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Severe COVID-19 disease requiring ICU admission is possible in the fully vaccinated population, especially in those with immunocompromised status and other comorbidities. Interventions to improve vaccine response might be necessary in this population. Peer Reviewed "Article signat per 23 autors/es: Anna Motos, Alexandre López-Gavín, Jordi Riera, Adrián Ceccato, Laia Fernández-Barat, Jesús F. Bermejo-Martin, Ricard Ferrer, David de Gonzalo-Calvo, Rosario Menéndez, Raquel Pérez-Arnal, Dario García-Gasulla, Alejandro Rodriguez, Oscar Peñuelas, José Ángel Lorente, Raquel Almansa, Albert Gabarrus, Judith Marin-Corral, Pilar Ricart, Ferran Roche-Campo, Susana Sancho Chinesta, Lorenzo Socias, Ferran Barbé, Antoni Torres on behalf of the CIBERESUCICOVID Project (COV20/00110, ISCIII)"

Breast milk is a vehicle to transfer protective antibodies from the lactating mother to the neonate. After SARS-CoV-2 infection, virus-specific IgA and IgG have been identified in breast milk, however, there are limited data on the impact of different COVID-19 vaccine types in lactating women. This study is aimed to evaluate the time course of induction of SARS-CoV-2-specific IgA and IgG in breast milk after vaccination., This work was supported by the research grant from LaMarató-TV3 (MilkCORONA, ref. 202106). The funders played no role in the conduct of this work, review, analysis, or interpretation of findings and were not involved in the preparation of this manuscript. We also acknowledge support from the CSIC Open Access Publication Initiative through its Unit of Information Resources for Research (URICI).

We studied changes in serotype distribution and antimicrobial susceptibility in adult pneumococcal pneumonia in Spain (2011-2019). Among 895 pneumococci collected (433 bacteremic [BPP] and 462 non-bacteremic [non-BPP]), serotypes 3 (17%), 19A (10%), 8 (6.7%) and 11A (6.7%) were the most frequent. Serotypes 16F, 19A and 24F were associated with old people (≥65) and serotypes 4, 7F, 8, 12F and 19F to young adults. Serotypes 12F, 24F and 1 were significantly more frequent in BPP and serotypes 11A, 23A and 19F in non-BPP. Amoxicillin resistance was higher in non-BPP (17% vs. 11%) while penicillin non-susceptibility (37% vs. 24%) and macrolide resistance (29% vs. 14%) were higher in older adults. In the period 2017-2019, the vaccine coverages were: 32% (PCV13), 39% (PCV15), 65% (PCV20) and 69% (PPV23). Differences were found in serotype composition and antimicrobial resistance by age and type of infection. The maintenance of serotype 3 as a leading cause of adult pneumococcal pneumonia and the increase in highly invasive (serotype 8) or antimicrobial-resistant (serotype 11A) serotypes is worrisome. Further studies will be required to analyse the impact of the upcoming broader conjugate vaccines. This work was supported by grants from the Fondo de Investigaciones Sanitarias de la Seguridad Social [PI (PI14/00627; PI18/00339, and by CIBER de Enfermedades Respiratorias, CIBERES; [CB06/06/0037], run by the Instituto de Salud Carlos III (ISCIII), Madrid, Spain. Financial support was also provided by the European Regional Development Fund/European Social Fund (ERDF/ESF, “Investing in your future”). We thank CERCA Programme/Generalitat de Catalunya for institutional support. Sí

Vaccines against the severe acute respiratory coronavirus 2, which are the first to be used in humans against any coronavirus, were developed and produced in record time. Dermatologic adverse effects appeared during clinical trials and have also been described in the population since approval. Just as descriptions and categorization of skin manifestations of the coronavirus disease 2019 proved important for understanding the disease itself, characterizing the effects of vaccines may also further that goal. This paper reviews the properties of the different types of vaccines currently available and under development and describes how they interact with the immune system and the clinical signs they may cause. We focus on dermatologic adverse effects reported to date and recommendations for managing them.Las vacunas contra el SARS-CoV-2 son las primeras vacunas que han sido usadas en humanos contra coronavirus y su desarrollo se ha producido en un tiempo récord. En los análisis de seguridad de los ensayos clínicos previos a su aprobación y en la fase postautorización en la población, se han descrito efectos secundarios dermatológicos. La descripción y categorización de las manifestaciones cutáneas de la COVID-19 fueron importantes para el conocimiento de la enfermedad y de la misma forma pueden serlo las generadas por las vacunas. En este artículo hacemos un repaso a las características de los diferentes tipos de vacunas disponibles y en desarrollo, su modo de interacción con el sistema inmune, las consecuentes manifestaciones clínicas que pueden generar, con especial interés en los efectos secundarios dermatológicos hasta el momento descritos, y las actitudes terapéuticas recomendadas ante cada una de estas reacciones.

