ABSTRACT
Introduction: Pleural tuberculosis (PlTB), the most common site of extrapulmonary TB, is characterized by a paucibacillary nature and a compartmentalized inflammatory response in the pleural cavity, both of which make diagnosis and management extremely challenging. Although transcriptional signatures for pulmonary TB have already been described, data obtained by using this approach for extrapulmonary tuberculosis and, specifically, for pleural tuberculosis are scarce and heterogeneous. In the present study, a set of candidate genes previously described in pulmonary TB was evaluated to identify and validate a transcriptional signature in clinical samples from a Brazilian cohort of PlTB patients and those with other exudative causes of pleural effusion. Methods: As a first step, target genes were selected by a random forest algorithm with recursive feature elimination (RFE) from public microarray datasets. Then, peripheral blood (PB) and pleural fluid (PF) samples from recruited patients presenting exudative pleural effusion were collected during the thoracentesis procedure. Transcriptional analysis of the selected top 10 genes was performed by quantitative RT-PCR (RT-qPCR). Results: Reanalysis of the public datasets identified a set of candidate genes (CARD17, BHLHE40, FCGR1A, BATF2, STAT1, BTN3A1, ANKRD22, C1QB, GBP2, and SEPTIN4) that demonstrated a global accuracy of 89.5% in discriminating pulmonary TB cases from other respiratory diseases. Our validation cohort consisted of PlTB (n = 35) patients and non-TB (n = 34) ones. The gene expressions of CARD17, GBP2, and C1QB in PF at diagnosis were significantly different between the two (PlTB and non-TB) groups (p < 0.0001). It was observed that the gene expressions of CARD17 and GBP2 were higher in PlTB PF than in non-TB patients. C1QB showed the opposite behavior, being higher in the non-TB PF. After anti-TB therapy, however, GBP2 gene expression was significantly reduced in PlTB patients (p < 0.001). Finally, the accuracy of the three above-cited highlighted genes in the PF was analyzed, showing AUCs of 91%, 90%, and 85%, respectively. GBP2 was above 80% (sensitivity = 0.89/specificity = 0.81), and CARD17 showed significant specificity (Se = 0.69/Sp = 0.95) in its capacity to discriminate the groups. Conclusion: CARD17, GBP2, and C1QB showed promise in discriminating PlTB from other causes of exudative pleural effusion by providing accurate diagnoses, thus accelerating the initiation of anti-TB therapy.
Subject(s)
Pleural Effusion , Tuberculosis, Pleural , Tuberculosis, Pulmonary , Humans , Tuberculosis, Pleural/diagnosis , Tuberculosis, Pleural/genetics , Exudates and Transudates , Pleural Effusion/diagnosis , Pleural Effusion/genetics , Pleural Effusion/metabolism , Brazil , Butyrophilins , Antigens, CDABSTRACT
OBJECTIVE: This study aimed to describe the clinical and laboratory findings of patients diagnosed with pleural tuberculosis at two hospitals in southern Brazil. METHODS: Patients aged < 18 years were evaluated retrospectively. The patients' medical and epidemiological history, tuberculin skin test results, radiological and pathological findings, and pleural fluid analysis results were retrieved. RESULTS: Ninety-two patients with pleural tuberculosis were identified. The mean age was 10.9 years old. Twenty-one percent were children aged six years or less. The most common symptoms were fever (88%), cough (72%), and chest pain (70%). Unilateral pleural effusion was observed in 96% of the cases. Lymphocyte predominance was found in 90% of the pleural fluid samples. The adenosine deaminase activity of the pleural fluid was greater than 40 U/L in 85% of patients. A diagnosis of community-acquired pneumonia with antibiotic prescriptions was observed in 76% of the study population. CONCLUSIONS: Tuberculosis etiology must be considered in unilateral pleural effusion in a child with contact with a case of tuberculosis. Pleural fluid biomarkers contribute to the diagnosis of pleural tuberculosis in children and adolescents.
Subject(s)
Pleural Effusion , Tuberculosis, Pleural , Child , Adolescent , Humans , Tuberculosis, Pleural/diagnosis , Tuberculosis, Pleural/epidemiology , Tuberculosis, Pleural/pathology , Brazil/epidemiology , Retrospective Studies , Pleural Effusion/diagnosis , Pleural Effusion/etiology , BiomarkersABSTRACT
INTRODUCCIÓN: El Xpert MTB/RIF Ultra (Ultra) ha mejorado dramáticamente el diagnóstico de la tuberculosis (TBC). Con él ha nacido la categoría de trazas, que es la menor carga bacilar detectable por este examen. OBJETIVO: Describir las características clínicas de los pacientes con presencia de trazas en el Ultra y evaluar la confirmación de la TBC como diagnóstico clínico. MATERIALES Y MÉTODOS: Estudio descriptivo de serie de casos. Se extrajo la información de fichas clínicas de pacientes con positividad a trazas. Se confrontaron datos clínicos, microbiológicos e histopatológicos. RESULTADOS: Se analizaron 21 pacientes. La edad promedio fue de 52 años. Todos los casos presentaron baciloscopias negativas. Cuatro cultivos en medio líquido MGIT fueron positivos, dos en pleura parietal, uno en líquido pleural y otro en expectoración. En pleura parietal, tres casos presentaron granulomas con necrosis caseosa y un granuloma esbozos de necrosis. En tejido pulmonar se observaron dos casos con granulomas con esbozos de necrosis y dos con granulomas no necrotizantes. Tres pacientes tenían el antecedente de TBC previa, se interpretó la positividad de trazas en ellos como falsos positivos. Finalmente se diagnosticaron 13 casos como TBC activa, donde cinco de ellos fueron TBC pleurales. La mayor concordancia clínica, microbiológica e histopatológica fue en muestras de líquido y tejido pleural. DISCUSIÓN: Se debe interpretar con cautela los hallazgos de esta prueba en muestras de vía aérea; el análisis multidisciplinario (clínica, imágenes, microbiología, histología) es crucial en las decisiones de nuestras conductas clínicas futuras. El hallazgo de trazas en pleura tiene, a nuestro parecer, un alto valor diagnóstico en el estudio de la tuberculosis en esta localización.
