Pleural Tuberculosis Patients Research Articles

IFN-<i>γ</i>-, IL-4-, IL-17-, PD-1-Expressing T Cells and B Cells in Peripheral Blood from Tuberculosis Patients

Although the efficacy of tuberculosis (TB) vaccines is tightly linked to cell-mediated immunity, some functions of T and B cells in TB patients remain unclear. To address how Mycobacterium tuberculosis infection inhibits T effector responses, we assessed the proportions of T cell subsets and B cells in peripheral blood from pulmonary TB (PTB) patients, pleural TB (PLTB) patients, and healthy subjects (HS, who showed purified protein derivative (PPD)-positive reactions) with flow cytometry. Compared to HS, PTB and PLTB patients exhibited higher proportions of B cells and Th17 cells, and lower proportions of Th2 cells and ratios of Th1 to Th17 cells and of Th2 to Th17 cells. PTB patients had higher CD4+ T cells and PD-1+ CD4+ T cells than HS. Newly diagnosed PTB patients (nPTB) had higher proportions of B cells than HS; in contrast, PTB patients subjected to effective treatments (oPTB) and HS shared similar proportions of B cells. oPTB patients had higher proportions of CD4+ T cells, Th17 cells, and PD-1+ CD4+ T cells than HS, but this difference did not occur in nPTB patients. These findings suggest that shifting ratios of Th1 to Th17 cells may be beneficial for M. tuberculosis to amplify.

Pesquisa de IgA contra o antígeno recombinante HspX de Mycobacterium tuberculosis no diagnóstico de tuberculose pleural

To evaluate the accuracy of determining specific IgA to HspX recombinant antigen in pleural fluid and serum samples for the diagnosis of pleural tuberculosis in patients with pleural effusion. This was a cross-sectional study. Serum and pleural fluid samples of patients with pleural effusion and suspected of having pleural tuberculosis were tested with indirect ELISA in order to determine the optical density of specific IgA to HspX. We evaluated serum and pleural fluid samples from 132 patients: 97 diagnosed with pleural tuberculosis (study group) and 35 diagnosed with pleural effusion due to other causes (control group). The determination of IgA in pleural fluid satisfactorily discriminated between pleural tuberculosis patients and control patients. The sensitivity of the test in pleural fluid and in serum was 69% and 30%, respectively, whereas the specificity was 83% and 84%, respectively. Our data suggest that this test can be used in the diagnosis of pleural tuberculosis. Further studies, involving larger patient samples and different epidemiological scenarios, are warranted.

Assessment of the N-PCR Assay in Diagnosis of Pleural Tuberculosis: Detection of M.tuberculosis in Pleural Fluid and Sputum Collected in Tandem

BackgroundThe 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.Methodology/Principal FindingsPleural fluid and sputum samples of 58 tuberculous and 42 non-tuberculous pleural effusion patients were processed for AFB smear microscopy, culture and the N-PCR assay. Mycobacteria were detected exclusively in tuberculous pleural effusion samples. None of the non-tuberculous pleural effusion samples were positive for mycobacteria. Comparative analysis showed that the N-PCR assay had the highest sensitivity. Inclusion of sputum along with pleural fluid increased N-PCR sensitivity from 51.7 to 70.6% (p<0.0001).This improved sensitivity was reflected in AFB smear microscopy and isolation by culture. The sensitivity enhanced on inclusion of sputum from 3.4 (p = 0.50) to 10.3% (p = 0.038) for AFB smear microscopy and for isolation of mycobacteria from 10.3(p = 0.03) to 22.4% (p = 0.0005). Thirteen isolates were obtained from 58 pleural tuberculosis patients. Eleven mycobacterial isolates were identified as M.tuberculosis and two as M.fortuitum and M.chelonae. Complete concordance was seen between the biochemical identification of isolates and the N-PCR identification of mycobacterial species prior to isolation.Conclusions/SignificanceTo the best of our knowledge this is the first PCR based report on utility of sputum for diagnosis of pleural tuberculosis. The present study demonstrates that a combination of pleural fluid with sputum sample and N-PCR improved the diagnosis of pleural tuberculosis.

