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BackgroundThree months of weekly rifapentine plus isoniazid (3HP) therapy for latent tuberculosis infection (LTBI) is recommended worldwide. The development of symptoms and systemic drug reactions (SDRs) on 3HP have not been fully characterized. We aimed to determine the patterns of symptom development and identify SDRs and associated factors in patients taking 3HP.MethodsWe analyzed symptoms data in participants receiving 3HP in the Tuberculosis Trials Consortium's iAdhere study (Study 33). We examined the patterns of symptom reporting across participants from baseline and 4 monthly visits. Bivariate analyses and multivariable regression models were used to identify factors associated with SDRs. Risk ratios (RRs) and 95% confidence intervals (CIs) were calculated.ResultsAmong 1002 participants receiving 3HP, 768 (77%) reported at least 1 symptom; 97% of these symptoms were grade 1 (79%) or grade 2 (18%). Most symptoms developed in the first month and resolved. A total of 111 (11%) participants had symptoms that met criteria for SDRs; however, 53 (48%) of these participants completed therapy. Factors associated with SDRs and discontinuation included female sex (RR: 2.05; 95% CI: 1.19–3.54), age ≥45 years (RR: 1.99; 95% CI: 1.19–3.31), and use of concomitant medications (RR: 2.26; 95% CI: 1.15–4.42).ConclusionsAlthough most patients receiving 3HP reported symptoms, most were mild, occurred early, and resolved without stopping treatment. Among patients experiencing SDRs, nearly half were able to complete therapy. Patient and provider education should focus on differentiating severe reactions where 3HP should be stopped from minor symptoms that will resolve.

The SMA-TB Consortium has developed a leaflet with basic information on Tuberculosis to be distributed to general public during communication activities. This leaflet was created within the SMA-TB Project jointly by the IGTP team andthe Public Health Agency of Barcelona (ASPB). The Fundació Lluita contra les Infeccions (Fight Infections Foundation)has also contributed to it,and Laura Ginès and Pepón Meneses illustrated it. Theleaflethas been translated toseveral languagesbymembers of theSMA-TB Consortium partners (all listed as contributors)in order others can reuse it: Catalan Spanish French Italian Portuguese Polish Deutsch Norwegian Ukrainian Georgian Afrikaans Per each language, two versions are provided: one to be printed in a home printer and another one to be printed in a printshop.

BackgroundDiabetes mellitus (DM) is one of the leading chronic diseases globally and one of the most common causes of death, morbidity, and poor quality of life. According to the WHO, DM is also one of the main risk factors for developing active tuberculosis (TB). Subjects with DM are at a higher risk of infections, in addition to frequent micro and macrovascular complications, and therefore sought to determine whether poor glycemic control is linked to a higher risk of developing TB.MethodsWe used a retrospective cohort of diabetic subjects to predict the incidence of TB. All DM patients were recruited from Ciutat Vella (the inner-city of Barcelona) from January 2007 until December 2016, with a follow-up period until December 2018 (≥2 years). Data were extracted from Barcelona's Primary Care medical record database - SIDIAP, and linked to the Barcelona TB Control Program. The incidence of TB and the impact of glycemic control were estimated using time-to-event curves analyzed by Cox proportional hazard regression. Hazard ratios (HRs) and 95% confidence intervals (CIs), unadjusted and adjusted by potential confounding variables, were also assessed, which included age, sex, diabetes duration, macrovascular and microvascular signs, BMI, smoking habit, alcohol consumption and geographical origin.ResultsOf 8,004 DM patients considered for the study (equating to 68,605 person-years of follow-up), 84 developed TB [incidence rate = 70 (95% CI: 52–93) per 100,000 person-years]. DM subjects with TB were younger (mean: 52.2 vs. 57.7 years old), had higher values of glycosylated hemoglobin (HbA1c) (7.66 vs. 7.41%) and total triglycerides (122 vs. 105 mg/dl), and had twice the frequency of diabetic nephropathy (2.08 vs. 1.18%). The calculated incidence rate increased with increasing HbA1c: 120.5 (95% CI 77.2–179.3) for HbA1c ≥ 7.5%, 143 (95% CI 88.3–218.1) for HbA1c ≥ 8% and 183.8 (95% CI 105–298) for HbA1c ≥ 9%. An increase in the risk of TB was also observed according to a poorer optimization of glycemic control: adjusted HR 1.80 (95% CI 0.60–5.42), 2.06 (95% CI 0.67–6.32), and 2.82 (95% CI 0.88–9.06), respectively.ConclusionDiabetic subjects with worse glycemic control show a trend toward a higher risk of developing TB.

Background The COVID-19 pandemic could have negative effects on tuberculosis (TB) control. The objective was to assess the impact of the pandemic in contact tracing, TB and latent tuberculosis infection (LTBI) in contacts of patients with pulmonary TB in Catalonia (Spain). Methods Contact tracing was carried out in cases of pulmonary TB detected during 14 months in the pre-pandemic period (1 January 2019 to 28 February 2020) and 14 months in the pandemic period (1 March 2020 to 30 April 2021). Contacts received the tuberculin skin test and/or interferon gamma release assay and it was determined whether they had TB or LTBI. Variables associated with TB or LTBI in contacts (study period and sociodemographic variables) were analyzed using adjusted odds ratio (aOR) and the 95% confidence intervals (95% CI). Results The pre-pandemic and pandemic periods showed, respectively: 503 and 255 pulmonary TB reported cases (reduction of 50.7%); and 4676 and 1687 contacts studied (reduction of 36.1%). In these periods, the proportion of TB cases among the contacts was 1.9% (84/4307) and 2.2% (30/1381) (P = 0.608); and the proportion of LTBI was 25.3% (1090/4307) and 29.2% (403/1381) (P Conclusions COVID-19 is affecting TB control due to less exhaustive TB and LTBI case detection. An increase in LTBI was observed during the pandemic period. Efforts should be made to improve detection of TB and LTBI among contacts of TB cases.