INTRODUCTION: Xpert MTB/RIF Ultra has dramatically changed the diagnosis of tuberculosis. A new category called traces appeared, which is the smallest amount of bacillar load detectable. OBJECTIVE: Describe the clinical characteristics of patients that present traces in Xpert MTB/RIF Ultra test, and to evaluate the confirmation of tuberculosis as clinical diagnosis. METHODS: We perform a descriptive case series study. Information was recovered from clinical records of patients with positive test for traces. Clinical, histopathological and microbiological results were confronted. RESULTS: Twenty one patients were analyzed. The mean age was 52 years-old. All cases had negative smear microscopy and four MGIT cultures were positive, two in pleural fluid and another in sputum. In parietal pleura, three cases presented granulomas with caseous necrosis, and one showed granuloma with very little necrosis. In pleural tissue we observed two cases of granulomas with traces of necrosis and two with non-necrotizing granulomas. Three patients had history of previous tuberculosis and positive traces, the test was interpreted as a false positive result. Finally, active tuberculosis was diagnosed in 13 cases, and five of them were pleural tuberculosis. The highest clinical, microbiological and histopathological agreement was in fluid and pleural tissue samples. DISCUSSION: The findings of Xpert MTB/RIF Ultra in airway samples must be interpreted carefully. Multi-disciplinary analysis is crucial in future clinical decisions. The finding of traces in pleura has, in our opinion, a high diagnostic value in the study of tuberculosis in this location.
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Tuberculosis, Pleural/diagnosis , Tuberculosis, Pleural/microbiology , Tuberculosis, Pulmonary/diagnosis , Tuberculosis, Pulmonary/microbiology , Bacteriological Techniques/methods , Sputum/microbiology , Tuberculosis, Pleural/pathology , Tuberculosis, Pulmonary/pathology , Mycobacterium tuberculosisABSTRACT
OBJECTIVES: Pleural tuberculosis (PlTB) diagnosis is a challenge due to its paucibacillary nature and to the need of invasive procedures. This study aimed to identify easily available variables and build a predictive model for PlTB diagnosis which may allow earlier and affordable alternative strategy to be used in basic health care units. METHODS: An observational cross-sectional study compared PlTB and non-TB patients followed at a tertiary Brazilian hospital between 2010 and 2018. Unconditional logistic regression analysis was performed and a Decision Tree Classifier (DTC) model was validated and applied in additional PlTB patients with empiric diagnosis. The accuracy (Acc), sensitivity (Se), specificity (Sp), positive and negative predictive values were calculated. RESULTS: From 1,135 TB patients, 160 were considered for analysis (111 confirmed PlTB and 49 unconfirmed PlTB). Indeed, 58 non-TB patients were enrolled as controls. Hyporexia [adjusted odds ratio (aOR) 27.39 (95% CI 6.26 - 119.89)] and cellular/biochemical characteristics on pleural fluid (PF) (polimorphonuclear in two categories: 3-14% aOR 26.22, 95% CI 7.11 - 96.68 and < 3% aOR 28.67, 95% CI 5.51 - 149.25; and protein ≥ 5g/dL aOR 7.24, 95% CI 3.07 - 17.11) were associated with higher risk for TB. The DTC constructed using these variables showed Acc=87.6%, Se=89.2%, Sp=84.5% for PlTB diagnosis and was successfully applied in unconfirmed PlTB patients. CONCLUSION: The DTC model showed an excellent performance for PlTB diagnosis and can be considered as an alternative diagnostic strategy by using clinical patterns in association with PF cellular/biochemical characteristics, which were affordable and easily performed in basic health care units.
Subject(s)
Pleural Effusion , Tuberculosis, Pleural , Brazil , Cross-Sectional Studies , Humans , Pleural Effusion/diagnosis , Predictive Value of Tests , Sensitivity and Specificity , Tuberculosis, Pleural/diagnosisABSTRACT
The determination of adenosine deaminase (ADA) is useful in countries where the prevalence of tuberculosis (TB) is high/ moderate. The objective of this study was to analyze the cut-off point for ADA in patients with TB at our institution. All patients with pleural effusion were included, from May 2016 to March 2019, except those with positive serology for HIV and transudates. They were grouped into the following diagnoses: TB, neoplasm, parapneumonic or other with an unclear cause. ADA determination and culture for mycobacteria were performed on all samples of pleural fluid. A ROC curve was performed to establish the best ADA cut-off point for the diagnosis of TB. Information was collected from 309 patients; 220 were included and 87 had a diagnosis of TB. The best cut-off point obtained for ADA was 52 U/l, with a sensitivity of 79% and a specificity of 90%. The area under the curve (AUC) was 0.90. In patients under 40 years old the best cut-off point was 41 U/l, below that obtained for the total study population. In our population the cut-off point for the ADA value in pleural exudate for the diagnosis of tuberculosis of 52 U/l presents the highest specificity and sensitivity.
La determinación de adenosina deaminasa (ADA) es de utilidad en países donde la prevalencia de tuberculosis (TB) es alta/moderada. El objetivo del trabajo fue analizar el punto de corte de ADA en pacientes con tuberculosis en nuestra institución. Se incluyeron todos los pacientes con derrame pleural, desde mayo del 2016 a marzo 2019. Se excluyeron aquellos con serología positiva para HIV y los trasudados. Todos fueron agrupados en los siguientes diagnósticos: TB, neoplasia, paraneumónico u otro de causa no aclarada. Se efectuó determinación de ADA y cultivo para micobacterias a todas las muestras de líquido pleural. Se realizó una curva ROC para establecer el mejor punto de corte de ADA para el diagnóstico de TB. Se recolectó información de 309 pacientes, se incluyeron 220, 87 tuvieron diagnóstico de TB. El mejor punto de corte obtenido para el ADA fue de 52 U/l, con una sensibilidad de 79% y una especificidad de 90%. El área bajo la curva (AUC) resultó de 0.90. En los menores de 40 años, el mejor punto de corte fue de 41 U/l, por debajo del obtenido para el total de la población en estudio. En nuestra población, el punto de corte para el valor de ADA en exudado pleural para el diagnóstico de tuberculosis de 52 U/l, presentó la mayor especificidad y sensibilidad.
