Increased Detection of Mycobacterium tuberculosis Disease Using a Tissue-Based Laboratory-Developed Polymerase Chain Reaction Assay Compared to Standard Diagnostics.

Standard diagnostics for Mycobacterium tuberculosis (MTB) including acid-fast bacilli (AFB) smear and culture, and Xpert™ MTB/RIF real-time Polymerase Chain Reaction (RT-PCR; Xpert) have variable sensitivity and/or long turnaround times. We describe the clinical performance of a laboratory-developed tissue-based MTB PCR compared with AFB culture and Xpert using a composite reference standard (CRS). Over an 8-year period, MTB PCR was performed on pulmonary, pleural, or lymph node specimens for 36 patients. Of these, 11 met criteria for confirmed/probable MTB using CRS. MTB PCR was positive in 100% (11/11), AFB cultures were positive in 73% (8/11), and Xpert in 0% (0/4). MTB PCR was negative in 25 cases of "No MTB" (100% specific). The MTB PCR assay resulted faster than positive AFB culture (mean time 4.3 versus 21.2 days). Tissue-based MTB PCR was associated with increased and rapid detection of MTB, improving clinical sensitivity in strongly suspected MTB cases.

Deep Learning for Detection of Pulmonary Metastasis on Chest Radiographs.

Background A computer-aided detection (CAD) system may help surveillance for pulmonary metastasis at chest radiography in situations where there is limited access to CT. Purpose To evaluate whether a deep learning (DL)-based CAD system can improve diagnostic yield for newly visible lung metastasis on chest radiographs in patients with cancer. Materials and Methods A regulatory-approved CAD system for lung nodules was implemented to interpret chest radiographs from patients referred by the medical oncology department in clinical practice. In this retrospective diagnostic cohort study, chest radiographs interpreted with assistance from a CAD system after the implementation (January to April 2019, CAD-assisted interpretation group) and those interpreted before the implementation (September to December 2018, conventional interpretation group) of the CAD system were consecutively included. The diagnostic yield (frequency of true-positive detections) and false-referral rate (frequency of false-positive detections) of formal reports of chest radiographs for newly visible lung metastasis were compared between the two groups using generalized estimating equations. Propensity score matching was performed between the two groups for age, sex, and primary cancer. Results A total of 2916 chest radiographs from 1521 patients (1546 men, 1370 women; mean age, 62 years) and 5681 chest radiographs from 3456 patients (2941 men, 2740 women; mean age, 62 years) were analyzed in the CAD-assisted interpretation and conventional interpretation groups, respectively. The diagnostic yield for newly visible metastasis was higher in the CAD-assisted interpretation group (0.86%, 25 of 2916 [95% CI: 0.58, 1.3] vs 0.32%, 18 of 568 [95% CI: 0.20, 0.50%]; P = .004). The false-referral rate in the CAD-assisted interpretation group (0.34%, 10 of 2916 [95% CI: 0.19, 0.64]) was not inferior to that in the conventional interpretation group (0.25%, 14 of 5681 [95% CI: 0.15, 0.42]) at the noninferiority margin of 0.5% (95% CI of difference: -0.15, 0.35). Conclusion A deep learning-based computer-aided detection system improved the diagnostic yield for newly visible metastasis on chest radiographs in patients with cancer with a similar false-referral rate. © RSNA, 2021 Online supplemental material is available for this article.

Micro-Computed Tomography Analysis of the Human Tuberculous Lung Reveals Remarkable Heterogeneity in Three-dimensional Granuloma Morphology.

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.

Associated factors of co-existent pulmonary tuberculosis and lung cancer: A case-control study.

BACKGROUND: Although the incidence of co-existent pulmonary tuberculosis (PTB) and lung cancer in China is increasing, risk factors related to its development are still poorly understood. We aimed to investigate which clinical factors were associated with the odds of co-existent PTB and lung cancer (PTB-lung cancer) cases in a case-control study. METHOD: A total of 125 PTB-lung cancer patients were enrolled by Beijing Chest Hospital as the case group between January 2012 and December 2016. Age- and sex-matched PTB-only (N = 125) and lung cancer-only (N = 125) patients were selected as the control groups. Data were collected from the medical records and computed tomography (CT) reports. The case group was further categorized into three sub-groups according to the diagnosis intervals between previous PTB and lung cancer (<1 year, 1-10 years, and > 10 years). RESULT: Compared with both controls of PTB-only and lung cancer-only patients, the PTB-lung cancer case group had significantly higher proportions of patients with irritant cough, expectoration, hemoptysis, fever and CT features of irregular mass and pleural thickening. For PTB patients, fibrous calcification (OR, 2.193; 95%CI, 1.168-4.117) was associated with higher odds of lung cancer (P-value < .05). CONCLUSION: Distinct clinical symptoms and CT tests may help with the early diagnosis of PTB-lung cancer cases. PTB patients with fibrous calcification may have a higher risk of lung cancer. Further multicenter prospective studies are required to validate our findings.

