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Interferon-Gamma Release Assay Performance of Pleural Fluid and Peripheral Blood in Pleural Tuberculosis  [PDF]
Fei Liu, Mengqiu Gao, Xia Zhang, Fengjiao Du, Hongyan Jia, Xinting Yang, Zitong Wang, Liqun Zhang, Liping Ma, Xiaoguang Wu, Li Xie, Zongde Zhang
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0083857
Abstract: Background The diagnosis of pleural tuberculosis (TB) remains to be difficult. Interferon-gamma release assay (IGRA) is a promising method for diagnosing TB in low TB burden countries. The release of interferon-gamma (IFN-γ) by T lymphocytes increases at a localized site of infection with Mycobacterium tuberculosis antigen. This study aimed to examine the clinical accuracy of T-SPOT.TB on pleural fluid and peripheral blood for the diagnosis of pleural TB in high TB burden country. Methods 168 subjects with pleural effusion were enrolled prospectively and examined with T-SPOT.TB on pleural fluid and peripheral blood samples simultaneously. Results The receiver operating characteristic (ROC) curve and cut-off value of pleural fluid T-SPOT.TB was established according to spot forming cells (SFC) between culture/biopsy-confirmed pleural TB group and no pleural TB group. The sensitivity of pleural fluid T-SPOT.TB and peripheral blood T-SPOT.TB was similar (96.3% and 92.7%, respectively) (P= 0.691). In contrast, the specificity of pleural fluid T-SPOT.TB (94.5%) was significantly higher than that of peripheral blood T-SPOT.TB (76.1%) (P=0.002). 2% (2/98) of pleural fluid T-SPOT.TB results were indeterminate. Conclusion The diagnostic accuracy of peripheral blood T-SPOT.TB is low in high TB burden countries due to latent tuberculosis infection. Pleural fluid T-SPOT.TB is a relatively useful and supplementary test to explore pleural TB in high TB burden countries, but its diagnostic accuracy needs to be validated in further large scale research.
Diagnostic value of pleural fluid interferon-gamma and adenosine deaminase in patients with pleural tuberculosis in Qatar
Khan FY, Hamza M, Omran AH, Saleh M, Lingawi M, Alnaqdy A, Abdel Rahman MO, Ahmedullah HS, Hamza A, Ani AA, Errayes M, Almaslamani M, Mahmood AA
International Journal of General Medicine , 2013, DOI: http://dx.doi.org/10.2147/IJGM.S39345
Abstract: gnostic value of pleural fluid interferon-gamma and adenosine deaminase in patients with pleural tuberculosis in Qatar Original Research (671) Total Article Views Authors: Khan FY, Hamza M, Omran AH, Saleh M, Lingawi M, Alnaqdy A, Abdel Rahman MO, Ahmedullah HS, Hamza A, Ani AA, Errayes M, Almaslamani M, Mahmood AA Published Date January 2013 Volume 2013:6 Pages 13 - 18 DOI: http://dx.doi.org/10.2147/IJGM.S39345 Received: 18 October 2012 Accepted: 06 December 2012 Published: 10 January 2013 Fahmi Yousef Khan,1 Maha Hamza,2 Aisha Hussein Omran,2 Muhannad Saleh,2 Mona Lingawi,2 Adel Alnaqdy,3 Mohamed Osman Abdel Rahman,3 Hasan Syed Ahmedullah,4 Alan Hamza,1 Ahmed AL Ani,1 Mehdi Errayes,1 Mona Almaslamani,4 Ahmed Ali Mahmood2 1Department of Medicine, 2Department of Pulmonary Medicine, 3Laboratory Department, 4Infectious Disease Division, Department of Medicine, Hamad General Hospital, Doha, Qatar Objective: To investigate the diagnostic utility of interferon-gamma (IFN-γ) and adenosine deaminase (ADA) in tuberculous pleural effusions by determining the best cutoff levels of these two markers for pleural tuberculosis, in the context of the local epidemiological settings in Qatar. Methods: We prospectively studied IFN-γ and ADA levels in the pleural fluid of patients presenting to Hamad General Hospital between June 1, 2009 and May 31, 2010. Results: We studied 103 patients with pleural effusions, 72 (69.9%) with pleural tuberculosis, and 31 (30.1%) with nontuberculous etiologies. The mean IFN-γ concentration for the group with tuberculous effusions was significantly higher than that in the group with nontuberculous effusions (1.98 ± 81 vs 0.26 ± 10 pg/mL [P < 0.0001]). The mean ADA activity for the tuberculous effusions group was significantly higher than that in group with nontuberculous effusions (41.30 ± 20.09 vs 14.93 ± 14.87 U/L [P < 0.0001]). By analysis of receiver operating characteristic (ROC) curves, the best cutoff values for IFN-γ and ADA were 0.5 pg/mL and 16.65 U/L, respectively. The results for IFN-γ vs ADA were: for sensitivity, 100% vs 86%, respectively; for specificity, 100% vs 74%, respectively; for positive predictive value, 100% vs 88.5%, respectively; and for negative predictive value, 100% vs 69.7%, respectively. Conclusion: IFN-γ and ADA could be used as valuable parameters for the differentiation of tuberculous from nontuberculous effusion, and IFN-γ was more sensitive and specific for tuberculous effusion than ADA.