The COVID-19 pandemic has raised questions among individuals who are breastfeeding, both because of the possibility of viral transmission to infants during breastfeeding and, more recently, of the potential risks and benefits of vaccination in this specific population. Previous studies have reported the presence of anti–SARS-CoV-2 antibodies in breast milk of COVID-19–infected lactating women,1 and recently several studies have demonstrated the passage of postvaccine antibodies through breast milk in women vaccinated with novel mRNA-based vaccines.1,2 In the present study, conducted between February and March 2021 at Parc Sanitari Sant Joan de Deu, an urban hospital in Spain, we sought to characterize the levels of specific SARS-CoV-2 antibodies in the breast milk of mRNA-vaccinated women across time, as well as their correlation with serum antibody levels.

The Ninth Interactive Infectious Disease workshop TIPICO was held on November 22–23, 2018, in Santiago de Compostela, Spain. This 2-day academic experience addressed current and topical issues in the field of infectious diseases and vaccination. Summary findings of the meeting include: cervical cancer elimination will be possible in the future, thanks to the implementation of global vaccination action plans in combination with appropriate screening interventions. The introduction of appropriate immunization programs is key to maintain the success of current effective vaccines such as those against meningococcal disease or rotavirus infection. Additionally, reduced dose schedules might improve the efficiency of some vaccines (i.e., PCV13). New vaccines to improve current preventive alternatives are under development (e.g., against tuberculosis or influenza virus), while others to protect against infectious diseases with no current available vaccines (e.g., enterovirus, parechovirus and flaviviruses) need to be developed. Vaccinomics will be fundamental in this process, while infectomics will allow the application of precision medicine. Further research is also required to understand the impact of heterologous vaccine effects. Finally, vaccination requires education at all levels (individuals, community, healthcare professionals) to ensure its success by helping to overcome major barriers such as vaccine hesitancy and false contraindications FMT and AS research activities received support from the Instituto de Salud Carlos III (Proyecto de Investigación en Salud, Acción Estratégica en Salud): project GePEM ISCIII/PI16/01478/Cofinanciado FEDER, and project ReSVinext ISCIII/PI16/01569/Cofinanciado FEDER; Consellería de Sanidade, Xunta de Galicia (RHI07/2-intensificación actividad investigadora, PS09749 and 10PXIB918184PR), Instituto de Salud Carlos III (Intensificación de la actividad investigadora 2007–2012, PI16/01569), Fondo de Investigación Sanitaria (FIS; PI070069/PI1000540) del plan nacional de I+D+I and ‘fondos FEDER’, and 2016-PG071 Consolidación e Estructuración REDES 2016GI-1344 G3VIP (Grupo Gallego de Genética Vacunas Infecciones y Pediatría, ED341D R2016/021). Research on flaviviruses at the AG-S laboratory is partially funded by NIAID grants R21AI129486, R21AI142337 and U19AI118610 Research on influenza virus vaccines and immunity at the AG-S laboratory is partly funded by NIAID grants U19AI117873, U01AI124297, R01AI127658, P01AI097092, U19AI135972, and R01 AI141226-01, by the Bill and Melinda Gates Foundations (OPP1084518), by a research contract from GSK and by CRIP (Center for Research on Influenza Pathogenesis), an NIAID funded Center of Excellence for Influenza Research and Pathogenesis (CEIRS, contract number HHSN272201400008C) SI

Vaccine hesitancy is considered as one of the leading causes for the resurgence of vaccine preventable diseases. A non-negligible minority of parents does not fully adhere to the recommended vaccination schedule, leading their children to be partially immunized and at higher risk of contracting vaccine preventable diseases. Here, we leverage more than one million comments of 201,986 users posted from March 2008 to April 2019 on the public online forum BabyCenter US to learn more about such parents. For 32% with geographic location, we find the number of mapped users for each US state resembling the census population distribution with good agreement. We employ Natural Language Processing to identify 6884 and 10,131 users expressing their intention of following the recommended and alternative vaccination schedule, respectively RSUs and ASUs. From the analysis of their activity on the forum we find that ASUs have distinctly different interests and previous experiences with vaccination than RSUs. In particular, ASUs are more likely to follow groups focused on alternative medicine, are two times more likely to have experienced adverse events following immunization, and to mention more serious adverse reactions such as seizure or developmental regression. Content analysis of comments shows that the resources most frequently shared by both groups point to governmental domains (.gov). Finally, network analysis shows that RSUs and ASUs communicate between each other (indicating the absence of echo chambers), however with the latter group being more endogamic and favoring interactions with other ASUs. While our findings are limited to the specific platform analyzed, our approach may provide additional insights for the development of campaigns targeting parents on digital platforms., Author summary The importance and effectiveness of vaccines is generally high, but concerns toward vaccination contribute to eroding confidence in vaccination. Recently, alternative vaccination schedules are becoming popular as they allow parents to selectively delay or refuse certain vaccines depending on their specific concerns. Not being expressly anti-vaccination, these parents are challenging to identify on social media, however understanding the determinants of their hesitancy toward vaccines could help addressing parents’ concerns through targeted interventions. In this work, we create a Natural Language Processing pipeline to automatically identify parents who state their adherence to the recommended or alternative vaccination schedule on a popular parenting forum, BabyCenter US. We find that these users have distinct interests and different experiences with vaccination, although they frequently share similar sources of information (e.g., .gov websites). Differently from what is observed on most popular digital platforms like Facebook or Twitter, where users communicate mainly with like-minded users, Babycenter users communicate between each other independently of the vaccination schedule they adopt. These observations suggest that parenting fora may be a more suitable medium to develop intervention aiming to influence positively the vaccination behavior of parents.

