Impact of Epstein-Barr virus serological status on clinical outcomes in adult patients with inflammatory bowel disease.

BACKGROUND: Little is known about the impact of Epstein-Barr virus (EBV) infection on clinical outcomes in adults with inflammatory bowel disease (IBD). AIM: To evaluate seroprevalence, seroconversion rate and complications associated with EBV infection in an adult IBD cohort attending a tertiary care hospital in Spain between 2006 and 2016. METHODS: EBV serological status was determined. In seronegative patients, the seroconversion rate was evaluated. The complications associated with primary and latent EBV infection are described. RESULTS: One thousand four hundred and eighty-three patients over the age of 17 were included in the study (mean age at EBV serological status determination was 48.3). Overall seroprevalence of EBV was 97.4% (95% CI: 96.6%-98.2%). The seroconversion rate was 29.7% (95% CI: 16.2-45.9) after a mean of 47.5 months. There were no differences in seroconversion rates between patients 35 years or younger and patients older than 35 years. A 66-year-old man, on treatment with thiopurines, developed lymphoma and a hemophagocytic syndrome during a primary EBV infection. Overall, six patients (one with primary infection and five with prior EBV infection) developed lymphoma. In three of five patients with lymphoma and thiopurine use, EBV was associated to the development of lymphoma. CONCLUSIONS: There is a small percentage of adults with IBD at risk of primary EBV infection. The risks of seroconversion and its complications remain through adulthood. Our results suggest that, when considering the use of thiopurines in IBD, the information on EBV serological status should be taken into account at any age.

High rates of tuberculin skin test positivity due to methotrexate therapy: False positive results?

RATIONALE: The tuberculin skin test (TST) and interferon ? release assays (IGRAs) are commonly used for latent tuberculosis infection (LTBI) screening. Unexpectedly high TST positivity rates have been reported in patients with rheumatic diseases, and methotrexate is frequently used in this population. We hypothesized that methotrexate use could be associated with false-positive TST results. OBJECTIVES: To investigate whether treatment with methotrexate and other factors are associated with false-positive TST results in patients with rheumatic diseases. METHODS: Prospective single-center study conducted between April 2013 and March 2016. Adult patients with rheumatic diseases were evaluated with a TST and two IGRAs for LTBI screening. We compared TST and IGRA results in patients treated and not treated with methotrexate and analyzed for factors associated with positive TST results. CONCLUSIONS: Our data suggest false-positive TST results associated with methotrexate therapy. Thus, we recommend against using the TST for LTBI screening in patients receiving methotrexate and the preferential use of IGRAs in such patients. MEASUREMENTS AND MAIN RESULTS: We studied 393 patients with rheumatic diseases, including ankylosing spondylitis (ASP, n = 90), rheumatoid arthritis (RA; n = 120), psoriatic arthritis (PA, n = 126), and other disorders (n = 57). The rate of TST positivity varied across the groups: ASP 22.2%, RA 25%, PA 35.7%, and other disorders (22.8%). Positivity rates were lower with IGRAs. Methotrexate use was associated with a statistically significant two-fold increase in the risk of a positive TST and a dose\x96 response relationship was observed. We found no statistically significant associations between methotrexate use and IGRA test positivity.

Micobacterias no tuberculosas. ¿Una amenaza emergente? / Non-Tuberculous Mycobacteria. An Emerging Threat?

Introducción y objetivo: Los aislamientos de micobacterias no tuberculosas (MNT) son cada vez más frecuentes. El objetivo principal de nuestro estudio fue conocer el número y la variedad de especies de MNT en nuestra región, su distribución según el origen de la muestra, y la edad y sexo de los pacientes; asimismo, analizar pormenorizadamente los aislamientos clínicamente significativos. Metodología: Estudio prospectivo que incluye todas las MNT aisladas en Asturias durante el período 2005-2012. Las muestras se procesaron siguiendo directrices internacionalmente aceptadas. Para el tratamiento estadístico de los datos se utilizaron tablas de contingencia 2 × 2 aplicando el test exacto de Fisher. Resultados: Se aislaron 3.284 micobacterias: 1.499 Mycobacterium tuberculosis complex (MTB) y 1.785 MNT. A lo largo del estudio se incrementaron los aislamientos de MNT y se redujeron los de MTB. Los aislamientos de MNT fueron más numerosos en hombres que en mujeres (p <0,001). M. gordonae, la especie más frecuentemente aislada, no originó enfermedad en ningún caso. El aislamiento fue clínicamente significativo en 212 pacientes (17,1%), siendo M. kansasii y M. avium las especies que más frecuentemente causaron enfermedad. La diferencia de aislamientos de M. kansasii entre mujeres y hombres fue estadísticamente significativa (p < 0,01). Conclusiones: En nuestro estudio, los aislamientos de MNT se incrementaron un 35%, frente a un descenso del 21% de los casos de MTB. Tanto los aislamientos de MNT como los casos clínicamente significativos fueron más frecuentes en hombres. Solo un 17,1% de las MNT aisladas, principalmente M. avium complex (MAC) y M. kansasii, ocasionaron enfermedad