Diagnostic significance of humoral immune responses to recombinant antigens of Mycobacterium tuberculosis in patients with pleural tuberculosis

Mycobacterium tuberculosis bacilli are seldom demonstrated in tuberculous pleural effusion (TPE) by conventional bacteriological methods. In this study, an indirect enzyme-linked immunosorbent assay (ELISA) was developed to detect IgG against four mycobacterial recombinant antigens (ESAT-6, PlcA, HspX and Tb8.4) in 69 pleural fluids of patients with TPE and 71 patients with malignant pleural effusion. To increase the sensitivity of the assay, a multi-antigen cocktail containing all the above antigens were also used. IgG positivity in ELISA for PlcA, HspX, Tb8.4, ESAT-6 antigens and multi-antigen complex were 49.3, 60.8, 49.3, 53.6 and 75.4% respectively. Each one of the above four antigens and their multi-antigen cocktail were highly specific in distinguishing tuberculous and malignant pleural effusion. This new generation immunoassay will serve as a useful marker for the diagnosis of pleural tuberculosis patients in whom M. tuberculosis bacilli were not demonstrated by bacteriological methods.

Differential cytokine/chemokines and KL-6 profiles in patients with different forms of tuberculosis

Cytokines are involved in the mediation and regulation of immunity, inflammation, and haematopoiesis. Secretion patterns may reflect the pathology or etiology of different diseases. In an attempt to increase our understanding of immunopathology during different forms of tuberculosis, and identify potential biological markers that may differentiate between forms of tuberculosis, we investigated the levels of 29 cytokines and KL-6 in the plasma of HIV uninfected patients with active pulmonary tuberculosis (TB) without pleural effusions and in pleural TB with and without HIV-co-infection. Healthy individuals with latent Mycobacterium tuberculosis infection and patients with non-TB pleural effusions were used as controls, We showed that pleural TB patients had increased levels of markers associated with systemic inflammation compared to pulmonary TB (EGF, G-CSF, IL-1β IL-6, IL-8, IL-10, MCP-1, MIP-1α, MIP-1β, TNF-α and VEGF), whereas pulmonary TB patients without effusions had higher levels of factors involved in cell-mediated immunity (IL-12p40 and sCD40L). Plasma levels of cytokines may therefore contribute to biosignatures of diseases like TB but the data also highlight systemic differences between pulmonary TB, pleural TB and other form of pleural effusion diseases.

Pleural Tuberculosis in Patients with Early HIV Infection Is Associated with Increased TNF-Alpha Expression and Necrosis in Granulomas

Although granulomas may be an essential host response against persistent antigens, they are also associated with immunopathology. We investigated whether HIV co-infection affects histopathological appearance and cytokine profiles of pleural granulomas in patients with active pleural tuberculosis (TB). Granulomas were investigated in pleural biopsies from HIV positive and negative TB pleuritis patients. Granulomas were characterised as necrotic or non-necrotic, graded histologically and investigated for the mRNA expression of IL-12, IFN-γ, TNF-α and IL-4 by in situ hybridisation. In all TB patients a mixed Th1/Th2 profile was noted. Necrotic granulomas were more evident in HIV positive patients with a clear association between TNF-α and necrosis. This study demonstrates immune dysregulation which may include TNF-α-mediated immunopathology at the site of disease in HIV infected pleural TB patients.

