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Resumen Objetivo El objetivo del estudio fue conocer la tendencia de las variables relacionadas con la tuberculosis (TB) en Espana a partir del registro del Programa Integrado de Investigacion en Tuberculosis (PII-TB) de la Sociedad Espanola de Neumologia y Cirugia Toracica (SEPAR) y evaluar el PII-TB mediante indicadores relacionados con sus objetivos cientificos. Metodo Estudio transversal multicentrico de base poblacional de casos nuevos de TB registrados prospectivamente por el PII-TB entre 2006 y 2016. La tendencia temporal de variables cuantitativas se realizo mediante un modelo de regresion lineal y las cualitativas mediante la prueba de χ2 de tendencia lineal. Resultados Se analizaron 6.892 casos de TB con una mediana anual de 531. La tendencia general fue significativamente decreciente en mujeres, inmigrantes, privados de libertad y en tratados inicialmente con 3 farmacos. Se incrementaron significativamente la tendencia de grupos de 40 -50 anos y > 50 anos, primera atencion por especialista de zona, hospitalizacion, retraso diagnostico, localizacion diseminada y extrapulmonar unica, cultivo (+), realizacion de antibiogramas, resistencia a farmacos, tratamiento directamente observado, prolongacion del tratamiento y muerte por otra causa. Los objetivos cientificos del PII-TB que incrementaron significativamente fueron las publicaciones alcanzando un maximo de 8 en 2016 y con un factor de impacto total de 49,664, y tambien mejoraron los proyectos iniciados anualmente, presentaciones en congresos y las tesis o tesinas. Conclusiones El PII-TB proporciona informacion relevante sobre la TB y sus factores asociados en Espana. Se ha formado un amplio equipo de investigadores y se han detectado aspectos cientificos positivos y otros mejorables.

Objective The objective of the study was to determine the trend of variables related to tuberculosis (TB) from the Integrated Tuberculosis Research Program (PII-TB) registry of the Spanish Society of Pulmonology and Thoracic Surgery (SEPAR), and to evaluate the PII-TB according to indicators related to its scientific objectives. Method Cross-sectional, population-based, multicenter study of new TB cases prospectively registered in the PII-TB between 2006 and 2016. The time trend of quantitative variables was calculated using a lineal regression model, and qualitative variables using the χy test for lineal trend. Results A total of 6,892 cases with an annual median of 531 were analyzed. Overall, a significant down-ward trend was observed in women, immigrants, prisoners, and patients initially treated with 3 drugs. Significant upward trends were observed in patients aged 40−50 and >50 years, first visit conducted by a specialist, hospitalization, diagnostic delay, disseminated disease and single extrapulmonary location, culture(+), drug susceptibility testing performed, drug resistance, directly observed treatment, prolonged treatment, and death from another cause. The scientific objectives of the PII-TB that showed a significant upward trend were publications, which reached a maximum of 8 in 2016 with a total impact factor of 49.664, numbers of projects initiated annually, presentations at conferences, and theses. Conclusions PII-TB provides relevant information on TB and its associated factors in Spain. A large team of researchers has been created; some scientific aspects of the registry were positive, while others could have been improved.

12 pages, 7 figures, 2 tables.-- This article is licensed under a Creative Commons Attribution 4.0 International License, Tuberculosis (TB) is the most lethal infection among infectious diseases. The specific aim of this study was to establish panels of serum protein biomarkers representative of active TB patients and their household contacts who were either infected (LTBI) or uninfected (EMI-TB Discovery Cohort, Pontevedra Region, Spain). A TMT (Tamdem mass tags) 10plex-based quantitative proteomics study was performed in quintuplicate containing a total of 15 individual serum samples per group. Peptides were analyzed in an LC-Orbitrap Elite platform, and raw data were processed using Proteome Discoverer 2.1. A total of 418 proteins were quantified. The specific protein signature of active TB patients was characterized by an accumulation of proteins related to complement activation, inflammation and modulation of immune response and also by a decrease of a small subset of proteins, including apolipoprotein A and serotransferrin, indicating the importance of lipid transport and iron assimilation in the progression of the disease. This signature was verified by the targeted measurement of selected candidates in a second cohort (EMI-TB Verification Cohort, Maputo Region, Mozambique) by ELISA and nephelometry techniques. These findings will aid our understanding of the complex metabolic processes associated with TB progression from LTBI to active disease, EMI-TB is a European Union Horizon2020-funded action (Grant No. 643558) focused on selecting and developing a novel vaccine candidate for TB