Subject(s)
Pleural Effusion , Tuberculosis, Pleural , Adenosine Deaminase , Adult , Exudates and Transudates , Humans , Pleural Effusion/diagnosis , Sensitivity and Specificity , Tuberculosis, Pleural/diagnosisABSTRACT
OBJECTIVE: To evaluate the accuracy of determining the adenosine deaminase (ADA) level, the 2'-deoxyadenosine/ADA ratio, and the LDH/ADA ratio in pleural fluid for the diagnosis of pleural tuberculosis (PT) in children and adolescents. METHODS: This was a retrospective cross-sectional study conducted at a tertiary hospital in a high-tuberculosis-incidence area, between 2001 and 2018. All patients with ADA in pleural fluid and a confirmed diagnosis of PT (cPT) or parapneumonic effusion (PPE) were included. RESULTS: The cPT and PPE groups comprised 25 and 68 individuals, respectively. At a cutoff of 40 U/L, ADA measurement showed the following: sensitivity, 88%; specificity, 31%; positive predictive value (PPV), 32%; negative predictive value (NPV), 88%; and overall accuracy, 46%. The best cutoffs were an ADA level of 125 U/L, a 2'-deoxyadenosine/ADA ratio of 0.5, and an LDH/ADA ratio of 8.3, with AUC of 0.67, 0.75, and 0.82, respectively. The sensitivity, specificity, PPV, NPV, and overall accuracy of the 125 U/L ADA cutoff were 84%, 65%, 47%, 92%, and 70%, respectively, compared with 79%, 79%, 59%, 91%, and 79%, respectively, for the 8.3 LDH/ADA ratio cutoff. Changing the LDH/ADA ratio cutoff to 3.0 increased the specificity to 98%. CONCLUSIONS: The ADA level and the 2'-deoxyadenosine/ADA ratio are not good biomarkers for the diagnosis of PT in pediatric patients. Determination of the LDH/ADA ratio provides the best overall accuracy for the diagnosis of PT in such patients.
Subject(s)
Pleural Effusion , Tuberculosis, Pleural , Adenosine Deaminase , Adolescent , Child , Cross-Sectional Studies , Humans , L-Lactate Dehydrogenase , Pleural Effusion/diagnosis , Retrospective Studies , Sensitivity and Specificity , Tuberculosis, Pleural/diagnosisABSTRACT
ABSTRACT Objective: To evaluate the accuracy of determining the adenosine deaminase (ADA) level, the 2'-deoxyadenosine/ADA ratio, and the LDH/ADA ratio in pleural fluid for the diagnosis of pleural tuberculosis (PT) in children and adolescents. Methods: This was a retrospective cross-sectional study conducted at a tertiary hospital in a high-tuberculosis-incidence area, between 2001 and 2018. All patients with ADA in pleural fluid and a confirmed diagnosis of PT (cPT) or parapneumonic effusion (PPE) were included. Results: The cPT and PPE groups comprised 25 and 68 individuals, respectively. At a cutoff of 40 U/L, ADA measurement showed the following: sensitivity, 88%; specificity, 31%; positive predictive value (PPV), 32%; negative predictive value (NPV), 88%; and overall accuracy, 46%. The best cutoffs were an ADA level of 125 U/L, a 2'-deoxyadenosine/ADA ratio of 0.5, and an LDH/ADA ratio of 8.3, with AUC of 0.67, 0.75, and 0.82, respectively. The sensitivity, specificity, PPV, NPV, and overall accuracy of the 125 U/L ADA cutoff were 84%, 65%, 47%, 92%, and 70%, respectively, compared with 79%, 79%, 59%, 91%, and 79%, respectively, for the 8.3 LDH/ADA ratio cutoff. Changing the LDH/ADA ratio cutoff to 3.0 increased the specificity to 98%. Conclusions: The ADA level and the 2'-deoxyadenosine/ADA ratio are not good biomarkers for the diagnosis of PT in pediatric patients. Determination of the LDH/ADA ratio provides the best overall accuracy for the diagnosis of PT in such patients.
RESUMO Objetivo: Avaliar a acurácia da determinação do nível de adenosina desaminase (ADA), da relação 2'-desoxiadenosina/ADA e da relação LDH/ADA no líquido pleural para o diagnóstico de tuberculose pleural (TP) em crianças e adolescentes. Métodos: Estudo transversal retrospectivo realizado em um hospital terciário em uma área de alta incidência de tuberculose entre 2001 e 2018. Todos os pacientes com determinação de ADA no líquido pleural e com diagnóstico confirmado de TP (TPc) ou de derrame parapneumônico (DPP) foram incluídos. Resultados: Os grupos TPc e DPP foram compostos por 25 e 68 indivíduos, respectivamente. Num ponto de corte de 40 U/L, a medida de ADA mostrou o seguinte: sensibilidade, 88%; especificidade, 31%; valor preditivo positivo (VPP), 32%; valor preditivo negativo (VPN), 88%; e acurácia geral, 46%. Os melhores pontos de corte foram ADA de 125 U/L, relação 2'-desoxiadenosina/ADA de 0,5 e relação LDH/ADA de 8,3, com ASC de 0,67, 0,75 e 0,82, respectivamente. A sensibilidade, especificidade, VPP, VPN e acurácia geral do ponto de corte de 125 U/L para ADA foram de 84%, 65%, 47%, 92% e 70%, respectivamente, em comparação com 79%, 79%, 59%, 91% e 79%, respectivamente, para o ponto de corte de 8,3 para a relação LDH/ADA. Ao alterar o ponto de corte da relação LDH/ADA para 3,0 a especificidade aumentou para 98%. Conclusões: O nível de ADA e a relação 2'-desoxiadenosina/ADA não são bons biomarcadores para o diagnóstico de PT em pacientes pediátricos. A determinação da relação LDH/ADA fornece a melhor acurácia geral para o diagnóstico de PT nesses pacientes.
