Caracterización clínica y microbiológica de pacientes con trazas en Xpert MTB/RIF Ultra / Clinical and microbiological characterization of patients with Xpert MTB/RIF Ultra traces

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.

Performance of the quantification of adenosine deaminase and determination of the lactate dehydrogenase/adenosine deaminase ratio for the diagnosis of pleural tuberculosis in children and adolescents / Desempenho da quantificação de adenosina desaminase e determinação da relação lactato desidrogenase/adenosina desaminase para o diagnóstico de tuberculose pleural em crianças e adolescentes

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.

Tuberculosis peritoneal y pleural en un paciente inmunocompetente con dolor abdominal crónico / Peritoneal and pleural tuberculosis in an immunocompetent patient with chronic abdominal pain

Objetivo: La tuberculosis es un grave problema de salud pública más acentuado en los países en desarrollo. De las manifestaciones extrapulmonares las que comprometen la cavidad abdominal están dentro de las menos frecuentes y se asocian con factores de predisposición específica. Se requiere un alto nivel de sospecha diagnóstica en el abordaje inicial de esta enfermedad. Presentamos el caso de un adulto masculino sin condiciones de predisposición quien consultó por un cuadro de dolor abdominal crónico y los estudios complementarios manifestaron una tuberculosis peritoneal con compromiso pleural sin síntomas respiratorios.

Objetive: Tuberculosis is a serious public health problem most prevalent in developing countries. Of extrapulmonary manifestations, those involving the abdominal cavity are among the least frequent and are associated with specific predisposing factors. A high level of diagnostic suspicion is required in the initial approach of this disease. We present the case of a male adult patient with no predisposing conditions who consulted for chronic abdominal pain. The complementary studies evidenced peritoneal tuberculosis with pleural involvement with no respiratory symptoms.

Tuberculosis vertebral con afectación pleural: reporte de un caso / Spinal tuberculosis with pleural involvement: a case report

Resumen La tuberculosis extrapulmonar representa hasta el 25% de todos los casos de tuberculosis. Los órganos más frecuentemente afectados son los ganglios linfáticos y la pleura. Alrededor del 10-11% de casos de tuberculosis extrapulmonar tienen afectación osteoarticular y de ellos la mitad con compromiso vertebral. La infección es causada por la diseminación hematógena del bacilo desde un foco primario al hueso esponjoso de los cuerpos vertebrales torácicos o lumbares principalmente. El síntoma característico es el dolor crónico de la columna vertebral, generalmente en el sitio afectado, sin otros síntomas o signos concomitantes. La asociación de tuberculosis vertebral con afectación pleural sin un foco pulmonar establecido es infrecuente, se ha descrito en 2.5% de pacientes e intriga acerca de su fisiopatología. En Colombia, no se encontraron reportes similares. Se describe el caso de una paciente joven con historia de dolor lumbar crónico que debutó con síntomas respiratorios persistentes asociado a síntomas constitucionales; en quien se comprobó la infección por Mycobacterium tuberculosis en vértebras toracolumbares y pleura. Este caso evidencia una historia natural atípica de la enfermedad, en la cual el mecanismo fisiopatológico parece haber sido la diseminación directa por contigüidad, y resalta la importancia de la sospecha clínica para garantizar un diagnóstico y tratamiento oportuno. MÉD.UIS.2020;33(3): 67-73

Abstract Extrapulmonary tuberculosis represents up to 25% of all cases of tuberculosis. The most frequently affected organs are lymph nodes, pleura and bone. Around 10-11% of cases of extrapulmonary tuberculosis have osteoarticular involvement and a half of them present vertebral involvement. The infection is caused by hematogenous spread of the bacillus from a primary focus to the cancellous bone of the thoracic or lumbar vertebral bodies mainly. The characteristic symptom is the chronic pain in the spine, usually in the affected site, without other concomitant symptoms or signs. The association between vertebral tuberculosis and pleural involvement without an established pulmonary focus is infrequent, it has been described in 2.5% of patients, an intrigue about its pathophysiology. Similar cases in Colombia have not been reported. This article describes a case of a young patient with a history of chronic low back pain that debuts with persistent respiratory symptoms associated with constitutional symptoms; whose Mycobacterium tuberculosis infection was proven in thoracolumbar vertebrae and pleura. This case shows an atypical natural history of the disease, in which the pathophysiological mechanism of the disease would seem to have been the direct dissemination by contiguity, and emphasizes the importance of clinical suspicion to ensure timely diagnosis and treatment. MÉD.UIS.2020;33(3): 67-73