Pleural Tuberculosis in the United States: Incidence and Drug Resistance

Background Pleural tuberculosis (TB) should be considered in any patient with a lymphocytic pleural effusion. The diagnostic approach is under debate. Knowledge of pleural TB epidemiology would be beneficial. To help clarify pleural TB epidemiology, we analyzed US national TB surveillance data for 1993 to 2003. Methods We compared pleural TB to pulmonary TB (where each was reported as the major site of TB disease, and no additional sites of disease were reported). Applicable statistical tests were performed; p < 0.05 was considered to be significant. Results From 1993 through 2003, 7,549 cases of pleural TB and 156,779 cases of pulmonary TB were reported (in 2003: pleural TB, 536 cases; pulmonary TB, 10,551 cases). The annual proportion of pleural TB was relatively stable (median rate, 3.6%; range, 3.3 to 4.0%) compared to that for pulmonary TB, which steadily decreased (average annual decrease, 0.9%; p < 0.01). Pleural TB occurred significantly more often than pulmonary TB among persons ≥ 65 years old (30.4% vs 23.3%, respectively; p < 0.01), and it occurred significantly less often among children < 15 years old (1.8% vs 6.1%, respectively; p < 0.01) and persons 45 to 64 years old (22.9% vs 27.9%, respectively; p < 0.01). Pleural TB patients (63.4%) were born slightly more often in the United States than were pulmonary TB patients (60.9%; p < 0.01). Drug-resistance patterns of pleural TB broadly reflected those of pulmonary TB. However, isolates from pleural TB patients were less often resistant to at least isoniazid (6.0% vs 7.8%, respectively; p < 0.01) and to at least one first-line TB drug (9.9% vs 11.9%, respectively; p < 0.01) compared with pulmonary TB patients. Conclusions Knowledge of pleural TB demographic, clinical, and drug-resistance patterns may assist clinicians in making diagnostic and therapeutic decisions. Pleural tuberculosis (TB) should be considered in any patient with a lymphocytic pleural effusion. The diagnostic approach is under debate. Knowledge of pleural TB epidemiology would be beneficial. To help clarify pleural TB epidemiology, we analyzed US national TB surveillance data for 1993 to 2003. We compared pleural TB to pulmonary TB (where each was reported as the major site of TB disease, and no additional sites of disease were reported). Applicable statistical tests were performed; p < 0.05 was considered to be significant. From 1993 through 2003, 7,549 cases of pleural TB and 156,779 cases of pulmonary TB were reported (in 2003: pleural TB, 536 cases; pulmonary TB, 10,551 cases). The annual proportion of pleural TB was relatively stable (median rate, 3.6%; range, 3.3 to 4.0%) compared to that for pulmonary TB, which steadily decreased (average annual decrease, 0.9%; p < 0.01). Pleural TB occurred significantly more often than pulmonary TB among persons ≥ 65 years old (30.4% vs 23.3%, respectively; p < 0.01), and it occurred significantly less often among children < 15 years old (1.8% vs 6.1%, respectively; p < 0.01) and persons 45 to 64 years old (22.9% vs 27.9%, respectively; p < 0.01). Pleural TB patients (63.4%) were born slightly more often in the United States than were pulmonary TB patients (60.9%; p < 0.01). Drug-resistance patterns of pleural TB broadly reflected those of pulmonary TB. However, isolates from pleural TB patients were less often resistant to at least isoniazid (6.0% vs 7.8%, respectively; p < 0.01) and to at least one first-line TB drug (9.9% vs 11.9%, respectively; p < 0.01) compared with pulmonary TB patients. Knowledge of pleural TB demographic, clinical, and drug-resistance patterns may assist clinicians in making diagnostic and therapeutic decisions.

Dosagem da atividade da adenosina deaminase no líquido pleural para o diagnóstico da tuberculose pleural

INTRODUÇÃO: O diagnóstico da tuberculose pleural permanece um desafio, pois a sensibilidade dos testes tradicionais é baixa. O exame histopatológico da pleura é o método mais preciso, com até 80% de sensibilidade. A dosagem da adenosina deaminase foi introduzida mais recentemente, mas sua utilidade no diagnóstico da tuberculose pleural no Brasil não foi suficientemente esclarecida. OBJETIVO: Verificar a sensibilidade e a especificidade de um método experimental de dosagem da atividade da adenosina deaminase em uma série de pacientes com derrame pleural investigados entre agosto de 1998 e novembro de 2002 no Rio de Janeiro (RJ). RESULTADOS: De 137 casos, em 111 havia amostras de líquido pleural disponíveis, das quais 83 pertenciam a pacientes com tuberculose pleural. Entre os 67 pacientes testados com tuberculose pleural, 10 apresentavam co-infecção pelo vírus da imunodeficiência humana (14,9%). O valor de corte da adenosina deaminase de 35U/L foi determinado por uma curva receiver operator characteristic. A sensibilidade, especificidade, e razões de verossimilhança positiva e negativa da adenosina deaminase foram de 92,8%, 93,2%, 25,8 e 13,9, respectivamente. A média de adenosina deaminase no grupo com tuberculose pleural foi de 84,7 ± 43,1 U/L e no grupo com outras doenças de 15,9 ±11,1 U/L. Não houve diferença significativa na dosagem da adenosina deaminase entre pacientes com tuberculose pleural co-infectados ou não pelo vírus da imunodeficiência humana. CONCLUSÃO: A dosagem da adenosina deaminase no líquido pleural é um método sensível e específico para o diagnóstico da tuberculose pleural e seu uso rotineiro pode reduzir a necessidade de realização de biópsias pleurais na abordagem inicial de um derrame pleural. O valor de corte de 35U/L para a adenosina deaminase é recomendado.

