A study of analysis on prevalence, serological marker and prognosis of tuberculosis in tertiary care hospital.

BACKGROUND: Tuberculosis is an infectious disease responsible for a significant cause of ill health. According to the WHO global tuberculosis report 2021. 9.9 million cases fell sick with TB in 2020. Significantly, the prevalence of tuberculosis in India is 25%. OBJECTIVE: To analyze the prevalence of tuberculosis in the suburban areas of the metropolitan city in South India. To analyze the serological marker and prognosis of tuberculosis among males and females. To determine the importance of molecular testing - PCR confirmation on TB after AFB smear. METHODS: A retrospective study to analyze 462 patients enrolled by the respiratory medicine department on suspecting pulmonary- 356 (M-264 & F-92) and extra-pulmonary-106 (M-73&F-33) patients and diagnosed Zhiel-Neelsen staining, Mantoux test, Chip-based RT-PCR test, Erythrocyte sedimentation rate, and analyzed serological test such as C-Reactive Protein, Chemiluminescence immune assay. RESULTS: 23 patients were positive in Ziehl-Neelsen staining, 65 were positive in molecular True-Nat PCR test, Mantoux skin test induration in 10 patients, 98 TB Positive patients examined in the serological analysis, 1 & 3 patients reacted in HIV/HBsAg, and HBsAg test respectively, by chemiluminescence immunoassay, 8 PTB and 4 EPTB and 47 non-TB patients were positive in C-reactive protein, 46 TB and 94 non-TB patients detected abnormal values out of these 160 patients in ESR test. CONCLUSION: The Prevalence of tuberculosis is significantly rising, especially in the middle-aged population. The rapid molecular diagnostics to detect TB are highly sensitive and specific. Serological markers are essential for the analysis of disease prognosis and need to focus on the guidance of DOTS and RNTCP to End TB.

Efficacy and safety of video-assisted thoracoscopic surgery for pulmonary TB.

OBJECTIVE: Compared with thoracotomy, video-assisted thoracoscopic surgery (VATS) has the advantage of post-operative recovery for patients undergoing surgery. However, studies comparing the efficacy of VATS with conventional traditional thoracotomy for treating patients with pulmonary TB (PTB) are inconsistent.METHODS: Five electronic databases were used to search studies on VATS and conventional thoracotomy for PTB up to 15 March 2022. Standardised mean differences (SMDs) and odds ratios (ORs) were calculated for comparison.RESULTS: A total of 14 were included. Compared with traditional thoracotomy, patients with drug-resistant TB treated using VATS had shorter operative time, less intra-operative bleeding, faster post-operative recovery and fewer post-operative complications (operation time: SMD -0.87, 95% CI -1.29 to -0.45; blood loss: SMD -1.31, 95% CI -1.71 to -0.92; duration of hospital stay: SMD -1.68, 95% CI -2.46 to -0.90; catheterisation time: SMD -1.56, 95% CI -2.39 to -0.73; post-operative complication: OR 0.40, 95% CI 0.27 to 0.60).CONCLUSION: Compared with conventional thoracotomy, VATS for patients with multidrug-resistant PTB undergoing lobectomy and wedge resection has the advantages of minor bleeding, shorter operative time, shorter hospital stay and post-operative pleural cavity drainage duration, and fewer post-operative complications, which can accelerate the post-operative recovery of patients.

The short-term effect of air pollution on the incidence of pulmonary tuberculosis in Chongqing, China, 2014-2020.

INTRODUCTION: Tuberculosis (TB) is one of the top ten causes of death in the world. The purpose of this study was to explore the relationship between the short-term exposure to air pollutants and the risk of pulmonary TB in Chongqing. METHODOLOGY: A distributed lag nonlinear model was used to explore the effect of short-term exposure to air pollutants on the risk of pulmonary TB. Stratified analysis was used to explore the impact of gender and age on the risk of pulmonary TB. RESULTS: There were 170,934 confirmed cases of pulmonary TB in Chongqing from January 1st, 2014 to December 30th, 2020. There was a positive correlation between the exposure to particulate matter with aerodynamic diameter less than 2.5 µm (PM2.5), particulate matter with aerodynamic diameter less than 10 µm (PM10) ozone (O3) and the incidence risk of TB. The maximum lag-specific relative risk (RR) of pulmonary TB was 1.012 (95% CI: 1.001-1.023, 14 days delay) for each 10 µg/m3 increase in PM2.5; 1.010 (95% CI: 1.003-1.017, 14 days delay) for each 10µg/m3 increase in PM10; and 1.002 (95% CI:1.000-1.004, 2 days delay) for each 10 mg/m3 increase in O3. Stratified analysis showed that the exposure effects of PM2.5, PM10 and O3 were different between different genders and age. CONCLUSIONS: This study suggested that exposure to PM2.5, PM10, and O3 was associated with the risk of pulmonary TB, and the risk was higher for males than females, while the exposure to PM2.5 and PM10 was riskier for people aged 15-60 years.