Burkitt lymphoma associated with human immunodeficiency virus infection and pulmonary tuberculosis: A case report.

INTRODUCTION: The association of human immunodeficiency virus (HIV) infection with Burkitt lymphoma is related to the presence of Epstein Barr virus infection and the impact of the HIV antigen on the expansion of B-polyclonal cells. In Southeast Europe, the association is rare, and recognizing this is important in the therapeutic decision to increase patient survival rate. The association of HIV with Burkitt lymphoma and tuberculosis is even more rarely described in the literature. PATIENT CONCERNS: We present the case of a 40-year-old patient who presented with a 3-week history of fever (max. 38.7 °C), painful axillary swelling on the right side, lumbar pain, gait disorders, headache, and night sweats. Clinical manifestations included marked weight loss (about 30 kg in the last 2 months before his admission). DIAGNOSIS: A LyCD4 count of 38/µL and a HIV1 viral load of 384,000/mm3, classified the patient into a C3 stage. A biopsy of the right axillary lymph node was performed for suspected ganglionic tuberculosis due to immunodeficiency. Histopathological examination confirmed the diagnosis of Burkitt lymphoma. Cultures on Löwenstein-Jensen medium from sputum harvested at first admission were positive for Mycobacterium tuberculosis. INTERVENTIONS: Highly active antiretroviral therapy, chemotherapeutic agents for Burkitt lymphoma, anti-tuberculous drug therapy, neurosurgical intervention of spinal cord decompression, and antibiotic therapy of the associated bacterial infection. OUTCOME: Burkitt lymphoma disseminated rapidly, with central nervous system, spinal cord, osteomuscular, adrenal, and spleen involvement. The evolution under treatment was unfavorable, with patient death occurring 6 months after diagnosis. CONCLUSIONS: The association of HIV infection with Burkitt lymphoma and tuberculosis is rare in the highly active antiretroviral therapy (HAART) era, posing prompt and multidisciplinary therapeutic management issues. Similar cases of HIV-TB and Burkitt lymphoma association have been described, but none of the other cases showed the involvement of the central nervous system or of the bilateral adrenal glands.

Pulmonary tuberculosis and pneumocystis jirovecii concurrent pneumonia in HIV infected patients at a resource limited setting in Eastern India: A case series.

Pneumocytis jirovecii pneumonia (PJP) and Pulmonary TB (PTB) both are common opportunistic infections among HIV infected individuals. But concurrent infections pose a diagnostic challenge owing to similar clinical features. Data suggests a high prevalence of such concurrent infections in developing countries but limited diagnostic modalities especially in resource constraint setup limits accurate diagnosis. At our centre we came across 6 newly diagnosed PTB patients among HIV infected ones had persistent shortness of breath (SOB) and hypoxia despite starting anti-tuberculous treatment (ATT). We excluded concomitant bacterial pneumonia by imaging, sputum examination and blood culture. Serum lactate dehydrogenase (LDH) was estimated and hypoxia by arterial blood gas (ABG). We found all 6 patients had elevated serum LDH, hypoxia and imaging suggestive of PJP were offered sputum for Geisma stain and standard treatment for PJP in form of Bactrim-double strength and steroid. 1 patient had PJ cysts in sputum. 5 patient's classical radiologic findings in form of ground glass opacities in lower lobes along with bilateral infiltrates and 1 had honeycombing. Serum LDH was elevated all 6 subjects. 5 were newly diagnosed HIV and 4 had CD4 count below 50 cells/mm3 and 2 had below 200 cells/mm3.1 patient had developed bilateral pneumothorax as complication. 4 patients responded to treatment and 2 (33.3%) died of respiratory failure during treatment. We were able to diagnose only severe PJP cases as concurrent infection with PTB as there was no availability of broncho alveolar lavage (BAL) as well as direct fluorescent antigen (DFA) test for PJ detection. A high index of suspicion for PJP even in PTB patients with low CD4 count will guide to appropriate therapy for both infections and eventually reduces morbidity and mortality.

