Tuberculosis latente: diagnóstico y tratamiento actual / Latent tuberculosis: current diagnosis and treatment

Resumen La infección tuberculosa latente (TL) afecta al 23% de la población y constituye un reservorio de tuberculosis (TBC) ya que 10% progresa hacia una TBC. La TL se reconoce por pruebas como la tuberculina (PPD o TST) y los ensayos de liberación de Interferón gama (IGRAs). La sensibilidad de IGRAs (versión Quantiferon TB Gold plus) es 94% y del PPD 77%. La especificidad del Quantiferon TB Gold Plus es 97% y del PPD 68%. El valor predictivo de progresión a TBC activa de estas pruebas es bajo (PPD: 1,5%, IGRAs: 2,7%) pero mejora en personas de alto riesgo de contraer TBC (PPD: 2,4%, IGRAs: 6,8%). Las personas con pruebas negativas que posteriormente presentan viraje (prueba positiva) tienen mayor riesgo de progresión a TBC activa. Estas pruebas son útiles en el seguimiento de contactos intradomiciliarios, extranjeros de países con altas tasas de TBC, inmunosuprimidos, enfermedad renal crónica, diabetes, silicosis y secuelas pulmonares de TBC no tratada. En la terapia de TL se utiliza isoniazida (H) auto-administrada por plazos de 6 a 12 meses con eficacia protectora de 60% y riesgo de toxicidad hepática de 2% pero con baja adherencia (50-70%). La asociación de H con rifapentina en dosis única semanal durante 12 semanas tiene eficacia de 81%, adherencia de 82% y baja toxicidad hepática (0,4%). Nuevos biomarcadores de TL y vacunas que mejoren la inmunidad en TL se encuentran en estudio. El tratamiento de la TL puede reducir la incidencia de TBC a largo plazo.

Latent tuberculosis infection (LT) affects 23% of the population and constitutes a reservoir of tuberculosis (TB) as 10% progresses to TB. LT is recognized by tests such as tuberculin (PPD or TST) and Interferon gamma release assays (IGRAs). The sensitivity of IGRAs (Quantiferon TB Gold plus version) is 94% and PPD 77%. The specificity of Quantiferon TB Gold Plus is 97% and PPD 68%. The predictive value of progression to active TB of these tests is low (PPD: 1.5%, IGRAs: 2.7%) but improves in people at high risk of contracting TB (PPD: 2.4%, IGRAs: 6.8%). People with negative tests who subsequently turn around (positive) have a higher risk of progression to active TB. These tests are useful in the follow-up of intra-household contacts, foreigners from countries with high rates of TB, immunosuppressed, chronic kidney disease, diabetes, silicosis and pulmonary sequelae of untreated TB. In LT therapy, self-administered isoniazid (H) is used for periods from 6 to 12 months with protective efficacy of 60% and risk of liver toxicity of 2%, but with low adherence (50-70%). The association of H with rifapentine in a single weekly dose for 12 weeks has efficacy of 81%, adherence of 82% and low liver toxicity (0.4%). New LT biomarkers and vaccines that improve immunity in LT are under study. Treatment of LT may reduce the incidence of TB in the long term.

Comparison between Diagnostic Yield of Pleural Fluid ELISPOT and Thoracoscopic Guided Pleural Biopsy in Undiagnosed Pleural Effusion

Context: Despite recent advances in the available diagnostic modalities, diagnosis of pleural tuberculosis remains a challenge because of the low yield of conventional methods. Pleural biopsy is the gold standard for confirmation of diagnosis, which is invasive and cumbersome. The concentration of mycobacterial peptide-specific activated lymphocytes at the site of infection can be utilized as the basis for using IGRA (interferon-gamma release assays) based evaluation of undiagnosed exudative pleural effusions.  Aim: To evaluate the performance of IGRA (Enzyme-linked Immunospot (ELISPOT) in pleural fluid for the diagnosis of pleural tuberculosis in histopathologically confirmed cases. Settings and Design: A prospective observational study compared the utility of ELISPOT with thoracoscopy guided pleural biopsies for the diagnosis of tubercular pleural effusions. Methods and Material: Forty-two consecutive cases of undiagnosed pleural effusions were enrolled and subjected to thoracoscopy guided pleural biopsy. Thirteen patients were confirmed to have tuberculosis, 27 had malignancy, and 2 had normal pleura. A total of 1x103 pleural fluid mononuclear cells (PFMCs) were cultured in the presence of early secretory antigenic target-6 (ESAT-6) and culture filtrate protein-10 (CFP-10) for 24 hours. The individual spots were then counted using an automated analyzer ELISPOT reader system.  Results: The number of spots developed in the pleural fluid was significantly higher in tubercular pleural effusions as compared to non-tubercular effusions (CFP-10:154.76±14.61 vs 49.24±8.9; ESAT-6: 150.3±17.27 v/s 45.34±8.23, p<0.001). At a cut-off value of more than 67 spots taken as positive for tuberculosis, the sensitivity of the test was 100% (95% CI 75.29% to 100.00%), specificity was 96.5% (95 % CI 82.24% to 99.91%), positive predictive value was 92.86% (95 % CI 65.45% to 98.89%) and negative predictive value was 100%.  Conclusions: ELISPOT can be a useful non-invasive test for the evaluation of undiagnosed pleural effusions and making a diagnosis of pleural tuberculosis with confidence.

Interferon Gamma Release Assays from T Lymphocytes in Patients with Tuberculosis Infection / 现代检验医学杂志

Objective To explore the application value of interferon gamma release assay (IGRAs)in the clinical detection of tuberculosis infected T lymphocytes.Methods Used IGRAs method to detect the 11 968 outpatients and hospitalized pa-tients from 2013 to 2016 with tuberculosis screening.According to the distribution department analysis,also of positive case detection according to age and gender were analysis and comparison and analysis on the uncertainty of results,different methods were compared.Results Among the 11 968 cases,2 048 cases were positive,the positive rate was 17.11%,and the uncertain result was 107 cases,which accounted for 0.89% of the total number.The positive rates from 2013 to 2016 were 19.65%,21.35%,15.82% and 13.56%,respectively.In the detection and screening of pulmonary and pulmonary tuberculo-sis,the positive rates of the department of respiration,the digestive department,the oncology department,the department of neurology and the department of gynecology were 22.07%,20.27%,23.38%,12.84% and 11.86%,respectively.In the positive screening,men accounted for 62.11%,women accounted for 37.89%,men were significantly higher than women.By age group,was less than or equal to 15,16~25,26~45,46~65,was more than orequal to 66 years old,positive rate were 1.96%,18.51%,16.54%,21.25% and 25.73%,respectively.Analysis of uncertain outcome data,department of respira-tion,rheumatism,department of hematology,accounted for 1.99% and 2.35%,respectively.Compared with other laboratory methods,the IGRAs method had obvious advantages.Conclusion Tuberculosis occurs in various body organs,there were differences in gender and age of Mycobacterium tuberculosis infection.IGRAs is a sensitive and specific method for rapid de-tection of Mycobacterium tuberculosis infection,although it can not be used as a diagnostic indicator,but in patients with suspected tuberculosis IGRAs has a larger clinical application value for the further diagnosis of disease.