Subject(s)
Humans , Child , Adolescent , Pleural Effusion/diagnosis , Tuberculosis, Pleural/diagnosis , Adenosine Deaminase , Cross-Sectional Studies , Retrospective Studies , Sensitivity and Specificity , L-Lactate DehydrogenaseABSTRACT
Pleural tuberculosis (PlTB), a common form of extrapulmonary TB, remains a challenge in the diagnosis among many causes of pleural effusion. We recently reported that the combinatorial analysis of interferon gamma (IFN-γ), IFN-γ-inducible protein 10 (IP-10), and adenosine deaminase (ADA) from the pleural microenvironment was useful to distinguish pleural effusion caused by TB (microbiologically confirmed or not) among other etiologies. In this cross-sectional cohort study, a set of inflammatory mediators was quantified in blood and pleural fluid (PF) from exudative pleural effusion cases, including PlTB (n = 27) and non-PlTB (nTB) (n = 25) patients. The levels of interleukin-2 (IL-2), IL-4, IL-6, IL-10, IL-17A, IFN-γ, tumor necrosis factor (TNF), IP-10, transforming growth factor ß1 (TGF-ß), and ADA were determined using cytometric bead assay, enzyme-linked immunosorbent assay (ELISA), or biochemical tests. IFN-γ, IP-10, TNF, TGF-ß, and ADA quantified in PF showed significantly higher concentrations in PlTB patients than in nTB patients. When blood and PF were compared, significantly higher concentrations of IL-6 and IL-10 in PF were identified in both groups. TGF-ß, solely, showed significantly increased levels in PF and blood from PlTB patients when both clinical specimens were compared to those from nTB patients. Principal-component analysis (PCA) revealed a T helper type 1 (Th1) pattern attributed mainly to higher levels of IP-10, IFN-γ, TGF-ß, and TNF in the pleural cavity, which was distinct between PlTB and nTB. In conclusion, our findings showed a predominantly cellular immune response in PF from TB cases, rather than other causes of exudative effusion commonly considered in the differential diagnosis of PlTB.
Subject(s)
Exudates and Transudates/immunology , Mycobacterium tuberculosis/immunology , Pleural Effusion/immunology , Th1 Cells/immunology , Tuberculosis, Pleural/immunology , Adult , Aged , Aged, 80 and over , Biomarkers , Comorbidity , Cytokines/metabolism , Female , Host-Pathogen Interactions/immunology , Humans , Inflammation Mediators/metabolism , Male , Middle Aged , Th1 Cells/metabolism , Tuberculosis, Pleural/diagnosis , Tuberculosis, Pleural/metabolism , Tuberculosis, Pleural/microbiology , Young AdultABSTRACT
BACKGROUND: A previous study demonstrated pleural fluid (PF) IgA immunodominance for the fused MT10.3:MPT64 protein in pleural tuberculosis (PLTB) cases. However, no clue on the role of IgA and IgG against this and other antigens in PF and serum concerning improved diagnosis is available. Thus, the aim of the present study was to validate PF IgA-MT10.3:MPT64 and evaluate PF and serum IgA and IgG reactivity against this protein, its peptides (F2) and single MPT64, MT10.3 and the PPE59 mycobacterial specific antigens. IgA and IgG ELISA were measured against the antigen in PLTB (n = 29) and other non-TB pleurisy (n = 39) patient samples. RESULTS: The immunodominance of PF IgA-MT10.3:MPT64 was confirmed in PLTB (86.2%) followed by PPE59 (62%), while serum IgA-F2 exhibited 51.7% sensitivity. PF and serum IgG-MT10.3:MPT64 led to 65.5 and 51.7% sensitivity, respectively. However, MT10.3 and MPT64 displayed overall lower sensitivity (≤34.5) for both antibodies. All results at 95% fixed specificity. Combinatory results indicated 93.1% sensitivity for PF IgA-MT10.3:MPT64/-PPE59 and IgA/IgG-MT10.3:MPT64 at 92.3% specificity, followed by IgA-MT10.3:MPT64/-MPT64 or /-F2 (89.6%) without jeopardizing specificity (94.9%). The combinatory results of the PF adenosine deaminase test (ADA) and IgA-MT10.3:MPT64/-F2 demonstrated the highest sensitivity (96.6%), with a specificity of 92.3%. CONCLUSIONS: The PF IgA-MT10:MPT64 immune dominance was validated in PLTB, and its combinatory results with PPE59 or MPT64 or F2 antigens as well as with IgG, are reported herein for the first time, improving their potential to assist diagnosis. Combining PF-ADA and IgA-MT10.3:MPT64/-F2 results achieved better accuracy. Moreover, serum IgG, although less accurate, displays potential beyond microbiological tests.
Subject(s)
Antibodies, Bacterial/immunology , Antigens, Bacterial/immunology , Immunoglobulin A/immunology , Immunoglobulin G/immunology , Mycobacterium tuberculosis/immunology , Pleural Effusion/immunology , Tuberculosis, Pleural/immunology , Biomarkers , Enzyme-Linked Immunosorbent Assay , Female , Humans , Male , Pleural Effusion/pathology , ROC Curve , Reproducibility of Results , Sensitivity and Specificity , Tuberculosis, Pleural/blood , Tuberculosis, Pleural/diagnosisABSTRACT
La tuberculosis es una enfermedad infecciosa por Mycobacterium tuberculosis conocida desde la antigüedad y con gran importancia en la actualidad ubicándose como una de las principales causas de morbimortalidad, puede tener presentación pulmonar y extrapulmonar. Se presenta el caso clínico de una adolescente inmunocompetente con tuberculosis con descripción de la historia natural, a raíz del cual se realiza y presenta una revisión de literatura actual confrontando con artículos de revisiones de temas en búsqueda electrónica en bases de datos de RIMA, MEDLINE, PUBMED, MEDSCAPE, de 2013 a 2018. CONCLUSIONES: Es primordial conocer la presentación extrapulmonar corresponde al 21% de los casos de tuberculosis puede ser asintomático o sintomático con fiebre, tos y dolor pleurítico.
Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis that has been known since antiquity and with great importance at present, being one of the main causes of morbidity and mortality, it can have pulmonary and extrapulmonary presentation. METHOD: review of current literature comparing articles with reviews of subjects in electronic search in databases of RIMA, MEDLINE, PUB-MED, MEDSCAPE, from 2013 to 2018 Clinical case: the clinical case of an immunocompetent adolescent with tuberculosis is represented. description of the natural history CONCLUSIONS: It is essential to know the extrapulmonary presentation corresponds to 21% of cases of tuberculosis can be asymptomatic or symptomatic with fever, cough and pleuritic pain.
