Risk of tuberculosis among pulmonary tuberculosis contacts: the importance of time of exposure to index cases.

INTRODUCTION: The intensity of exposure to index cases of tuberculosis [TB] may increase the risk of TB in their contacts. The aim was to determine TB risk factors among contacts of TB index cases. METHODS: A cohort study was carried out in the contacts of pulmonary TB cases registered by the epidemiological surveillance network from 01/01/2019 to 06/30/2021. The factors associated with the risk of TB in contacts were determined using the adjusted odds ratio [aOR] and its 95% confidence interval [CI]. RESULTS: From 847 TB cases, 7087 contacts were identified. The prevalence of TB was 2.0% [145/7087] and was higher in < 5 years compared to those ≥ 65 years [4.4% versus 1.2%; p < 0.001], in those exposed ≥ 6 h daily [4%], and < 6 h daily [1.6%] with respect to weekly exposure of < 6 h [0.7%; p < 0.001]. Those contacts exposed ≥ 6 h daily [aOR= 6.9; 95%CI:2.1-22.1], < 5 years [aOR= 8.3; 95%CI:1.8-37.8] and immigrants [aOR= 1.7; 95%CI:1.1-2.7] had a higher risk of TB. CONCLUSIONS: The risk of TB increases with the time of exposure to the index case and this risk is also higher in < 5 years and immigrants. Contact tracing has a high yield for detecting new cases of TB.

Glycemic control and the risk of tuberculosis in patients with diabetes: A cohort study in a Mediterranean city.

Background: Diabetes 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. Methods: We 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. Results: Of 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. Conclusion: Diabetic subjects with worse glycemic control show a trend toward a higher risk of developing TB.

Subjects With Diabetes Mellitus Are at Increased Risk for Developing Tuberculosis: A Cohort Study in an Inner-City District of Barcelona (Spain).

Background: Tuberculosis 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. Objective: To investigate whether diabetic patients were at increased risk of tuberculosis living in an inner-district of a large city of northeastern Spain. Methods: Observational 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). Results: Among 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). Conclusion: People 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.

El papel de los farmacéuticos comunitarios en la prevención y control de la Covid-19 en Cataluña / Role of community pharmacists in the prevention and control of Covid-19 in Catalonia

Introducción: En las últimas décadas, tanto la farmacia como el farmacéutico han estado en constante evolución, siendo fundamentales en el control de enfermedades infecciosas. Los objetivos de este artículo son mostrar el papel de los farma-céuticos comunitarios en el control de la COVID-19 y conocer la percepción que tienen sobre su papel en el control de esta pandemia.Métodos: Se realizó y envió una encuesta a 8556 farmacéuticos comunitarios colegiados en Cata-luña, donde se les preguntaba por su opinión y la percepción que tenían de su rol en distintas acti-vidades de control de la COVID-19. Se realizó un análisis bivariante y descriptivo de las diferentes variables de la encuesta de manera global y estra-tificado por grupos de edad (<40 años, 40-60 años, >60 años) y por tipo de farmacia (urbana vs otras).Resultados: La tasa de respuesta de la encuesta fue del 14,63% (1253). A pesar de la percepción po-sitiva que tienen los farmacéuticos sobre su rol en la pandemia, el 90,9% de los encuestados conside-ra que la Administración Sanitaria no contó mucho con las farmacias al inicio de esta. Se han encon-trado diferencias estadísticamente significativas en determinados aspectos, como por ejemplo en la percepción que el farmacéutico tiene sobre el nivel de información del usuario, o en la frecuencia de encuentros con negacionistas, ambos hechos rela-cionados con la edad del farmacéutico (p=0,047 y p=0,001 respectivamente).Conclusiones: Las farmacias son establecimientos sanitarios estratégicamente posicionados para rea-lizar actividades de salud pública para colaborar en el control de pandemias. Por lo que el farmacéutico comunitario, en tanto que profesional de la salud, debe ser considerado una pieza más del engranaje para mejorar la eficiencia del sistema sanitario (AU)