Diagnostic value of pleural fluid interferon-gamma and adenosine deaminase in patients with pleural tuberculosis in Qatar
Khan FY,Hamza M,Omran AH,Saleh M
International Journal of General Medicine , 2013,
Abstract: Fahmi Yousef Khan,1 Maha Hamza,2 Aisha Hussein Omran,2 Muhannad Saleh,2 Mona Lingawi,2 Adel Alnaqdy,3 Mohamed Osman Abdel Rahman,3 Hasan Syed Ahmedullah,4 Alan Hamza,1 Ahmed AL Ani,1 Mehdi Errayes,1 Mona Almaslamani,4 Ahmed Ali Mahmood21Department of Medicine, 2Department of Pulmonary Medicine, 3Laboratory Department, 4Infectious Disease Division, Department of Medicine, Hamad General Hospital, Doha, QatarObjective: To investigate the diagnostic utility of interferon-gamma (IFN-γ) and adenosine deaminase (ADA) in tuberculous pleural effusions by determining the best cutoff levels of these two markers for pleural tuberculosis, in the context of the local epidemiological settings in Qatar.Methods: We prospectively studied IFN-γ and ADA levels in the pleural fluid of patients presenting to Hamad General Hospital between June 1, 2009 and May 31, 2010.Results: We studied 103 patients with pleural effusions, 72 (69.9%) with pleural tuberculosis, and 31 (30.1%) with nontuberculous etiologies. The mean IFN-γ concentration for the group with tuberculous effusions was significantly higher than that in the group with nontuberculous effusions (1.98 ± 81 vs 0.26 ± 10 pg/mL [P < 0.0001]). The mean ADA activity for the tuberculous effusions group was significantly higher than that in group with nontuberculous effusions (41.30 ± 20.09 vs 14.93 ± 14.87 U/L [P < 0.0001]). By analysis of receiver operating characteristic (ROC) curves, the best cutoff values for IFN-γ and ADA were 0.5 pg/mL and 16.65 U/L, respectively. The results for IFN-γ vs ADA were: for sensitivity, 100% vs 86%, respectively; for specificity, 100% vs 74%, respectively; for positive predictive value, 100% vs 88.5%, respectively; and for negative predictive value, 100% vs 69.7%, respectively.Conclusion: IFN-γ and ADA could be used as valuable parameters for the differentiation of tuberculous from nontuberculous effusion, and IFN-γ was more sensitive and specific for tuberculous effusion than ADA.Keywords: pleural effusion, parapneumonic effusion, malignant effusion
Evaluation of immune responses in HIV infected patients with pleural tuberculosis by the QuantiFERON? TB-Gold interferon-gamma assay
Kamaldeen Baba, Steinar S?rnes, Anwar A Hoosen, Jacob M Lekabe, Mathew J Mpe, Nina Langeland, Anne M Dyrhol-Riise
BMC Infectious Diseases , 2008, DOI: 10.1186/1471-2334-8-35
Abstract: The QuantiFERON TB?-Gold (QFT-TB) test was analysed in blood and pleural fluid from 34 patients presenting with clinically suspected pleural TB. Clinical data, HIV status and CD4 cell counts were recorded. Adenosine deaminase activity (ADA) analysis and TB culture were performed on pleural fluid.The patients were categorised as 'confirmed TB' (n = 12), 'probable TB' (n = 16) and 'non-TB' pleuritis (n = 6) based on TB culture results and clinical and biochemical criteria. The majority of the TB patients were HIV infected (82%). The QFT-TB in pleural fluid was positive in 27% and 56% of the 'confirmed TB' and 'probable TB' cases, respectively, whereas the corresponding sensitivities in blood were 58% and 83%. Indeterminate results in blood (25%) were caused by low phytohemagglutinin (PHA = positive control) IFN-γ responses, significantly lower in the TB patients as compared to the 'non-TB' cases (p = 0.02). Blood PHA responses correlated with CD4 cell count (r = 0.600, p = 0.028). In contrast, in pleural fluid indeterminate results (52%) were caused by high Nil (negative control) IFN-γ responses in both TB groups. Still, the Nil IFN-γ responses were lower than the TB antigen responses (p < 0.01), offering a conclusive test for half of the patients. We did not find any correlation between blood CD4 cell count and IFN-γ responses in pleural fluid.The QFT-TB test in blood could contribute to the diagnosis of TB pleuritis in the HIV positive population. Still, the number of inconclusive results is too high to recommend the commercial QFT-TB test for routine use in pleural fluid in a TB/HIV endemic resource-limited setting.Tuberculosis (TB) is globally a major health burden and human immunodefiency virus (HIV) infection is a strong risk factor for the progression from latent infection to active TB. In South Africa 60% of the adult TB cases are HIV positive [1]. TB pleuritis occurs in about 30% of TB patients, the majority of cases in the HIV positive population [2].The dia