Aspectos clínico-imagenológicos de pacientes diagnosticados con tuberculosis extrapulmonar, La Habana 2016-2019 / Clinical and imaging aspects of the patients diagnosed with extrapulmonary tuberculosis, Havana 2016-2019

RESUMEN Introducción: La tuberculosis extrapulmonar muestra una complejidad diagnóstica que influye sobre la morbilidad y mortalidad. Objetivo: Caracterizar desde una perspectiva clínico-imagenológica a los pacientes diagnosticados con tuberculosis extrapulmonar, en el Hospital Neumológico Benéfico Jurídico de La Habana, en el período 2016-2019. Método: Se realizó un estudio descriptivo, retrospectivo y transversal en 34 pacientes con diagnóstico de tuberculosis extrapulmonar. Las variables medidas fueron: edad, sexo, factores de riesgo para padecer la enfermedad, síntomas y signos clínicos, hallazgos radiológicos, métodos diagnósticos utilizados y su localización. Resultados: Predominaron pacientes del sexo masculino con edad entre 26 a 35 años (29,4 %). El 73,5 % de los pacientes presentó factores de riesgos para esta enfermedad, los más frecuentes fueron: ser contactos de pacientes con tuberculosis (29,4 %), los exreclusos (17,6 %) y los alcohólicos (14,7 %). El 58,8 % presentó fiebre y síntomas o signos generales como anorexia (44,1 %), pérdida de peso (41,2 %) y astenia (38,2 %). El hallazgo radiológico más común fue el derrame pleural (47 %) y la forma extrapulmonar más frecuente dada por 15 casos (44,1 %) fue la pleuritis tuberculosa. El método clínico-radiológico posibilitó el diagnóstico en el 50 % de los pacientes. Conclusiones: Las manifestaciones clínicas más evidentes fueron la fiebre, la pérdida de peso y la astenia. El método diagnóstico clínico-radiológico es el más utilizado y el hallazgo radiológico más reportado es el derrame pleural. La localización pleural es la forma extrapulmonar más frecuente.

ABSTRACT Introduction: Extrapulmonary tuberculosis shows a complexity that can influence in its morbidity and mortality rates. Objective: To characterize the patients with extrapulmonary tuberculosis from a clinical-imaging perspective in the Hospital Neumológico Benéfico Jurídico in Havana in the period 2016-2019. Method: A descriptive, retrospective and cross-sectional study was carried out in 34 patients with the diagnosis of extrapulmonary tuberculosis. The variables taken into account were: age, gender, risk factors for the disease, symptoms and clinical signs, radiological findings, diagnosis methods used, and location. Results: Male patients with ages ranging between 26 to 35 years predominated in the study (29.4%). 73.5% of the patients presented risk factors of the disease, being most common: contact of previous tuberculosis patients (29.4%), ex-inmates (17.6%) and alcoholics (14.7%). 58.8% of the patients presented fever and general symptoms like anorexia (44.1%), weight loss (41.2%) and asthenia (38.2%). The most common radiological finding was pleural effusion (47%), and the most frequent extrapulomary form of the disease was tuberculous pleurisy (15 cases representing a 44.1%). The clinical-radiological method made diagnose possible in 50% of the patients. Conclusions: The most common clinical manifestations were fever, weight loss and asthenia. The clinical-radiological method is the most frequently used, and the most frequent radiological finding was the pleural effusion. Pleural location was the most common extrapulmonary form of tuberculosis.

Aspectos clínicos y epidemiológicos de los pacientes con tuberculosis extrapulmonar en la provincia de Santiago de Cuba / Clinical and epidemiological aspects of patients with extrapulmonary tuberculosis in Santiago de Cuba

