Epidemiological Characteristics and Factors Associated with Repeat Sexually Transmitted Infections in Barcelona, Spain Over a Decade.

In the last few years, the frequency of sexually transmitted infections (STI) has increased, as has the number of people with multiple infections. The aim of our study was to describe the epidemiological characteristics of persons with repeated bacterial STI and to determine the risk factors for these episodes in persons living in Barcelona during the period 2007-2018. We studied all cases of bacterial STI included in the STI registry of Barcelona. Repeated STI were defined as a diagnosis of gonorrhea, syphilis, or lymphogranuloma venereum (LGV) after a first episode of one of these infections. Analysis was stratified by sex and place of birth. The factors associated with time to reinfection were determined by Kaplan-Meier estimates, while the factors associated with risk of infection were determined by a Cox proportional hazards model. Of 9927 persons with a diagnosis of bacterial STI, 1690 (17.0%) had at least two episodes of STI during the study period. On multivariate analysis, repeat STI were independently associated with male sex assigned at birth (HR: 3.45; 95%CI 2.22-5.36), age less than 34 years (HR: 1.22; 95%CI 1.10-1.35); gay, bisexual, and other men who have sex with men, and transgender o transsexual woman (GBSMS/Trans) (HR: 4.03; 95%CI 3.24-5.03), having gonorrhea as first diagnosis (HR:1.49, 95%CI 1.34-1.66) or LGV (HR:1.75; 95%CI 1.47-2.08) and coinfection with HIV (HR:1.98; 95%CI 1.78-2.21). Sexual health programs should be strengthened to prevent STI and reinfection in key populations.

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.].

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.

Evolution of acute hepatitis C virus infection in a large European city: Trends and new patterns.

The aims of this study were to describe the evolution of acute hepatitis C virus (HCV) infections since 2004 and to determine its associated factors. Acute HCV infections diagnosed in Barcelona from 2004 to 2015 were included. Incidence ratios (IR) were then estimated for sex and age groups. Cases were grouped between 2004-2005, 2006-2011 and 2012-2015, and their incidence rate ratios (IRR) were calculated. In addition, risk factors for acute HCV infection were identified using multinomial logistic regression for complete, available and multiple imputed data. 204 new HCV cases were identified. Two peaks of higher IR of acute HCV infection in 2005 and 2013 were observed. Men and those aged 35-54 had higher IR. IRR for men was 2.9 times greater than in women (95% confidence intervals (CI): 1.8 ‒ 4.7). Factors related to the period 2012-2015 (versus 2006-2011) were: a) sexual risk factor for transmission versus nosocomial (relative-risk ratio (RRR): 13.0; 95% CI: 2.3 ‒ 72.1), b) higher educated versus lower (RRR: 5.4; 95% CI: 1.6 ‒ 18.7), and c) HIV co-infected versus not HIV-infected (RRR: 53.1; 95% CI: 5.7 ‒ 492.6). This is one of the few studies showing IR and RRRs of acute HCV infections and the first focused on a large city in Spain. Sexual risk for transmission between men, higher educational level and HIV co-infection are important factors for understanding current HCV epidemic. There has been a partial shift in the pattern of the risk factor for transmission from nosocomial to sexual.

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

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 <0.05 was considered statistically significant. RESULTS: We detected 3,284 cases. Incidence decreased from 144.8/100,000 inhabitants in 1991 to 53.4/100,000 in 2013. Individuals born in Pakistan-India-Bangladesh had the highest average annual incidence (675/100,000). In all, 2,156 cases (65.7%) were male. 2,272 (69.2%) had pulmonary TB, of which 48.2% were smear-positive. 33% of the cases (1,093) lived in the inner city. Contact tracing (CT) coverage in smear-positive individuals rose from 56.8% in 1991-1999 to 81.4% in 2000-2013 (p<0.01); this value was less than 50% in people from Africa and Eastern European countries. The case fatality rate was 3.6% overall and 9.8% among those born in high-income countries (p<0.01). The highest rate of treatment default (12.8%) was observed among cases from the Maghreb. The rate of successful treatment increased from 69.9% in 1991-1999 to 87.5% in 2000-2013 (p<0.01). CONCLUSION: The incidence of TB in immigrants is decreasing in Barcelona. Organizational actions, such as incorporating CHWs and TBCUs, have been decisive for the observed improvements.

Evaluation of reported cases of pertussis: epidemiological study in a large city in Spain.