A systematic review and meta-analysis on the association between ambient air pollution and pulmonary tuberculosis.

There is inconclusive evidence on the association between ambient air pollution and pulmonary tuberculosis (PTB) incidence, tuberculosis-related hospital admission and mortality. This review aimed to assess the extent to which selected air pollutants are associated to PTB incidence, hospital admissions and mortality. This was a systematic review of studies published in English from January 1st, 1946, through May 31st, 2022, that quantitatively assessed the association between PM2.5, PM10, NO2, SO2, CO, O3 and the incidence of, hospital admission or death from PTB. Medline, Embase, Scopus and The Cochrane Library were searched. Extracted data from eligible studies were analysed using STATA software. Random-effect meta-analysis was used to derive pooled adjusted risk and odds ratios. A total of 24 studies (10 time-series, 5 ecologic, 5 cohort, 2 case-control, 1 case cross-over, 1 cross-sectional) mainly from Asian countries were eligible and involved a total of 437,255 tuberculosis cases. For every 10 µg/m3 increment in air pollutant concentration, there was a significant association between exposure to PM2.5 (pooled aRR = 1.12, 95% CI: 1.06-1.19, p < 0.001, N = 6); PM10 (pooled aRR = 1.06, 95% CI: 1.01-1.12, p = 0.022, N = 8); SO2 (pooled aRR = 1.08, 95% CI: 1.04-1.12, p < 0.001, N = 9); and the incidence of PTB. There was no association between exposure to CO (pooled aRR = 1.04, 95% CI: 0.98-1.11, p = 0.211, N = 4); NO2 (pooled aRR = 1.08, 95% CI: 0.99-1.17, p = 0.057, N = 7); O3 (pooled aRR = 1.00, 95% CI: 0.99-1.02, p = 0.910, N = 6) and the incidence of PTB. There was no association between the investigated air pollutants and mortality or hospital admissions due to PTB. Overall quality of evidence was graded as low (GRADE approach). Exposure to PM2.5, PM10 and SO2 air pollutants was found to be associated with an increased incidence of PTB, while exposure to CO, NO2 and O3 was not. There was no observed association between exposure to these air pollutants and hospital admission or mortality due to PTB. The quality of the evidence generated, however, remains low. Addressing the tuberculosis epidemic by 2030 as per the 4th Sustainable Development Goal may require a more rigorous exploration of this association.

Pulmonary tuberculosis associated with immune checkpoint inhibitors: a pharmacovigilance study.

We examined case reports of immune checkpoint inhibitors (ICIs) associated pulmonary tuberculosis (PT) using data from the Food and Drug Administration Adverse Event Reporting System database. Disproportionality analysis was performed by using the reporting OR (ROR) with relevant 95% CI. A total of 74 cases of PT related to ICIs therapy were identified. ICIs were significantly associated with over-reporting frequencies of PT (ROR=3.16, 95% CI: 2.51 to 3.98), while the signal was differed between anti-programmed death-1/ligand-1 and anti-cytotoxic T lymphocyte antigen-4 agents. Most indications were lung cancer (64.9%), the median onset age was 70 years, the median time to onset of PT was 70 days, ICIs were discontinued in most cases (85.2%).

Combination of Xpert® MTB/RIF and DetermineTM TB-LAM Ag improves the diagnosis of extrapulmonary tuberculosis at Jimma University Medical Center, Oromia, Ethiopia.