Introducción: La tuberculosis es una infección bacteriana contagiosa, causada por el Mycobacterium tuberculosis, que afecta principalmente a los pulmones, pero puede propagarse a otros órganos. Objetivo: Describir las características clínicas y epidemiológicas de los pacientes con tuberculosis extrapulmonar en la provincia de Santiago de Cuba. Métodos: Se realizó un estudio descriptivo y retrospectivo de los 124 pacientes con tuberculosis extrapulmonar pertenecientes a la provincia de Santiago de Cuba, desde enero de 2007 hasta diciembre de 2017, registrados a través de la tarjeta de notificación de enfermedades de declaración obligatoria. La información se procesó de forma computarizada, a través del paquete estadístico SPSS, versión 20.0. Se utilizaron las frecuencias absolutas y relativas. Resultados: En la serie predominaron el sexo masculino (75,8 %) y el grupo etario de 30-44 años (35,5 %); asimismo, la forma clínica de presentación más frecuente resultó ser la pleural y el municipio con más afectados fue Santiago de Cuba, pero el mayor riesgo de enfermar por tuberculosis extrapulmonar lo presentaron los habitantes del municipio de Mella. Por otra parte, el factor de riesgo que más incidió fue el hábito tabáquico. Conclusiones: Las características clínicas y epidemiológicas encontradas no difieren del contexto epidemiológico mundial. Se observó un desplazamiento hacia edades más tempranas y el VIH no se consideró un factor determinante en la aparición de la enfermedad; igualmente, la sospecha clínica y epidemiológica de esta afección continúa siendo un pilar importante para el diagnóstico de las formas extrapulmonares, especialmente en la población de riesgo.

Introduction: Tuberculosis is a contagious bacterial infection, caused by the Mycobacterium tuberculosis that affects mainly the lungs, but it can spread to other organs. Objective: To describe the clinical and epidemiological characteristics of the patients with extrapulmonary tuberculosis in Santiago de Cuba. Methods: A descriptive and retrospective study of 124 patients with extrapulmonary tuberculosis belonging to Santiago de Cuba, was carried out from January, 2007 to December, 2017, registered through the notification card of diseases of obligatory declaration. The information was processed by computer, through the statistical package SPSS, version 20.0. The absolute and relative frequencies were used. Results: In the series the male sex (75.8%) and the 30-44 years age group (35.5%) prevailed; also, the most frequent clinical form of presentation was the pleural form and the municipality with more patients affected was Santiago de Cuba, but the higher risk of becoming sick due to extrapulmonary tuberculosis was in the municipality of Mella. On the other hand, nicotine addiction was the risk factor of more incidence. Conclusions: The clinical and epidemiological characteristics found don not differ from the world epidemiological context. A displacement toward earlier ages was observed and HIV was not considered a determining factor in the emergence of the disease; likewise, the clinical and epidemiological suspicion of this disorder continues being an important pillar for the diagnosis of extrapulmonary forms, especially in the risk population.

Correlation between videothoracoscopy and biopsy in patients with pleural effusion and suspected tuberculosis in a high complexity military hospital / Correlación entre videotoracoscopia y biopsia en pacientes con derrame pleural y sospecha de tuberculosis en Hospital Militar de alta complejidad

Background: In the diagnostic process of pleural tuberculosis, the findings from video-assisted thoracoscopy (VATS) can be highly suggestive for the diagnosis of infection. Methods: We reviewed VATS records between the years 2012 to 2016 of patients over 16 years of age with pleural effusion and suspected pleural tuberculosis. Symptoms, macroscopic and chemical characteristics of the fluid, surgical descriptions and visual diagnosis of the surgeon were recorded and were compared with the histopathology. Results: 106 patients were selected, most of them men (71.7%), of whom approximately half were active military (51.3%). The predominant symptoms were dyspnea, pleuritic pain, fever and evolution time greater than 15 days (94.3%, 80.2%, 50% and 46,2%, respectively). These symptoms, in turn, were present more frequently in pleural tuberculosis patients than in non-tuberculosis patients. The fluid was mostly turbid yellow (44%) and lymphocytic cellularity exudate (77.4%). The VATS findings in patients with confirmed TBC included nodules (96.9%), adhesions (87.5%) and thickening (78.1%). The diagnosis made by the surgeon in relation to the histopathological diagnosis showed a sensitivity of 88.6% and a specificity of 98.4%. Conclusion: There are highly suggestive characteristics of the macroscopic report of VATS that would allow a quicker diagnosis of pleural tuberculosis.