Development of chronic lung impairment in Mozambican TB patients and associated risks.

BACKGROUND: Pulmonary tuberculosis (PTB) is frequently associated with chronic respiratory impairment despite microbiological cure. There are only a few clinical research studies that describe the course, type and severity as well as associated risk factors for lung impairment (LI) in TB patients. METHODS: A prospective cohort study was conducted at TB Research Clinic of Instituto Nacional de Saúde in Mavalane, Maputo, from June 2014 to June 2016. PTB patients were prospectively enrolled and followed for 52 weeks after TB diagnosis. Lung function was evaluated by spirometry at 8, 26 and 52 weeks after TB treatment initiation, and spirometric values of below the lower limit of normality were considered as LI. Descriptive statistical analysis was performed to summarize the proportion of patients with different lung outcomes at week 52, including type and severity of LI. Risk factors were analysed using multinomial regression analysis. RESULTS: A total of 69 PTB patients were enrolled, of which 62 had a valid spirometry result at week 52 after TB treatment start. At week 8, 26 and 52, the proportion of patients with LI was 78, 68.9 and 64.5%, respectively, and 35.5% had moderate or severe LI at week 52. The majority of patients with LI suffered from pulmonary restriction. Female sex, low haemoglobin and heavy smoking were significantly associated with LI. CONCLUSION: Moderate or severe LI can be observed in a third of cured TB patients. Further research is urgently needed to gain deeper insight into the characteristics of post TB LI, the causal pathways and potential treatment strategies.

Active case finding for Tuberculosis among migrant brick kiln workers in South India.

BACKGROUND: "Active case finding among key populations" is one of the four main thrust areas under the National Strategic Plan for Tuberculosis (NSP) 2017-25. OBJECTIVE: This study aims to actively screen for TB symptoms and disease among migrant brick kiln workers and their care seeking behaviour for the symptoms through a private-public partnership effort. METHODS: This was a cross sectional study conducted among all migrant brick kiln workers working in the brick kilns in the field practice area of the Rural Health Centre of a medical college hospital. A pretested structured questionnaire was used for the interview. Productive Cough with or without other symptoms for 2 weeks or more was considered suggestive of TB. Sputum smear microscopy and Gene Xpert were used to diagnose TB among symptomatics. SPSS version 16.0 was used for analysis. RESULTS: Among 580 brick kiln workers, the prevalence of TB symptoms was 9.7%. Upon sputum examination, one was found to be positive for TB. Smoking was found to be associated with TB symptoms (p < 0.05). Only 50% of the symptomatics sought health care and the main reason for not seeking was low severity of symptoms. CONCLUSION: Active case finding is helpful in screening and diagnosing TB among the marginalised community of brick kiln workers.

Mycobacterium tuberculosis Sulfolipid-1 Activates Nociceptive Neurons and Induces Cough.

Pulmonary tuberculosis, a disease caused by Mycobacterium tuberculosis (Mtb), manifests with a persistent cough as both a primary symptom and mechanism of transmission. The cough reflex can be triggered by nociceptive neurons innervating the lungs, and some bacteria produce neuron-targeting molecules. However, how pulmonary Mtb infection causes cough remains undefined, and whether Mtb produces a neuron-activating, cough-inducing molecule is unknown. Here, we show that an Mtb organic extract activates nociceptive neurons in vitro and identify the Mtb glycolipid sulfolipid-1 (SL-1) as the nociceptive molecule. Mtb organic extracts from mutants lacking SL-1 synthesis cannot activate neurons in vitro or induce cough in a guinea pig model. Finally, Mtb-infected guinea pigs cough in a manner dependent on SL-1 synthesis. Thus, we demonstrate a heretofore unknown molecular mechanism for cough induction by a virulent human pathogen via its production of a complex lipid.

Patient outcomes associated with post-tuberculosis lung damage in Malawi: a prospective cohort study.