BACKGROUND: Ethiopia is one of the high burden countries for extrapulmonary tuberculosis (EPTB); however, the prompt diagnosis of EPTB remains challenging. This study is aimed to evaluate the diagnostic performance of Xpert MTB/RIF and DetermineTM TB-LAM Ag (TB-LAM) for the prompt diagnosis of EPTB in Ethiopia. METHODS: A total of 147 presumptive EPTB patients, including 23 HIV- positive participants were enrolled. Extra-pulmonary samples were collected from all presumptive EPTB cases and tested for Mycobacterium tuberculosis complex (MTBC) using fluorescent microscopy, Xpert MTB/RIF, and culture. Additionally, urine samples were also collected from 126 participants and were tested by DetermineTM TB-LAM Ag (Alere Inc, Waltham, USA). The Sensitivity and specificity of Xpert and TB- LAM tests were calculated by comparing with a composite reference standard (CRS), which comprises smear microscopy, culture and response to empirical anti-TB treatment. RESULTS: Of 147 patients, 23 (15.6%) were confirmed EPTB cases (culture-positive), 14 (9.5%) were probable EPTB (clinically, radiologically or cytologically positive and received anti-TB treatment with good response), and 110 (74.8%) were classified as "non- TB" cases. Compared to the composite reference standard (CRS), the overall sensitivity and specificity of Xpert MTB/RIF were 43.2% and 100%, respectively with the highest sensitivity for Lymph node aspirate (85.7%) and lower sensitivity for pleural fluid (14.3%) and 100% specificity for all specimen types. The sensitivity and specificity of TB-LAM were 33.3% and 94.4% respectively with the highest sensitivity for HIV co-infected participants (83.3%). The sensitivity of the combination of Xpert MTB/RIF and TB-LAM tests regardless of HIV status was 61.1% whereas the sensitivity was improved to 83.3% for HIV-positive cases. CONCLUSION: TB-LAM alone has low sensitivity for EPTB diagnosis; however, the combination of TB-LAM and Xpert MTB/RIF improves the diagnosis of EPTB particularly for countries with high EPTB and HIV cases.

Cytomegalovirus acquisition in infancy and the risk of tuberculosis disease in childhood: a longitudinal birth cohort study in Cape Town, South Africa.

BACKGROUND: The risk of tuberculosis disease after recent exposure is greatest before age 5 years; however, the mechanisms explaining this increased risk are not well elucidated. Acquisition of viral infections, such as cytomegalovirus, in early life might modulate the immune system. We aimed to evaluate the acquisition of cytomegalovirus infection in infancy and the development of tuberculosis disease in children. METHODS: In this prospective, birth cohort study we enrolled pregnant women who were between 20 and 28 weeks of gestation attending antenatal care in Paarl, a periurban setting outside of Cape Town, South Africa. Participants were recruited from two clinics (TC Newman and Mbekweni). Infants were given Bacillus Calmette-Guérin vaccination at birth as per national policy. Nasopharyngeal swabs for cytomegalovirus detection using qPCR were done for infants at birth, age 3 and 6 weeks, and age 3, 6, 12, and 24 months. Children were prospectively followed up for tuberculosis disease until age 9 years using tuberculin skin testing, radiographic examinations, GeneXpert, and sputum testing. Tuberculin skin tests were done at the 6-month visit and then at age 12, 24, 36, 48, and 60 months, and at the time of lower respiratory tract infection. We compared tuberculosis disease incidence after age 1 year or after age 6 months in children with and without cytomegalovirus infection using Cox regression and hazard ratios (HRs) with 95% CIs. FINDINGS: Between March 5, 2012, and March 31, 2015, 1225 pregnant women were recruited and enrolled in the birth cohort. 88 (7%) women were excluded because of loss to antenatal follow-up or pregnancy losses. Of 1143 livebirths, 68 (6%) mother-infant pairs were excluded. In total, 963 children were serially tested for cytomegalovirus (7186 cytomegalovirus measurements taken; median six tests per child, IQR 2-11). The prevalence of congenital cytomegalovirus at age younger than 3 weeks was 2% (18 of 816). Cytomegalovirus positivity increased continuously with age from 3% (27 of 825) by age 6 weeks to 21% (183 of 882) by 3 months, 35% (315 of 909) by 6 months, and 42% (390 of 933) by 12 months. Mother-infant pairs were followed up for a median of 6·9 years (IQR 6·0-7·8). The risk of tuberculosis disease in children after age 1 year was higher in those with cytomegalovirus infection by age 6 weeks (adjusted HR 4·1, 95% CI 1·2-13·8; p=0·022), 3 months (2·8, 1·4-5·8; p=0·0040), 6 months (3·6, 1·7-7·3; p<0·0001), 12 months (3·2, 1·6-6·4; p=0·0010), and 24 months (4·2, 2·0-8·8; p<0·0001). The risk of microbiologically confirmed tuberculosis disease was also higher among children acquiring cytomegalovirus infection before age 3 months (adjusted HR 3·2, 95% CI 1·0-10·6; p=0·048), 6 months (3·9, 1·2-13·0; p=0·027), 12 months (4·4, 1·2-16·3; p=0·027), and 24 months (6·1, 1·3-27·9; p=0·020). In children older than 1 year, the risk of tuberculosis disease was consistently greater in those with high cytomegalovirus loads than in those with low cytomegalovirus loads that were acquired before age 3 months (adjusted HR 2·0 vs 3·7; ptrend=0·0020; both groups compared with cytomegalovirus negative reference) and before age 12 months (2·7 vs 3·7; ptrend=0·0009). INTERPRETATION: Infants that acquire cytomegalovirus in the first year of life are at high risk of subsequently developing tuberculosis disease. Efforts to prevent tuberculosis in early childhood in high-burden countries might need to deter or delay acquisition of cytomegalovirus perinatally or in the first months of life. FUNDING: Bill & Melinda Gates Foundation, MRC South Africa, National Research Foundation South Africa, and Wellcome Trust.

