Recurrències en tuberculosis entre pacients tractats correctament

Aquest estudi epidemiològic, desenvolupat conjuntament per investigadors de l'Agència de Salut Pública de Barcelona (ASPB), el CIBER d'Epidemiologia i Salut Pública i la Universitat Autònoma de Barcelona, ha analitzat la probabilitat de recaure en la tuberculosi i ha determinat els factors de risc associats entre pacients curats d'aquesta malaltia a la ciutat de Barcelona. Els resultats indiquen que haver tingut tuberculosi és un factor de risc per desenvolupar-la de nou, el que hauria d'impulsar polítiques socials entre la població de risc.Este estudio epidemiológico, desarrollado conjuntamente por investigadores de la Agència de Salut Pública de Barcelona (ASPB), elCIBER de Epidemiologia y Salud Pública y la Universitat Autònoma deBarcelona, ha analizado la probabilidad de recaer en la tuberculosis y ha determinado los factores de riesgo asociados entre pacientes curados de esta enfermedad en la ciudad de Barcelona. Los resultados indican que haber tenido tuberculosis es un factor de riesgo para desarrollarla de nuevo, lo que debería impulsar políticas sociales entre la población de riesgo

Población potencialmente excluida de cobertura sanitaria con el Real Decreto 16/2012 y sus repercusiones sanitarias: la experiencia desde la Cataluña Central

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<0,001). En cambio, la morbilidad infecciosa fue superior en los excluidos (p<0,001).ConclusionesLos resultados del estudio llevan a pensar que esta medida legislativa no parece justificada por razones médicas ni económicas. Además, podría provocar problemas de salud pública y contribuir al riesgo de fractura social.AbstractObjectiveTo assess the proportion of population potentially excluded from healthcare coverage since the Royal Decree-Law 16/2012. To describe the use of health services, the distribution of chronic and infectious diseases, and the pharmaceutical costs in 2012 of the persons potentially excluded compared to the those who maintain their coverage.Design and settingAn observational analytical cross-sectional study was designed and conducted on a Primary Care based population in the Central Catalonia Management Area of the Institut Català de la SalutParticipants and main measurementsIndividuals potentially excluded since the application of the Royal Decree-Law 16/2012 were selected and compared with individuals who maintained their healthcare coverage, randomly matched by sex, age and Primary Care service. The information obtained included the use of health services, the distribution of chronic and infectious diseases, and the pharmaceutical costs during the year 2012.ResultsA total of 1,699 individuals were identified as potentially excluded from healthcare coverage, 0.53% of the total of population (51.4% men), with a median of age of 34years (interquartile range, 28-43). The use of healthcare services, the chronic morbidity recorded, and the pharmaceutical costs during the year 2012 of the excluded individuals was lower than those of the non-excluded ones (P<.001). On the other hand, the infectious morbidity was higher in the excluded individuals (P<.001).ConclusionsThe results of the study suggests that this legislative measure does not seem to be justified for medical or economic reasons. It could also cause public health problems and contribute to the risk of social fracture

Trends in the Epidemiology of Leishmaniasis in the City of Barcelona (1996-2019)

Background: Leishmaniasis is a neglected zoonosis produced by 20 different flagellated parasites of the Leishmania genus, a protozoan transmitted to humans and other vertebrates by the bite of dipteran insects of the Phlebotominae subfamily. It is endemic in Mediterranean countries and the number of cases is expected to increase due to climate change and migration. Prioritizing public health interventions for prevention and control is essential. The objective was to characterize the epidemiology and temporal trends in the incidence of human leishmaniasis in the city of Barcelona, between the years 1996 and 2019. Methods: A population-based, analytical observational study among residents in the city of Barcelona was conducted of all the cases of leishmaniasis reported between 1996 and 2019 to the Public Health Agency. The epidemiological survey contains clinical, diagnostic, and epidemiological data, including contact with suspicious mammals or insects. Annual incidence-rates were calculated by sex, age, and country of origin. Chi-square tests were used to assess association between studied risk factors, periods of time and type of leishmaniasis. Results: During the study period a total of 177 cases of leishmaniasis were reported in Barcelona, being 74.6% (n = 132) of the total cases in Spanish born, although within the foreign-born population the incidence was higher. Median age was 34 years (IQR = 10-48) and 121 (66.8%) were male. The main type was cutaneous (46%) followed by visceral (35.1%). The cumulative incidence was 0.47 per 100,000 inhabitants, with the highest incidence found in 2017 (1.60 per 100,000 inhabitants). A higher incidence was observed in the 0-4-year-old group (1.73 per 100,000 inhabitants), but increased during the study period for all age groups. There was an increase of foreign origin cases, and a decrease in the number of cases associated to any immunosuppression. Conclusion: In Barcelona, leishmaniasis incidence continues to be higher in people under 5 years of age, and 25-64 years old males, but it has also increased in population from foreign country of birth. There is an increase of the cases since 2016, probably due to the changes in the notification system, increasing the diagnosis of cutaneous leishmaniasis. Improvements in the current surveillance system are needed. Notification of the disease, vector, and reservoir control activities are also essential for the control of the disease

