Jordi Solsona

Diagnosing TB infection in children: analysis of discordances using in vitro tests and the tuberculin skin test

The aim of the present study was to compare the performance of the interferon (IFN)-&ggr; tests (QuantiFERON®-TB Gold In-Tube (QFT-G-IT) and T-SPOT®.TB) with the tuberculin skin test (TST) in diagnosing tuberculosis (TB) infection in children, and to analyse discordant results. This was a prospective study including 98 children from contact-tracing studies and 68 children with TST indurations ≥5 mm recruited during public health screenings. Positive IFN-&ggr; tests results were associated with risk of exposure (p<0.0001). T-SPOT.TB was positive in 11 (78.6%) out of 14 cases with active TB and QFT-G-IT in nine (64.3%) out of 14 cases. Sensitised T-cells against Mycobacterium avium were detected in six out of 12 children not vaccinated with bacille Calmette-Guérin (BCG), a TST induration 5–9 mm in diameter and both IFN-&ggr; tests negative. In concordant IFN-&ggr; tests results, a positive correlation was found (p = 0.0001) between the number of responding cells and the amount of IFN-&ggr; released. However, in discordant IFN-&ggr; tests results this correlation was negative (p = 0.371): an increase in the number of spot-forming cells correlated with a decrease in the amount of IFN-&ggr; released. The use of IFN-&ggr; tests is helpful for the diagnosis of TB infection, avoiding cross-reactions with BCG immunisation and nontuberculous mycobacterial infections. The analysis of highly discordant results requires further investigation to elucidate possible clinical implications.

Immunogenicity of 60 novel latency-related antigens of Mycobacterium tuberculosis

The aim of our work here was to evaluate the immunogenicity of 60 mycobacterial antigens, some of which have not been previously assessed, notably a novel series of in vivo-expressed Mycobacterium tuberculosis (IVE-TB) antigens. We enrolled 505 subjects and separated them in individuals with and without latent tuberculosis infection (LTBI) vs. patients with active tuberculosis (TB). Following an overnight and 7 days stimulation of whole blood with purified recombinant M. tuberculosis antigens, interferon-γ (IFN-γ) levels were determined by ELISA. Several antigens could statistically significantly differentiate the groups of individuals. We obtained promising antigens from all studied antigen groups [dormancy survival regulon (DosR regulon) encoded antigens; resuscitation-promoting factors (Rpf) antigens; IVE-TB antigens; reactivation associated antigens]. Rv1733, which is a probable conserved transmembrane protein encoded in DosR regulon, turned out to be very immunogenic and able to discriminate between the three defined TB status, thus considered a candidate biomarker. Rv2389 and Rv2435n, belonging to Rpf family and IVE-TB group of antigens, respectively, also stood out as LTBI biomarkers. Although more studies are needed to support our findings, the combined use of these antigens would be an interesting approach to TB immunodiagnosis candidates.

Predicting the Development of Tuberculosis with the Tuberculin Skin Test and QuantiFERON Testing

RATIONALE The identification of patients with latent tuberculosis infection, who are at higher risk to develop active disease, is an important component of disease control. OBJECTIVES We aim to compare the usefulness of the QuantiFERON-TB Gold in-tube assay and the tuberculin skin test to predict the development of active tuberculosis during follow-up, using positive and negative predictive values, positive likelihood ratios, and stratified level of risk. METHODS The study included contacts of tuberculosis cases diagnosed between 2007 and 2009. All contacts included were from the first circle of exposure. Tuberculin skin test and QuantiFERON test were performed and a chest radiograph was obtained during the contacts study. MEASUREMENTS AND MAIN RESULTS A total of 1,335 contacts were followed up for 4 years: a smear-positive index case was identified for 937 contacts, of whom 15 developed active tuberculosis and had initially presented with positive tuberculin skin test/QuantiFERON results, a normal chest radiograph, and no symptoms. The positive predictive value was 4% for QuantiFERON and 2% for the tuberculin skin test (when ≥5 mm). The probability of developing active disease was 2.36 times higher with a positive QuantiFERON, and 1.3 times higher with a positive tuberculin skin test. The positive predictive value was 17%, and the positive likelihood ratio was 7.53 for untreated contacts with a positive QuantiFERON. Stratifying according to initial QuantiFERON results showed a 6.36 times higher risk of developing active tuberculosis for patients with a QuantiFERON result greater than or equal to 10 IU/ml. Among bacillus Calmette-Guérin-vaccinated patients, a tuberculin skin test induration greater than or equal to 15 mm correlated better with a positive QuantiFERON. CONCLUSIONS QuantiFERON results were more accurate than tuberculin skin test results in predicting tuberculosis. Although all contacts with QuantiFERON-positive results are at risk of developing tuberculosis, those with a tuberculin skin test induration greater than or equal to 15 mm and QuantiFERON greater than or equal to 10 IU/ml are at highest risk. This has important implications in the clinical management of tuberculosis contacts.