Background: In the last decades, both pharmacy and pharmacist have been in a constant evolution, being fundamental in the control of infectious dis-eases. The aim of this research is to show the role of community pharmacists in disease prevention and monitoring programs, specifically in the control of COVID-19. Besides, we want to know the percep-tion of pharmacists about their role in the control of the COVID-19 pandemic.Methods: An online survey was sent to 8556 community pharmacists registered in Catalonia, in which they were asked about their opinion and perception of their role in different COVID-19 control activities. A bivariant and descriptive analysis of the different variables was done globally, age stratified (<40 years, 40-60 years, >60 years) and according to the type of pharmacy (urban vs others).Results: The response rate was 14.63% (1253). However, despite the positive perception that pharmacists have about their role in the pandemic, 90,9% of the respondents consider that the Health Administration didn’t count much on them. Statistic significative differences were found in some as-pects, for example, in the pharmacists’ perception of the knowledge level of the pharmacy users, or in the frequency of encounters with COVID negation-ists, both aspects related with the pharmacist age (p=0,047 and p=0,0001 respectively).Conclusions: Pharmacies are sanitary establish-ments strategically located to perform public health activities and to control pandemics. Therefore, the pharmacist, as a health professional, should be considered one more piece of the gear to improve the efficiency of the health system (AU)

Impact of the COVID-19 pandemic on contact tracing of patients with pulmonary tuberculosis.

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 < 0.001). The pandemic period was associated to higher LTBI proportion (aOR = 1.3; 95% CI 1.1-1.5), taking into account the effect on LTBI of the other variables studied as sex, age, household contact and migrant status. 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.

Epidemiological characteristics and outcomes of COVID-19 cases: mortality inequalities by socio-economic status, Barcelona, Spain, 24 February to 4 May 2020.

BackgroundPopulation-based studies characterising outcomes of COVID-19 in European settings are limited, and effects of socio-economic status (SES) on outcomes have not been widely investigated. AimWe describe the epidemiological characteristics of COVID-19 cases, highlighting incidence and mortality rate differences across SES during the first wave in Barcelona, Catalonia, Spain.MethodsThis population-based study reports individual-level data of laboratory-confirmed COVID-19 cases diagnosed from 24 February to 4 May 2020, notified to the Public Health Agency of Barcelona and followed until 15 June 2020. We analysed end-of-study vital status and the effects of chronic conditions on mortality using logistic regression. Geocoded addresses were linked to basic health area SES data, estimated using the composed socio-economic index. We estimated age-standardised incidence, hospitalisation, and mortality rates by SES.ResultsOf 15,554 COVID-19-confirmed cases, the majority were women (n = 9,028; 58%), median age was 63 years (interquartile range: 46-83), 8,046 (54%) required hospitalisation, and 2,287 (15%) cases died. Prevalence of chronic conditions varied across SES, and multiple chronic conditions increased risk of death (≥ 3, adjusted odds ratio: 2.3). Age-standardised rates (incidence, hospitalisation, mortality) were highest in the most deprived SES quartile (incidence: 1,011 (95% confidence interval (CI): 975-1,047); hospitalisation: 619 (95% CI: 591-648); mortality: 150 (95% CI: 136-165)) and lowest in the most affluent (incidence: 784 (95% CI: 759-809); hospitalisation: 400 (95% CI: 382-418); mortality: 121 (95% CI: 112-131)).ConclusionsCOVID-19 outcomes varied markedly across SES, underscoring the need to implement effective preventive strategies for vulnerable populations.

Threats and Interventions During the Treatment of Tuberculosis in an Inner-city District / Factores de riesgo e intervenciones durante el tratamiento de la tuberculosis en un barrio marginal

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. (AU)

Antecedentes: Dado que existen medicamentos activos contra la tuberculosis (TB), las medidas de control más efectivas son asegurar la adherencia al tratamiento y realizar un seguimiento cercano. Debido a la larga duración del tratamiento y las características de algunos pacientes con TB, pueden entrar en juego ciertos factores que hacen peligrar la adherencia al tratamiento. Identificar estos factores y abordarlos es esencial para lograr los objetivos de control de la enfermedad.Objetivos: Identificar las características epidemiológicas de los pacientes con TB y los incidentes y factores que tienen lugar durante el tratamiento, describir las intervenciones realizadas para mejorar la adherencia al tratamiento y determinar si existen diferencias entre los pacientes nativos y extranjeros en la Unidad Clínica de TB de un hospital de referencia en el centro de la ciudad de Barcelona.Métodos: Se realizó un estudio descriptivo, observacional y transversal. Registramos las características sociodemográficas y clínicas de todos los pacientes con TB diagnosticados entre septiembre de 2013 y agosto de 2016, así como los incidentes y las intervenciones realizadas durante el tratamiento.Resultados: Se incluyeron 172 pacientes, el 62,2% eran nacidos en el extranjero. Los incidentes y los factores de riesgo más comunes fueron: complicaciones relacionadas con la medicación (43,0%), visitas de seguimiento perdidas (34,3%), problemas de comunicación (25,6%), complicaciones de las comorbilidades (23,8%), viajes (19,2%), miedo al rechazo social (16,9%) y cambio de domicilio (14,5%). Las intervenciones para el fomento de la adherencia fueron: llamadas de seguimiento, tratamiento directamente observado, informes médicos y humanitarios, visitas adicionales y mediación cultural. Los incidentes e intervenciones fueron más frecuentes en pacientes nacidos en el extranjero; sin embargo, no hubo diferencias en el éxito del tratamiento entre españoles y nacidos en el extranjero. (AU)