We investigated whether the difference of antigen tube 2 (TB2) minus antigen tube 1 (TB1) (TB22TB1) of the QuantiFERON-TB gold plus test, which has been postulated as a surrogate for the CD81 T-cell response, could be useful in identifying recent tuberculosis (TB) exposure. We looked at the interferon gamma (IFN-g) responses and differences in TB2 and TB1 tubes for 686 adults with QFT-plus positive test results. These results were compared among groups with high (368 TB contacts), low (229 patients with immune-mediated inflammatory diseases [IMID]), and indeterminate (89 asylum seekers or people from abroad [ASPFA]) risks of recent TB exposure. A TB2-TB1 value.0.6 IU.ml(-1) was deemed to indicate a true difference between tubes. In the whole cohort, 13.6%, 10.9%, and 11.2% of cases had a TB2>TB1 result in the contact, IMID, and ASPFA groups, respectively (P = 0.591). The adjusted odds ratios (aORs) for an association between a TB2-TB1 result of >0.6 IU.ml(-1) and risk of recent exposure versus contacts were 0.71 (95% confidence interval [CI], 0.31 to 1.61) for the IMID group and 0.86 (95% CI, 0.49 to 1.52) for the ASPFA group. In TB contact subgroups, 11.4%, 15.4%, and 17.7% with close, frequent, and sporadic contact had a TB2>TB1 result (P = 0.362). The aORs versus the close subgroup were 1.29 (95% CI, 0.63 to 2.62) for the frequent subgroup and 1.55 (95% CI, 0.67 to 3.60) for the sporadic subgroup. A TB2-TB1 difference of.0.6 IU.ml(-1) was not associated with increased risk of recent TB exposure, which puts into question the clinical potential as a proxy marker for recently acquired TB infection. IMPORTANCE Contact tuberculosis tracing is essential to identify recently infected people, who therefore merit preventive treatment. However, there are no diagnostic tests that can determine whether the infection is a result of a recent exposure or not. It has been suggested that by using the QuantiFERON-TB gold plus, an interferon gamma (IFN-gamma) release assay, a difference in IFN-gamma production between the two antigen tubes (TB2 minus TB1) of.0.6 IU.ml(-1) could serve as a proxy marker for recent infection. In this large multinational study, infected individuals could not be classified according to the risk of recent exposure based on differences in IFN- g in TB1 and TB2 tubes that were higher than 0.6 IU.ml(-1). QuantiFERON-TB gold plus is not able to distinguish between recent and remotely acquired tuberculosis infection, and it should not be used for that purpose in contact tuberculosis tracing. Funding Agencies|Department of Clinical Sciences of the University of Barcelona

Purpose Hypothyroidism has traditionally been associated with obesity, whereas hyperthyroidism has been linked to being underweight. However, very few studies have assessed these associations. The aim of this work is to evaluate the association between thyroid dysfunction and body mass index (BMI) at baseline and after normalization of the hormone levels. Patients and methods A retrospective, observational study of a cohort of otherwise healthy patients that were referred for evaluation of thyroid dysfunction to the Endocrine Department of Pontevedra University Complex Hospital, Spain was conducted. We collected data of BMI and thyroid hormone levels before treatment and after normalization of thyroid function within a follow-up period of 12 months. Results A total of 330 patients were initially selected for the study. In order to exclude variables that for any reason could influence on BMI, 235 were excluded for further studies. Another 61 patients were also excluded because incomplete data on their medical records, failure to achieve euthyroidism, or lost to follow-up. Therefore, the eligible final study group consisted of 34 patients (17 with hypothyroidism and 17 with hyperthyroidism). No differences were observed in mean baseline BMI between hypo and hyperthyroid patients (27.07±3.22 vs 26.39±4.44, p=0.609). Overweight or obesity was observed in 76.5% and 58.8% of hypothyroid and hyperthyroid patients, respectively (p=0.23). After normalization of thyroid function, the weight of hypothyroid patients decreased from 70.93±10.06 kg to 68.68±10.14 (p=0.000), while the weight of hyperthyroid patients increased from 65.45±11.64 kg to 68.37±12.80 (p=0.000). Their mean BMI was 26.22±3.36 and 27.57±4.98 (p=0.361) for hypo- and hyperthyroid patients, respectively. 58.8% and 64.7% patients remained in the overweight/obesity range in each group (p=0.72). Conclusion Untreated thyroid dysfunction is not associated with BMI. Normalization of thyroid levels significantly changed the weight of patients, but remaining most patients within overweight ranges.