Introduction: In recent decades, there has been an increase in extrapulmonary TB (EP-TB) rates in industrialized countries with a low incidence of tuberculosis (TB), especially among specific foreign-born population groups. The aim of this study was to describe sociodemographic, epidemiological, microbiological, clinical and treatment characteristics of EP-TB cases and associated risk factors in Spain. Methods: We performed a descriptive, retrospective, multi-center observational study of new TB cases in different regions in Spain (Comunidades Autónomas, CCAA) between 2006 and 2014. We used logistic regression and calculated odd ratios (OR) and 95% confidence intervals (CI) to determine EP-TB-associated factors. Results: The proportion of EPTB were higher among the foreign-born population (22.1%) than among native Spaniards (15.9%; p = 0.001). Foreign cases were mostly Asian, with up to 42.8% of India-Pakistan cases showing some form of EP-TB. The factors related were: immigrant status (OR:1.62; CI:1.35–1.95); age >50 years; (OR:1.70; CI:1.36–2.13); diagnosis delay of >51 days (OR:1.38; CI:1.17–1.62); co-infection with HIV (OR:1.77; CI:1.21–2.55); negative smear sputum microscopy (OR:3.01; CI:2.50;3.61); negative culture; (OR:8.1; CI:6.57–10.02); poor clinical progression during disease progression (OR:2.93; CI:1.30–6.39). Conclusions: We detected a high percentage of EP-TB forms in the foreign-born population, mostly in Asian people. Special attention should be devoted to the diagnosis of EP-TB in these groups. Other measures required include increased clinical suspicion and improved microbiological diagnosis to support earlier and adequate treatment. Resumen: Introducción: En las últimas décadas se ha producido un aumento de las tasas de tuberculosis extrapulmonar (TBEP) en los países industrializados con baja incidencia de tuberculosis (TB), especialmente en grupos específicos de población de origen extranjero. El objetivo de este estudio fue describir las características sociodemográficas, epidemiológicas, microbiológicas, clínicas y del tratamiento de los casos de TBEP en España y los factores de riesgo asociados. Métodos: Realizamos un estudio observacional descriptivo, retrospectivo y multicéntrico de los nuevos casos de TB en diferentes regiones de España (comunidades autónomas [CC. AA.]) entre 2006 y 2014. Utilizamos la regresión logística y calculamos las odds ratio (OR) y el intervalo de confianza (IC) del 95% para determinar los factores asociados a la TBEP. Resultados: La proporción de TBEP fue mayor entre la población nacida en el extranjero (22,1%) que entre los españoles nativos (15,9%; p = 0,001). Los casos extranjeros eran en su mayoría asiáticos; el 42,8% de los casos procedentes de India-Pakistán mostraban algún tipo de TBEP. Los factores relacionados fueron: situación de migrante (OR: 1,62; IC 95%: 1,35-1,95); edad > 50 años (OR: 1,70; IC 95%: 1,36-2,13); retraso en el diagnóstico de > 51 días (OR: 1,38; IC 95%: 1,17-1,62); coinfección con VIH (OR: 1,77; IC 95%: 1,21-2,55); examen microscópico de frotis de esputo negativo (OR: 3,01; IC 95%: 2,50-3,61); cultivo negativo (OR: 8,1; IC 95%: 6,57-10,02); mala evolución clínica durante la progresión de la enfermedad (OR: 2,93; IC 95%: 1,30-6,39). Conclusiones: Detectamos un alto porcentaje de formas TBEP en la población nacida en el extranjero, principalmente en personas asiáticas. Debe prestarse especial atención al diagnóstico de TBEP en estos grupos. Otras medidas requeridas incluyen una mayor sospecha clínica y un mejor diagnóstico microbiológico para apoyar un tratamiento temprano y más adecuado.

Resumen Introduccion Un buen control de la tuberculosis (TB) requiere disponer de personal multidisciplinario bien coordinado. El objetivo fue evaluar el impacto de la acreditacion de unidades de TB (UTB) fomentada por la Sociedad Espanola de Neumologia (SEPAR) y ver las diferencias entre los centros que se acreditaron y los que no. Material y metodos. Diseno Estudio observacional descriptivo basado en una encuesta autoadministrada entre octubre de 2014 y febrero de 2018 a 139 responsables de neumologia registrados por SEPAR, antes y despues de la acreditacion. Variables demograficas, epidemiologicas y sobre estudio de contactos, entre otras. Analisis: descriptiva basica, calculo de medianas para variables continuas y proporciones para categoricas. Se compararon las variables mediante el test chi-cuadrado y regresion logistica. Resultados La tasa de respuesta fue del 54,7 y del 43,2% en el periodo pre- y postacreditacion de UTB, respectivamente. No se observaron cambios en los diferentes ambitos de atencion y coordinacion entre la encuesta pre- y postacreditacion, ni tampoco en la organizacion, al analizar los centros acreditados. Al comparar los centros que se acreditaron con los que no, se detectaron diferencias significativas con relacion a recogida de conclusion final, manejo de resistencias, coordinacion con otros servicios, estudios de contactos o tratamiento directamente observado. Conclusiones Se ha objetivado como abordan la TB diferentes profesionales, se han detectado aspectos positivos y otros mejorables, y se han observando indicadores de mejor funcionamiento en los centros que se acreditaron frente a los que no lo hicieron. Se precisa una supervision cercana de las UTB para mejorar su efectividad.

Introduction Well-coordinated multidisciplinary teams are essential for better tuberculosis (TB) control. Our objective was to evaluate the impact of Spanish Society of Pneumology (SEPAR) accreditation of TB Units (TBU) and to determine differences between the accredited and non-accredited centers. Material and methods. Design Observational descriptive study based on a self-administered survey from October 2014 to February 2018 completed by 139 heads of respiratory medicine departments collected by SEPAR, before and after TBU accreditation. Variables demographic, epidemiological and contact tracing variables, among others. Analysis: basic descriptive analysis, and calculation of medians for continuous variables and proportions for categorical variables. The variables were compared using the Chi-squared test and logistic regression. Results The response rate was 54.7% and 43.2% in the pre- and post-TBU accreditation period, respectively. No differences were observed in the care and coordination variables between the pre- and post-accreditation survey, nor in the organization when only accredited centers were analyzed. When we compared the accredited and non-accredited centers, significant differences were detected in the collection of the final conclusion, management of resistance, coordination with other departments, contact tracing, and directly observed treatment. Conclusions The approach of different professionals with regard to TB has been addressed. Positive aspects and areas for improvement have been detected, and better results were observed in the accredited versus non-accredited centers. A closer supervision of TBUs is necessary to improve their effectiveness.

