Development and Evaluation of an NTM-IGRA to Guide Pediatric Lymphadenitis Diagnosis.

BACKGROUND: Diagnosis of nontuberculous mycobacteria (NTM) infections remains a challenge. In this study, we describe the evaluation of an immunological NTM-interferon (IFN)-γ release assay (IGRA) that we developed using glycopeptidolipids (GPLs) as NTM-specific antigens. METHODS: We tested the NTM-IGRA in 99 samples from pediatric patients. Seventy-five were patients with lymphadenitis: 25 were NTM confirmed, 45 were of unknown etiology but compatible with mycobacterial infection and 5 had lymphadenitis caused by an etiologic agent other than NTM. The remaining 24 samples were from control individuals without lymphadenitis (latently infected with M. tuberculosis , uninfected controls and active tuberculosis patients). Peripheral blood mononuclear cells were stimulated overnight with GPLs. Detection of IFN-γ producing cells was evaluated by enzyme-linked immunospot assay. RESULTS: NTM culture-confirmed lymphadenitis patient samples had a significantly higher response to GPLs than the patients with lymphadenitis of unknown etiology but compatible with mycobacterial infection ( P < 0.001) and lymphadenitis not caused by NTM ( P < 0.01). We analyzed the response against GPLs in samples from unknown etiology lymphadenitis but compatible with mycobacterial infection cases according to the tuberculin skin test (TST) response, and although not statistically significant, those with a TST ≥5 mm had a higher response to GPLs when compared with the TST <5 mm group. CONCLUSIONS: Stimulation with GPLs yielded promising results in detecting NTM infection in pediatric patients with lymphadenitis. Our results indicate that the test could be useful to guide the diagnosis of pediatric lymphadenitis. This new NTM-IGRA could improve the clinical handling of NTM-infected patients and avoid unnecessary misdiagnosis and treatments.

Sumario ejecutivo de la guía de práctica clínica sobre el uso de las pruebas de liberación de interferón-gamma para el diagnóstico de infección tuberculosa / Executive Summary of the Guidelines for the Use of interferon-gamma Release Assays in the Diagnosis of Tuberculosis Infection

El uso de las pruebas de liberación de interferón-gamma para el diagnóstico de la infección tuberculosa está muy generalizado en España. Sin embargo, no se ha alcanzado un consenso respecto a su aplicación en situaciones clínicas específicas. Con el fin de redactar una guía de empleo en la práctica clínica, un grupo de expertos que incluyó a especialistas en enfermedades infecciosas, enfermedades respiratorias, microbiología, pediatría y medicina preventiva, junto con un experto en metodología, efectuaron una búsqueda sistemática en la literatura, sintetizaron los resultados, calificaron la calidad de las evidencias y formularon recomendaciones de acuerdo con la metodología Grading of Recommendations of Assessment Development and Evaluations. Este documento es una guía basada en la evidencia para el empleo de las pruebas de liberación de interferón-gamma en el diagnóstico de la infección tuberculosa en pacientes en riesgo de padecer tuberculosis o en los que se sospeche enfermedad activa. La guía será aplicable tanto en atención primaria y especializada como en salud pública

Interferon-gamma release assays are widely used for the diagnosis of tuberculosis infection in Spain. However, there is no consensus on their application in specific clinical scenarios. To develop a guide-line for their use, a panel of experts comprising specialists in infectious diseases, respiratory diseases, microbiology, pediatrics and preventive medicine, together with a methodologist, conducted a systematic literature search, summarized the findings, rated the quality of the evidence, and formulated recommendations following the Grading of Recommendations of Assessment Development and Evaluations methodology. This document provides evidence-based guidance on the use of interferon-gamma release assays for the diagnosis of tuberculosis infection in patients at risk of tuberculosis or suspected of having active disease. The guidelines will be applicable to specialist and primary care, and public health

Executive summary of the guidelines for the use of interferon-gamma release assays in the diagnosis of tuberculosis infection / Sumario Ejecutivo de la Guía de Práctica Clínica sobre el uso de las pruebas de liberación de interferón-gamma para el diagnóstico de infección tuberculosa

