.05). In group COVID-19/TB the most frequently reported co-morbidities were chronic liver disease (17 [22.7%]), cardiovascular diseases (25 [33.3%]), and diseases of the nervous system (13 [17.3%]).Female gender, fever, dyspnea, pulmonary bilateral TB lesion, and three or more co-morbidities have a statistically significant positive effect on the severity of the disease among patients with COVID-19/TB. ConclusionIt is important to perform rapid molecular testing and computed tomography to correctly distinguish COVID-19 and TB because of the similar clinical characteristics of both diseases. Bilateral pulmonary TB lesion and co-morbidity should be considered risk factors for severe COVID-19.

Lightweight YOLOv4 with Multiple Receptive Fields for Detection of Pulmonary Tuberculosis.

The characteristics of pulmonary tuberculosis are complex, and the cost of manual screening is high. The detection model based on convolutional neural network is an essential method for assisted diagnosis with artificial intelligence. However, it also has the disadvantages of complex structure and a large number of parameters, and the detection accuracy needs to be further improved. Therefore, an improved lightweight YOLOv4 pulmonary tuberculosis detection model named MIP-MY is proposed. Firstly, over 300 actual cases are selected to make a common dataset by professional physicians, which is used to evaluate the performance of the model. Subsequently, by introducing the inverted residual channel attention and the pyramid pooling module, a new structure of MIP is created and used as the backbone extractor of MIP-MY, which could further decrease the number of parameters and fuse context information. Then the multiple receptive field module is added after the three effective feature layers of the backbone extractor, which effectively enhances the information extraction ability of the deep feature layer and reduces the miss detection rate of small pulmonary tuberculosis lesions. Finally, the pulmonary tuberculosis detection model MIP-MY with lightweight and multiple receptive field characteristics is constructed by combining each improved modules with multiscale structure. Compared to the original YOLOv4, the model parameters of MIP-MY is reduced by 47%, while the mAP value is raised to 95.32% and the miss detection rate is decreased to 6%. It is verified that the model can effectively assist radiologists in the diagnosis of pulmonary tuberculosis.

Cellular Heterogeneity and Intercellular Crosstalk Characterize Pulmonary Tuberculosis Lesions Based on PET/CT Localization

Cellular Heterogeneity and Intercellular Crosstalk Characterize Pulmonary Tuberculosis Lesions Based on PET/CT Localization

Chest ultrasound findings in pulmonary tuberculosis

Objective The current observational study aims to identify the role of ultrasound (US) in detecting pleuropulmonary lesions in active pulmonary tuberculosis (TB) patients. Background Owing to the fact that US is the predominant criterion in determining major disorders, it provides quantitative data from which pleural effusions can be calculated, along with reporting lung consolidation. This process is found to be useful to increase the end-expiratory pressure. Patients and methods This research involved 30 patients with active pulmonary TB (sputum positive for acid-fast bacilli) by direct smear microscopy, clinical manifestation, and radiological abnormalities who were admitted to the Chest Department, Faculty of Medicine, Menoufia University Hospitals, from April 2018 to March 2019. Full assessment of history, and routine, physical, and bacteriologic examination and radiological examination were performed. Results Outcomes showed a statistically significant difference between the males and females in occupation, sputum, smoking, and dyspnea (P&lt;0.001). Most importantly, 15 out of 30 patients (half of them) showed a massive effusion with clear fluid. The second most noteworthy finding was the presence of a minimal effusion in 5/30 patients. In terms of radiograph results, however, half the patients revealed massive effusion and almost the same number of patients (16/30) had comorbidities; five of them suffered from hypertension and diabetes. Nevertheless, there were no statistically significant differences between the males and females with respect to US findings (P=0.179) and radiograph findings (0.202). Conclusion TB appears to be highly prevalent among male patients than the female ones. However, the increased incidence of TB among males has been proven to be independent of other risk factors of TB. It can be concluded that US is an efficient and suitable method for the evaluation of different pleural diseases in TB patients. US is mostly sensitive and specific in diagnosing pleural effusions.

Massive Cerebral Air Embolism Causing Stroke Secondary to Pulmonary Tuberculosis.