Tuberculosis recurrence after completion treatment in a European city: reinfection or relapse?

Background Tuberculosis (TB) recurrence can be due to reinfection or relapse. The contribution of each to TB incidence and the factors associated with recurrence are not well known. Effectiveness of TB control programs is assessed in part by recurrence rates. The aim of this study was to establish the recurrence rate of TB in Barcelona, the associated risk factors and the role of reinfection. Methods A population-based retrospective longitudinal study was performed in Barcelona, Spain. TB patients with positive culture results who completed treatment between Jan 1st, 2003 and Dec 31st, 2006 were followed-up until December 31st, 2009 by the TB Control Program. The incidence rate of recurrence was calculated per person-year of follow-up (py). Kaplan-Meier and Cox regression methods were used for the survival analysis by calculating the hazard ratio (HR) with 95% confidence intervals (CI). Results Of the 1,823 TB cases identified, 971 fulfilled the inclusion criteria and 13 (1.3%) had recurrent TB. The recurrence rate was 341 cases per 100,000 py, 13 times higher than the TB incidence of the general population. Likelihood of TB recurrence at the 1st, 3rd and 5th year of follow-up was 0.1%, 1.4% and 1.6%, respectively. Factors associated with recurrence were HIV infection (HR: 4.7, CI: 1.4-15.7), living in the inner city district (HR: 3.9, CI: 1.3-11.8) and history of TB treatment (HR: 5.2, CI: 1.7-16.2). Genotyping results of recurrent cases were available for 6 patients (3 reinfections and 3 relapses). Conclusion The rate of TB recurrence in Barcelona is low and most episodes occur within the first three years. Patients at higher risk of recurrence are co-infected with HIV, living in neighborhoods with high TB incidence or with a history of TB treatment. When available, genotyping results help determine whether the recurrence is due to reinfection or relapse

Predictors of Death among Patients Who Completed Tuberculosis Treatment: A Population-Based Cohort Study

Background: Mortality among patients who complete tuberculosis (TB) treatment is still high among vulnerable populations. The objective of the study was to identify the probability of death and its predictive factors in a cohort of successfully treated TB patients. Methods: A population-based retrospective longitudinal study was performed in Barcelona, Spain. All patients who successfully completed TB treatment with culture-confirmation and available drug susceptibility testing between 1995-1997 were retrospectively followed-up until December 31, 2005 by the Barcelona TB Control Program. Socio-demographic, clinical, microbiological and treatment variables were examined. Mortality, TB Program and AIDS registries were reviewed. Kaplan-Meier and a Cox regression methods with time-dependent covariates were used for the survival analysis, calculating the hazard ratio (HR) with 95% confidence intervals (CI). Results: Among the 762 included patients, the median age was 36 years, 520 (68.2%) were male, 178 (23.4%) HIV-infected, and 208 (27.3%) were alcohol abusers. Of the 134 (17.6%) injecting drug users (IDU), 123 (91.8%) were HIV-infected. A total of 30 (3.9%) recurrences and 173 deaths (22.7%) occurred (mortality rate: 3.4/100 person-years of follow-up). The predictors of death were: age between 41-60 years old (HR: 3.5; CI:2.1-5.7), age greater than 60 years (HR: 14.6; CI:8.9-24), alcohol abuse (HR: 1.7; CI:1.2-2.4) and HIV-infected IDU (HR: 7.9; CI:4.7-13.3). Conclusions: The mortality rate among TB patients who completed treatment is associated with vulnerable populations such as the elderly, alcohol abusers, and HIV-infected IDU. We therefore need to fight against poverty, and promote and develop interventions and social policies directed towards these populations to improve their survival