Extrapulmonary and pulmonary tuberculosis in antananarivo (madagascar): high clustering rate in female patients.

Antananarivo, the capital city of Madagascar, has an endemic focus of tuberculosis (TB). We specifically studied patients with extrapulmonary TB (EPTB) and grouped patients according to infected body site. The strains were characterized by IS6110 fingerprinting and compared with those isolated from patients with pulmonary TB (PTB) during the same period in order to determine the possible association between the genotype and the clinical expression of TB. A total of 316 TB patients were included in this study: 151 individuals with EPTB, 10 with both PTB and EPTB, and 155 with PTB alone. Pleural TB was the major EPTB localization (77%) and was found more often in older patients, while PTB or EPTB in which the localization was other than pleural (other EPTB) was found in younger patients. The male-to-female ratio was slightly higher in pleural TB patients (3.06:1) than in patients with other EPTB (1.35:1). There was no significant difference in the BCG status among patients with PTB, pleural TB, and other EPTB. Analysis of IS6110 patterns showed that 167 patients (52.8%) were assigned to 37 clusters of 2 to 34 patients. Analysis of the IS6110 clusters and the IS6110 families did not show any association with a particular clinical expression of the disease. Patients with PTB or other EPTB were more likely to have strains with one IS6110 copy than patients with pleural TB. The clustering rate was found to be significantly higher in female patients (62%) than in male patients (48%) (P = 0.029), suggesting that Malagasy women were more likely to progress to disease after infection than men.

Pleural effusion, tuberculosis and HIV-1 infection in Kigali, Rwanda.

An increasing number of diagnoses of pleural effusions (PE) have been made over the last 8 years in the Department of Internal Medicine of the Centre Hospitalier de Kigali, Rwanda. In order to determine the aetiology of PE and to examine its possible association with HIV-1 infection, we performed an aetiological work-up, including thoracocentesis and pleural punch biopsy, of all new patients with PE of undetermined aetiology referred to the Division of Pulmonary Diseases of the Department of Internal Medicine of the Centre Hospitalier de Kigali between 14 September 1988 and 16 October 1989. HIV-1 serological testing was performed for most of the patients. A total of 127 patients (81 men, 46 women; mean age, 34 years; range, 16-71 years) with PE of undetermined aetiology were enrolled. Pleural tuberculosis was diagnosed in 110 (86%) and confirmed histologically and/or bacteriologically in 90 (82%). Of 98 pleural tuberculosis patients tested for HIV-1-antibody, 82 (83%) were HIV-1-seropositive. Metastatic cancer was responsible for PE in six (5%) patients, Kaposi's sarcoma in three, lymphoma in one (all four HIV-1-seropositive), anaplastic carcinoma in one, and adenocarcinoma in one (both HIV-1-seronegative). Non-tuberculous pneumonia was documented in five (4%) patients and was associated with HIV-1 infection in four. Other causes of PE were congestive heart failure (three patients), decompensated cirrhosis (one), constrictive percarditis (one), or undetermined (one); only one of these patients was HIV-1-seropositive. We conclude that tuberculosis is the predominant cause of PE in our patients and is strongly associated with HIV-1 infection. Although less frequent, non-tuberculous pneumonia, Kaposi's sarcoma and lymphoma are other causes of HIV-1-associated PE. In an African area highly endemic for HIV-1 and Mycobacterium tuberculosis co-infection, PE should be considered a good marker of tuberculosis as well as HIV-1 infection.