Threats and Interventions During the Treatment of Tuberculosis in an Inner-city District.

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.

Tuberculosis infection in children visiting friends and relatives in countries with high incidence of tuberculosis: A study protocol.

INTRODUCTION: Tuberculosis (TB) is a global infectious disease. In low-incidence countries, paediatric TB affects mostly immigrant children and children of immigrants. We hypothesize that these children are at risk of exposure to Mycobacterium tuberculosis when they travel to the country of origin of their parents to visit friends and relatives (VFR). In this study, we aim to estimate the incidence rate and risk factors associated to latent tuberculosis infection (LTBI) and TB in VFR children. METHODS AND ANALYSIS: A prospective study will be carried out in collaboration with 21 primary health care centres (PCC) and 5 hospitals in Catalonia, Spain. The study participants are children under 15 years of age, either immigrant themselves or born to immigrant parents, who travel to countries with high incidence of TB (≥ 40 cases/100,000 inhabitants). A sample size of 492 children was calculated. Participants will be recruited before traveling, either during a visit to a travel clinic or to their PCC, where a questionnaire including sociodemographic, epidemiological and clinical data will be completed, and a tuberculin skin test (TST) will be performed and read after 48 to 72 hours; patients with a positive TST at baseline will be excluded. A visit will be scheduled eight to twelve-weeks after their return to perform a TST and a QuantiFERON-TB Gold Plus test. The incidence rate of LTBI will be estimated per individual/month and person/year per country visited, and also by age-group. ETHICS AND DISSEMINATION: The study protocol was approved by the Clinical Research Ethics Committee of the Hospital Universitari Mútua Terrassa (code 02/16) and the Clinical Research Ethics Committee of the Fundació Institut Universitari per a la Recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (code P16/094). Articles will be published in indexed scientific journals. TRIAL REGISTRATION: Clinical-Trials.gov: NCT04236765.

Correction: Epidemiology of Tuberculosis in Immigrants in a Large City with Large-Scale Immigration (1991-2013).

[This corrects the article DOI: 10.1371/journal.pone.0164736.].

Evidences supporting the inclusion of immigrants in the universal healthcare coverage.

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.

Organización del control de la tuberculosis en España: evaluación de una estrategia dirigida a fomentar la acreditación de unidades de tuberculosis / Organization of Tuberculosis Control in Spain: Evaluation of a Strategy Aimed at Promoting the Accreditation of Tuberculosis Units

INTRODUCCIÓN: Un buen control de la tuberculosis (TB) requiere disponer de personal multidisciplinario bien coordinado. El objetivo fue evaluar el impacto de la acreditación de unidades de TB (UTB) fomentada por la Sociedad Española de Neumología (SEPAR) y ver las diferencias entre los centros que se acreditaron y los que no. MATERIAL Y MÉTODOS: DISEÑO: Estudio observacional descriptivo basado en una encuesta autoadministrada entre octubre de 2014 y febrero de 2018 a 139 responsables de neumología registrados por SEPAR, antes y después de la acreditación. VARIABLES: demográficas, epidemiológicas y sobre estudio de contactos, entre otras. Análisis: descriptiva básica, cálculo de medianas para variables continuas y proporciones para categóricas. Se compararon las variables mediante el test chi-cuadrado y regresión logística. RESULTADOS: La tasa de respuesta fue del 54,7 y del 43,2% en el período pre- y postacreditación de UTB, respectivamente. No se observaron cambios en los diferentes ámbitos de atención y coordinación entre la encuesta pre- y postacreditación, ni tampoco en la organización, al analizar los centros acreditados. Al comparar los centros que se acreditaron con los que no, se detectaron diferencias significativas con relación a recogida de conclusión final, manejo de resistencias, coordinación con otros servicios, estudios de contactos o tratamiento directamente observado. CONCLUSIONES: Se ha objetivado cómo 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 supervisión 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 (CT) 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

Tuberculosis recurrences and predictive factors in a vulnerable population in Catalonia.