A better understanding of the response against Tuberculosis (TB) infection is required to accurately identify the individuals with an active or a latent TB infection (LTBI) and also those LTBI patients at higher risk of developing active TB. In this work, we have used the information obtained from studying the gene expression profile of active TB patients and their infected –LTBI- or uninfected –NoTBI- contacts, recruited in Spain and Mozambique, to build a class-prediction model that identifies individuals with a TB infection profile. Following this approach, we have identified several genes and metabolic pathways that provide important information of the immune mechanisms triggered against TB infection. As a novelty of our work, a combination of this class-prediction model and the direct measurement of different immunological parameters, was used to identify a subset of LTBI contacts (called TB-like) whose transcriptional and immunological profiles are suggestive of infection with a higher probability of developing active TB. Validation of this novel approach to identifying LTBI individuals with the highest risk of active TB disease merits further longitudinal studies on larger cohorts in TB endemic areas. Xunta de Galicia | Ref. ED431C 2016/041 Ministerio de Educación, Cultura y Deporte | Ref. FPU13/03026

Diagnosis of tuberculous uveitis (TBU) is often challenging and is usually made after excluding other causes of uveitis. We analysed the characteristics of TBU and variables associated with visual outcome. A retrospective, observational analysis was performed in patients with presumptive TBU who were started on specific TB treatment between January 2006 and June 2016. Demographic, clinical, radiological, analytical and ophthalmic examination variables were studied. After completing TB treatment, a follow-up of at least 9 months was performed. A univariate and logistic regression analysis was applied to identify the variables associated with visual acuity and recurrences of uveitis. Forty affected eyes of 24 individuals were identified; 79% of patients were diagnosed during the last 3 years of the study period. Median delay from onset of symptoms to diagnosis was 12 weeks. Loss of visual acuity was the most frequent symptom (87.5%). Posterior uveitis was the most frequent localization (72.9%); 19 patients (79.2%) presented at least one of the Gupta signs predictive of TBU, but there were no confirmed diagnoses. There was improvement in visual acuity in 74.4% of the eyes, but a complete response was achieved only in 56.4%. There was recurrence in two patients. The initiation of treatment ≥ 24 weeks after onset of symptoms was significantly associated with no improvement (p = 0.026). TBU can cause permanent damage to visual acuity, particularly in patients with delayed diagnosis. A prompt initiation of systemic TB treatment is essential to improve visual prognosis.

Summary Objectives To identify new potential host biomarkers in blood to discriminate between active TB patients, uninfected (NoTBI) and latently infected contacts (LTBI). Methods A blood cell count was performed to study parent leukocyte populations. Peripheral blood mononuclear cells (PBMCs) were isolated and a multi-parameter flow cytometry assay was conducted to study the distribution of basal and Mycobacterium tuberculosis (Mtb)-stimulated lymphocytes. Differences between groups and the area under the ROC curve (AUC) were investigated to assess the diagnostic accuracy. Results Active TB patients presented higher Monocyte-to-lymphocyte and Neutrophil-to-lymphocyte ratios than LTBI and NoTBI contacts (p 0.8). Lymphocyte subsets with differences (p >0.05; AUC >0.7) between active TB and both contact groups include the basal distribution of Th1/Th2 ratio, Th1-Th17, CD4+ Central Memory (TCM) or MAIT cells. Expression of CD154 is increased in Mtb-activated CD4+ TCM and Effector Memory T cells in active TB and LTBI compared to NoTBI. In CD4+ T cells, expression of CD154 showed a higher accuracy than IFNγ to discriminate Mtb-specific activation. Conclusions We identified different cell subsets with potential use in tuberculosis diagnosis. Among them, distribution of CD4 TCM cells and their expression of CD154 after Mtb-activation are the most promising candidates.