Subject(s)
Humans , Female , Adolescent , Tuberculosis, Pleural/diagnosis , ImmunocompetenceABSTRACT
Tuberculous chylothorax is a rare infectious disease that occurs when the thoracic duct is obstructed. Treatment is directed to the tuberculosis infection. A 55-year-old male, driver, born in Trujillo (Peru) is admitted to the emergency department with increasing dyspnea and a 5-day dry cough. The physical examination revealed vocal fremitus, dullness to percussion, and a vesicular murmur that was decreased on the lower 2/3 of the left hemithorax. The X-ray and the thoracic ultrasound revealed significant left pleural effusion. The thoracocentesis drained fluid identified as chylothorax. Subsequently, a thoracic tube was placed, with a decrease in pleural fluid volume and later normalization of the cytochemical changes. Diagnostic video bronchoscopy was performed with a bronchoalveolar aspirate, revealing acid-fast bacilli. The patient received antituberculosis treatment with a favorable outcome. Tuberculous chylothorax is an important cause of chylothorax to be considered in endemic areas of tuberculosis. Proper treatment of the infection leads to resolution of the disease.
El quilotórax tuberculoso es una patología infecciosa infrecuente, que se produce como consecuencia del bloqueo del conducto torácico. Su tratamiento está dirigido a combatir la infección tuberculosa. Se presenta el caso de un varón de 55 años de edad, chofer, natural de Trujillo-Perú, que acudió a emergencia por disnea progresiva y tos seca de cinco días de evolución. El examen físico reveló frémito vocal, matidez y murmullo vesicular disminuido en 2/3 inferiores del hemitórax izquierdo. La radiografía y ecografía torácica evidenciaron derrame pleural significativo, y la toracocentesis reveló quilotórax. Posteriormente, se colocó un tubo de drenaje torácico, con disminución progresiva del volumen del líquido pleural y cambios citoquímicos. Se realizó videobroncoscopía diagnóstica con aspirado broncoalveolar, revelando bacilos ácido-alcohol resistentes. El paciente recibió tratamiento antituberculoso, con evolución favorable. El quilotórax tuberculoso constituye una causa importante de quilotórax a considerar en zonas endémicas de tuberculosis. El tratamiento adecuado de la infección, conlleva a resolución de la enfermedad.
Subject(s)
Antitubercular Agents/administration & dosage , Chylothorax/diagnosis , Pleural Effusion/diagnosis , Tuberculosis, Pleural/diagnosis , Bronchoscopy , Chylothorax/drug therapy , Chylothorax/microbiology , Cough/etiology , Dyspnea/etiology , Humans , Male , Middle Aged , Peru , Tuberculosis, Pleural/drug therapyABSTRACT
Background: Tuberculosis (TB) is the world's leading cause of death from infectious disease. The World Health Organization (WHO) recognized 6.3 million new TB cases in 2017, 16% corresponding to extrapulmonary forms; pleural tuberculosis (PT) is the most common extrapulmonary form in adults. PT diagnosis is often challenging because the scarcity of bacilli in pleural fluid (PF), sometimes requiring invasive procedures to obtain pleural tissue for histological, microbiological or molecular examination. In regions of medium and high disease prevalence, adenosine deaminase (ADA), interferon gamma (IFN-γ) and interleukin 27 (IL-27) dosages are useful to establish presumptive diagnosis in patients with compatible clinical/radiological picture who present with lymphocytic pleural effusion. PT treatment is similar to the pulmonary TB treatment regimen recommended by WHO. Area covered: In this update, we present a PT review, including epidemiology, pathogenesis, clinical features, diagnosis, and therapy. Expert opinion: There is no PF test alone accurate for PT diagnosis, despite the evolution in clinical laboratory. ADA, IFN-γ and IL-27 are valuable laboratory biomarkers; however, IFN-γ and IL-27 are quite expensive. Molecular tests present low sensitivity in PF, being useful for diagnostic confirmation. Multidrug therapy remains the PT treatment choice. Advancing research in immunotherapy may bring benefits to PT patients.
Subject(s)
Tuberculosis, Pleural/diagnosis , Adenosine Deaminase/blood , Biomarkers/blood , Disease Management , Drug Therapy, Combination , Humans , Interferon-gamma/blood , Interleukin-27/blood , Leprostatic Agents , Pleural Effusion/diagnosis , Tuberculosis, Pleural/drug therapy , Tuberculosis, Pleural/epidemiology , Tuberculosis, Pleural/etiologyABSTRACT
El quilotórax tuberculoso es una patología infecciosa infrecuente, que se produce como consecuencia del bloqueo del conducto torácico. Su tratamiento está dirigido a combatir la infección tuberculosa. Se presenta el caso de un varón de 55 años de edad, chofer, natural de Trujillo-Perú, que acudió a emergencia por disnea progresiva y tos seca de cinco días de evolución. El examen físico reveló frémito vocal, matidez y murmullo vesicular disminuido en 2/3 inferiores del hemitórax izquierdo. La radiografía y ecografía torácica evidenciaron derrame pleural significativo, y la toracocentesis reveló quilotórax. Posteriormente, se colocó un tubo de drenaje torácico, con disminución progresiva del volumen del líquido pleural y cambios citoquímicos. Se realizó videobroncoscopía diagnóstica con aspirado broncoalveolar, revelando bacilos ácido-alcohol resistentes. El paciente recibió tratamiento antituberculoso, con evolución favorable. El quilotórax tuberculoso constituye una causa importante de quilotórax a considerar en zonas endémicas de tuberculosis. El tratamiento adecuado de la infección, conlleva a resolución de la enfermedad.