Tuberculosis pleural
Molina,Pablo; Espinoza,Abraham;
Revista Costarricense de Ciencias Médicas , 2005,
Abstract: pleural tuberculosis is a condition present in more than 30% of patients with tuberculosis, in fact it is a rather common initial presentation. pleural tuberculosis diagnostic is often difficult by direct confirmation of mycobacterium tuberculosis in cultures and stains, it has lead the development of new criteria and interventions focused in the improvement of the sensibility diagnostic methods. we describe a patient with unilateral pleural effusion who met the criteria of this clinical condition.
Evaluation of real-time PCR of patient pleural effusion for diagnosis of tuberculosis
Franciele Rosso, Candice T Michelon, Rosa D Sperhacke, Mirela Verza, Liliane Olival, Marcus B Conde, Renata L Guerra, Arnaldo Zaha, Maria LR Rossetti
BMC Research Notes , 2011, DOI: 10.1186/1756-0500-4-279
Abstract: For this cross-sectional study, 150 consecutive patients with pleural effusion diagnosed by chest radiography, who were referred for diagnostic thoracocentesis and pleural biopsy and met eligibility criteria, had a pleural fluid specimen submitted for real-time PCR testing. Overall, 98 patients had pleural TB and 52 had pleural effusion secondary to other disease. TB diagnosis was obtained using acid-fast bacilli (AFB) smear or culture for mycobacteria and/or histopathologic examination in 94 cases and by clinical findings in 4 cases. Sensitivity, specificity, positive and negative predictive values of PCR testing for pleural TB diagnosis were 42.8% (95% CI 38.4 - 44.8), 94.2% (95% CI 85.8 - 98.0), 93.3% (95% CI 83.6 - 97.7), and 48.5% (95% CI 44.2 - 50.4), respectively. The real-time PCR test improved TB detection from 30.6% to 42.9% when compared to AFB smear and culture methods performed on pleural fluid specimens, although the best sensitivity was achieved by combining the results of culture and histopathology of pleural tissue specimens.The real-time PCR test of pleural fluid specimens is a useful and non-invasive additional assay for fast diagnosis of pleural TB.Diagnosis of pleural tuberculosis (TB) remains a challenge due to its nonspecific clinical presentation and paucibacillary nature. Conventional methods, such as direct testing for acid-fast bacilli (AFB) and culture of pleural fluid, lack sensitivity (less than 5% and 40%, respectively) [1-3]. Despite improved detection rates with new methods, high pleural fluid levels of adenosine deaminase (ADA) may be found in other diseases, especially empyema and parapneumonic effusions, and there is no established cut-off value for measurement of interferon-gamma in pleural fluid [4,5].Therefore, a definitive diagnosis of pleural TB still depends on demonstration of M. tuberculosis or caseous granulomas in pleural biopsy, an invasive method with possible complications requiring specialized medical care that is no
Immune responses in the lungs of patients with tuberculous pleural effusion without pulmonary tuberculosis  [cached]
Qama Diana,Choi Won-Il,Kwon Kun
BMC Immunology , 2012, DOI: 10.1186/1471-2172-13-45
Abstract: Background Tuberculous pleural effusion (TPE) is one of the most common forms of extrapulmonary tuberculosis. Because most studies of TPE focused on the pleural space, little information regarding lung parenchyma is available. We therefore aimed to investigate immune responses in the lung parenchyma of TPE patients without pulmonary tuberculosis. Methods Patients with any evidence of pulmonary tuberculosis, either from radiologic or bacteriologic evaluation, were excluded. Bronchoalveolar lavage fluid (BALF) was collected from 10 newly diagnosed, untreated, HIV-negative TPE patients and 10 healthy controls. We analyzed T-lymphocyte subpopulations and measured 10 cytokines in BALF. Cytokine levels in BALF were standardised using urea. Results The concentrations of interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), vascular endothelial growth factor (VEGF), and the CD4+/CD8+ ratio of T-lymphocytes were significantly higher in TPE patients without pulmonary tuberculosis than in the controls. Of the cytokines measured in BALF, VEGF showed the highest concentration. No difference was observed in T-helper type 2 cytokines between the 2 groups. Conclusion There were significant immune responses and increases in IFN-γ, TNF-α, and VEGF in the lung parenchyma of TPE patients without pulmonary tuberculosis. This result suggests that TPE may induce a significant immune response in lung parenchyma.