BACKGROUND: Post-tuberculosis lung damage (PTLD) is a recognised consequence of pulmonary TB (pTB). However, little is known about its prevalence, patterns and associated outcomes, especially in sub-Saharan Africa and HIV-positive adults. METHODS: Adult (≥15 years) survivors of a first episode of pTB in Blantyre, Malawi, completed the St George's Respiratory Questionnaire, 6-minute walk test, spirometry and high-resolution CT (HRCT) chest imaging at TB treatment completion. Symptom, spirometry, health seeking, TB-retreatment and mortality data were collected prospectively to 1 year. Risk factors for persistent symptoms, pulmonary function decline and respiratory-related health-seeking were identified through multivariable regression modelling. RESULTS: Between February 2016 and April 2017, 405 participants were recruited. Median age was 35 years (IQR: 28 to 41), 77.3% (313/405) had had microbiologically proven pTB, and 60.3% (244/403) were HIV-positive. At pTB treatment completion, 60.7% (246/405) reported respiratory symptoms, 34.2% (125/365) had abnormal spirometry, 44.2% (170/385) had bronchiectasis ≥1 lobe and 9.4% (36/385) had ≥1 destroyed lobe on HRCT imaging. At 1 year, 30.7% (113/368) reported respiratory symptoms, 19.3% (59/305) and 14.1% (43/305) of patients had experienced declines in FEV1 or FVC of ≥100 mL, 16.3% (62/380) had reported ≥1 acute respiratory event and 12.2% (45/368) had symptoms affecting their ability to work. CONCLUSIONS: PTLD is a common and under-recognised consequence of pTB that is disabling for patients and associated with adverse outcomes beyond pTB treatment completion. Increased efforts to prevent PTLD and guidelines for management of established disease are urgently needed. Low-cost clinical interventions to improve patient outcomes must be evaluated.

Lack of an Association Between Household Air Pollution Exposure and Previous Pulmonary Tuberculosis.

CONTEXT: Observational studies investigating household air pollution (HAP) exposure to biomass fuel smoke as a risk factor for pulmonary tuberculosis have reported inconsistent results. OBJECTIVE: To evaluate the association between HAP exposure and the prevalence of self-reported previous pulmonary tuberculosis. DESIGN: We analyzed pooled data including 12,592 individuals from five population-based studies conducted in Latin America, East Africa, and Southeast Asia from 2010 to 2015. We used multivariable logistic regression to model the association between HAP exposure and self-reported previous pulmonary tuberculosis adjusted for age, sex, tobacco smoking, body mass index, secondary education, site and country of residence. RESULTS: Mean age was 54.6 years (range of mean age across settings 43.8-59.6 years) and 48.6% were women (range of % women 38.3-54.5%). The proportion of participants reporting HAP exposure was 38.8% (range in % HAP exposure 0.48-99.4%). Prevalence of previous pulmonary tuberculosis was 2.7% (range of prevalence 0.6-6.9%). While participants with previous pulmonary tuberculosis had a lower pre-bronchodilator FEV1 (mean - 0.7 SDs, 95% CI - 0.92 to - 0.57), FVC (- 0.52 SDs, 95% CI - 0.69 to - 0.33) and FEV1/FVC (- 0.59 SDs, 95% CI - 0.76 to - 0.43) as compared to those who did not, we did not find an association between HAP exposure and previous pulmonary tuberculosis (adjusted odds ratio = 0.86; 95% CI 0.56-1.32). CONCLUSIONS: There was no association between HAP exposure and self-reported previous pulmonary tuberculosis in five population-based studies conducted worldwide.

Assessment of lung function in successfully treated tuberculosis reveals high burden of ventilatory defects and COPD.

BACKGROUND: Burden, phenotype and risk-factors of lung function defects in successfully treated tuberculosis cases are unclear. METHODS: We performed spirometry with bronchodilators in new drug-sensitive adult (≥18 years) pulmonary tuberculosis cases during the 12 months following successful treatment in India. Airflow obstruction was defined as pre-bronchodilator FEV1/FVC<5th percentile of Global Lung Initiative mixed-ethnicity reference (lower limit of normal [LLN]). Chronic obstructive pulmonary disease (COPD) was defined as post-bronchodilator FEV1/FVC

Risk factors for tuberculosis: A case-control study in Addis Ababa, Ethiopia.