Introduction and objective: Non-tuberculous mycobacteria (NTM) isolates are becoming more common. The main objective of our study was to establish the number and diversity of NTM species in our region and their distribution according to the source sample, age and gender of the patients, and to analyse clinically significant isolates. Methodology: Prospective study of all NTM isolated in Asturias from 2005 to 2012. Samples were processed following internationally accepted guidelines. Statistical analysis was based on Fisher's exact test for 2 × 2 contingency tables. Results: A total of 3,284 mycobacteria were isolated: 1,499 Mycobacterium tuberculosis complex (MTB) and 1,785 NTM. During the study, NTM isolation rates increased while MTB isolation decreased. NTM were more frequent in men (P < .001). M. gordonae was the most frequently isolated species but did not cause disease in any case. NTM isolates from 212 patients were associated with clinically significant disease (17.1%). M. kansasii and M. avium were most commonly associated with disease. The number of M. kansasii isolates from men was statistically significant (P < .01). Conclusions: In our study, NTM isolates increased by 35%, compared with a 21% decline in cases of MTB. Both isolation of NTM and clinically significant cases were more common in men. Only 17.1% of NTM isolates were associated with disease, most commonly M. avium complex and M. kansasii

Non-Tuberculous Mycobacteria. An Emerging Threat? / Micobacterias no tuberculosas. ¿Una amenaza emergente?

INTRODUCTION AND OBJECTIVE: Non-tuberculous mycobacteria (NTM) isolates are becoming more common. The main objective of our study was to establish the number and diversity of NTM species in our region and their distribution according to the source sample, age and gender of the patients, and to analyse clinically significant isolates. METHODOLOGY: Prospective study of all NTM isolated in Asturias from 2005 to 2012. Samples were processed following internationally accepted guidelines. Statistical analysis was based on Fisher's exact test for 2×2 contingency tables. RESULTS: A total of 3,284 mycobacteria were isolated: 1,499 Mycobacterium tuberculosis complex (MTB) and 1,785 NTM.During the study, NTM isolation rates increased while MTB isolation decreased. NTM were more frequent in men (P<.001). M.gordonae was the most frequently isolated species but did not cause disease in any case. NTM isolates from 212 patients were associated with clinically significant disease (17.1%). M.kansasii and M.avium were most commonly associated with disease. The number of M.kansasii isolates from men was statistically significant (P<.01). CONCLUSIONS: In our study, NTM isolates increased by 35%, compared with a 21% decline in cases of MTB. Both isolation of NTM and clinically significant cases were more common in men. Only 17.1% of NTM isolates were associated with disease, most commonly M.avium complex and M.kansasii.

Utilidad de los métodos fenotípicos y genotípicos en el estudio de resistencias de Mycobacterium tuberculosis a fármacos antituberculosos de primera línea / Utility of phenotypic and genotypic testing in the study of Mycobacterium tuberculosis resistance to first-line anti-tuberculosis drugs