Antecedentes: Los hallazgos de toracoscopia asistida por video (VATS) durante el diagnostico de tuberculosis pleural, que son altamente sugestivos de la infección han sido poco descritos. Metodos: Se revisaron los registros de VATS entre los años 2012 a 2016 of de pacientes mayores de 16 años con efusión pleural y sospechosos de etiología tuberculosa. Se analizaron los síntomas, las características macroscópicas y bioquímicas del líquido, la descripción quirúrgica y el diagnostico visual y se compararon con los resultados de la histopatologia. Resultados: Se estudiaron los registros de 106 pacientes, la mayoría fueron sexo masculino (71.7%), y aproximadamente la mitad en servicio militar activo (51.3%). Los síntomas predominantes fueron disnea, dolor pleuritico, fiebre y tiempo de evolución mayor a 15 días (94.3%, 80.2%, 50% y 46,2%, respectivamente). Estos sintomas a su vez fueron más frecuentes en tuberculosis pleural que en no tuberculosis. El liquido fue más amarillo turbio (44%) y con exudado de tipo linfocitario (77.4%). Los hallazgos de VATS en pacientes con tuberculosis confirmada incluyeron nodulos (96.9%), adhesiones (87.5%) y engrosamiento (78.1%). El diagnóstico hecho por el cirujano con relación al histopatológico, tuvo una sensibilidad de 88.6% y una especificidad de 98.4%. Conclusion: Existen características en el VATS altamente sugestivas de tuberculosis pleural.

Historia natural de la tuberculosis pleural en una paciente inmunocompetente / Natural history of pleural tuberculosis in an immunocompetent patient

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.

Reporte de un caso de quilotórax tuberculoso / A case report of tuberculous chylothorax

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.

Tuberculosis pleural en paciente pediátrico: reporte de un caso y revisión de la literatura / Pleural tuberculosis in a pediatric patient: case report and review

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

Preanalytical conditions can interfere with M. tuberculosis detection by PCR in respiratory samples

OBJECTIVES: Tuberculosis is one of the most prevalent infections in humans. Although culture is the reference for diagnosis, its sensitivity is compromised, especially in paucibacillary samples. Because polymerase chain reaction (PCR) amplifies mycobacterial DNA, it is more sensitive than culture for the diagnosis of Mycobacterium tuberculosis (Mtb). However, its performance can be affected by intrinsic sample inhibitors and by the extraction/detection techniques used. METHODS: We evaluated the influence of preanalytical conditions on Mtb detection in samples of sputum (SPU), bronchoalveolar lavage (BAL), and pleural fluid (PF) using combinations of extraction/detection methods. Respiratory samples were prepared to contain different concentrations of red blood cells and nucleated cells to which increasing amounts of Mtb colonies were inoculated and submitted to PCR. RESULTS: Up to 102 CFU/ml of Mtb were detected in the SPU in all methods, except for the Roche extraction/detection method, regardless of the preanalytical sample condition. In BAL samples, medium and high concentrations of cells and high concentrations of red blood cells contributed to a lower Mtb detection, regardless of the extraction method used. In PF, red blood cells were the variable that most interfered with Mtb detection, with better recovery (102 CFU/ml) observed with the Qiagen/Nanogen combination. CONCLUSION: The choice of Mtb extraction and detection method is of fundamental importance for PCR analytical sensitivity, especially when paucibacillary samples and/or samples containing potential PCR inhibitors are analyzed.

Real-time PCR assay for the diagnosis of pleural tuberculosis / Reacción en cadena de la polimerasa en tiempo real para el diagnóstico de tuberculosis pleural

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.

Acerca de la tuberculosis extrapulmonar / On extrapulmonary tuberculosis

La tuberculosis es una enfermedad infecciosa de gran prevalencia en países en vía de desarrollo como el nuestro. Aunque el compromiso pulmonar es el más frecuente y de impacto en la salud pública, existen varias formas extrapulmonares con diversas presentaciones clínicas y de difícil diagnóstico, recalcando la importancia de sospechar estas patologías para intervenciones oportunas y que impacten en la morbimortalidad. En este artículo se presentan cuatro casos clínicos donde se sospechó tuberculosis extrapulmonar (pericárdica, peritoneal, pleural y meníngea) en el Hospital de San José de Bogotá, describiendo la forma en que se realizó o se descartó la tuberculosis extrapulmonar y haciendo una breve descripción del rendimiento de diferentes pruebas diagnósticas.

Tuberculosis (TB) is an infectious disease with high-prevalence in developing countries as ours. Although pulmonary involvement is most common and is associated with greater impact on public health, there are various forms of extrapulmonary TB (EPTB) exhibiting various often difficult to diagnose clinical presentations, highlighting the importance of suspecting these pathologies in order to conduct timely interventions that impact their morbidity and mortality rates. This article presents four clinical cases at San José Hospital in Bogotá where EPTB disease was suspected (pericardium, peritoneum, pleura and meninges), describing the way EPTB disease was diagnosed or ruled out and briefly defining the diagnostic performance of various tests.