ABSTRACTCerebral air embolism due to pulmonary tuberculosis is an extremely rare cause of stroke. We report an unusual case of a presentation of cerebral air embolism likely due to pulmonary tuberculosis lesions during a severe cough. We discuss the relationship between the pulmonary tuberculosis and the occurrence of the cerebral air embolism. A 55-year-old man with lung tuberculosis suddenly experienced a nontraumatic loss of consciousness after a severe cough. The magnetic resonance imaging confirmed an ischemic stroke due to cerebral air embolism. The thoracic scan revealed tuberculosis with a parenchymatous cavity. Patients with intrapulmonary tuberculosis cavities should be strongly considered for surgical repair and should be warned about the risk of rupture of the cavity in the situation of increasing thoracic pressure.How to cite this article: Bouaggad A, Moussaoui M, Abassi O, Hassen S, Essodegui F. Massive Cerebral Air Embolism Causing Stroke Secondary to Pulmonary Tuberculosis. Indian J Crit Care Med 2021;25(8):942–944.

A STUDY TO DETECT THE PROPORTION OF ALTERED SERUM CALCIUM, PHOSPHOROUS AND VITAMIN D3 LEVEL IN NEWLY DIAGNOSED PULMONARY TUBERCULOSIS PATIENTS ATTENDING CHEST OPD IN BURDWAN MEDICAL COLLEGE &amp; HOSPITAL

Introduction: Pulmonary Tuberculosis (PTB) is still a very common cause of morbidity &amp; morbidity in India.[7] Calcium and phosphorus metabolism plays an important role in the healing of lesions in PTB. Vitamin D deficient individuals have a greater susceptibility to develop TB[14] and worse disease progression if infected with TB.[15] Due to paucity of studies this study was carried out to estimate the mean value of serum calcium phosphorous and Vitamin D3 level in newly diagnosed PTB patients and find out correlation among the altered values of these biochemical parameters.&#x0D; Methods: This was an observational cross sectional hospital based study carried out on 120 patients attending Burdwan Medical College over a period of one and a half years. All patients of PTB were included, while patients with Sarcoidosis, hepatitis, chronic kidney disease, post menopausal women were excluded from study. Serum Calcium, Phosphorus and Vitamin D3 were estimated in these patients. Data collected was entered in Excel Spreadsheet, and analysed in SPSS version 19.0 using descriptive statistical methods, percentiles and scatter diagrams.&#x0D; Main Findings: Serum calcium and phosphorus was not significantly decreased in our study. Moderate prevalence of vitamin D deficiency was found among newly diagnosed PTB patients. Significant correlation was found between altered vitamin D3, serum phosphorus and serum calcium level.&#x0D; Conclusion: Since Serum vitamin D3 is significantly decreased in pulmonary tuberculosis it is essential to monitor the serum levels of vitamin D3 in PTB patients and provide adequate supplementation of vitamin D3.&#x0D; Keywords: Pulmonary Tuberculosis, Calcium, Vitamin D3, Phosphorus

_PROGNOSTIC MARKER OF TUBERCULOSIS SEVERITY AND TREATMENT EFFECTIVENESS IN PULMONARY TUBERCULOSIS

The aim: Was to investigate human-beta-defensin-1 level in blood serum depending on tuberculosis severity and treatment effectiveness. Materials and methods: 100 patients with pulmonary tuberculosis and 20 healthy persons were included to the study. HBD-1 level was measured by ELISA in all the healthy persons and in all the patients at the treatment onset and at the end of initial phase of treatment. Additionally, the patients were examined with chest X-ray, sputum microscopy and culture, blood test and blood biochemistry. Results: HBD-1 level was higher in patients with tuberculosis (21.5 ± 2.9 μmol/L) compared with healthy individuals (8.9 ± 2.5 μmol/L). A positive correlation of middle strength was found between the size of lung lesion and the level of HBD-1 and between the level of HBD-1 and the massiveness of bacterial excretion. We found weakly negative correlations between the level of HBD-1 at the beginning of treatment and parameters of life quality rated on sf-36 scale. Patients with initially high level of HBD-1 had preservation of bacterial excretion, as well as signs of inflammatory activity. In patients with an effective intensive phase of treatment, the initial level of HBD-1. Conclusions: The larger pulmonary tuberculosis lesion, as well as the more pronounced clinical manifestations lead to the higher level of HBD-1. The possibility of using human-beta-defensin-1 as a prognostic marker of treatment effectiveness is confirmed by the fact that human-beta-defensin-1 level prevails at the beginning of treatment in patients with subsequently non-effective intensive phase of treatment.