BACKGROUND: Tuberculosis remains a major public-health problem in the world, despite several efforts to improve case identification and treatment compliance. It is well known cause of ill-health among millions of people each year and ranks as the second leading cause of death from infectious disease worldwide. Despite implementation of the World health organization recommended strategy, the reductions in the incidence of TB have been minimal in high burden countries. OBJECTIVES AND METHODS: A case control study was carried out to assess the risk factors of TB, where cases were newly registered bacteriologically confirmed pulmonary TB patients with age greater than 15 years who present at twenty health centres in Addis Ababa. Controls were age and sex matched attendees who presented in the same health centers for non-TB health problems. RESULTS: A total of 260 cases and 260 controls were enrolled in the study and 45.8% of cases and 46.2% of controls were in the 26-45 years age bracket. According to the multivariable logistic regression analysis, seven variables were found to be independent predictors for the occurrence of TB after controlling possible confounders. Patients who live in house with no window or one window were almost two times more likely to develop tuberculosis compared to people whose house has multiple windows (AOR = 1.81; 95% CI:1.06, 3.07). Previous history of hospital admission was found to pose risk almost more than three times (AOR = 3.39; 95% CI: 1.64-7.03). Having a household member who had TB was shown to increase risk of developing TB by three fold (AOR = 3.00; 95% CI: 1.60, 5.62). The study showed that illiterate TB patients were found to be more than twice more likely to develop TB compared to subjects who can atleast read and write (AOR, 95% CI = 2.15, 1.05, 4.40). Patients with household income of less than 1000 birrs per month were more than two times more likely to develop TB compared to those who had higher income (AOR = 2.2; 95% CI: 1.28, 3.78). Smoking has also been identified as important risk factor for developing TB by four times (AOR = 4.43; 95% CI: 2.10, 9.3). BCG was found to be protective against TB reducing the risk by one-third (AOR = 0.34; 95% CI: 0.22, 0.54). CONCLUSION: This study showed that TB is more common among the most agile and economically active age group, and number of windows, history of hospital admission, a household member who had TB, illiteracy, low household income and smoking and lack of BCG scar were identified as independent risk factors. Therefore it is imperative that the TB control effort need a strategy to address socio economic issues such as poverty, overcrowding, smoking, and infection control at health care facilities level is an important intervention to prevent transmission of TB within the facilities.

Advanced glycation end products (AGE) and receptor for AGE (RAGE) in patients with active tuberculosis, and their relationship between food intake and nutritional status.

INTRODUCTION: The receptor for advanced glycation end products (RAGE) is expressed in normal lungs and is upregulated during infection. AGEs and RAGE cause oxidative stress and apoptosis in lung cells. The objective of this study is to evaluate levels of AGEs and its soluble receptor (sRAGE), and to investigate their relationship with food intake and nutritional status, in a university-affiliated hospital in Brazil. METHODS: Case-control study, from June 2017 to June 2018. AGE (carboxymethyl lysine, CML) and sRAGE were measured from blood samples by Elisa. Nutritional assessment was performed by body mass index, triceps skin-fold thickness, mid-arm circumference, mid-arm muscle circumference, bioelectrical impedance analysis, and food frequency questionnaire. RESULTS: We included in the study 35 tuberculosis (TB) patients and 35 controls. The mean sRAGE levels were higher in TB patients than in controls (68.5 ± 28.1 vs 57.5 ± 24.0 pg/mL; p = 0.046). Among cases that were current smokers, lower sRAGE levels were associated with mortality, evaluated at the end of hospitalization (p = 0.006), and with weight loss (p = 0.034). There was no statistically significant difference in CML levels and diet CML content between cases and controls. Malnutrition was more frequent in cases, but there was no correlation between nutritional parameters and CML or sRAGE levels. CONCLUSIONS: TB patients had higher sRAGE levels than controls, although it is not clear that this difference is clinically relevant. Also, sRAGE was associated with weight loss and mortality.

Immunonutritional status and pulmonary cavitation in patients with tuberculosis: A revisit with an assessment of neutrophil/lymphocyte ratio.