Tuberculosis and associated risk factors among children and adolescent population in Serbia: 12 year's retrospective study.

INTRODUCTION: Recognition and epidemiological control of childhood and adolescent tuberculosis (TB) is essential to achieve effective control of TB in general as it presents high risk for transmission in the community. The aim of the study is to provide a descriptive and analytic overview of the trends in childhood and adolescent TB notifications and treatment outcomes and to identify factors associated with treatment success in a twelve-year period in Serbia. METHODOLOGY: We performed a retrospective trend analysis and analysis of treatment outcomes of 596 child and adolescent TB cases notified in Serbia in the period 2005-2016 from all health facilities, as well as logistic regression analysis to identify predictors of treatment success. RESULTS: Factors independently associated with treatment success were: new TB (OR=2.60; 95% CI: 1.45-3.74), male sex (OR=2.55; 95% CI: 2.09-3.00), pulmonary TB (OR=3.34; 95% CI: 2.34-4.34), comorbidities (OR=2.58; 95% CI: 2.24-2.91), age below 5 years (OR=0.37; 95% CI: 0.32-0.43), and social vulnerability (OR=0.40; 95% CI: 0.34-0.46). CONCLUSIONS: In order to improve TB treatment outcomes among children and adolescent population in Serbia, it is important to focus on female, age group 5-18, EPTB, retreatment cases and socially vulnerable groups.

Case Report: Development of Miliary Pulmonary Tuberculosis in a Patient with Peritoneal Tuberculosis after COVID-19 Upper Respiratory Tract Infection.

We report a 29-year-old patient who presented with coronavirus disease 2019 (COVID-19) upper respiratory tract infection in addition to clinical, laboratory, and radiological findings highly suggestive of peritoneal tuberculosis (TB) without pulmonary involvement. Two weeks after the resolution of COVID-19 infection, he presented with shortness of breath and oxygen desaturation requiring intubation and admission to the intensive care unit. The workup confirmed miliary pulmonary TB. The patient subsequently improved on antitubercular treatment. We discuss the possible contribution of COVID-19 infection to the rapid progression of TB infection to involve the lung in a miliary pattern, and how the coexistence of the two diseases might have led to a worse outcome.

The child ecosystem and childhood pulmonary tuberculosis: A South African perspective.

INTRODUCTION: This study investigates drivers of childhood pulmonary tuberculosis (PTB) using a childhood ecosystem approach in South Africa. An ecosystem approach toward identifying risk factors for PTB may identify targeted interventions. METHODS: Data were collected as part of a prospective cohort study of children presenting at a primary care facility or tertiary hospital with possible TB. Characterization of the childhood ecosystem included proximal, medial, and distal determinants. Proximal determinants included child characteristics that could impact PTB outcomes. Medial determinants included relational factors, such as caregiver health, which might impact interactions with the child. Distal determinants included macro-level determinants of disease, such as socioeconomic status and food insecurity. Children who started on TB treatment were followed for up to 6 months. Multivariate regression models tested independent associations between factors associated with PTB in children. RESULTS: Of 1202 children enrolled, 242 (20%) of children had confirmed PTB, 756 (63%) were started on TB treatment, and 444 (37%) had respiratory conditions other than TB. In univariate analyses, childhood malnutrition and caregiver smoking were associated with treated or confirmed PTB. In multivariate analyses, proximal factors, such as male gender and hospitalization, as well as low socioeconomic status as a distal factor, were associated with PTB. CONCLUSIONS: Interventions may need to target subgroups of children and families with elevated proximal, medial, and distal risk factors for PTB. Screening for risk factors, such as caregiver's health, may guide targeting. The provision of social protection programs to bolster economic security may be an important intervention for attenuating childhood exposure to risk factors.