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 Clínics 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.

Organization of Tuberculosis Control in Spain: Evaluation of a Strategy Aimed at Promoting the Accreditation of Tuberculosis Units. / Organización del control de la tuberculosis en España: evaluación de una estrategia dirigida a fomentar la acreditación de unidades de tuberculosis.

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. 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 (CT) 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.

Clinical Presentations and Outcomes Related to Tuberculosis in Children Younger Than 2 Years of Age in Catalonia.

Introduction: Children younger than 2 years have an increased risk of complications associated with tuberculosis (TB) due to the immaturity of the innate and adaptive immune response. We aimed to identify TB clinical presentations and outcomes as well as risk factors for complications in this age group. Materials and Methods: Multicenter, retrospective, cross-sectional study of TB cases in children aged <2 years in Catalonia (2005-2013). Epidemiological and clinical data were collected from the hospital medical records. TB complications, sequelae included, were defined as any tissue damage generating functional or anatomical impairment after being diagnosed or after TB treatment being completed. Statistical analyses were based on bivariate chi-square and multivariate logistic regression, and it was carried out with Stata® version 13.1. Odds ratios (OR) and its 95% confidence intervals were calculated (CI). Results: A total of 134 patients were included, 50.7% were male, the median [IQR] age was 13[8-18] months, and 18.7% (25/134) showed TB-associated complications. Pulmonary TB was diagnosed in 94.0% (126/134) of children, and the most common complications were lobar collapse (6/126). TB meningitis was diagnosed in 14/134 (10.4%), and hydrocephalus and mental impairment occurred in 1 and 2 patients, respectively. Two patients with spinal TB developed vertebral destruction and paraplegia, respectively. Only one of the patients died. At multivariate level, tachypnea (OR = 4.24; 95% CI 1.17-15.35) and meningeal (OR = 52.21; 95% CI 10.05-271.2) or combined/extrapulmonary forms (OR = 11.3; 95% CI 2.85-45.1) were associated with the development of TB complications. Discussion: TB complications are common in children under 2 years old. Extrapulmonary TB forms in this pediatric age remain a challenge and require prompt diagnosis and treatment in order to prevent them. The presence of tachypnea at the time of TB diagnosis is an independent associated factor to the development of TB complications in infants. This clinical sign should be closely monitored in patients in this age group. It is necessary to perform further studies in this age group in a prospective design in order to understand whether there are other factors associated to TB complications.

Tuberculosis incidence among infected contacts detected through contact tracing of smear-positive patients.

BACKGROUND: The contacts of people with pulmonary tuberculosis (PTB) have a high risk of becoming infected and developing tuberculosis (TB). Our aim was to determine the incidence of TB and its risk factors in a cohort of contacts with latent TB infection (LTBI) detected through contact tracing of smear-positive PTB cases. METHODS AND FINDINGS: We performed a population-based retrospective cohort study including contacts that had LTBI, and were contacts of people with PTB who started treatment between 2008 and 2014. We followed up contacts until they developed TB or until the end date for follow-up (31st December 2016). We used Kaplan-Meier curves to compute incidence at 2 and 5 years, and Cox regression to compute hazard ratios (HR) and their 95% confidence intervals (CI). We analyzed 3097 close contacts of 565 PTB cases. After exclusion of 81 co-prevalent TB cases, 953 contacts had LTBI, of which 14 developed TB. Their risk of developing TB after two and five years was 0.7% (CI: 0.3-1.6) and 1.8% (CI: 1.1-3.1) respectively. Contacts who had not been referred for LTBI treatment had a 1.0% (CI: 0.2-4.0) risk at 5 years. Risk of developing TB at 5 years was 1.2% (CI: 0.5-3.0) among people who completed treatment, and 11.1% (CI: 5.1-23.3) for those who did not. Risk factors for TB were not completing LTBI treatment (HR 9.4, CI: 2.9-30.8) and being female (HR 3.5, CI: 1.1-11-3). CONCLUSIONS: LTBI treatment plays a fundamental role in decreasing the risk of developing TB. It is necessary to achieve a maximum contact tracing coverage and the highest possible compliance with LTBI treatment.