Tuberculous chylothorax is a rare infectious disease that occurs when the thoracic duct is obstructed. Treatment is directed to the tuberculosis infection. A 55-year-old male, driver, born in Trujillo (Peru) is admitted to the emergency department with increasing dyspnea and a 5-day dry cough. The physical examination revealed vocal fremitus, dullness to percussion, and a vesicular murmur that was decreased on the lower 2/3 of the left hemithorax. The X-ray and the thoracic ultrasound revealed significant left pleural effusion. The thoracocentesis drained fluid identified as chylothorax. Subsequently, a thoracic tube was placed, with a decrease in pleural fluid volume and later normalization of the cytochemical changes. Diagnostic video bronchoscopy was performed with a bronchoalveolar aspirate, revealing acid-fast bacilli. The patient received antituberculosis treatment with a favorable outcome. Tuberculous chylothorax is an important cause of chylothorax to be considered in endemic areas of tuberculosis. Proper treatment of the infection leads to resolution of the disease.
Subject(s)
Humans , Male , Middle Aged , Pleural Effusion/diagnosis , Tuberculosis, Pleural/diagnosis , Chylothorax/diagnosis , Antitubercular Agents/administration & dosage , Peru , Tuberculosis, Pleural/drug therapy , Bronchoscopy , Chylothorax/microbiology , Chylothorax/drug therapy , Cough/etiology , Dyspnea/etiologyABSTRACT
BACKGROUND: Pleural tuberculosis (PlTB) is the most common extrapulmonary manifestation of this infectious disease which still presents high mortality rates worldwide. Conventional diagnostic tests for PlTB register multiple limitations, including the lack of sensitivity of microbiological methods on pleural specimens and the need of invasive procedures such as pleural biopsy performance. In this scenario, the search for biological markers on pleural fluid (PF) has been the target of several studies as a strategy to overcome the limitations of PlTB diagnosis. This study aims to evaluate the use either isolated or in combination with adenosine deaminase (ADA), interferon-gamma (IFN-γ), interferon-gamma inducible protein of 10-kD (IP-10) levels on PF in order to guide an accurate anti-TB treatment in microbiologically non-confirmed cases. METHODS AND FINDINGS: Eighty patients presenting pleural effusion under investigation were enrolled in a cross-sectional study conducted at Pedro Ernesto University Hospital, Rio de Janeiro, RJ, Brazil. Peripheral blood (PB) and PF samples collected from all patients were applied to the commercial IFN-γ release assay, QuantiFERON-TB Gold In-Tube, and samples were analyzed for IFN-γ and IP-10 by immunoassays. ADA activity was determined on PF by the colorimetric method. Based on microbiological and histological criteria, patients were categorized as follow: confirmed PlTB (n = 16), non-confirmed PlTB (n = 17) and non-PlTB (n = 47). The Mycobacterium tuberculosis antigen-specific production of IFN-γ and IP-10 on PB or PF did not show significant differences. However, the basal levels of these biomarkers, as well as the ADA activity on PF, were significantly increased in confirmed PlTB in comparison to non-PlTB group. Receiver operating characteristics curves were performed and the best cut-off points of these three biomarkers were estimated. Their either isolated or combined performances (sensitivity [Se], specificity [Sp], positive predictive value [PPV], negative predictive value [NPV] and accuracy [Acc]) were determined and applied to Venn's diagrams among the groups. Based on the confirmed PlTB cases, IFN-γ showed the best performance of them at a cut-off point of 2.33 IU/mL (Se = 93.8% and Sp = 97.9%) followed by ADA at a cut-off of 25.80 IU/L (Se = 100% and Sp = 84.8%) and IP-10 (Cut-point = 4,361.90 pg/mL, Se = 75% and Sp = 82.6%). IFN-γ plus ADA (cut-point: 25.80 IU/L) represent the most accurate biomarker combination (98.4%), showing Se = 93.7%, Sp = 100%, PPV = 100% and NPV = 97.9%. When this analysis was applied in non-confirmed PlTB, 15/17 (88.2%) presented at least two positive biomarkers in combination. CONCLUSION: IFN-γ, IP-10, and ADA in PlTB effusions are significantly higher than in non-PlTB cases. IFN-γ is an excellent rule-in and rule-out test compared to IP-10 and ADA. The combination of IFN-γ and ADA, in a reviewed cut-off point, showed to be particularly useful to clinicians as their positive results combined prompts immediate treatment for TB while both negative results suggest further investigation.
Subject(s)
Chemokine CXCL10/metabolism , Interferon-gamma/metabolism , Tuberculosis, Pleural/metabolism , Adenosine Deaminase/metabolism , Adult , Aged , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Tuberculosis, Pleural/diagnosis , Tuberculosis, Pleural/pathologyABSTRACT
OBJECTIVES: To develop a clinical prediction rule (CPR) for the diagnosis of pleural tuberculosis (PT) in patients with pleural exudates in Peru. METHODS: Clinical and laboratory information was collected from patients with exudative pleural effusion attending two reference hospitals in Lima, Peru. Predictive findings associated with PT in a multiple logistic regression model were used to develop the CPR. A definite diagnosis of PT was based on a composite reference standard including bacteriological and/or histological analysis of pleural fluid and pleural biopsy specimens. RESULTS: A total of 238 patients were included in the analysis, of whom 176 had PT. Age, sex, previous contact with a TB patient, presence of lymphadenopathy, and pleural adenosine deaminase (ADA) levels were found to be independently associated with PT. These predictive findings were used to construct a CPR, for which the area under the receiver operating characteristics curve (AUC) was 0.92. The single best cut-off point was a score of ≥60 points, which had a sensitivity of 88%, specificity of 92%, a positive likelihood ratio of 10.9, and a negative likelihood ratio of 0.13. CONCLUSIONS: The CPR is accurate for the diagnosis of PT and could be useful for treatment initiation while avoiding pleural biopsy. A prospective evaluation is needed before its implementation in different settings.