Resumen Objetivo Analizar los costes directos e indirectos derivados del diagnostico y tratamiento de la tuberculosis (TB) y sus factores asociados. Pacientes y metodos Estudio prospectivo de pacientes diagnosticados de TB entre septiembre de 2014 y septiembre de 2015. Se calcularon los costes directos (estancias hospitalarias, consultas, estudios diagnosticos y tratamiento), e indirectos (absentismo laboral y perdida de productividad, estudio de contactos y medidas rehabilitadoras). Los costes se compararon atendiendo a las variables: edad, sexo, pais de origen, ingreso hospitalario, pruebas diagnosticas, tratamiento, resistencia farmacologica, tratamiento directamente observado (TDO) y dias de baja laboral. Se compararon proporciones mediante Chi cuadrado y las variables significativas se incluyeron en un modelo de regresion logistica calculandose las odds ratio (OR) y sus correspondientes intervalos de confianza del 95% (IC). Resultados Fueron incluidos 319 pacientes con una edad media de 56,72 ± 20,79 anos. El coste medio fue de 10.262,62 ± 14.961,66 €, y aumentaba significativamente en relacion con el ingreso hospitalario, el uso de la PCR, la realizacion de baciloscopia y cultivo, antibiograma, tomografia axial computarizada de torax, biopsia pleural, tratamiento de mas de 9 meses, TDO y baja laboral. En el analisis multivariante mantenian asociacion independiente: ingreso hospitalario (OR = 96,8; IC: 29-472,3), antibiograma (OR = 4,34; IC: 1,71-12,1), tomografia axial computarizada de torax (OR = 2,25; IC: 1,08-4,77), TDO (OR = 20,76; IC: 4,11-148) y baja laboral (OR = 26,9; IC: 8,51-122). Conclusion La Tuberculosis acarrea un gasto sanitario significativo. Medidas dirigidas a mejorar el control de la enfermedad y disminuir los ingresos hospitalarios serian importantes para reducirlo.

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.

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.

Resumen Introduccion Las normativas internacionales y espanolas recomiendan el tratamiento intensivo de la tuberculosis (TB) con cuatro farmacos. El objetivo es determinar si en Espana se sigue esta recomendacion y los factores asociados a utilizar tres farmacos (pauta estandar sin etambutol). Metodologia Estudio multicentrico descriptivo, retrospectivo, en el que se analizaron los datos de los pacientes diagnosticados de TB en practicamente todas las Comunidades Autonomas espanolas entre 2007 y 2012. El estudio de factores asociados a prescribir tres farmacos se baso en regresion logistica, calculandose las odds ratio (OR) y sus correspondientes intervalos de confianza del 95% (IC). Resultados Se incluyeron 3.189 pacientes, de los que 1.413 (44,3%) fueron tratados con tres farmacos. Este porcentaje fue del 41,2% en los pacientes con baciloscopia positiva, del 36,1% en los que tenian al menos resistencia a un farmaco, del 31,4% en los que tenian infeccion por VIH y del 24,8% en los inmigrantes. Los factores asociados al uso de tres farmacos fueron: ser mujer (OR = 1,18; IC: 1,00-1,39); ser autoctono (OR = 3,09; IC: 2,58-3,70); estar jubilado (OR = 1,42; IC: 1,14-1,77); vivir sin techo (OR = 3,10; IC: 1,52-6,43), vivir solo (OR = 1,62; IC: 1,11-2,36) o en familia (OR = 1,97; IC: 1,48-2,65); ser atendido por especialistas de zona (OR = 1,37; IC: 1,10;1,70); no estar infectado por el VIH (OR = 1,63; IC: 1,09-2,48) y tener baciloscopia negativa con cultivo positivo (OR = 1,59; IC: 1,25-2,02). Conclusiones Existe una proporcion importante de tratamiento intensivo con tres farmacos. Se deben seguir las recomendaciones del tratamiento de la TB, tanto en la practica clinica habitual como por parte del Plan para la Prevencion y Control de la TB en Espana.