Tuberculosis pulmonar asociada a Infliximab: a propósito del primer caso reportado en Cuba / Infliximab-associated pulmonary tuberculosis: regarding the first case reported in Cuba

La terapia con fármacos antagonistas del factor de necrosis tumoral alfa ha sido beneficiosa en el tratamiento de varias enfermedades como las del tejido conectivo e inflamatorias del intestino, pero no está exenta de riesgos. Las principales complicaciones de estas drogas inmunosupresoras son las infecciones, y la tuberculosis pulmonar es una de las principales afecciones, que se pueden observar en los pacientes con este tipo de tratamiento.Se presentó una mujer de 31 años, atendida en el Hospital Clínico Quirúrgico Hermanos Ameijeiras, La Habana, Cuba, con antecedentes de colitis ulcerativa, que hace 3 meses recibe terapia con Infliximab. Acude al hospital por referir 4 días previos al ingreso, fiebre de 390 C dos veces al día, acompañándose de cefalea, pérdida del apetito y dolor en la región perineal. Se le realizó radiografía de tórax, donde se describe radiopacidad heterogénea que va desde el cuerno superior del hilio derecho hasta planos axilares, en la tomografía axial de tórax reportan consolidación en segmento anterior del lóbulo superior derecho con presencia de broncograma aéreo y en el lavado bronquial microbiológico para bacilos ácido-alcohol resistentes se informó codificación 8, positivo a Mycobacterium tuberculosis. El diagnóstico preciso de tuberculosis relacionada con el uso de fármacos antagonistas del factor de necrosis tumoral alfa requiere un alto índice de sospecha y una investigación detallada. Existe un alto grado de complejidad diagnóstica, por la existencia de un amplio espectro clínico y la necesidad de excluir otras enfermedades.

Tumor necrosis factor alpha antagonist drug therapy has been beneficial in the treatment of several diseases such as connective tissue and inflammatory bowel diseases, but it is not without risks. The main complications of these immunosuppressive drugs are infections, and pulmonary tuberculosis is one of the main conditions, which can be observed in patients with this type of treatment. A 31-year-old woman, treated at the Hermanos Ameijeiras Clinical Surgical Hospital, Havana, Cuba, with a history of ulcerative colitis, who has been receiving Infliximab therapy for 3 months, presented. He went to the hospital for referring 4 days prior to admission, a fever of 390 C twice a day, accompanied by headache, loss of appetite and pain in the perineal region. A chest X-ray was performed, which described heterogeneous radiopacity that goes from the upper horn of the right hilum to axillary planes, in the chest axial tomography they report consolidation in the anterior segment of the right upper lobe with the presence of air bronchogram and in the bronchial lavage microbiological for acid-fast bacilli coding 8, positive for mycobacterium tuberculosis was reported. Accurate diagnosis of tuberculosis related to the use of tumor necrosis factor alpha antagonist drugs requires a high index of suspicion and detailed investigation. There is a high degree of diagnostic complexity, due to the existence of a wide clinical spectrum and the need to exclude other diseases.

Tuberculosis case notifications in Malawi have strong seasonal and weather-related trends.

Seasonal trends in tuberculosis (TB) notifications have been observed in several countries but are poorly understood. Explanatory factors may include weather, indoor crowding, seasonal respiratory infections and migration. Using enhanced citywide TB surveillance data collected over nine years in Blantyre, Malawi, we set out to investigate how weather and seasonality affect temporal trends in TB case notification rates (CNRs) across different demographic groups. We used data from prospective enhanced surveillance between April 2011 and December 2018, which systematically collected age, HIV status, sex and case notification dates for all registering TB cases in Blantyre. We retrieved temperature and rainfall data from the Global Surface Summary of the Day weather station database. We calculated weekly trends in TB CNRs, rainfall and temperature, and calculated 10-week moving averages. To investigate the associations between rainfall, temperature and TB CNRs, we fitted generalized linear models using a distributed lag nonlinear framework. The estimated Blantyre population increased from 1,068,151 in April 2011 to 1,264,304 in December 2018, with 15,908 TB cases recorded. Overall annual TB CNRs declined from 222 to 145 per 100,000 between 2012 and 2018, with the largest declines seen in HIV-positive people and adults aged over 20 years old. TB CNRs peaks occurred with increasing temperature in September and October before the onset of increased rainfall, and later in the rainy season during January-March, after sustained rainfall. When lag between a change in weather and TB case notifications was accounted for, higher average rainfall was associated with an equivalent six weeks of relatively lower TB notification rates, whereas there were no changes in TB CNR associated with change in average temperatures. TB CNRs in Blantyre have a seasonal pattern of two cyclical peaks per year, coinciding with the start and end of the rainy season. These trends may be explained by increased transmission at certain times of the year, by limited healthcare access, by patterns of seasonal respiratory infections precipitating cough and care-seeking, or by migratory patterns related to planting and harvesting during the rainy season.