A deep learning system that generates quantitative CT reports for diagnosing pulmonary Tuberculosis

The purpose of this study was to establish and validate a new deep learning system that generates quantitative computed tomography (CT) reports for the diagnosis of pulmonary tuberculosis (PTB) in clinic. 501 CT imaging datasets were collected from 223 patients with active PTB, while another 501 datasets, which served as negative samples, were collected from a healthy population. All the PTB datasets were labeled and classified manually by professional radiologists. Then, four state-of-the-art 3D convolution neural network (CNN) models were trained and evaluated in the inspection of PTB CT images. The best model was selected to annotate the spatial location of lesions and classify them into miliary, infiltrative, caseous, tuberculoma, and cavitary types. The Noisy-Or Bayesian function was used to generate an overall infection probability of this case. The results showed that the recall and precision rates of detection, from the perspective of a single lesion region of PTB, were 85.9% and 89.2%, respectively. The overall recall and precision rates of detection, from the perspective of one PTB case, were 98.7% and 93.7%, respectively. Moreover, the precision rate of type classification of the PTB lesion was 90.9%. Finally, a quantitative diagnostic report of PTB was generated including infection possibility, locations of the lesion, as well as the types. This new method might serve as an effective reference for decision making by clinical doctors.

Comparison of 68Ga-DOTANOC with 18F-FDG using PET/MRI imaging in patients with pulmonary tuberculosis

We compared the somatostatin analog radioligand, DOTANOC, with FDG, to determine whether there was increased detection of active or sub-clinical lesions in pulmonary tuberculosis (TB) with DOTANOC. Three groups were recruited: (1) active pulmonary TB; (2) IGRA-positive household TB contacts; (3) pneumonia (non-TB). DOTANOC PET/MRI followed by FDG PET/MRI was performed in active TB and pneumonia groups. TB contacts underwent FDG PET/MRI, then DOTANOC PET/MRI if abnormalities were detected. Quantitative and qualitative analyses were performed for total lung and individual lesions. Eight active TB participants, three TB contacts and three pneumonia patients had paired PET/MRI scans. In the active TB group, median SUVmax[FDG] for parenchymal lesions was 7.69 (range 3.00–15.88); median SUVmax[DOTANOC] was 2.59 (1.48–6.40). Regions of tracer uptake were fairly similar for both radioligands, albeit more diffusely distributed in the FDG scans. In TB contacts, two PET/MRIs had parenchymal lesions detected with FDG (SUVmax 5.50 and 1.82), with corresponding DOTANOC uptake < 1. FDG and DOTANOC uptake was similar in pneumonia patients (SUVmax[FDG] 4.17–6.18; SUVmax[DOTANOC] 2.92–4.78). DOTANOC can detect pulmonary TB lesions, but FDG is more sensitive for both active and sub-clinical lesions. FDG remains the preferred ligand for clinical studies, although DOTANOC may provide additional value for pathogenesis studies.

Galactomannan detection in bronchoalveolar lavage fluids: A diagnostic approach for fungus ball in patients with pulmonary tuberculosis?

Several previous studies have shown cavitary lung lesions in old pulmonary tuberculosis (PTB) increase the risk of fungus ball. Detection of galactomannan (GM) in bronchoalveolar lavage (BAL) is also proposed as a diagnostic approach for the fungus ball. We evaluated the diagnosis of fungus balls and GM levels in BAL samples in PTB patients. A total of 110 PTB patients were evaluated for fungus ball during 2017-2019. The patients were evaluated for radiological, histopathological results and mycological findings of BAL including GM detection and culture. The sensitivity, specificity and positive and negative predictive value for GM test were calculated. The optimal cut-off for BAL GM testing was determined by receiver operating characteristic (ROC). Of 110 PTB patients, nine (8.18%) showed fungus ball, all with old PTB. The molecularly confirmed Aspergillus species were A. flavus, A. fumigatus and A. ochraceus. The sensitivity and specificity of BAL GM ≥ 0.5 in old PTB patients with fungus ball were 100%, 41.5%, respectively. The statistical analysis of the mean ± SEM of BAL GM levels was demonstrated a higher levels of GM in patients with fungus ball/aspergilloma compared to old PTB patients without fungus ball/aspergilloma. The optimal cut-off value for BAL GM was determined as 0.50 by ROC curve analysis. According to our results, we can recommend the detection of GM in BAL samples as a diagnostic approach for fungus ball in PTB patients.