Impacto de la disponibilidad de un servicio externo de medicina nuclear en la aplicación de la biopsia del ganglio centinela en cirugía del cáncer de mama

Resumen Introduccion La realizacion de la tecnica de la biopsia selectiva del ganglio centinela (BSGC) en el tratamiento del cancer de mama requiere disponer de un servicio de medicina nuclear (SMN) y de la validacion de su tecnica. El objetivo del presente estudio es analizar la posibilidad de realizar esta tecnica con un SMN externo ya validado, y estudiar su impacto en la indicacion de la linfadenectomia axilar radical (LAR) y en la estancia postoperatoria. Pacientes y metodos Estudio prospectivo en una cohorte de pacientes con cancer de mama a partir de la implantacion en nuestro centro de la tecnica de la BSGC gracias a la colaboracion de un SMN externo que realizaba la linfogammagrafia y la deteccion del ganglio centinela (GC), en tanto que su identificacion intraoperatoria se llevaba a cabo mediante una sonda portatil. Se analiza la viabilidad del proyecto y su impacto clinico tomando como resultados finales la disminucion del numero de linfadenectomias y la estancia hospitalaria. Resultados Se ha tratado a 196 pacientes, con 201 carcinomas de mama. Las intervenciones mayoritarias fueron la tumorectomia (TC) con BSGC en 124 casos (62%), y la TC con BSGC y LAR en 62 casos (31%). La visualizacion del GC en la linfogammagrafia se obtuvo en 187 de 201 casos (93,1%) y se ha detectado el GC durante la intervencion en 182 de los 187 (97,4%) casos. La deteccion de GC en la cadena mamaria interna se ha producido en 23 de los 201 casos (11,4%). Se ha evitado la LAR en 131 de los 201 casos (65%). La diferencia de dias de ingreso postoperatorio con o sin LAR fue de una media de 1,8 dias (3,1 frente a 1,3; p Conclusiones La tecnica de BSGC ha sido factible con la colaboracion de un SMN externo; se evito el 65% de las LAR y disminuyo la estancia media en 1,8 dias.

Mastopatía diabética en diabetes mellitus tipo 2

La mastopatia diabetica es una entidad muy poco conocida y, por ello, poco descrita que puede confundirse facilmente con carcinoma mamario. Ha sido descrita principalmente en pacientes con diabetes mellitus tipo 1 y, en mucho menor medida, otras endocrinopatias. En este articulo se muestra un caso clinico en el que la mastopatia diabetica se encuentra asociada a diabetes mellitus tipo 2 y presenta una evolucion muy rapida en muy poco tiempo. El gran desconocimiento de esta entidad puede llevar a multitud de actuaciones clinicas equivocas. Al no reconocer histologicamente la lesion y carecer de datos clinicos de sospecha, es posible emitir un diagnostico negativo de neoplasia. se puede juzgar de erronea la toma de muestras y requerir una nueva prueba innecesaria. Unicamente sospechandola se puede llegar a un diagnostico correcto y a la actuacion clinica adecuada. Los resultados de las pruebas diagnosticas son inespecificos, y la biopsia con aguja gruesa es la clave diagnostica.

Monitoring changes in anti-tuberculosis treatment: associated factors determined at the time of diagnosis.

OBJECTIVES To determine predictive factors for changes in standard anti-tuberculosis chemotherapy at the time of diagnosis. METHODS A prospective study was performed among tuberculosis (TB) patients treated at specialised centres during 2008-2009. Treatment outcome was monitored per standard guidelines. Treatment was considered successful if the patient was cured or completed treatment. Factors associated with treatment modification were analysed at the bivariate and multivariate levels using logistic regression. RESULTS A total of 427 patients were included in the study. The initial standard treatment regimen was retained for 249 patients (58.3%), extended to 9 months for 36 (8.4%) and changed for 142 (33.3%). Factors associated with a change of regimen at the multivariate level were female sex, age ≥ 50 years, human immunodeficiency virus infection, comorbidities, alcoholism, hospitalisation and culture-positive sputum. Drug resistance and toxicity were analysed independently. Treatment outcome was successful in 97.2% of cases without a regimen change and in 87.3% of those with a changed regimen (P < 0.001). CONCLUSION Factors associated with changes in the initial anti-tuberculosis regimen should be considered for rigorous follow-up. Results obtained through individualised treatment provided by specialists were good despite the complexity of the cases treated.