The Role of ß-Catenin in Th1 Immune Response against Tuberculosis and Profiles of Expression in Patients with Pulmonary Tuberculosis.

ß-Catenin is a key molecule of canonical Wnt/ß-catenin pathway. Its roles and expression profiles in T cells of tuberculosis (TB) remain unclear. The aim of this study was to explore the role of ß-catenin in CD4+ T cells and its expression characteristics in patients with pulmonary tuberculosis (PTB). In this study, CD4+ T cell-specific ß-catenin conditional knockout mice (ß-CAT-cKO mice) were aerosol infected with Mycobacteria tuberculosis (Mtb) H37RV with wild-type mice as controls. Four weeks after infection, the mRNA expression of IFN-γ, TNF-α, and TCF-7 in the lungs of mice was measured. CD4, CD8, ß-catenin, IFN-γ, and TNF-α in mononuclear cells from the lungs and spleens were measured by flow cytometry, and the pathological changes of lungs were also observed. Patients with PTB were enrolled, with blood samples collected and PBMCs isolated. The expressions of ß-catenin, IFN-γ, TNF-α, and PD-1 in CD4+ and CD8+ T cells were measured by flow cytometry. Results showed a decreased frequency of and reduced IFN-γ/TNF-α mRNA expression and secretion by CD4+ T cells in the lungs of infected ß-CAT-cKO mice compared with infected wild-type controls, and only slightly more inflammatory changes were observed in the lungs. ß-catenin expressions in CD4+ and CD8+ T cells were significantly decreased in blood cells of patients with severe PTB compared with those in mild PTB. The stimulation of peripheral blood mononuclear cells (PBMCs) with lithium chloride (LiCl), a stimulant of ß-catenin, resulted in the increase in CD4+ T cell frequency, as well as their secretion of IFN-γ and TNF-α. ß-Catenin demonstrated a moderately positive correlation with PD-1 in CD4+ T cells. ß-Catenin along with PD-1 and IFN-γ in CD4+ T cells had a high correlation with those in CD8+ T cells. In conclusion, ß-catenin may be involved in the regulation of Th1 response and CD4+ T cell frequency in TB.

Unexpected exposure to Mycobacterium tuberculosis during bronchoscopy using radial probe endobronchial ultrasound.

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.

S100A2: A potential biomarker to differentiate malignant from tuberculous pleural effusion.

BACKGROUND: S100 calcium binding protein A2 (S100A2)-which has been testified to have an abnormal expression in non-small cell lung cancer (NSCLC)-is considered as an effective biomarker in the diagnosis and prognosis of this malignancy. In this study, we detected the S100A2 levels in pleural effusion, aiming to evaluate its potential value in differentiating malignant pleural effusion (MPE) from tuberculous pleural effusion (TPE). METHODS: We collected pleural effusion from 104 NSCLC patients with MPE and 96 tubercular pleurisy cases. Enzyme-linked immunosorbent assay (ELISA) was performed to measure the levels of S100A2 in these samples. Meanwhile, the serum S100A2 levels were also examined in same subjects. The data concerning the expression of those commonly-used markers, including CEA, CYFRA211 and NSE, were obtained from medical records. RESULTS: Like other classified biomarkers, S100A2 had an over-expression in both pleural effusion and sera of the NSCLC patients compared with controls (P = 0.000), though having a lower P value. Receiver operating characteristic (ROC) analysis showed that the levels of S100A2 in pleural effusion (PE) could distinguish MPE from tuberculous pleurisy (Area Under the Receiver Operating Characteristic Curve (AUC) = 0.887), and its diagnostic value in hydrothorax was obviously higher than in serum (AUC = 0.709). CONCLUSION: Our results indicate that levels of S100A2 are significantly elevated in MPE, and that S100A2 may serve as a diagnostic biomarker for NSCLC patients with MPE. In further studies, we will validate our findings with a larger sample population.

Exploring the Role of C-C Motif Chemokine Ligand-2 Single Nucleotide Polymorphism in Pulmonary Tuberculosis: A Genetic Association Study from North India.