Hydrogen sulfide dysregulates the immune response by suppressing central carbon metabolism to promote tuberculosis

The ubiquitous gasotransmitter hydrogen sulfide (H2S) has been recognized to play a crucial role in human health. Using cystathionine γ-lyase (CSE)-deficient mice, we demonstrate an unexpected role of H2S in Mycobacterium tuberculosis (Mtb) pathogenesis. We showed that Mtb-infected CSE-/- mice survive longer than WT mice, and support reduced pathology and lower bacterial burdens in the lung, spleen, and liver. Similarly, in vitro Mtb infection of macrophages resulted in reduced colony forming units in CSE-/- cells. Chemical complementation of infected WT and CSE-/- macrophages using the slow H2S releaser GYY3147 and the CSE inhibitor DL-propargylglycine demonstrated that H2S is the effector molecule regulating Mtb survival in macrophages. Furthermore, we demonstrate that CSE promotes an excessive innate immune response, suppresses the adaptive immune response, and reduces circulating IL-1β, IL-6, TNF-α, and IFN-γ levels in response to Mtb infection. Notably, Mtb infected CSE-/- macrophages show increased flux through glycolysis and the pentose phosphate pathway, thereby establishing a critical link between H2S and central metabolism. Our data suggest that excessive H2S produced by the infected WT mice reduce HIF-1α levels, thereby suppressing glycolysis and production of IL-1β, IL-6, and IL-12, and increasing bacterial burden. Clinical relevance was demonstrated by the spatial distribution of H2S-producing enzymes in human necrotic, nonnecrotic, and cavitary pulmonary tuberculosis (TB) lesions. In summary, CSE exacerbates TB pathogenesis by altering immunometabolism in mice and inhibiting CSE or modulating glycolysis are potential targets for host-directed TB control.

Mycobacterial antigens accumulation in foamy macrophages in murine pulmonary tuberculosis lesions: Association with necrosis and making of cavities.

Understanding mechanisms of cavitation in tuberculosis (TB) is the missing link that could advance the field towards better control of the infection. Descriptions of human TB suggest that postprimary TB begins as lipid pneumonia of foamy macrophages that undergoes caseating necrosis and fragmentation to produce cavities. This study aimed to investigate the various mycobacterial antigens accumulating in foamy macrophages and their relation to tissue destruction and necrosis. Pulmonary tissues from mice with slowly progressive TB were studied for histopathology, acid-fast bacilli (AFB) and presence of mycobacterial antigens. Digital quantification using Aperio ImageScope was done. Until week 12 postinfection, mice were healthy, and lesions were small with scarce AFB and mycobacterial antigens. Colony-forming units (CFUs) increased exponentially. At week 16-33, mice were sick, macrophages attained foamy appearance with an increase in antigens (P<.05), 1.5 log increase in CFUs and an approximately onefold increase in AFB. At week 37-41, mice started dying with a shift in morphology towards necrosis. A >20-fold increase in mycobacterial antigens was observed with only less than one log increase in CFUs and sevenfold increase in AFB. Secreted antigens were significantly (P<.05) higher compared to cell-wall antigens throughout infection. Focal areas of necrosis were associated with an approximately 40-fold increase in antigen MPT46, functionally active thioredoxin, and a significant increase in all secreted antigens. In conclusion, mycobacterial antigens accumulate in the foamy macrophages in TB lesions during slowly progressive murine pulmonary TB. Secreted antigens and MPT46 correlated with necrosis, thereby implying that they might trigger the formation of cavities.