Subject(s)
Decision Support Techniques , Pleural Effusion/diagnosis , Tuberculosis, Pleural/diagnosis , Adenosine Deaminase/metabolism , Adult , Biopsy , Exudates and Transudates , Female , Humans , Incidence , Logistic Models , Male , Middle Aged , Peru , Sensitivity and Specificity , Specimen HandlingABSTRACT
Tuberculosis (TB) is a common cause of pleural effusion in young people from endemic areas. Among the forms of extrapulmonary TB in people with immunodeficiencies, the most frequent localization is the pleura. The use of immunological and molecular biology tests for the diagnosis of TB in pleural fluid and other locations with high sensitivity and specificity is highlighted. We present a clinical case with the objective of giving an overview of the treatment of the patient with suspected pleural tuberculosis
La Tuberculosis (TB) es una causa común de derrame pleural en jóvenes en zonas endémicas. Dentro de las formas de TB extrapulmonar en personas que cursan con inmunodeficiencias, la localización más frecuente es la TB pleural. Se destaca el uso de las pruebas inmunológicas y de biología molecular para el diagnóstico de TB en líquido pleural y de otras localizaciones con una elevada sensibilidad y especificidad. Se presenta un caso clínico con el objetivo de describir una visión general del abordaje del paciente con sospecha de tuberculosis pleural
Subject(s)
Humans , Female , Adolescent , Pleural Effusion/etiology , Tuberculosis, Pleural/complications , Tuberculosis, Pleural/diagnosis , Pleural Effusion/enzymology , Tuberculosis, Pleural/enzymology , Tuberculosis, Pleural/diagnostic imaging , Radiography, Thoracic , Tomography, X-Ray Computed , Adenosine DeaminaseABSTRACT
INTRODUCTION: The diagnosis of pleural tuberculosis requires an invasive and time-consuming reference method. Polymerase chain reaction (PCR) is rapid, but validation in pleural tuberculosis is still weak. OBJECTIVE: To establish the operating characteristics of real-time polymerase chain reaction (RT-PCR) hybridization probes for the diagnosis of pleural tuberculosis. METHODS: The validity of the RT-PCR hybridization probes was evaluated compared to a composite reference method by a cross-sectional study at the Hospital Universitario de la Samaritana. 40 adults with lymphocytic pleural effusion were included. Pleural tuberculosis was confirmed (in 9 patients) if the patient had at least one of three tests using the positive reference method: Ziehl-Neelsen or Mycobacterium tuberculosis culture in fluid or pleural tissue, or pleural biopsy with granulomas. Pleural tuberculosis was ruled out (in 31 patients) if all three tests were negative. The operating characteristics of the RT-PCR, using the Mid-P Exact Test, were determined using the OpenEpi 2.3 Software (2009). RESULTS: The RT-PCR hybridization probes showed a sensitivity of 66.7% (95% CI: 33.2%-90.7%) and a specificity of 93.5% (95% CI: 80.3%-98.9%). The PPV was 75.0% (95% CI: 38.8%-95.6%) and a NPV of 90.6% (95% CI: 76.6%-97.6%). Two false positives were found for the test, one with pleural mesothelioma and the other with chronic pleuritis with mesothelial hyperplasia. CONCLUSIONS: The RT-PCR hybridization probes had good specificity and acceptable sensitivity, but a negative value cannot rule out pleural tuberculosis.
INTRODUCCIÓN: El diagnóstico de tuberculosis pleural requiere un método de referencia invasivo y demorado. La reacción en cadena de la polimerasa es rápida, pero su validación en tuberculosis pleural aún es débil. OBJETIVO: Establecer las características operativas de la reacción en cadena de la polimerasa en tiempo real (RT-PCR) sondas de hibridación para el diagnóstico de tuberculosis pleural. MÉTODOS: Se evaluó la validez de la RT-PCR sondas de hibridación comparada con un método de referencia compuesto mediante un estudio transversal en el Hospital Universitario de la Samaritana. Se incluyeron 40 adultos con derrame pleural linfocitario. Tuberculosis pleural fue confirmada (en 9 pacientes) si el paciente tenía mínimo una de tres pruebas del método de referencia positiva: Ziehl-Neelsen o cultivo para Mycobacterium tuberculosis en líquido o tejido pleural, o biopsia pleural con granulomas; se descartó tuberculosis pleural (en 31 pacientes) si las tres pruebas eran negativas. Se determinaron las características operativas de la RT-PCR, mediante la Prueba Mid-P Exact, con el Software OpenEpi 2.3 (2009). RESULTADOS: La RT-PCR sondas de hibridación mostró una sensibilidad del 66.7% (IC 95%: 33.2%-90.7%) y una especificidad del 93.5% (IC 95%: 80.3%-98.9%). El VPP fue de 75.0% (IC 95%: 38.8%-95.6%) y un VPN de 90.6% (IC 95%: 76.6%-97.6%). Se encontraron dos falsos positivos para la prueba, uno con mesotelioma pleural y otro con pleuritis crónica con hiperplasia mesotelial. CONCLUSIONES: La RT-PCR sondas de hibridación tuvo una buena especificidad y una aceptable sensibilidad, pero un valor negativo no puede descartar tuberculosis pleural.
Subject(s)
Pleural Effusion/diagnosis , Real-Time Polymerase Chain Reaction/methods , Tuberculosis, Pleural/diagnosis , Adult , Colombia , Cross-Sectional Studies , Female , Hospitals, University , Humans , Male , Mesothelioma/diagnosis , Middle Aged , Mycobacterium tuberculosis/isolation & purification , Pleurisy/diagnosis , Predictive Value of Tests , Sensitivity and SpecificityABSTRACT
OBJECTIVES: Diagnosis of pleural tuberculosis (PT) is still a challenge, particularly in resource-constrained settings. Alternative diagnostic tools are needed. We aimed at evaluating the utility of Clinical Prediction Rules (CPRs) for diagnosis of pleural tuberculosis in Peru. METHODS: We identified CPRs for diagnosis of PT through a structured literature search. CPRs using high-complexity tests, as defined by the FDA, were excluded. We applied the identified CPRs to patients with pleural exudates attending two third-level hospitals in Lima, Peru, a setting with high incidence of tuberculosis. Besides pleural fluid analysis, patients underwent closed pleural biopsy for reaching a final diagnosis through combining microbiological and histopathological criteria. We evaluated the performance of the CPRs against this composite reference standard using classic indicators of diagnostic test validity. RESULTS: We found 15 eligible CPRs, of which 12 could be validated. Most included ADA, age, lymphocyte proportion and protein in pleural fluid as predictive findings. A total of 259 patients were included for their validation, of which 176 (67%) had PT and 50 (19%) malignant pleural effusion. The overall accuracy of the CPRs varied from 41% to 86%. Two had a positive likelihood ratio (LR) above 10, but none a negative LR below 0.1. ADA alone at a cut-off of ≥40 IU attained 87% diagnostic accuracy and had a positive LR of 6.6 and a negative LR of 0.2. CONCLUSION: Many CPRs for PT are available. In addition to ADA alone, none of them contributes significantly to diagnosis of PT.