BACKGROUND: Several reports have described the importance of immunological and nutritional factors in the morbidity and/or mortality of patients with tuberculosis. The aim of this study was to evaluate the association between pulmonary cavitation and immunonutritional status, assessed by parameters such as neutrophil/lymphocyte ratio (NLR) and prognostic nutritional index (PNI), in patients with pulmonary tuberculosis. METHODS: We retrospectively analyzed the data of 137 patients with culture-positive active pulmonary tuberculosis without bacterial pneumonia diagnosed at Kainan Hospital between April 2008 and March 2016. The associations between the levels of serum albumin, lymphocytes, NLR, PNI, platelet to lymphocyte ratio (PLR), and body mass index (BMI) and pulmonary cavitation were evaluated in the patients. RESULTS: A total of 83 men and 63 women (median age, 75 years; range, 16-94 years) were included in the study. Sixty-six patients had smoking history; 55 patients had respiratory symptoms, while 44 patients did not have any symptoms. Patient׳s delay, defined as medical examination performed over 60 days after the onset of symptoms was observed in 25 patients. Univariate analysis showed that high NLR (≥ 5), high PLR (≥200), low serum albumin (<3 g/dL), high neutrophil count (≥6000/mm3), and low lymphocyte count (<1000/mm3) were associated with pulmonary cavitation. Multivariate analysis showed that high NLR and low serum albumin were associated with pulmonary cavitation. CONCLUSION: Malnutrition and increased severity of inflammation may be associated with pulmonary cavitation in patients with tuberculosis. Further studies are warranted to confirm the findings of the present study.

THE ROLE OF CIGARETTE SMOKING AND ALCOHOL CONSUMPTION IN PULMONARY TUBERCULOSIS DEVELOPMENT AND RECURRENCE.

During a two-year period (2001-2003), 464 patients were treated for tuberculosis at Jordanovac Department for Lung Diseases in Croatia. Besides pulmonary tuberculosis in 97.7% of patients, patients were also treated for tuberculous pleurisy (0.9%), tuberculous laryngitis (0.6%), tuberculous meningitis (0.2%), tuberculous pericarditis (0.2%) and urogenital tuberculosis (0.4%). Out of the total number of patients, 57.3% declared themselves to be active smokers (men were predominant and made up to 80.8%) and 20.9% to be active alcohol consumers. Both risk factors, i.e. smoking and alcohol consumption, were present in 15.1% of all patients. The most common comorbidities were diabetes mellitus (30.4%), cardiac diseases (11.2%) and chronic obstructive pulmonary disease (8.0%). Lung carcinoma was the most common malignant disease (n=51), with Mycobacterium tuberculosis isolated in 33% of them. Seventy-two of 464 (15.5%) patients had recurrences of tuberculosis. Of these, 30.5% had one of the risk factors (20.8% were smokers and 9.7% consumed alcohol), while 32.5% of patients had both risk factors. In conclusion, cigarette smoking was proved to be the most significant risk factor for development of pulmonary tuberculosis and its recurrence.

Relevance of TNF-α, IL-6 and IRAK1 gene expression for assessing disease severity and therapy effects in tuberculosis patients.

INTRODUCTION: Tuberculosis (TBC) is a contagious chronic respiratory disease which despite the known cause, Mycobacterium tuberculosis (Mtb), and many decades of successful therapy, remains one of the leading global health problems. Immune responses against Mtb infection involve both of types of immunity, but cellular immunity, in which certain cytokines and Th1 cells play a key role, is crucial. A better understanding of the functions of the cytokine network involved in the state and progression of TBC could identify specific molecular markers for monitoring of disease activity as well as therapy outcomes in TBC patients. METHODOLOGY: We investigated expression of TNF-α, IL-6 and IRAK1 genes using an RT-qPCR technique in peripheral blood mononuclear cells of 33 TBC patients and 10 healthy individuals. RESULTS: Comparison between TBC patients and healthy individuals revealed statistically significant differences for all analyzed genes. The levels of expression of TNF-α and IL-6 mRNA were higher, while the level of IRAK1 mRNA was lower in the TBC group compared to controls. Moreover, a strong positive correlation was observed between TNF-α and IL-6 gene expression. When clinical parameters were analyzed, increased levels of TNF-α mRNA were detected in patients with a longer duration of therapy (>2 months) compared to those with a shorter therapy duration (< 2 months), and in patients without anemia. CONCLUSIONS: Our results indicate that the inflammatory genes we examined play a crucial role in the pathogenesis of tuberculosis, and that the expression of the TNF-α gene could be a marker for monitoring the clinical effect of the ant-tuberculosis drugs during therapy.