Identification of 10 Candidate Biomarkers Distinguishing Tuberculous and Malignant Pleural Fluid by Proteomic Methods

PURPOSE: Pleural effusion, an accumulation of fluid in the pleural space, usually occurs in patients when the rate of fluid formation exceeds the rate of fluid removal. The differential diagnosis of tuberculous pleurisy and malignant pleural effusion is a difficult task in high tuberculous prevalence areas. The aim of the present study was to identify novel biomarkers for the diagnosis of pleural fluid using proteomics technology. MATERIALS AND METHODS: We used samples from five patients with transudative pleural effusions for internal standard, five patients with tuberculous pleurisy, and the same numbers of patients having malignant effusions were enrolled in the study. We analyzed the proteins in pleural fluid from patients using a technique that combined two-dimensional liquid-phase electrophoresis and matrix assisted laser desorption/ionization-time of flight-mass spectrometry. RESULTS: We identified a total of 10 proteins with statistical significance. Among 10 proteins, trasthyretin, haptoglobin, metastasis-associated protein 1, t-complex protein 1, and fibroblast growth factor-binding protein 1 were related with malignant pleural effusions and human ceruloplasmin, lysozyme precursor, gelsolin, clusterin C complement lysis inhibitor, and peroxirexdoxin 3 were expressed several times or more in tuberculous pleural effusions. CONCLUSION: Highly expressed proteins in malignant pleural effusion were associated with carcinogenesis and cell growth, and proteins associated with tuberculous pleural effusion played a role in the response to inflammation and fibrosis. These findings will aid in the development of novel diagnostic tools for tuberculous pleurisy and malignant pleural effusion of lung cancer.

Progression of Tuberculous Pleurisy: From a Lymphocyte-Predominant Free-Flowing Effusion to a Neutrophil-Predominant Loculated Effusion / 결핵및호흡기질환

No abstract available.

Pleural tuberculosis in the state of Roraima, Brazil, between 2005 and 2013: quality of diagnosis / Tuberculose pleural no estado de Roraima no período de 2005-2013: qualidade diagnóstica

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.

Objetivo: Avaliar a qualidade dos diagnósticos e o perfil epidemiológico de portadores de tuberculose pleural no estado de Roraima, visando embasar tecnicamente o fomento e a aplicação de políticas públicas para o enfrentamento dessa doença. Métodos: Estudo transversal, desenhado para determinar a prevalência de formas pleurais da tuberculose em Roraima entre 2005 e 2013 e avaliar os critérios diagnósticos utilizados e seus determinantes. Este estudo foi baseado na revisão de dados secundários do Sistema de Informação de Agravos de Notificação, incluindo todos os casos notificados como tuberculose pleural no estado durante o período de estudo. Diagnósticos baseados em confirmação bacteriológica ou histopatológica foram definidos como de qualidade. Resultados: Dos 1.395 casos de tuberculose notificados no período do estudo, 116 (8,3%) foram da apresentação pleural, totalizando 38,9% das formas extrapulmonares na amostra. A taxa de incidência dessa apresentação clínica não acompanhou a tendência decrescente da forma pulmonar da doença no período. A prevalência de diagnósticos de qualidade encontrada foi de 28,5% (IC95%: 20,4-37,6%) e, na análise univariada, nenhuma variável explicativa dentre as características demográficas e clínicas coletadas do banco de dados tiveram um impacto significativo no desfecho (como variáveis explicativas). Conclusões: A qualidade dos diagnósticos na amostra estudada foi considerada insatisfatória. O acesso limitado a métodos diagnósticos específicos pode ter contribuído para esses resultados.

Tuberculosis pleural en un hospital del Noreste Argentino / Pleural tuberculosis in a hospital in Northeast Argentina