The C-C motif chemokine ligand-2 (CCL2) was evidenced to be associated with tuberculosis susceptibility in some ethnic groups. In the present study, effort was made to find out the association of CCL2-2518 A>G and -362 G>C variants with susceptibility to TB in a population from North India. The genotyping was carried out in 373 participants with pulmonary TB (PTB) and 248 healthy controls (HCs) for CCL2-2518 A>G and -362 G>C polymorphisms by PCR-RFLP and by melting curve analysis using fluorescence-labeled hybridization fluorescent resonance energy transfer (FRET) probes, respectively, followed by DNA sequencing in a few representative samples. Genotype and allele frequencies were compared by the chi-squared test and crude and Mantel-Haenszel (M-H) odds ratio (OR). OR was calculated using STATA/MP16.1 software. Further, CCL2, IL-12p70, IFN-γ, TNF-α, and TGF-ß levels were measured in serum samples of these participants using commercially available kits. Our analysis indicated that the homozygous mutant in both -2518 GG (OR = 2.07, p = 0.02) and -362 CC (OR = 1.92, p = 0.03) genotypes was associated with susceptibility to pulmonary TB. Further, heterozygous genotypes -2518AG (OR = 0.60, p = 0.003) and -362GC (OR = 0.64, p = 0.013) provide resistance from PTB disease. Haplotype analysis revealed AC haplotype (p = 0.006) to be a risk factor associated with PTB susceptibility. The serum CCL2 level was significantly elevated among participants with -2518 AA genotype compared to -2518 GG genotype. CCL2 level was observed to be positively correlated with IL12p70, IFN-γ and TNF-α, thus suggesting the immunological regulatory role of CCL2 against pulmonary tuberculosis. CCL2-2518 GG and -362 CC genotypes were found to be associated with susceptibility to pulmonary tuberculosis and CCL2-2518AG and CCL2-362GC with resistance from PTB. AC haplotype was found to be a risk factor for PTB in the present study. It may be hypothesized from the findings that -2518G allele could be responsible for lower production of CCL2 which leads to defective Th1 response and makes a host susceptible for pulmonary tuberculosis.

Logistic regression analysis of environmental and other variables and incidences of tuberculosis in respiratory patients.

The objective of this study was to examine the association of 14 variables with TB in respiratory patients. The variables included: urban/rural, persons in 1200 sqft area, TB in family, crowding, smoking (family member), gender, age, education, smoking, workplace, kitchen location, cooking fuel, ventilation, and kerosene uses. Eight hundred respiratory patients were tested for sputum positive pulmonary TB; 500 had TB and 300 did not. An analysis of the unadjusted odds ratio (UOR) and adjusted OR (AOR) was undertaken using logistic regression to link the probability of TB incidences with the variables. There was an inconsistency in the significance of variables using UOR and AOR. A subset model of 4 variables (kerosene uses, ventilation, workplace, and gender) based on significant AOR was adjudged acceptable for estimating the probability of TB incidences. Uses of kerosene (AOR 2.62 (1.95, 3.54)) consistently related to incidences of TB. It was estimated that 50% reduction in kerosene uses could reduce the probability of TB by 13.29% in respiratory patients. The major recommendation was to replace kerosene uses from households with a supply of clean fuel like liquid petroleum or natural gas and rural electrification.

Phosphorylated STAT3 suppresses microRNA-19b/1281 to aggravate lung injury in mice with type 2 diabetes mellitus-associated pulmonary tuberculosis.

Type 2 diabetes mellitus (T2DM) is a risk factor for pulmonary tuberculosis (PTB) and increased mortality. This work focused on the functions of phosphorylated STAT3 in lung injury in mouse with T2DM-associated PTB and the molecules involved. A mouse model with T2DM-PTB was induced by administrations of streptozotocin, nicotinamide and mycobacterium tuberculosis (Mtb). A pSTAT3-specific inhibitor AG-490 was given into mice and then the lung injury in mice was observed. The molecules involved in AG-490-mediated events were screened out. Altered expression of miR-19b, miR-1281 and NFAT5 was introduced to identify their involvements and roles in lung injury and PTB severity in the mouse model. Consequently, pSTAT3 expression in mice with T2DM-associated PTB was increased. Down-regulation of pSTAT3 by AG-490 prolonged the lifetime of mice and improved the histopathologic conditions, and inhibited the fibrosis, inflammation, Mtb content and number of apoptotic epithelial cells in mouse lung tissues. pSTAT3 transcriptionally suppressed miR-19b/1281 expression to up-regulate NFAT5. Inhibition of miR-19b/1281 or up-regulation of NFAT5 blocked the protective roles of AG-490 in mouse lung tissues. To conclude, this study evidenced that pSTAT3 promotes NFAT5 expression by suppressing miR-19b/1281 transcription, leading to lung injury aggravation and severity in mice with T2DM-associated PTB.