In our work, we aim to identify new candidate host biomarkers to discriminate between active TB patients (n = 28), latent infection (LTBI; n = 27) and uninfected (NoTBI; n = 42) individuals. For that, active TB patients and their contacts were recruited that donated serum and saliva samples. A multiplex assay was performed to study the concentration of different cytokines, chemokines and growth factors. Proteins with significant differences between groups were selected and logistic regression and the area under the ROC curve (AUC) was used to assess the diagnostic accuracy. The best marker combinations that discriminate active TB from NoTBI contacts were [IP-10 + IL-7] in serum and [Fractalkine + IP-10 + IL-1α + VEGF] in saliva. Best discrimination between active TB and LTBI was achieved using [IP-10 + BCA-1] in serum (AUC = 0.83) and IP-10 in saliva (p = 0.0007; AUC = 0.78). The levels of TNFα (p = 0.003; AUC = 0.73) in serum and the combination of [Fractalkine+IL-12p40] (AUC = 0.83) in saliva, were able to differentiate between NoTBI and LTBI contacts. In conclusion, different individual and combined protein markers could help to discriminate between active TB and both uninfected and latently-infected contacts. The most promising ones include [IP-10 + IL-7], [IP-10 + BCA-1] and TNFα in serum and [Fractalkine + IP-10 + IL-1α + VEGF], IP-10 and [Fractalkine+IL-12p40] in saliva. Xunta de Galicia | Ref. ED431C 2016/041 Ministerio de Ecucación, Cultura y Deporte | Ref. FPU 13/03026

BACKGROUND: Screening strategies based on interferon-? release assays in tuberculosis contact tracing may reduce the need for preventive therapy without increasing subsequent active disease. METHODS: We conducted an open-label, randomized trial to test the noninferiority of a 2-step strategy with the tuberculin skin test (TST) followed by QuantiFERON-TB Gold In-Tube (QFT-GIT) as a confirmatory test (the TST/QFT arm) to the standard TST-alone strategy (TST arm) for targeting preventive therapy in household contacts of patients with tuberculosis. Participants were followed for 24 months after randomization. The primary endpoint was the development of tuberculosis, with a noninferiority margin of 1.5 percentage points. RESULTS: A total of 871 contacts were randomized. Four contacts in the TST arm and 2 in the TST/QFT arm developed tuberculosis. In the modified intention-to-treat analysis, this accounted for 0.99% in the TST arm and 0.51% in the TST/QFT arm (-0.48% difference; 97.5% confidence interval [CI], -1.86% to 0.90%); in the per-protocol analysis, the corresponding rates were 1.67% and 0.82% in the TST and TST/QFT arms, respectively (-0.85% difference; 97.5% CI, -3.14% to 1.43%). Of the 792 contacts analyzed, 65.3% in the TST arm and 42.2% in the TST/QFT arm were diagnosed with tuberculosis infection (23.1% difference; 95% CI, 16.4% to 30.0%). CONCLUSIONS: In low-incidence settings, screening household contacts with the TST and using QFT-GIT as a confirmatory test is not inferior to TST-alone for preventing active tuberculosis, allowing a safe reduction of preventive treatments. CLINICAL TRIALS REGISTRATION: NCT01223534.

Objective: To determine the current use and potential acceptance (by tuberculosis experts worldwide) of novel rapid tests for the diagnosis of tuberculosis that are in line with World Health Organization target product profiles. Methods: A multilingual survey was disseminated online between July and November of 2016. Results: A total of 723 individuals from 114 countries responded to the survey. Smear microscopy was the most commonly used rapid tuberculosis test (available to 90.9% of the respondents), followed by molecular assays (available to 70.7%). Only a small proportion of the respondents in middle- and low-income countries had access to interferon-gamma-release assays. Serological and lateral flow immunoassays were used by more than a quarter (25.4%) of the respondents. Among the respondents who had access to molecular tests, 46.7% were using the Xpert assay overall, that proportion being higher in lower middle-income countries (55.6%) and low-income countries (76.6%). The data also suggest that there was some alignment of pricing for molecular assays. Respondents stated they would accept novel rapid tuberculosis tests if available, including molecular assays (acceptable to 86.0%) or biomarker-based serological assays (acceptable to 81.7%). Simple biomarker-based assays were more commonly deemed acceptable in middle- and low-income countries. Conclusions: Second-generation molecular assays have become more widely available in high- and low-resource settings. However, the development of novel rapid tuberculosis tests continues to be considered important by tuberculosis experts. Our data also underscore the need for additional training and education of end users.