Mycobacterium tuberculosis; Child; Passive smoking Tuberculosis micobacteriana; Niño; Tabaquismo pasivo Tuberculosi micobacteriana; Infant; Tabaquisme passiu Little is known about whether second-hand smoke (SHS) exposure affects tuberculosis (TB). Here, we investigate the association of cigarette smoke exposure with active TB and latent TB infection (LTBI) in children, analyzing Interferon-Gamma Release Assays’ (IGRAs) performance and cytokine immune responses. A total of 616 children from contact-tracing studies were included and classified regarding their smoking habits [unexposed, SHS, or smokers]. Risk factors for positive IGRAs, LTBI, and active TB were defined. GM-CSF, IFN-γ, IL-2, IL-5, IL-10, IL-13, IL-22, IL-17, TNF-α, IL-1RA and IP-10 cytokines were detected in a subgroup of patients. Being SHS exposed was associated with a positive IGRA [aOR (95% CI): 8.7 (5.9–12.8)] and was a main factor related with LTBI [aOR (95% CI): 7.57 (4.79–11.94)] and active TB [aOR (95% CI): 3.40 (1.45–7.98)]. Moreover, IGRAs’ sensitivity was reduced in active TB patients exposed to tobacco. IL-22, GM-CSF, IL-5, TNF-α, IP-10, and IL-13 were less secreted in LTBI children exposed to SHS. In conclusion, SHS is associated with LTBI and active TB in children. In addition, false-negative IGRAs obtained on active TB patients exposed to SHS, together with the decrease of specific cytokines released, suggest that tobacco may alter the immune response. This research was supported by: (i) a grant from the Instituto de Salud Carlos III (PI 13/01546, PI16/01912, and PI18/00411), integrated in the Plan Nacional I+D+I and co-funded by the ISCIII Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER) and CERCA Programme/Generalitat de Catalunya; and (ii) a grant from the Sociedad Española de Neumología y Cirugía Torácica (SEPAR; Barcelona, Spain) (Smoking Integrated Research Programme Call).

Background Residents of Nursing Homes (NHs) have suffered greater impacts from the COVID-19 pandemic. However, the rates of COVID-19 in these institutions are heterogeneously distributed. Describing and understanding the structural, functional, and socioeconomic differences between NHs is extremely important to avoid new outbreaks. Objectives Analyze inequalities in the cumulative incidences (CIs) and in the mortality rates (MRs) due to COVID-19 in the NHs of Barcelona based on the characteristics of the NHs. Methods Exploratory ecological study of 232 NHs. The dependent variables were the cumulative incidence and mortality rate due to COVID-19 in NHs between March and June 2020. Structural variables of the NHs were evaluated such as neighborhood socioeconomic position (SEP), isolation and sectorization capacity, occupancy, overcrowding and ownership. Results The cumulative incidence and mortality rate were higher in the low SEP neighborhoods and lower in those of high SEP neighborhoods. Regarding the isolation and sectorization capacity, Type B NHs had a higher risk of becoming infected and dying, while Type C had a lower risk of dying than Type A. Greater overcrowding was associated with greater morbidity and mortality, and higher occupancy was associated with higher incidence. The risk of becoming infected and dying in public NHs was significantly higher than for-profit NH. Conclusions The social components together with the functional and infrastructure characteristics of the NHs influence the cumulative incidence and the mortality rate by COVID-19. It is necessary to redefine the care model in the NHs to guarantee the health of the residents.

Concomitant treatment for chronic hepatitis C virus infection and multidrug-resistant tuberculosis is safe and effective.

BackgroundTuberculosis is the leading cause of mortality from lung infectious disease worldwide in recent years, and its incidence has re-emerged in large cities in low-incidence countries due to migration and socioeconomic deprivation causes. Diabetes mellitus and tuberculosis are syndemic diseases, with diabetes being considered a risk factor for developing tuberculosis.ObjectiveTo investigate whether diabetic patients were at increased risk of tuberculosis living in an inner-district of a large city of northeastern Spain.MethodsObservational matched retrospective cohort study based on clinical records from the population of the lowest socioeconomic status in Barcelona (Ciutat Vella district). A cohort including patients with type 1 and type 2 diabetes mellitus in 2007 and new cases until 2016 (8004 subjects), matched 1:1 by sex and age with a non-diabetic cohort. Follow-up period was until December 31st 2018. We evaluated the risk of developing tuberculosis in diabetic patients compared to non-diabetic patients during the follow up period. We used time-to-event analysis to estimate the incidence of tuberculosis, and competing risks regression by clusters and conditional Cox regression models to calculate the hazard ratio (HR) and its 95% confidence intervals (CI).ResultsAmong the 16,008 included subjects, the median follow-up was 8.7 years. The mean age was 57.7 years; 61.2% men and 38.8% women in both groups. The incidence of tuberculosis was 69.9 per 100,000 person-years in diabetic patients, and 40.9 per 100,000 person-years in non-diabetic patients (HR = 1.90; CI: 1.18–3.07). After adjustment for the country of origin, chronic kidney disease, number of medical appointments, BMI, alcoholism and smoking, the risk remained higher in diabetic patients (1.66: CI 0.99–2.77). Additionally, subjects from Hindustan or with a history of alcohol abuse also showed a higher risk of developing tuberculosis (HR = 3.51; CI:1.87–6.57, and HR = 2.73; CI:1.22–6.12 respectively).ConclusionPeople with diabetes mellitus were at higher risk of developing tuberculosis in a large cohort recruited in an inner-city district with a high incidence for this outcome, and low socioeconomic conditions and high proportion of migrants. This risk was higher among Hindustan born and alcohol abusers.