Interferon-gamma release assays are widely used for the diagnosis of tuberculosis infection in Spain. However, there is no consensus on their application in specific clinical scenarios. To develop a guideline for their use, a panel of experts comprising specialists in infectious diseases, respiratory diseases, microbiology, pediatrics and preventive medicine, together with a methodologist, conducted a systematic literature search, summarized the findings, rated the quality of the evidence, and formulated recommendations following the GRADE (Grading of Recommendations of Assessment Development and Evaluations) methodology. This document provides evidence-based guidance on the use of interferon-gamma release assays for the diagnosis of tuberculosis infection in patients at the risk of tuberculosis or suspected of having active disease. The guidelines will be applicable to specialist and primary care, and public health

Las técnicas de detección in vitro de interferón-gamma (IGRA, del inglés interferon-gamma release assays), están ampliamente implantadas para el diagnóstico de infección tuberculosa en España. Sin embargo, no hay consenso sobre su aplicación en diferentes escenarios clínicos. Para desarrollar una guía de práctica clínica sobre su uso, un grupo de trabajo compuesto por especialistas en enfermedades infecciosas, neumología, microbiología, pediatría y medicina preventiva, junto con un metodólogo, llevaron a cabo una búsqueda sistemática de la literatura, sintetizaron la evidencia y gradaron su calidad, y formularon las recomendaciones siguiendo el método GRADE (Grading of Recommendations of Assessment Development and Evaluations). Este documento proporciona una guía basada en la evidencia para el uso de los IGRA para el diagnóstico de infección tuberculosa en pacientes en riesgo de tuberculosis o con sospecha de enfermedad activa. Esta guía es aplicable en la atención especializada y primaria, y salud pública

Estudio de los brotes de tuberculosis que han generado informes epidemiológicos en Cataluña (1998-2002) / Study of Tuberculosis Outbreaks Reported in Catalonia, 1998-2002

Objetivo: Analizar las características de los brotes de tuberculosis (TB) estudiados por los servicios de vigilancia epidemiológica de Cataluña. Métodos: Estudio descriptivo de los brotes de 1998-2002 que disponían de informe epidemiológico. Se definió como brote epidémico cuando había 3 o más casos asociados en un año. En 2 regiones sanitarias se compararon los brotes detectados con los que además tenían informes. Resultados: Se analizaron 27 brotes y la mayoría (n = 19; el 70%) ocurrió en el ámbito familiar. Un total de 22 brotes fueron declarados a partir del caso índice auténtico y 5 a partir de un caso secundario. La incidencia media anual de brotes fue de 0,40/100.000 habitantes. La mayoría fueron generados por varones de 16 a 40 años, con lesiones cavitarias y un importante retraso diagnóstico. Los 27 brotes provocaron 69 casos secundarios. Se observó que a mayor retraso diagnóstico correspondía mayor número de casos secundarios (p = 0,08). En las 2 regiones sanitarias analizadas sólo se realizó informe epidemiológico en 2 de los 14 brotes detectados (14,4%). Conclusiones: Los brotes de TB son frecuentes pero poco investigados, y el retraso diagnóstico se asoció al tamaño del brote. Se deben priorizar el diagnóstico rápido de los enfermos, el estudio de contactos y la realización de un informe sanitario en cada brote detectado

Objective: To analyze the characteristics of tuberculosis outbreaks declared under vigilance programs in Catalonia. Methods: Descriptive study of outbreaks from 1998 through 2002 for which reports were available. An outbreak was defined as 3 or more associated cases appearing within a year. For 2 health care regions, outbreaks for which there were full surveillance reports with contact tracing were compared to outbreaks identified but which had not been fully reported. Results: Twenty-seven outbreaks were analyzed. Nineteen (70%) occurred within families. A total of 22 outbreaks were declared upon identification of the true index case and 5 upon detection of secondary cases.The mean annual incidence of outbreaks was 0.40/100 100 inhabitants. Most cases were in males 16 to 40 years of age and involved cavitary lesions and a clinically significant diagnostic delay. Twenty-seven outbreaks caused 69 secondary cases. A longer diagnostic delay was seen to correspond to a larger number of secondary cases (P=.08). In the 2 health care regions analyzed, full surveillance reports with contact tracing were issued for 2 of the 14 outbreaks detected (14.4%). Conclusions: Tuberculosis outbreaks are common but investigative follow-up is scarce. The size of the outbreak is related to the length of diagnostic delay. Rapid diagnosis, contact tracing, and the issuance of a public health report should be priorities in all outbreaks detected