Objetivo: Conocer la utilidad de las técnicas moleculares para el diagnóstico de resistencias y la situación de las resistencias a fármacos de primera línea en nuestra área geográfica. Material y método: Desde 2004 a 2013, 1.889 cepas de Mycobacterium tuberculosis complex aisladas en Asturias, España, fueron estudiadas mediante pruebas de sensibilidad fenotípicas (directrices del Clinical and Laboratory Standards Institute) y moleculares (INNOLiPA RIF-TB©; GenotypeMDRplus©; GenotypeMDRsl©). Resultados: Mil setecientas cincuenta y nueve cepas (94,52%) eran sensibles a todos los fármacos de primera línea y 102 cepas (5,48%) presentaban alguna resistencia: 81 cepas (4,35%) a un solo fármaco, 14 (0,75%) con polirresistencia y 7 (0,37%) multirresistentes (resistencia a rifampicina e isoniacida). En total hubo 137 resistencias a fármacos: 60 a isoniacida (3,22%), 7 a rifampicina (0,37%), 9 a pirazinamida (0,48%), 11 a etambutol (0,59%) y 50 a estreptomicina (2,68%). El 75,9% de las mutaciones detectadas (63/83) se correlacionaron con resistencia; mientras que un 24,09% de las mutaciones detectadas (20/83) no implicaban resistencia, correspondiendo 16 a una mutación silente en el codón 514 del gen rpoB. Entre un 0 y un 90% de cepas, dependiendo del fármaco que se considere, eran resistentes aunque no presentaban mutaciones en los genes incluidos en los sistemas comerciales. Conclusiones: Las técnicas moleculares resultan muy útiles sobre todo por la rapidez en la obtención de resultados, aunque estos deben confirmarse con las pruebas de sensibilidad fenotípicas de referencia. La tasa de resistencias a fármacos en nuestra región es baja y los casos de multirresistencia (0,37%) son esporádicos

Objective: To determine the utility of molecular techniques in the diagnosis of resistance and the extent of resistance to first-line drugs in our region. Material and method: From 2004 to 2013, 1,889 strains of Mycobacterium tuberculosis complex isolated in Asturias, Spain, were studied using phenotypic (Clinical and Laboratory Standards Institute guidelines) and molecular (INNOLiPA RIF-TB©; GenotypeMDRplus©; GenotypeMDRsl©) sensitivity tests. Results: 1,759 strains (94.52%) were sensitive to all first-line drugs, and 102 strains (5.48%) showed some resistance: 81 strains (4.35%) were resistant to 1 single drug, 14 (0.75%) were polyresistant, and 7 (0.37%) were multiresistant (resistant to rifampicin and isoniazid). In total, 137 resistances were identified: 60 to isoniazid (3.22%), 7 to rifampicin (0.37%), 9 to pyrazinamide (0.48%), 11 to ethambutol (0.59%), and 50 to streptomycin (2.68%). Of the mutations detected, 75.9% (63/83) correlated with resistance, while 24.09% of mutations detected (20/83) were not associated with resistance; 16 of these involved a silent mutation at codon 514 of the rpoB gene. Between 0 and 90% of strains, depending on the drug under consideration, were resistant even when no gene mutations were detected using marketed systems. Conclusions: Molecular techniques are very useful, particularly for obtaining rapid results, but these must be confirmed with standard phenotypic sensitivity testing. The rate of resistance in our region is low and multi-drug resistant cases (0.37%) are sporadic

Utility of Phenotypic and Genotypic Testing in the Study of Mycobacterium tuberculosis Resistance to First-Line Anti-Tuberculosis drugs. / Utilidad de los métodos fenotípicos y genotípicos en el estudio de resistencias de Mycobacterium tuberculosis a fármacos antituberculosos de primera línea.

OBJECTIVE: To determine the utility of molecular techniques in the diagnosis of resistance and the extent of resistance to first-line drugs in our region. MATERIAL AND METHOD: From 2004 to 2013, 1,889 strains of Mycobacterium tuberculosis complex isolated in Asturias, Spain, were studied using phenotypic (Clinical and Laboratory Standards Institute guidelines) and molecular (INNOLiPA RIF-TB©; GenotypeMDRplus©; GenotypeMDRsl©) sensitivity tests. RESULTS: 1,759 strains (94.52%) were sensitive to all first-line drugs, and 102 strains (5.48%) showed some resistance: 81 strains (4.35%) were resistant to 1 single drug, 14 (0.75%) were polyresistant, and 7 (0.37%) were multiresistant (resistant to rifampicin and isoniazid). In total, 137 resistances were identified: 60 to isoniazid (3.22%), 7 to rifampicin (0.37%), 9 to pyrazinamide (0.48%), 11 to ethambutol (0.59%), and 50 to streptomycin (2.68%). Of the mutations detected, 75.9% (63/83) correlated with resistance, while 24.09% of mutations detected (20/83) were not associated with resistance; 16 of these involved a silent mutation at codon 514 of the rpoB gene. Between 0 and 90% of strains, depending on the drug under consideration, were resistant even when no gene mutations were detected using marketed systems. CONCLUSIONS: Molecular techniques are very useful, particularly for obtaining rapid results, but these must be confirmed with standard phenotypic sensitivity testing. The rate of resistance in our region is low and multi-drug resistantcases (0.37%) are sporadic.