The aim of this study was to test the use of IP-10 detection in dried plasma from contact studies individuals (contacts of smear positive patients), by comparing it with IP-10 and IFN-γ detection in direct plasma, to establish IP-10 detection in DPS as a useful assay for LTBI diagnosis. Whole blood samples were collected from 80 subjects: 12 with active tuberculosis (TB), and 68 from contact studies. The amount of IFN-γ produced by sensitized T cells was determined in direct plasma by QuantiFERON Gold In-Tube test. IP-10 levels were determined in direct and dried plasma by an in-house ELISA. For dried plasma IP-10 determination, two 25 µl plasma drops were dried in Whatman903 filter paper and sent by mail to the laboratory. Regarding TB patients, 100.0%, 91.7% and 75.0% were positive for IFN-γ detection and IP-10 detection in direct and dried plasma, respectively. In contacts, 69.1%, 60.3% and 48.5% had positive results after IFN-γ and IP-10 in direct and dried plasma, respectively. The agreement among in vitro tests was substantial and IP-10 levels in direct and dried plasma were strongly correlated (r = 0.897). In conclusion, IP-10 detection in dried plasma is a simple and safe method that would help improve LTBI management.

Interferon gamma (IFN-γ) release assays (IGRAs) are increasingly used to test for latent tuberculosis (TB) infection. Although highly specific, IGRAs have a relatively high false-negative rate in active TB patients. A more sensitive assay is needed. IFN-γ-induced protein 10 (IP-10) is an alternative biomarker with a 100-fold-higher expression level than IFN-γ, allowing for different analysis platforms, including molecular detection. The PCR technique is already an integrated tool in most TB laboratories and, thus, an obvious platform to turn to. In this case-control study, we investigated the diagnostic sensitivity and specificity of a molecular assay detecting IP-10 mRNA expression following antigen stimulation of a blood sample. We included 89 TB patients and 99 healthy controls. Blood was drawn in QuantiFeron-TB gold in-tube (QFT) assay tubes. Eight hours poststimulation, IP-10 mRNA expression was analyzed, and 20 h poststimulation, IP-10 and IFN-γ protein plasma levels were analyzed using an in-house IP-10 enzyme-linked immunosorbent assay (ELISA) and the official QFT ELISA, respectively. The IP-10 mRNA assay provided high specificity (98%), sensitivity (80%), and area under the concentration-time curve (AUC) (0.97); however, the QFT assay provided a higher overall diagnostic potential, with specificity of 100%, sensitivity of 90%, and AUC of 0.99. The IP-10 protein assay performed on par with the QFT assay, with specificity of 98%, sensitivity of 87%, and AUC of 0.98. We have provided proof of high technical performance of a molecular assay detecting IP-10 mRNA expression. As a diagnostic tool, this assay would gain from further optimization, especially on the kinetics of IP-10 mRNA expression.

Interferon (IFN)-γ release assays (IGRAs) are used to diagnose latent tuberculosis (TB) infection (LTBI). To improve the accuracy of these tests, different approaches, such as alternative cytokine detection and using different antigens, are considered. Following this purpose, this study aims to evaluate the addition of EspC, EspF and Rv2348-B to those present in the QuantiFERON-TB Gold In-Tube (QFN-G-IT). We included 115 subjects: 74 active TB patients, 17 LTBI individuals and 24 healthy controls. Whole blood samples were collected in QFN-G-IT and in-house tubes containing different combinations of EspC, EspF and Rv2348-B, together with ESAT-6, CFP-10, and TB7.7. After overnight incubation at 37 ºC, plasma was harvested and IFN-γ quantified. IFN-γ levels in the QFN-G-IT and in-house tubes correlated very good (Spearman Rho(r) > 0.86). In-house antigen combinations distinguished healthy individuals from those with active TB and LTBI (specificities and sensitivities higher than 87.5% and 96.3%, respectively [AUC > 0.938]). Adding EspC, EspF and Rv2348-B, increased the sensitivity of the test, being the addition of EspC and Rv2348-B the combination that yielded a higher sensitivity with no specificity loss. Addition of these antigens could improve diagnosis in patients with impaired or immature immune response who are at high risk of developing TB.

The aim of this study was to promote the rapid identification of the contacts of patients infected with SARS-CoV-2 and therefore the control of the pandemic. Different methodologies and recommendations on contact tracing for Primary Health Care (PHC) and Public Health Services (PHS), like articles in Pubmed about COVID-19 and contact tracing, official contact definitions, the classic contact tracing model in tuberculosis (TB), information about apps for contact tracing and the role of the diagnostic tests, were reviewed. To establish efficient prevention and control measures, it is always necessary to implement contact tracing based on clinical suspicion, early diagnosis and isolation of cases and contacts and their follow-up. The classic contact tracing model in TB can be applied to this new infection, but accelerating the process given its acute nature and its potential severity. Good coordination between PHC and PHS and having sufficient resources is essential.

Background Since there are active drugs against tuberculosis (TB), the most effective control measures are to assure treatment adherence and to perform contact tracing. Given the long treatment duration and characteristics of some TB patients, threats that put at risk treatment adherence may appear. Identify and address them is essential to achieve the objectives of disease control. Objectives To identify the epidemiological characteristics of TB patients and the incidents and threats occurring during treatment, to describe the interventions performed to enhance treatment adherence and to determine if there are differences among native and foreign-born patients in the TB clinical unit of a referral hospital in the inner city of Barcelona. Methods A descriptive, observational, cross-sectional study was performed. We recorded information on sociodemographic and clinical characteristics, incidents and interventions during treatment in all patients with TB diagnosed between September 2013 and August 2016. Results 172 patients were included, 62.2% were foreign-born. The most common incidents and threats were medication-related complications (43.0%), missed follow-up visits (34.3%), communication problems (25.6%), comorbidities complications (23.8%), trips (19.2%), fear of social rejection (16.9%) and change of address (14.5%). The adherence-promoting interventions were: follow-up calls, directly observed treatment, medical and humanitarian reports, extra visits and cultural mediation. Incidents and interventions were more frequent in foreign-born patients, however there were no differences in treatment success among Spanish and foreign-born. Conclusion In this inner city several incidents occurred during TB treatment that can threaten adherence and are more common among foreign-born patients. Coordination among professionals from different healthcare settings was able to overcome obstacles in most cases and achieve TB treatment completion.