El declive de la incidencia de enfermedad meningocócica en Barcelona entre 1988 y 2015: la influencia de la vacunación frente al serogrupo C / The decline of the incidence of meningococcal disease in Barcelona between 1988 and 2015: the influence of the vaccine against serogroup C

Introducción y objetivo: El objetivo es conocer la evolución de la enfermedad meningocócica en la ciudad de Barcelona entre 1988 y 2015 y evaluar el impacto de la vacuna contra el serogrupo C. Materiales y métodos: Se analizó la evolución de casos de enfermedad meningocócica y por serogrupo a partir del registro de enfermedades de declaración obligatoria. Se comparó la incidencia de todos los serogrupos antes y después de la introducción de la vacunación contra el serogrupo C en el año 2000. Se analizó la cobertura vacunal entre los casos, el serogrupo entre casos vacunados y la tasa de mortalidad y letalidad. Resultados: La enfermedad meningocócica ha pasado de una incidencia en menores de un año de 63,09 casos por 100.000 en 1997-2000 a 15,44 en 2001-2015. Todos los serogrupos han disminuido su incidencia tras la implementación vacunal, especialmente en niños de uno a 4 años para el C. A partir del 2000 la cobertura vacunal en los casos por este serogrupo era del 7,6% y en los afectos por el B era del 35,0% (p<0,01). De los vacunados, el 66,4% de los casos fue serogrupo B y un 5,2% fue C (p<0,01). La tasa global de letalidad y de mortalidad fue del 7,7% y del 0,19/100.000 respectivamente, sin cambios significativos en el tiempo en cuanto a la letalidad. Conclusiones: La incidencia por serogrupo C y también por B ha disminuido tras la vacunación sistemática contra el serogrupo C. La vacunación contra el serogrupo B podría reducir aún más esta grave enfermedad con una letalidad importante que no ha disminuido en todo el periodo

Introduction and objective: The purpose of this study was to describe the evolution of meningococcal disease (MD) in the city of Barcelona between 1988 and 2015 and to assess the impact of the vaccine against serogroup C. Materials and methodology: The evolution of MD and by serogroup was analysed using the information included in the mandatory notification diseases registry. Incidences of all serogroups between the periods of before and after the implementation of the serogroup C vaccine in 2000 were compared. Vaccination coverage among cases, serogroup among vaccinated cases and mortality and case fatality rates were analysed. Results: MD has evolved from an incidence rate in children aged under 1 of 63.09 cases per 100,000 in 1997-2000 to 15.44 per 100,000 in 2001-2015. All MD serogroups incidences decreased after the implementation of the vaccine, especially for serogroup C among children aged between 1 and 4. Since 2000 vaccine coverage in MD cases by this serogroup was 7.6% while in those affected by serogroup B it was 35.0% (p<.01). Among those vaccinated, 66.4% of cases were serogroup B and 5.2% were C (p<.01). Mortality and case fatality rates were 7.7% and 0.19/100,000 respectively, without significant changes in time regarding case fatality. Conclusions: Incidence caused by serogroups B and C has decreased after the systematic vaccination against serogroup C. Vaccination against serogroup B could further reduce the impact of this lethal disease which has not decreased during this period

The decline of the incidence of meningococcal disease in Barcelona between 1988 and 2015: the influence of the vaccine against serogroup C. / El declive de la incidencia de enfermedad meningocócica en Barcelona entre 1988 y 2015: la influencia de la vacunación frente al serogrupo C.

INTRODUCTION AND OBJECTIVE: The purpose of this study was to describe the evolution of meningococcal disease (MD) in the city of Barcelona between 1988 and 2015 and to assess the impact of the vaccine against serogroup C. MATERIALS AND METHODOLOGY: The evolution of MD and by serogroup was analysed using the information included in the mandatory notification diseases registry. Incidences of all serogroups between the periods of before and after the implementation of the serogroup C vaccine in 2000 were compared. Vaccination coverage among cases, serogroup among vaccinated cases and mortality and case fatality rates were analysed. RESULTS: MD has evolved from an incidence rate in children aged under 1 of 63.09 cases per 100,000 in 1997-2000 to 15.44 per 100,000 in 2001-2015. All MD serogroups incidences decreased after the implementation of the vaccine, especially for serogroup C among children aged between 1 and 4. Since 2000 vaccine coverage in MD cases by this serogroup was 7.6% while in those affected by serogroup B it was 35.0% (p<.01). Among those vaccinated, 66.4% of cases were serogroup B and 5.2% were C (p<.01). Mortality and case fatality rates were 7.7% and 0.19/100,000 respectively, without significant changes in time regarding case fatality. CONCLUSIONS: Incidence caused by serogroups B and C has decreased after the systematic vaccination against serogroup C. Vaccination against serogroup B could further reduce the impact of this lethal disease which has not decreased during this period.