Efficacy of regional arterial embolization before pleuropulmonary resection in 32 patients with tuberculosis-destroyed lung.

BACKGROUND: Treatment of tuberculous-destroyed lung (TDL) with pleuropulmonary resection is challenging. Pulmonary hemorrhage is a frequent complication of this surgical procedure. Continuous efforts have been made to investigate clinical procedures that may reduce intraoperative bleeding effectively. In this study, we evaluated the feasibility and safety of regional arterial embolization before pleuropulmonary resection in patients with TDL. METHODS: The clinical data of 32 patients with TDL were retrospectively reviewed and analyzed. These patients were admitted to the hospital between July 2009 and November 2016. All of the patients had moderate to massive hemoptysis and received regional arterial embolization in affected areas. Then, these patients underwent pleuropulmonary resection within 1 week to 2 months after embolization. RESULTS: The results showed that 25 patients (78.1%) had bronchial artery, and all patients had non-bronchial systemic artery found in affected areas. Mild to moderate chest pain was reported in 6 patients, and fever was reported in 2 patients. Intraoperative blood loss during pleuropulmonary resection in patients who had received preoperative regional arterial embolization was 625.6 ± 352.6 ml. Duration of the operation was 120.3 ± 75.2 min. Bronchopleural fistulae and empyema were found in 3 cases (9.4%). CONCLUSION: Performance of regional arterial embolization before pleuropulmonary resection offers a safe and feasible option that reduces intraoperative blood loss and shortens operative time in patients with TDL.

The relation between leptin and inflammatory markers with respiratory and peripheral muscle strength in tuberculosis: A case-control study.

BACKGROUND: Muscle weakness is a part of the wasting syndrome associated with TB. Cytokines are candidates as the initial causative agents of the metabolic changes in TB. The objective of this study is to assess the peripheral and respiratory muscle strength in patients with TB and controls and relate these findings with leptin, IL-6 and TNF-α serum levels. METHODS: Case-control study. Hospitalized patients with pulmonary TB and controls were included. Maximal voluntary handgrip strength (HS), maximal inspiratory pressure (MIP) and maximum expiratory pressure (MEP) were measured. Leptin, IL-6 and TNF-α dosage were performed. RESULTS: We included 35 cases and 35 controls. Leptin was lower and TNF-α levels were higher in TB patients than in controls (P < .0001 for both). Body mass index (BMI), HS, MIP and MEP were all significantly lower in cases than in controls (P < .0001). Lower leptin and higher TNF-α levels are associated with malnutrition and reduced MIP, MEP and HS. Patients who reported fever and those with positive culture for Mycobacterium tuberculosis had higher serum levels of IL-6. CONCLUSION: Peripheral and respiratory muscle strength and leptin levels were reduced in patients with active TB. Lower levels of leptin and higher levels of TNF-α were associated with malnutrition and with reduced MIP, MEP and HS.

A comparative study of the socio-economic risk factors for pulmonary tuberculosis in the Saharia tribe of Madhya Pradesh, India.

Background: To determine the socio-economic risk factors for pulmonary tuberculosis (PTB) in the Saharia tribal community in Madhya Pradesh, Central India. Methods: PTB cases detected during the year 2013-14 through a community active TB prevalence survey in the Shivpuri district, Madhya Pradesh were included in the study. For each case, three controls were selected randomly among the non-cases from the same village and the data on socio-economic risk factors were collected. Using logistic regression analysis, the risk factors for PTB disease were identified. Results: A total of 220 cases and 660 controls participated in the study. Of the 13 risk factors studied, on multivariate analysis the risk of PTB was found to be significantly associated with malnutrition (adjusted odds ratio [AOR] 2.02 [95% confidence interval {CI} 1.46 to 2.79]), living in a kaccha (built of naturally occurring materials) house (AOR 2.72 [95% CI 1.44 to 5.11]) and tobacco smoking (mostly beedis; AOR 1.59 [95% CI 1.12 to 2.18]). Conclusions: The findings highlight that malnutrition, poor living conditions in a Kaccha house (built of naturally occurring materials) and tobacco smoking are the major risk factors for PTB among Saharias, which need to be studied among other tribal populations in the country. There is a need to strengthen health and nutrition programmes in this community.