Background Patients with a history of tuberculosis (TB) have a high probability of recurrence because long-term cure is not always maintained in successfully treated patients. The aim of this study was to identify the probability of TB recurrence and its predictive factors in a cohort of socially vulnerable patients who completed treatment in the TB referral center in Catalonia, which acts as the center for patients with social and health problems. Methods This retrospective open cohort study included all patients diagnosed with TB who were admitted and successfully treated in Serveis Clinics between 2000 and 2016 and who remained disease-free for a minimum of 1 year after treatment completion. We calculated the incidence density of TB recurrences per person-years of follow-up. We also estimated the cumulative incidence of TB recurrence at 1, 2, 5, and 10 years of follow-up. Bivariate analysis was conducted using Kaplan-Meier curves. Multivariate analysis was conducted using Cox regression. Hazard ratios (HR) were calculated with their 95% confidence intervals (95%CI). Results There were 839 patients and 24 recurrences (2.9%), representing 0.49 per 100 person-years. The probability of a recurrence was 0.63% at 1 year of follow-up, 1.35% at 2 years, and 3.69% at 5 years. The multivariate analysis showed that the predictive factors of recurrence were age older than 34 years (aHR = 3.90; CI = 1.06-14.34 at age 35-45 years and aHR = 3.88; CI = 1.02-14.80 at age > 45 years) and resistance to at least one anti-TB drug (aHR = 2.91; CI = 1.11-7.65). Conclusions Attention should be paid to socially vulnerable persons older than 34 years with a previous episode of resistant TB. Surveillance resources should be directed toward adequately treated patients who nevertheless have a high risk of recurrence.

In 2012, the Spanish government enforced a healthcare exclusion policy against undocumented immigrants. The newly elected government has recently derogated this policy. To analyze how this decree could have affected population health, we looked at primary health patients who would have been excluded and compared with a matched sample of non-excluded patients. Potentially excluded patients had decreased odds of: depression, chronic obstructive pulmonary disease, dyslipidaemia, heart failure and hypertension while diabetes mellitus rates were similar to non-excluded. Infectious diseases were more frequent in potentially excluded population (HIV, tuberculosis and syphilis). The exclusion of patients impedes the control of infectious diseases at a community level.

Despite efforts to improve tuberculosis (TB) detection, limitations in access, quality and timeliness of diagnostic services in low- and middle-income countries are challenging for current TB diagnostics. This study aimed to identify and characterise a metabolic profile of TB in urine by high-field nuclear magnetic resonance (NMR) spectrometry and assess whether the TB metabolic profile is also detected by a low-field benchtop NMR spectrometer. We included 189 patients with tuberculosis, 42 patients with pneumococcal pneumonia, 61 individuals infected with latent tuberculosis and 40 uninfected individuals. We acquired the urine spectra from high and low-field NMR. We characterised a TB metabolic fingerprint from the Principal Component Analysis. We developed a classification model from the Partial Least Squares-Discriminant Analysis and evaluated its performance. We identified a metabolic fingerprint of 31 chemical shift regions assigned to eight metabolites (aminoadipic acid, citrate, creatine, creatinine, glucose, mannitol, phenylalanine, and hippurate). The model developed using low-field NMR urine spectra correctly classified 87.32%, 85.21% and 100% of the TB patients compared to pneumococcal pneumonia patients, LTBI and uninfected individuals, respectively. The model validation correctly classified 84.10% of the TB patients. We have identified and characterised a metabolic profile of TB in urine from a high-field NMR spectrometer and have also detected it using a low-field benchtop NMR spectrometer. The models developed from the metabolic profile of TB identified by both NMR technologies were able to discriminate TB patients from the rest of the study groups and the results were not influenced by anti-TB treatment or TB location. This provides a new approach in the search for possible biomarkers for the diagnosis of TB.

Las infecciones por arbovirus son un grupo de enfermeda - des cuya incidencia está aumentando y que suponen un problema importante para la salud pública. El objetivo de este estudio fue describir los casos detec - tados de arbovirosis en la ciudad de Barcelona y las actuaciones de vigilancia y control realizadas para reducir el riesgo de transmisión. Métodos: Estudio descriptivo transversal de casos confirmados de den - gue, chikungunya y Zika en Barcelona durante el período de 2014 al 2016. Los casos sospechosos detectados en la ciudad se notificaron al Servicio de Epidemiología de la Agencia de Salud Pública de Barcelona (ASPB), don - de se realizó una encuesta epidemiológica y, si procedía, se contactaba con el Servicio de Vigilancia y Control de Plagas Urbanas. Desde allí se realizó la inspección entomológica y se llevaron a cabo acciones de control y segui - miento. Se recogieron variables sociodemográficas, epidemiológicas, clínicas y entomológicas de los casos. Resultados: En 2014 se detectaron 50 casos de virus chikungunya y 20 de dengue, realizándose 25 inspecciones entomológicas en domicilios y 38 en la vía pública. En 2015 se detectaron 47 casos de chikungunya, 51 de dengue y 2 de Zika, realizándose 27 inspecciones entomológicas en domicilios y 80 en vía pública. En 2016 se detectaron 17 casos de chikungunya, 52 de dengue y 48 de Zika, realizándose 50 inspecciones entomológicas en domicilio y 103 en vía pública. No se detectó ningún caso autóctono. Conclusiones: Se observó un aumento creciente de los casos de arboviro - sis durante los 3 años de estudio. Se intensificaron progresivamente las actua - ciones de vigilancia y control vectorial (inspecciones, muestras recogidas...).

Introduction: Treatment of MDRTB is complex: regimens require microbiological data; adverse events are frequent; availability of drugs and authorization for new drugs varies. The aim of this study was to scope the available national resources. Method: A survey to determine whether practising physicians could access MDRTB advice was sent to TBnet members by email. The ERS Office also contacted national respiratory societies. Questions included the name and contact details for their national advisory service, whether it was national policy to use the service for each patient with MDRTB and whether advice was required to access bedaquiline and delaminid. Results: 65 replies were received (14 were uninformative). 26/31 EU/EEA and 10/19 other countries in the WHO European Region were represented. 7 countries referred all MDRTB to a tertiary centre; 12 countries had tertiary referral centres that also gave advice to physicians treating MDRTB. 11 countries had an electronic system for advice, 6 with multidisciplinary team meetings to review patients’ progress. Lead clinicians were identified for a further 8 countries, one of which had no national advisory service and the other 7 had not responded by the time of abstract submission. For 18 (58%) countries, discussion of MDRTB by a national /regional committee was national policy and most (15/18) required consultation to use bedaquiline or delamanid. Electronic platforms had a wide range of functionality but few retained anonymised data and audited patient outcomes. Conclusion: MDRTB management is often concentrated in tertiary centres. Clinical governance, regarding audit and outcome, are at an early stage in managing MDRTB.