Validation of an immunochromatographic assay kit for the identification of the Mycobacterium tuberculosis complex
Toihir, Al-Habib Omar Said;Rasolofo, Voahangy;Andrianarisoa, Samuel Hermas;Ranjalahy, Gabriel Marie;Ramarokoto, Herimanana;
Memórias do Instituto Oswaldo Cruz , 2011, DOI: 10.1590/S0074-02762011000600022
Abstract: the performance of the immunochromatographic assay, sd bioline tb ag mpt64 rapid?, was evaluated in madagascar. using mouse anti-mpt64 monoclonal antibodies for rapid discrimination between the mycobacterium tuberculosis complex and nontuberculous mycobacteria, the kit was tested on mycobacteria and other pathogens using conventional methods as the gold standard. the results presented here indicate that this kit has excellent sensitivity (100%) and specificity (100%) compared to standard biochemical detection and can be easily used for the rapid identification of m. tuberculosis complex.
Evaluation of an immunochromatographic test for the diagnosis of pulmonary tuberculosis in Madagascar
Al-habib O Said Toihir, Vincent Richard, Vaomalala Raharimanga, Samuel H Andrianarisoa, Gabriel M Ranjalahy, Herimanana Ramarokoto, Voahangy Rasolofo
BMC Research Notes , 2011, DOI: 10.1186/1756-0500-4-403
Abstract: We conducted a population-based case-control study. The sera of 60 confirmed TB patients and 60 healthy contacts paired for sex and age were tested. The controls were healthy contacts who were exposed to TB but had no clinical or radiological evidence of TB. The SD Rapid TB kit was used with serum samples according to the instructions of the manufacturer. Sensitivity, specificity, accuracy and predictive values were calculated using culture on L?venstein-Jensen media as "gold standard".In this study, the sensitivity of the test was 55% and the specificity 90%. The positive predictive value and the negative predictive value were 84.61% and 66.66%, respectively, for diagnosis of pulmonary TB.This study shows that the SD Rapid TB test is a simple and fast method. This test has a good specificity and could therefore help rule in TB if positive, but lacks adequate sensitivity.Tuberculosis (TB) poses a significant health threat worldwide with an estimated 9 million new cases and 2 million deaths every year worldwide [1]. Morbidity associated with TB has been decreasing but Human Immunodeficiency Virus (HIV) associated TB and multidrug resistant (MDR) are on the rise [2]. According to the 2010 World Health Organization (WHO) report [1], the incidence of TB in Madagascar is estimated at 248 per 100 000 population for all forms of TB and 111/100 000 for smear-positive pulmonary TB. The prevalence of TB is estimated at 415/100 000 and the rate of human immunodeficiency virus (HIV) infection among TB patients at 0.4%.The vast majority of TB patients live in developing countries, where the diagnosis of TB relies on the identification of acid-fast bacilli on unprocessed sputum smears using conventional light microscopy. However, 40 to 60% of patients with pulmonary disease and ~75% of patients with extrapulmonary disease are smear negative, and in this situation even contemporary culture methods take several weeks to become positive [3].Rapid diagnostic tests for TB are needed t
Assessment of the N-PCR Assay in Diagnosis of Pleural Tuberculosis: Detection of M.tuberculosis in Pleural Fluid and Sputum Collected in Tandem  [PDF]
Parameet Kumar,Manas K. Sen,Devendra S. Chauhan,Vishwa M. Katoch,Sarman Singh,Hanumanthappa K. Prasad
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0010220
Abstract: The nonspecific clinical presentation and paucibacillary nature of tuberculous pleuritis remains a challenge for diagnosis. Diagnosis of tuberculous pleural effusion depends on the demonstration of the presence of tubercle bacilli in the sputum, pleural fluid, or pleural biopsy specimen, or demonstration of granuloma in pleura by histological examination. We examined the clinical utility of the diagnosis of pleural tuberculosis using the in house N-PCR assay, AFB smear microscopy and culture. Besides pleural fluid the inclusion of sputum in the efficacy of diagnosis of pleural tuberculosis was scrutinized.
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