Subject(s)
Adenosine Deaminase/analysis , Pleural Effusion/microbiology , Tuberculosis, Pleural/diagnosis , Biomarkers/analysis , Biopsy, Needle , Clinical Enzyme Tests , Decision Support Techniques , Humans , Incidence , Mycobacterium/isolation & purification , Peru/epidemiology , Pleural Effusion/diagnostic imaging , Predictive Value of Tests , Radiography, Thoracic , Sputum/microbiology , Thoracentesis/methods , Tuberculosis, Pleural/enzymology , Tuberculosis, Pleural/epidemiology , Tuberculosis, Pleural/microbiology , UltrasonographyABSTRACT
Abstract Introduction: The diagnosis of pleural tuberculosis requires an invasive and time-consuming reference method. Polymerase chain reaction (PCR) is rapid, but validation in pleural tuberculosis is still weak. Objective: To establish the operating characteristics of real-time polymerase chain reaction (RT-PCR) hybridization probes for the diagnosis of pleural tuberculosis. Methods: The validity of the RT-PCR hybridization probes was evaluated compared to a composite reference method by a cross-sectional study at the Hospital Universitario de la Samaritana. 40 adults with lymphocytic pleural effusion were included. Pleural tuberculosis was confirmed (in 9 patients) if the patient had at least one of three tests using the positive reference method: Ziehl-Neelsen or Mycobacterium tuberculosis culture in fluid or pleural tissue, or pleural biopsy with granulomas. Pleural tuberculosis was ruled out (in 31 patients) if all three tests were negative. The operating characteristics of the RT-PCR, using the Mid-P Exact Test, were determined using the OpenEpi 2.3 Software (2009). Results: The RT-PCR hybridization probes showed a sensitivity of 66.7% (95% CI: 33.2%-90.7%) and a specificity of 93.5% (95% CI: 80.3%-98.9%). The PPV was 75.0% (95% CI: 38.8%-95.6%) and a NPV of 90.6% (95% CI: 76.6%-97.6%). Two false positives were found for the test, one with pleural mesothelioma and the other with chronic pleuritis with mesothelial hyperplasia. Conclusions: The RT-PCR hybridization probes had good specificity and acceptable sensitivity, but a negative value cannot rule out pleural tuberculosis.
Resumen Introducción: El diagnóstico de tuberculosis pleural requiere un método de referencia invasivo y demorado. La reacción en cadena de la polimerasa es rápida, pero su validación en tuberculosis pleural aún es débil. Objetivo: Establecer las características operativas de la reacción en cadena de la polimerasa en tiempo real (RT-PCR) sondas de hibridación para el diagnóstico de tuberculosis pleural. Métodos: Se evaluó la validez de la RT-PCR sondas de hibridación comparada con un método de referencia compuesto mediante un estudio transversal en el Hospital Universitario de la Samaritana. Se incluyeron 40 adultos con derrame pleural linfocitario. Tuberculosis pleural fue confirmada (en 9 pacientes) si el paciente tenía mínimo una de tres pruebas del método de referencia positiva: Ziehl-Neelsen o cultivo para Mycobacterium tuberculosis en líquido o tejido pleural, o biopsia pleural con granulomas; se descartó tuberculosis pleural (en 31 pacientes) si las tres pruebas eran negativas. Se determinaron las características operativas de la RT-PCR, mediante la Prueba Mid-P Exact, con el Software OpenEpi 2.3 (2009). Resultados: La RT-PCR sondas de hibridación mostró una sensibilidad del 66.7% (IC 95%: 33.2%-90.7%) y una especificidad del 93.5% (IC 95%: 80.3%-98.9%). El VPP fue de 75.0% (IC 95%: 38.8%-95.6%) y un VPN de 90.6% (IC 95%: 76.6%-97.6%). Se encontraron dos falsos positivos para la prueba, uno con mesotelioma pleural y otro con pleuritis crónica con hiperplasia mesotelial. Conclusiones: La RT-PCR sondas de hibridación tuvo una buena especificidad y una aceptable sensibilidad, pero un valor negativo no puede descartar tuberculosis pleural.
Subject(s)
Adult , Female , Humans , Male , Middle Aged , Pleural Effusion/diagnosis , Tuberculosis, Pleural/diagnosis , Real-Time Polymerase Chain Reaction/methods , Pleurisy/diagnosis , Cross-Sectional Studies , Predictive Value of Tests , Sensitivity and Specificity , Colombia , Hospitals, University , Mesothelioma/diagnosis , Mycobacterium tuberculosis/isolation & purificationABSTRACT
OBJECTIVE: To evaluate the quality of diagnosis and the epidemiological profile of patients with pleural tuberculosis in the state of Roraima, Brazil, in order to provide technical support for the development and implementation of public policies to combat the disease. METHODS: This was a cross-sectional study designed to determine the prevalence of pleural forms of tuberculosis in Roraima between 2005 and 2013 and to evaluate the diagnostic criteria used, as well as their determinants. This study was based on secondary data from the Brazilian Case Registry Database, including all reported cases of pleural tuberculosis in the state during the study period. Diagnoses based on bacteriological or histopathological confirmation were defined as high-quality diagnoses. RESULTS: Among the 1,395 cases of tuberculosis reported during the study period, 116 (8.3%) were cases of pleural tuberculosis, accounting for 38.9% of all cases of extrapulmonary tuberculosis in the sample. The incidence rate of pleural tuberculosis did not follow the downward trend observed for the pulmonary form of the disease during the same period. The prevalence of cases with a high-quality diagnosis was 28.5% (95% CI: 20.4-37.6%). In a univariate analysis, none of the demographic or clinical characteristics collected from the database were found to have a significant impact on the outcome (as explanatory variables). CONCLUSIONS: The quality of the diagnoses in our study sample was considered unsatisfactory. Limited access to specific diagnostic methods might have contributed to these results.