Well-coordinated multidisciplinary teams are essential for better tuberculosis (TB) control. Our objective was to evaluate the impact of Spanish Society of Pneumology (SEPAR) accreditation of TB Units (TBU) and to determine differences between the accredited and non-accredited centers.Observational descriptive study based on a self-administered survey from October 2014 to February 2018 completed by 139 heads of respiratory medicine departments collected by SEPAR, before and after TBU accreditation.demographic, epidemiological and contact tracing (CT) variables, among others.basic descriptive analysis, and calculation of medians for continuous variables and proportions for categorical variables. The variables were compared using the Chi-squared test and logistic regression.The response rate was 54.7% and 43.2% in the pre- and post-TBU accreditation period, respectively. No differences were observed in the care and coordination variables between the pre- and post-accreditation survey, nor in the organization when only accredited centers were analyzed. When we compared the accredited and non-accredited centers, significant differences were detected in the collection of the final conclusion, management of resistance, coordination with other departments, contact tracing, and directly observed treatment.The approach of different professionals with regard to TB has been addressed. Positive aspects and areas for improvement have been detected, and better results were observed in the accredited versus non-accredited centers. A closer supervision of TBUs is necessary to improve their effectiveness.

Background: Expanding latent tuberculosis treatment is important to decrease active disease globally. Once-weekly isoniazid and rifapentine for 12 doses is effective but limited by requiring direct observation. Objective: To compare treatment completion and safety of once-weekly isoniazid and rifapentine by self-administration versus direct observation. Design: An open-label, phase 4 randomized clinical trial designed as a noninferiority study with a 15% margin. Seventy-five percent or more of study patients were enrolled from the United States for a prespecified subgroup analysis. (ClinicalTrials. gov: NCT01582711) Setting: Outpatient tuberculosis clinics in the United States, Spain, Hong Kong, and South Africa. Participants: 1002 adults (aged >= 18 years) recommended for treatment of latent tuberculosis infection. Intervention: Participants received once-weekly isoniazid and rifapentine by direct observation, self-administration with monthly monitoring, or self-administration with weekly text message reminders and monthly monitoring. Measurements: The primary outcome was treatment completion, defined as 11 or more doses within 16 weeks and measured using clinical documentation and pill counts for direct observation, and self-reports, pill counts, and medication eventmonitoring devices for self-administration. The main secondary outcome was adverse events. Results: Median age was 36 years, 48% of participants were women, and 77% were enrolled at the U. S. sites. Treatment completion was 87.2% (95% CI, 83.1% to 90.5%) in the directobservation group, 74.0% (CI, 68.9% to 78.6%) in the selfadministration group, and 76.4% (CI, 71.3% to 80.8%) in the self-administration-with-reminders group. In the United States, treatment completion was 85.4% (CI, 80.4% to 89.4%), 77.9% (CI, 72.7% to 82.6%), and 76.7% (CI, 70.9% to 81.7%), respectively. Self-administered therapy without reminders was noninferior to direct observation in the United States; no other comparisons met noninferiority criteria. A few drug-related adverse events occurred and were similar across groups. Limitation: Persons with latent tuberculosis infection enrolled in South Africa would not routinely be treated programmatically. Conclusion: These results support using self-administered, once-weekly isoniazid and rifapentine to treat latent tuberculosis infection in the United States, and such treatment could be considered in similar settings when direct observation is not feasible.

Este artículo contiene 13 páginas, 6 figuras, 1 tabla., Background: On February 1st 2016 the WHO declared the Zika Virus (ZIKV) infection a worldwide public health emergency because of its rapid expansion and severe complications, such as Guillain-Barré Syndrome or microcephaly in newborn. The huge amount of people traveling to endemic areas and the presence of Aedes albopictus in Barcelona increase the risk of autochtonous transmission. The objective of this study was to describe the first ZIKV cases diagnosed in our city and to analyze the surveillance, prevention, and control measures implemented to avoid autochthonous transmission. Methods: An observational cross-sectional population-based study in Barcelona, Spain was performed.An analysis of the socio-demographic, epidemiological, clinical characteristics, and mosquito control activities of the ZIKV cases detected between January 1st and December 2016 was carried out using a specific ZIKV epidemiological survey of the Barcelona Public Health Agency. Results: A total of 118 notifications of possible ZIKV infections were received, and 44 corresponded to confirmed cases in Barcelona residents.Amongst these, the median age was 35 years and 57% were women. All cases were imported, 48% were Spanish-born and 52% foreign-born. Dominican Republic was the most visited country amongst foreign-born patients and Nicaragua amongst Spanish-born. The most frequent symptoms were exanthema, fever, and arthralgia. Among the 24 diagnosed women, 6 (25%) were pregnant. There was one case of microcephaly outside Barcelona city. Entomological inspections were done at the homes of 19 cases (43.2% of the total) and in 34 (77.3%) public spaces. Vector activity was found in one case of the 44 confirmed cases, and 134 surveillance and vector control were carried out associated to imported ZIKV cases. In all cases prevention measures were recommended to avoid mosquito bites on infected cases.Conclusion: Epidemiological and entomological surveillance are essential for the prevention of autochthonous transmission of arbovirosis that may have a great impact on Public Health.The good coordination between epidemiologists, entomologists, microbiologists, and clinicians is a priority in a touristic city with an intense relationship with endemic countries to minimize the risk of local transmission by competent vectors., MJ, JG, NR, and JM receives funds from 2014 SGR 26 grant from the Department d’Universitats, Recerca i Societat de la Informacio de la Generalitat de Catalunya (AGAUR) and from RD12/0018/0010 grant, ISCIII RETIC (MICINN, Spain). PROSICS authors are supported by the 6th National Plan (PN) of Research + Development + Innovation (I + D + I) 2008–2011, ISCIII-General Division Networks and Cooperative Research Centres + FEDER funds + Collaborative Research Network on Tropical Diseases (RICET): RD12/0018/0020.