18 p.-4 fig.-6 tab. López, María et al., Acinetobacter baumannii is an important pathogen that causes nosocomial infections generally associated with high mortality and morbidity in Intensive Care Units (ICUs). Currently, little is known about the Quorum Sensing (QS)/Quorum Quenching (QQ) systems of this pathogen. We analyzed these mechanisms in seven clinical isolates of A. baumannii. Microarray analysis of one of these clinical isolates, Ab1 (A. baumannii ST-2_clon_2010), previously cultured in the presence of 3-oxo-C12-HSL (a QS signalling molecule) revealed a putative QQ enzyme (α/ß hydrolase gene, AidA). This QQ enzyme was present in all non-motile clinical isolates (67% of which were isolated from the respiratory tract) cultured in nutrient depleted LB medium. Interestingly, this gene was not located in the genome of the only motile clinical strain growing in this medium (A. baumannii strain Ab421_GEIH-2010 [Ab7], isolated from a blood sample). The AidA protein expressed in E. coli showed QQ activity. Finally, we observed downregulation of the AidA protein (QQ system attenuation) in the presence of H2O2 (ROS stress). In conclusion, most of the A. baumannii clinical strains were not surface motile (84%) and were of respiratory origin (67%). Only the pilT gene was involved in surface motility and related to the QS system. Finally, a new QQ enzyme (α/ß hydrolase gene, AidA protein) was detected in these strains., This study was funded by grant PI13/02390 awarded to MT within the State Plan for R+D+I 2013-2016 (National Plan for Scientific Research, Technological Development and Innovation 2008-2011) and co-financed by the ISCIII-Deputy General Directorate of evaluation and Promotion of Research - European Regional Development Fund "A way of Making Europe" and Instituto de Salud Carlos III FEDER, Spanish Network for the Research in Infectious Diseases (REIPI RD12/0015).

Oncohematological patients undergoing chemotherapy who have latent tuberculosis infection (LTBI) are at a high risk of developing active tuberculosis (TB). The identification and treatment of these patients can prevent LTBI progressing to active TB. This study analyzed the degree of adherence with and safety of the treatment of latent tuberculosis infection (TLTBI) in oncohematological patients undergoing antineoplastic chemotherapy.This is a retrospective study of a cohort of oncohematological patients receiving TLTBI and antineoplastic chemotherapy simultaneously, between January 2007 and June 2010. The proportions of toxicity and adherence to TLTBI in these patients were compared with a non-oncohematological control group, matched for age, sex, and year in which the TLTBI was started. In addition, a minimum 2-year follow-up was carried out for all patients.A total of 105 patients who received TLTBI were included, 21 of whom had received antineoplastic chemotherapy simultaneously. The mean age of the patients was 63 years. There were no significant baseline differences in transaminase values. The percentages of patients completing treatment were 76.2% in the control group and 71.4% in the oncohematological group [risk ratio (RR): 1.07, 95% confidence interval (CI): 0.79-1.43]. The voluntary dropout proportion was similar in both groups (12.3 vs. 11.8%, RR: 1.05, 95% CI: 0.25-4.42). Treatment was discontinued because of toxicity in three oncohematological patients and in 11 patients from the control group (RR: 1.14; 95% CI: 035-3.66). No patient developed TB during the follow-up period.The safety of TLTBI is not influenced by simultaneous antineoplastic chemotherapy in oncohematological patients.

Objective To analyze the direct and indirect costs of diagnosis and management of tuberculosis (TB) and associated factors. Patients and methods Prospective study of patients diagnosed with TB between September 2014 and September 2015. We calculated direct (hospital stays, visits, diagnostic tests, and treatment) and indirect (sick leave and loss of productivity, contact tracing, and rehabilitation) costs. The following cost-related variables were compared: age, gender, country of origin, hospital stays, diagnostic testing, sensitivity testing, treatment, resistance, directed observed therapy (DOT), and days of sick leave. Proportions were compared using the chi-squared test and significant variables were included in a logistic regression analysis to calculate odds ratio (OR) and corresponding 95% confidence intervals. Results 319 patients were included with a mean age of 56.72±20.79 years. The average cost was €10,262.62±14,961.66, which increased significantly when associated with hospital admission, polymerase chain reaction, sputum smears and cultures, sensitivity testing, chest computed tomography, pleural biopsy, drug treatment longer than nine months, DOT and sick leave. In the multivariate analysis, hospitalization (OR=96.8; CI 29–472), sensitivity testing (OR=4.34; CI 1.71–12.1), chest CT (OR=2.25; CI 1.08–4.77), DOT (OR=20.76; CI 4.11–148) and sick leave (OR=26.9; CI 8.51–122) showed an independent association with cost. Conclusion Tuberculosis gives rise to significant health spending. In order to reduce these costs, more control of transmission, and fewer hospital admissions would be required.