Use of steroids to treat anti-tumor necrosis factor α induced tuberculosis-associated immune reconstitution inflammatory syndrome: Case report and literature review.

INTRODUCTION: Individuals with tuberculosis (TB) who are being treated with anti-tumor necrosis factor α (anti-TNFα) for coexisting conditions may experience unexpected exacerbations of TB after the initiation of antituberculous therapy, so-called anti-TNFα-induced TB-immune reconstitution inflammatory syndrome (anti-TNFα-induced TB-IRIS). Anti-TNFα-induced TB-IRIS is often treated empirically with corticosteroids; however, the evidence of the effectiveness of corticosteroids is lacking and the management can be a challenge. PATIENT CONCERNS: A 32-year-old man on long-term infliximab therapy for Crohn disease visited a clinic complaining of persistent fever and cough that had started 1 week previously. His most recent infliximab injection had been administered 14 days before the visit. A chest X-ray revealed a left pleural effusion, and he was admitted to a local hospital. DIAGNOSIS: A chest computed tomography (CT) scan revealed miliary pulmonary nodules; acid-fast bacilli were found in a sputum smear and a urine sediment sample; and polymerase chain reaction confirmed the presence of Mycobacterium tuberculosis in both his sputum and the pleural effusion. He was diagnosed with miliary TB. INTERVENTIONS: Antituberculous therapy was started and he was transferred to our hospital for further management. His symptoms initially improved after the initiation of antituberculous therapy, but 2 weeks later, his symptoms recurred and shadows on chest X-ray worsened. A repeat chest CT scan revealed enlarged miliary pulmonary nodules, extensive ground-glass opacities, and an increased volume of his pleural effusion. This paradoxical exacerbation was diagnosed as TB-IRIS associated with infliximab. A moderate-dose of systemic corticosteroid was initiated [prednisolone 25 mg/day (0.5 mg/kg/day)]. OUTCOMES: After starting corticosteroid treatment, his radiological findings improved immediately, and his fever and cough disappeared within a few days. After discharge, prednisolone was tapered off over the course of 10 weeks, and he completed a 9-month course of antituberculous therapy uneventfully. He had not restarted infliximab at his most recent follow-up 14 months later. CONCLUSION: We successfully managed a patient with anti-TNFα-induced TB-IRIS using moderate-dose corticosteroids. Due to the limited evidence currently available, physicians should consider the necessity, dosage, and duration of corticosteroids for each case of anti-TNFα-induced TB-IRIS on an individual patient-by-patient basis.

The effect of micro-nutrients on malnutrition, immunity and therapeutic effect in patients with pulmonary tuberculosis: A systematic review and meta-analysis of randomised controlled trials.

OBJECTIVE: Micro-nutrients are closely related to pulmonary tuberculosis (PTB). Most patients with PTB suffer from micro-nutrients deficiency. We aimed to evaluate the efficacy of micro-nutrients support on clinical therapy and chronic inflammation in patients with PTB. METHODS: We searched Pubmed, Springer link, Web of Science, Cochrane, Wan Fang and CNKI databases for randomised controlled trials (RCTs). The patients with anti-TB treatments were divided into two groups, the control group with nutritional advice or placebo, and the experimental group with micro-nutrients support for more than 2 weeks. Two reviewers conducted data extraction and quality assessment of the studies independently, and ReviewManager 5.2 software was used to input and analyse the data. The dichotomous variable was expressed in the risk ratios (RRS) and 95% CI, the continuous data were expressed in the mean difference (MD) and 95% CI, and the heterogeneity of subgroup was evaluated by I (Kerantzas and Jacobs, Jr., 2017) [2] test. RESULTS: A total of 13 trials (2847 participants) were included. First, micro-nutrients improved sputum smears or culture negative conversion rates (OR 0.16 0.03-0.77, 2.29; MD -2.36, -4.72~-0.01, z = 1.97). Meanwhile, micro-nutrients support increased lymphocytes and decreased leukocytes, neutrophils, CRP and ESR (MD 0.20, 0.06-0.35, z = 2.78; MD -0.42, -0.65~-0.18, z = 3.48; MD -0.66, -1.12~-0.20, z = 2.82). However it had not impact on body weight, MUAC, haemoglobin, albumin or monocytes (p > 0.05). CONCLUSION: Micro-nutrients support can reduce chronic inflammation and improve sputum smears or culture conversions to contribute to anti-TB treatment.