INTRODUCTION The Barcelona Tuberculosis Programme was established in 1987, and in 2007 five tuberculosis (TB) clinical units were created to improve the follow-up of cases and contacts. This included the designation of a nurse for case management. OBJECTIVE To assess the impact of the TB clinical units on the screening programme for TB contacts. METHODS Before-after population-based study before (2003-2007) and after (2008-2013) the creation of the clinical units. To determine which factors were related to contact tracing, we fitted a multivariate logistic regression model to estimate odds ratios (OR) with their 95% confidence intervals (CIs). RESULTS Following the creation of the clinical units, the proportion of prescriptions for latent tuberculous infection among contacts in the clinical units increased from 40.7% to 57.4% (P < 0.001), and treatment adherence from 75.9% to 80.3% (P = 0.035). One factor associated with contact tracing was receiving care after the creation of the clinical units (2008-2013) (OR 1.2, 95%CI 1.0-1.3). During the second period, receiving care outside the clinical units reduced the probability of contact tracing (OR 0.7, 95%CI 0.5-0.9). CONCLUSION The creation of the TB clinical units represents an organisational improvement for the study and management of contacts of patients with TB.

Background The increase in immigration in Barcelona between 2000 and 2008 forced a reorganization of the control of tuberculosis (TB). TB clinical units (TBCU) were created and community health workers (CHW) were gradually included. Objective To understand trends in the incidence of TB among immigrants, their main characteristics and treatment compliance during the period 1991-2013. Design We conducted a cross-sectional population-based study of cases detected among immigrants by the Tuberculosis Program in Barcelona, Spain. Sociodemographic, clinical characteristics and risk factors were described. The annual incidence was calculated for various periods and geographical areas of origin. In the linear trend analysis, a p-value of

Objectives: To investigate the immune response against M. tuberculosis (MTB) by Interferon Gamma Release Assays (IGRAs) in Tuberculosis (TB) and Latent TB Infected (LTBI) patients exposed to cigarette smoke. Methods: A cross sectional study from two clinics in Barcelona. Subjects included were: (i) 216 active pulmonary TB, (ii) 309 asymptomatic contact tracing individuals. At first visit blood was collected for IGRAs. The impact of cigarette smoke on MTB immune response was analyzed as the median of IFN-γ secreted (UI/mL) in QFN-G-IT and as the number (median) of T-cells producing IFN-γ [spot forming cells (SFC)] in T-SPOT.TB. Results: False-negative results in TB patients were higher in smokers (aOR:4.42; p Conclusions: Tobacco exposure was associated with IGRAs false-negative results in TB patients and was an independent risk factor for LTBI acquisition. A less IFN-γ response was observed in smokers than non-smokers. An increment on tobacco smoking produces a reduction on immune responses observed by both IGRAs. PII –Tabaquismo. 2013 SEPAR grant.

Arbovirus infections are a group of diseases whose incidence is increasing and that entail an important problem for public health. The aim of this study was to describe detected cases of arbovirosis in Barcelona, and surveillance and control actions performed in order to reduce the risk of transmission.Descriptive cross-sectional study of confirmed dengue, chikungunya and Zika cases in Barcelona during 2014-2016 (1st trimester). Suspected cases detected in the city were notified to the Epidemiology Department of the Barcelona Public Health Agency, where an epidemiological survey is undertaken and, if appropriate, Urban Pests Surveillance and Control Department is contacted. They perform an entomological inspection and implement control and monitoring actions. We collected sociodemographical, epidemiological, clinical and entomological variables.In 2014, 50 chikungunya and 20 dengue cases were detected; 25 entomological inspections were carried out in residences and 38 in the street. In 2015, 47 chikungunya, 51 dengue and 2 Zika cases were detected; 27 inspections were carried out in residences and 80 in the street. In 2016, 17 chikungunya, 52 dengue and 48 Zika cases were detected; 50 inspections were carried out in residences and 103 in the street. No autochtonous case was detected.We observed an increasing incidence of arbovirosis cases during the 3-year study period. There was a progressive intensification of vector surveillance and control actions (inspections, sample collection…).Las infecciones por arbovirus son un grupo de enfermedades cuya incidencia está aumentando y que suponen un problema importante para la salud pública. El objetivo de este estudio fue describir los casos detectados de arbovirosis en la ciudad de Barcelona y las actuaciones de vigilancia y control realizadas para reducir el riesgo de transmisión.Estudio descriptivo transversal de casos confirmados de dengue, chikungunya y Zika en Barcelona durante el período de 2014 al 2016. Los casos sospechosos detectados en la ciudad se notificaron al Servicio de Epidemiología de la Agencia de Salud Pública de Barcelona (ASPB), donde se realizó una encuesta epidemiológica y, si procedía, se contactaba con el Servicio de Vigilancia y Control de Plagas Urbanas. Desde allí se realizó la inspección entomológica y se llevaron a cabo acciones de control y seguimiento. Se recogieron variables sociodemográficas, epidemiológicas, clínicas y entomológicas de los casos.En 2014 se detectaron 50 casos de virus chikungunya y 20 de dengue, realizándose 25 inspecciones entomológicas en domicilios y 38 en la vía pública. En 2015 se detectaron 47 casos de chikungunya, 51 de dengue y 2 de Zika, realizándose 27 inspecciones entomológicas en domicilios y 80 en vía pública. En 2016 se detectaron 17 casos de chikungunya, 52 de dengue y 48 de Zika, realizándose 50 inspecciones entomológicas en domicilio y 103 en vía pública. No se detectó ningún caso autóctono.Se observó un aumento creciente de los casos de arbovirosis durante los 3 años de estudio. Se intensificaron progresivamente las actuaciones de vigilancia y control vectorial (inspecciones, muestras recogidas…).