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.This study was supported by the Ministry of Science and Innovation, Institute of Health Carlos III (Project PI18/01751) and Fondo Europeo de Desarrollo Regional (FEDER-Una manera de hacer Europa)

Disulfide driven folding for a conditionally disordered protein

Altres ajuts: ICREA, ICREA-Academia 2015 to S.V.Conditionally disordered proteins are either ordered or disordered depending on the environmental context. The substrates of the mitochondrial intermembrane space (IMS) oxidoreductase Mia40 are synthesized on cytosolic ribosomes and diffuse as intrinsically disordered proteins to the IMS, where they fold into their functional conformations; behaving thus as conditionally disordered proteins. It is not clear how the sequences of these polypeptides encode at the same time for their ability to adopt a folded structure and to remain unfolded. Here we characterize the disorder-to-order transition of a Mia40 substrate, the human small copper chaperone Cox17. Using an integrated real-time approach, including chromatography, fluorescence, CD, FTIR, SAXS, NMR, and MS analysis, we demonstrate that in this mitochondrial protein, the conformational switch between disordered and folded states is controlled by the formation of a single disulfide bond, both in the presence and in the absence of Mia40. We provide molecular details on how the folding of a conditionally disordered protein is tightly regulated in time and space, in such a way that the same sequence is competent for protein translocation and activity

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

Altres ajuts: Institut Universitari per a la Recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (Institut Català de la Salut), PREDOC_ECO-19/2; Fundación redGDPS (Beca de apoyo José Luis Torres a la Investigación)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)

Altres ajuts: Spanish Ministry of Economy and the Institut Universitari per a la Recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (Catalan Health Institute, PREDOC_ECO-19/2).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

Cell-Mediated Immune Responses to in vivo -Expressed and Stage-Specific Mycobacterium tuberculosis Antigens in Latent and Active Tuberculosis Across Different Age Groups

A quarter of the global human population is estimated to be latently infected by Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB). TB remains the global leading cause of death by a single pathogen and ranks among the top-10 causes of overall global mortality. Current immunodiagnostic tests cannot discriminate between latent, active and past TB, nor predict progression of latent infection to active disease. The only registered TB vaccine, Bacillus Calmette-Guérin (BCG), does not adequately prevent pulmonary TB in adolescents and adults, thus permitting continued TB-transmission. Several Mtb proteins, mostly discovered through IFN-γ centered approaches, have been proposed as targets for new TB-diagnostic tests or -vaccines. Recently, however, we identified novel Mtb antigens capable of eliciting multiple cytokines, including antigens that did not induce IFN-γ but several other cytokines. These antigens had been selected based on high Mtb gene-expression in the lung in vivo, and have been termed in vivo expressed (IVE-TB) antigens. Here, we extend and validate our previous findings in an independent Southern European cohort, consisting of adults and adolescents with either LTBI or TB. Our results confirm that responses to IVE-TB antigens, and also DosR-regulon and Rpf stage-specific Mtb antigens are marked by multiple cytokines, including strong responses, such as for TNF-α, in the absence of detectable IFN-γ production. Except for TNF-α, the magnitude of those responses were significantly higher in LTBI subjects. Additional unbiased analyses of high dimensional flow-cytometry data revealed that TNF-α+ cells responding to Mtb antigens comprised 17 highly heterogeneous cell types. Among these 17 TNF-α+ cells clusters identified, those with CD8+TEMRA or CD8+CD4+ phenotypes, defined by the expression of multiple intracellular markers, were the most prominent in adult LTBI, while CD14+ TNF-α+ myeloid-like clusters were mostly abundant in adolescent LTBI. Our findings, although limited to a small cohort, stress the importance of assessing broader immune responses than IFN-γ alone in Mtb antigen discovery as well as the importance of screening individuals of different age groups. In addition, our results provide proof of concept showing how unbiased multidimensional multiparametric cell subset analysis can identify unanticipated blood cell subsets that could play a role in the immune response against Mtb