We retrospectively analysed the incidence rate of reported cases of pertussis in Barcelona during 2009-2012 according to age, sex, type of medical centre and vaccination status. We included 748 confirmed or suspected cases, 613 (82.0 %) of which were confirmed by laboratory testing and the remaining 135 (18.0 %) by epidemiological evidence. The highest reported incidence of pertussis was amongst <1 year olds [96.1 per 100,000 person-years, 95 % confidence interval (CI): 84.3-109.1]. The majority of confirmed and suspected cases were reported in 2011 and 2012, and the total incidence (confirmed or suspected) was 6.3 (95 % CI: 5.6-6.9) and 4.2 (95 % CI: 3.6-4.7) per 100,000 person-years, respectively. Incidence increased significantly (P = 0.001) in 2011-2012 compared with 2009. Most confirmed cases occurred in children <1 year old (87.9 %). Cases were confirmed by real-time (RT)-PCR (87.5 %; 95 % CI: 81.3-87.6) and bacterial culture (13.7 %; 95 % CI: 11.0-17.1). We recommend performing RT-PCR in suspected cases with no epidemiological link to a confirmed case.

Cancer-initiating enriched cell lines from human glioblastoma: preparing for drug discovery assays.

Glioblastoma multiforme (GBM) is the most lethal type of brain tumour in the adult humans. The cancer-initiating cell (CIC) hypothesis supports the notion that failures in current approaches to GBM treatment might be attributed to the survival of the CIC subpopulation. Recent evidence shows the idea that using CIC-enriched cell lines derived from human GBM as new targets for drug discovery programs, may improve the chance of successfully translating the basic research findings into clinical trials. Although this approach appears promising, many important biological and technical issues (characterization of functional CIC markers, inter- and intra-tumoral CIC heterogeneity, and isolation and maintenance inconsistency) need to be resolved.

Histological and ultrastructural comparison of cauterization and thrombosis stroke models in immune-deficient mice.

BACKGROUND: Stroke models are essential tools in experimental stroke. Although several models of stroke have been developed in a variety of animals, with the development of transgenic mice there is the need to develop a reliable and reproducible stroke model in mice, which mimics as close as possible human stroke. METHODS: BALB/Ca-RAG2-/-γc-/- mice were subjected to cauterization or thrombosis stroke model and sacrificed at different time points (48hr, 1wk, 2wk and 4wk) after stroke. Mice received BrdU to estimate activation of cell proliferation in the SVZ. Brains were processed for immunohistochemical and EM. RESULTS: In both stroke models, after inflammation the same glial scar formation process and damage evolution takes place. After stroke, necrotic tissue is progressively removed, and healthy tissue is preserved from injury through the glial scar formation. Cauterization stroke model produced unspecific damage, was less efficient and the infarct was less homogeneous compared to thrombosis infarct. Finally, thrombosis stroke model produces activation of SVZ proliferation. CONCLUSIONS: Our results provide an exhaustive analysis of the histopathological changes (inflammation, necrosis, tissue remodeling, scarring...) that occur after stroke in the ischemic boundary zone, which are of key importance for the final stroke outcome. This analysis would allow evaluating how different therapies would affect wound and regeneration. Moreover, this stroke model in RAG 2-/- γC -/- allows cell transplant from different species, even human, to be analyzed.

Ofd1, a human disease gene, regulates the length and distal structure of centrioles.

Centrosomes and their component centrioles represent the principal microtubule organizing centers of animal cells. Here, we show that the gene underlying orofaciodigital syndrome 1, Ofd1, is a component of the distal centriole that controls centriole length. In the absence of Ofd1, distal regions of centrioles, but not procentrioles, elongate abnormally. These long centrioles are structurally similar to normal centrioles but contain destabilized microtubules with abnormal posttranslational modifications. Ofd1 is also important for centriole distal appendage formation and centriolar recruitment of the intraflagellar transport protein Ift88. To model OFD1 syndrome in embryonic stem cells, we replaced the Ofd1 gene with missense alleles from human OFD1 patients. Distinct disease-associated mutations cause different degrees of excessive or decreased centriole elongation, all of which are associated with diminished ciliogenesis. Our results indicate that Ofd1 acts at the distal centriole to build distal appendages, recruit Ift88, and stabilize centriolar microtubules at a defined length.

Hedgehog signaling and primary cilia are required for the formation of adult neural stem cells.

Neural stem cells that continue to produce neurons are retained in the adult hippocampal dentate gyrus. The mechanisms by which embryonic neural progenitors expand and transform into postnatal neural stem cells, an essential process for the continual production of neurons throughout life, remain unknown. We found that radial astrocytes, the postnatal progenitors in the dentate gyrus, failed to develop after embryonic ablation of ciliary genes or Smoothened (Smo), an essential component for Sonic hedgehog (Shh) signaling. Postnatal dentate neurogenesis failed in these mutant mice, and the dentate gyrus became severely hypotrophic. In contrast, expression of a constitutively active Smo (SmoM2-YFP) resulted in a marked expansion of the dentate gyrus. Double-mutant analyses suggested that both wild-type Smo and SmoM2-YFP function through the primary cilia. We conclude that Shh signaling, acting through the primary cilia, has a critical role in the expansion and establishment of postnatal hippocampal progenitors.