Aims and objectives: There is a bidirectional association between the Diabetes Mellitus (DM) and Tuberculosis (TB). The study objectives are to know the response and Treatment Outcomes of this Association in a specialized DOT clinical unit. Methods: Cross-sectional analytical study of patients admitted to DOT with relation to the TB-DM and the outcome of TB treatment, during the period 2000-2014. We will to compare socio-demographic, clinical data, evolution and treatment outcomes of the TB-DM against TB-non-DM patients. Results: 1722 TB cases were adnitted: 100 were diabetics (DM type1: 11; DM type 2: 89).TB-DM patients were more aged (p Conclusions: Conclusions: Patients with TB-DM are difficult to control but through the DOT strategy can be managed to get treatment outcomes as the TB-non-DM. Some studies show high rates of treatment failure in this group. The DOT strategy can help to improve this problem.

Resumen Objetivo Conocer la proporción de población potencialmente excluida de cobertura sanitaria a partir del Real Decreto-Ley 16/2012. Describir el uso de servicios sanitarios, la distribución de patología crónica e infecciosa y el gasto farmacéutico en 2012 de las personas excluidas respecto a las que mantendrían su cobertura. Diseño y emplazamiento Estudio observacional analítico transversal de base poblacional en atención primaria. Gerencia Territorial de la Cataluña Central del Institut Català de la Salut. Participantes y mediciones principales Se seleccionaron las personas potencialmente excluidas a partir de la aplicación del Real Decreto-Ley 16/2012 y se compararon con las personas que mantendrían su cobertura sanitaria apareadas de forma aleatoria por edad, sexo y servicio de atención primaria. La información obtenida incluyó el uso de servicios sanitarios, la distribución de patologías crónicas e infecciosas y el gasto farmacéutico durante el año 2012. Resultados Se identificaron 1.699 personas, el 0,53% del total de la población (51,4% hombres), con una mediana de edad de 34 años (rango intercuartílico, 28-43) potencialmente excluidas de cobertura sanitaria. El uso de servicios sanitarios, la morbilidad crónica registrada y el gasto farmacéutico durante el año 2012 de los excluidos fueron inferiores a los de los no excluidos (p

ResumenEl control de la tuberculosis exige nuevas pautas terapéuticas que superen las actuales, disponibles desde hace más de 30 años. En virtud de un acuerdo, siete centros de la Unitat d'Investigació en Tuberculosi de Barcelona (UITB) vienen colaborando con la División para la Eliminación de la Tuberculosis de los Centers for Disease Control de Estados Unidos en el desarrollo de diversos ensayos clínicos en el tratamiento de la infección y la enfermedad tuberculosa. La colaboración se inició en 2004 con el Estudio 26, que compara la eficacia y la tolerabilidad de rifapentina + isoniazida administradas una vez por semana durante tres meses frente a la pauta estándar, para la forma latente. Incluimos 246 sujetos (3% del total). En febrero de 2008 se cerró la inclusión general. El estudio permanece abierto para sujetos VIH positivos y niños. Tratar con 12 dosis y no con 270 (terapia estándar) supondrá un éxito evidente. Habrá que esperar, sin embargo, hasta 2010 para conocer el análisis. El Estudio 28 (iniciado en 2006) comparó, para el tratamiento de la tuberculosis pulmonar, la pauta estándar con una experimental en la cual la isoniazida se sustituyó por moxifloxacino. La UITB incluyó 15 pacientes (3,5% del total). Los resultados provisionales (presentados en la 47o Interscience Conference on Antimicrobial Agents and Chemotherapy de Chicago de 2007) no mostraron diferencias entre las dos pautas en la conversión del esputo a las 8 semanas de tratamiento. Recientemente hemos comenzado el Estudio 29, en el cual la rifapentina sustituye a la rifampicina en la pauta estándar de tratamiento.AbstractNew treatment guidelines are required to improve the tuberculosis control strategies that have been used for 30 years. Seven centers of the Barcelona Tuberculosis Research Unit (BTRU) (Unitat d'Investigació en Tuberculosi de Barcelona) are collaborating with the Division of Tuberculosis Elimination of the United States Centers for Disease Control and Prevention in a series of clinical trials on latent tuberculosis infection and tuberculosis disease. BTRU participation began in 2004 with Study 26, an evaluation of the efficacy and tolerability of rifapentine plus isoniazid administered once weekly for 3 months compared with the standard treatment for latent tuberculosis infection. The BTRU centers together enrolled 246 patients (3% of the total). General enrollment was completed in February, 2008. HIV-infected patient and child enrollment continues. Treatment with 12 doses instead of 270 doses is expected to be a clear success. However, the analysis will be completed in 2010. Study 28 (started in 2006), designed for the treatment of pulmonary tuberculosis, compared standard treatment with an experimental regimen substituting moxifloxacin for isoniazid. BTRU centers together enrolled 15 patients (3.5% of the total). The provisional results (presented at the 47th Interscience Conference on Antimicrobial Agents and Chemotherapy in Chicago, 2007) showed no difference between the sputum conversion rate of each regimen at week 8 of treatment. Study 29 is currently underway, in which rifapentine was introduced in the experimental regimen for active tuberculosis treatment.

ResumenObjetivoConocer la proporción de población potencialmente excluida de cobertura sanitaria a partir del Real Decreto-Ley 16/2012. Describir el uso de servicios sanitarios, la distribución de patología crónica e infecciosa y el gasto farmacéutico en 2012 de las personas excluidas respecto a las que mantendrían su cobertura.Diseño y emplazamientoEstudio observacional analítico transversal de base poblacional en atención primaria. Gerencia Territorial de la Cataluña Central del Institut Català de la Salut.Participantes y mediciones principalesSe seleccionaron las personas potencialmente excluidas a partir de la aplicación del Real Decreto-Ley 16/2012 y se compararon con las personas que mantendrían su cobertura sanitaria apareadas de forma aleatoria por edad, sexo y servicio de atención primaria. La información obtenida incluyó el uso de servicios sanitarios, la distribución de patologías crónicas e infecciosas y el gasto farmacéutico durante el año 2012.ResultadosSe identificaron 1.699 personas, el 0,53% del total de la población (51,4% hombres), con una mediana de edad de 34años (rango intercuartílico, 28-43) potencialmente excluidas de cobertura sanitaria. El uso de servicios sanitarios, la morbilidad crónica registrada y el gasto farmacéutico durante el año 2012 de los excluidos fueron inferiores a los de los no excluidos (p