La tuberculosis (TB) pleural ocupa el primer lugar dentro de las localizaciones extrapulmonares. El objetivo de este trabajo fue estimar la proporción de TB pleural entre los casos de TB y caracterizar la forma de presentación, métodos de diagnóstico y evolución de los pacientes internados en el Servicio de Clínica Médica del hospital Ángela I. de Llano, Corrientes, Argentina, durante el período enero de 2011 a junio de 2014. Se realizó un estudio observacional y descriptivo. Fueron diagnosticados 10 pacientes con TB pleural. La edad media fue 48.5 ± 16.9 (16-63) años. El tiempo de evolución antes de la consulta fue 21.3 ± 11.6 (7-45) días. Todos fueron exudados unilaterales, con recuento celular de 2152 ± 687 (84-7000) células; 8 casos presentaron predominio linfocitario. El valor promedio de adenosina deaminasa (ADA) fue 92.7 ± 27.0 (60-150) UI/l. La baciloscopia del líquido pleural fue positiva en 4 casos; se obtuvo desarrollo de Mycobacterium tuberculosis en 3 casos. En el estudio histológico 3 presentaron granulomas caseificantes. Se registró un óbito. Si bien suele darse en hombres, de mediana edad, con un tiempo de evolución menor al mes, como un derrame pleural unilateral exudativo a predominio de linfocitos, el diagnóstico de certeza presenta sus limitaciones, por ende la clínica, la epidemiología, los estudios por imágenes, la anatomía patológica y los exámenes de laboratorio, como la determinación de los niveles de ADA, constituyen un aporte valioso para el diagnóstico.

Pleural tuberculosis ranks first in extrapulmonary sites. The aim of this study was to estimate the proportion pleural TB among TB cases, and characterize the presentation, diagnostic methods and outcomes of patients hospitalized in the Ángela I. de Llano hospital, Corrientes, Argentina, between January 1, 2011 and June 30, 2014. We performed a descriptive and observational study. Ten patients were diagnosed with TB pleural effusion. The mean age was 48.5 ± 16.9 (16-63) years. The average evolution time before the consultation was 21.3 ± 11.6 (7-45) days. All were unilateral, exudates, with cell count of 2152 ± 687 (84-7000) cells; 8 cases had lymphocyte predominance. The average value of adenosine deaminase determination (ADA) was 92.7 ± 27.0 (60-150) IU/l. The pleural effusion smear was positive in 4 cases; development of Mycobacterium tuberculosis was obtained in 3 cases; histologically, three presented caseating granulomas. One death was recorded. Although pleural TB usually occurs in male patients, middle-aged, as a unilateral exudative pleural effusion with lymphocytic predominance, with less than a month´s evolution, diagnostic certainty has its limitations, thus clinical suspicion, epidemiology, imaging, pathology and laboratory tests, and determination of adenosine deaminase levels, represent a valuable contribution to diagnosis.

Adenosina desaminase: uma enzima extraordinária e onipresente Adenosina desaminase: uma enzima extraordinária e onipresente / Adenosine deaminase: an extraordinary and omnipresent enzyme

Depois de introduzir os conceitos básicos da enzima adenosina desaminase (ADA), uma breve discussão sobre a estrutura, o mecanismo enzimático, terapia genética e potencial utilização terapêutica de inibidores de ADA são apresentados. O estudo da ADA é muito mais complexo do que simplesmente seu papel como biomarcador diagnóstico para tuberculose pleural que veio revolucionar o setor de diagnóstico na medicina clínica nos últimos anos. O aumento de sua atividade no líquido pleural, e em outros líquidos orgânicos, impede que o paciente na maioria dos casos com síndrome do derrame pleural por tuberculose seja submetido a procedimentos cirúrgicos invasivos com possíveis complicações potencialmente fatais AU.

After introducing the basic concepts of ADA, a brief discussion on the structure, enzymatic mechanism, gene therapy and potential therapeutic use of ADA inhibitors are presented. The study of the ADA is much more complex than simply its role as a biomarker for pleural tuberculosis that has revolutionized the diagnostic in clinical medicine in recent years. The increase in its activity in the pleural fluid, and other body fluids, prevents the patient in most cases with pleural effusion tuberculosis is subjected to invasive surgical procedures with possible life-threatening complications. AU

Tuberculosis extrapulmonar en el niño / Extrapulmonary tuberculosis in children

Pulmonary tuberculosis (TB) is the most common type of TB in children. Extrapulmonary tuberculosis is also prevalent (about 30-40 percent of cases) and it can occur in a variety of anatomical sites. This study presents a review of the literature on the main clinical manifestations of extrapulmonary tuberculosis in children, its diagnosis and treatment. At the end, some reflections on the importance of BCG for prevention are presented.

La tuberculosis (TB) pulmonar es el tipo más común de TB en niños. La tuberculosis extrapulmonar también es frecuente (alrededor de 30-40 por ciento de los casos) y se puede presentar en una gran variedad de sitios anatómicos. Se hace una revisión de la literatura sobre las principales manifestaciones clínicas extrapulmonares de la tuberculosis en niños, su diagnóstico y su tratamiento. Al final se hacen algunas reflexiones sobre la importancia de la BCG para su prevención.