Tuberculosis (TB) is an infectious disease that causes more than 1 million deaths worldwide every year. In addition, it is estimated that one third of the world population is infected with M. Tuberculosis in a latent state, which involves an eventual risk of progressing to active TB disease. Patients with immunodeficiencies, such as those suffering from haematological malignancies, have a greater risk of progressing to TB disease once infected. It is estimated that the Relative Risk of TB disease in patients with hematologic malignancies is 2-40 times that of general population. The diagnosis of TB in these patients is often difficult as they often present clinical characteristics that are distinct to those of patients without any other underlying disease. Mortality attributable to tuberculosis is higher. Therefore it is recommended to diagnose latent TB infection in order to offer a preventive therapy that could prevent the progression from a latent state to active TB disease. There are currently two methods for diagnosing latent TB infection: the Tuberculin Skin Test (TST) and the Interferon-Gamma Release Assays (IGRA). Due to the lack of sensitivity in patients with immunodeficient conditions, a combined TST-IGRA testing is probably the best way for latent TB diagnosis in order to gain sensitivity. Treatment of latent TB infection and TB disease should follow the general principles to that in general population.

Previous reports have identified interleukin-2 (IL-2), quantified in the supernatants of QuantiFERONA multicentre study of 161 consecutive adult patients undergoing evaluation for active TB at eight TB Units in Spain. Interferon-γ (IFN-γ) and IL-2 were assessed in the supernatant of QFT after 16-24 h and 72 h of incubation. The accuracy of IL-2 for indicating latent TB infection (LTBI) was assessed by receiving operating characteristic curves. .Twenty-eight participants were not infected, 43 had LTBI, 69 had TB, and 21 were not classifiable. Median (interquartile range) IL-2 concentrations after 72 h of incubation were 0.0 pg/mL (0.0-0.0) in uninfected individuals, 261.0 pg/mL (81.0-853.0) in LTBI individuals, 166.5 pg/mL (33.5-551.5) in patients with extrapulmonary TB, 95.0 pg/mL (26.0-283.0) in patients with smear-negative pulmonary TB, and 38.5 pg/mL (7.5-178.0) in patients with smear-positive pulmonary TB (p0.0001). The area under the curve of the receiving operating characteristic curve (95% CI) of IL-2 after 72 h of incubation for the diagnosis of LTBI was 0.63 (0.53-0.74) when all TB cases were considered as a single group, ranging from 0.59 (0.47-0.71) to 0.72 (0.58-0.85) when only extrapulmonary and smear-positive pulmonary TB cases respectively were considered.Quantification of IL-2 in the supernatant of QFT after a prolonged incubation is not useful to distinguish between LTBI and active disease in clinical practice.

Background: Objectives: To determine whether the incidence of tuberculosis with pregnancy is more common than would be expected from the crude birth rate; to see whether there is significant delay in the diagnosis of tuberculosis during pregnancy. Method: Design: A cross-sectional survey. Setting: 13 tuberculosis clinics within different European countries and the USA. Population/sample: All patients with tuberculosis seen at these clinics for a period > 1 year. Instrument: Questionnaire survey based on continuous data collection. Main outcome measures: number and proportion of women with tuberculosis who were pregnant; timing of diagnosis in relation to pregnancy, including those who were pregnant or delivered in the 3 months prior to the diagnosis of TB and those who developed TB within 3 months after delivery. Results: Pregnancy occurred in 224 (1.5 %) of 15,217 TB patients and followed the expected rate predicted from the crude birth rate for the clinic populations. TB was diagnosed more commonly in the 3 months after delivery (n = 103) than during pregnancy (n = 68; chi(2) = 25.1, P < 0.001). Conclusions: TB is diagnosed more frequently after delivery, despite variations in local TB incidence and healthcare systems.