Healthcare-Associated Mycobacterium bovis-Bacille Calmette-Guérin (BCG) Infection in Cancer Patients Without Prior BCG Instillation.

Background: Bacille Calmette-Guérin (BCG), an attenuated strain of Mycobacterium bovis, is widely used as adjunctive therapy for superficial bladder cancer. Intravesical administration of BCG has been associated with systemic infection. Disseminated infection due to M. bovis is otherwise uncommon. Methods: After identification of 3 patients with healthcare-associated BCG infection who had never received intravesical BCG administration, an epidemiologic study was performed. All patients with healthcare-associated BCG infection in the Barcelona tuberculosis (TB) program were reviewed from 1 January 2005 to 31 December 2015, searching for infections caused by M. bovis-BCG. Patients with healthcare-associated BCG infection who had not received intravesical BCG instillation were selected and the source of infection was investigated. Results: Nine oncology patients with infection caused by M. bovis-BCG were studied. All had permanent central venous catheters. Catheter maintenance was performed at 4 different outpatient clinics in the same room in which other patients underwent BCG instillations for bladder cancer without required biological precautions. All patients developed pulmonary TB, either alone or with extrapulmonary disease. Catheter-related infection was considered the mechanism of acquisition based on the epidemiologic association and positive catheter cultures for BCG in patients in whom mycobacterial cultures were performed. Conclusions: Physicians should be alerted to the possibility of TB due to nosocomially acquired, catheter-related infections with M. bovis-BCG in patients with indwelling catheters. This problem may be more common than expected in centers providing BCG therapy for bladder cancer without adequate precautions.

Safety and efficacy of the C-Tb skin test to diagnose Mycobacterium tuberculosis infection, compared with an interferon γ release assay and the tuberculin skin test: a phase 3, double-blind, randomised, controlled trial.

BACKGROUND: Targeted screening and treatment of Mycobacterium tuberculosis infection substantially reduces the risk of developing active tuberculosis. C-Tb (Statens Serum Institute, Copenhagen, Denmark) is a novel specific skin test based on ESAT-6 and CFP10 antigens. We investigated the safety and diagnostic potential of C-Tb compared with established tests in the contact-tracing setting. METHODS: Negative controls, close contacts, occasional contacts, and patients with active pulmonary tuberculosis were enrolled at 13 centres in Spain. We compared C-Tb with the QuantiFERON-TB Gold In-Tube ([QFT] Qiagen, Hilden, Germany) interferon γ release assay (IGRA) and the purified protein derivative (PPD) RT 23 tuberculin skin test ([TST] Statens Serum Institute). All participants older than 5 years were tested with QFT. Some participants in the negative control group received C-Tb without the TST to test for potential interactions between C-Tb and PPD RT 23. The rest were randomly assigned in blocks of ten and tested with both C-Tb and TST, with five in each block receiving injection of C-Tb in the right arm and the TST in the left arm and five vice versa. The primary and safety analyses were done in all participants randomly assigned to a group who received any test. This trial is registered with ClinicalTrials.gov, number NCT01631266, and with EudraCT, number 2011-005617-36. FINDINGS: From July 24, 2012, to Oct 2, 2014, 979 participants were enrolled, of whom 263 were negative controls, 299 were occasional contacts, 316 were close contacts, and 101 were patients with tuberculosis. 970 (99%) participants completed the trial. Induration sizes were similar for C-Tb and TST, but TST positivity was affected by BCG vaccination status. We found a strong positive trend towards C-Tb test positivity with increasing risk of infection, from 3% in negative controls to 16% in occasional contacts, to 43% in close contacts. C-Tb and QFT results were concordant in 785 (94%) of 834 participants aged 5 years and older, and results did not differ significantly between exposure groups. The safety profile of C-Tb was similar to that for the TST. INTERPRETATION: C-Tb delivered IGRA-like results in a field-friendly format. Being unaffected by BCG vaccination status, the C-Tb skin test might provide more accurate treatment guidance in settings where the TST is commonly used. FUNDING: Statens Serum Institut.