Streptococcus pneumoniae serotype 1 (ST1) was an important cause of invasive pneumococcaldisease (IPD) globally before the introduction of pneumococcal conjugate vaccines (PCVs) containingST1 antigen. The Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE)project gathered ST1 IPD surveillance data from sites globally and aimed to estimatePCV10/13 impact on ST1 IPD incidence. We estimated ST1 IPD incidence rate ratios (IRRs) comparingthe pre‐PCV10/13 period to each post‐PCV10/13 year by site using a Bayesian multi‐level, mixedeffectsPoisson regression and all‐site IRRs using a linear mixed‐effects regression (N = 45 sites).Following PCV10/13 introduction, the incidence rate (IR) of ST1 IPD declined among all ages. Aftersix years of PCV10/13 use, the all‐site IRR was 0.05 (95% credibility interval 0.04–0.06) for all ages,0.05 (0.04–0.05) for &lt, 5 years of age, 0.08 (0.06–0.09) for 5–17 years, 0.06 (0.05–0.08) for 18–49 years,0.06 (0.05–0.07) for 50–64 years, and 0.05 (0.04–0.06) for ≥65 years. PCV10/13 use in infant immunizationprograms was followed by a 95% reduction in ST1 IPD in all ages after approximately 6years. Limited data availability from the highest ST1 disease burden countries using a 3+0 scheduleconstrains generalizability and data from these settings are needed.

espanolAntecedentes y objetivos El aumento de la reticencia vacunal amenaza los avances logrados en salud publica y causa brotes de enfermedades inmunoprevenibles en comunidades infra vacunadas. El objetivo de este estudio es explorar y comparar las actitudes y percepciones hacia la vacunacion de los usuarios de farmacia, los estudiantes de farmacia y los farmaceuticos comunitarios. Metodos Se realizo un estudio observacional transversal mediante encuestas sobre las actitudes hacia la vacunacion en la provincia de Barcelona (Espana) durante marzo-abril de 2020. El analisis estadistico se llevo a cabo mediante la prueba χ2 y una regresion multivariable. El nivel de significacion estadistica se considero cuando P Resultados Los resultados obtenidos muestran un 44% de reticencia en la poblacion a pesar de tener una cobertura vacunal del 80%. Se observo desconfianza en el Sistema de Salud (23,3%) y se asocio experiencia negativa previa con la vacunacion y reticencia (OR: 3,04; IC 95% de 1,16 a 7,93; P = 0,02). Del total de encuestados, los mayores de 44 anos mostraron una principal reticencia a las vacunas (OR: 2,63; IC 95% de 1,11 a 6,19; P = 0,03). Un 40% de los encuestados infravaloraron la vacuna antigripal. Los estudiantes de farmacia y los farmaceuticos comunitarios mostraron una actitud positiva hacia la vacunacion. Aunque solo el 14% estaban vacunados contra la gripe, la mayoria considero que su vacunacion es importante. Conclusiones Una promocion activa, educacion poblacional y comunicacion especializada sobre vacunas son algunas de las necesidades que el farmaceutico comunitario puede resolver, reafirmado asi su papel como profesional de la salud altamente calificado en contacto constante con la poblacion. EnglishBackground and objectives The increase in vaccine hesitancy threatens advances in public health and causes vaccine-preventable diseases outbreaks in infra-vaccinated communities. This study aims to determine and compare the perception and attitudes towards vaccination among pharmacy users, pharmacy students and community pharmacists. Methods A cross-sectional observational study was conducted during March and April 2020, surveying perceptions and attitudes towards vaccination in Barcelona (Spain). Statistical analysis was assessed by chi2 test and multivariate regression. Statistical significance when P Results A high percentage of hesitant opinions (44%) among pharmacy users was observed, despite high vaccine coverage (80%). Some showed mistrust in the health system (23.3%) and a statistically significant association was found between previous negative experiences with vaccination and hesitant attitudes (OR: 3.04; 95%CI 1.16 to 7.93; P = .02). Of all surveyed pharmacy users, those over 44 years old showed a stronger hesitant attitude towards vaccines (OR: 2.63; 95%CI 1.11 to 6.19; P = .03), and 40% undervalued influenza vaccine, including risk groups. Both pharmacy students and community pharmacists had a positive attitude towards vaccination. While only 16% of surveyed pharmacists vaccinated against influenza during the 2019/2020 influenza seasonal campaign, most of them considered their vaccination important to the profession (61%). Conclusions Active promotion and education of the population and reliable communication on vaccines are some of the needs that community pharmacists can solve, claiming their role as highly qualified health professionals in daily contact with the population.

Migration to the European Union (EU)/European Economic Area (EEA) affects the epidemiology of infectious diseases, including tuberculosis (TB), HIV, hepatitis B/C, and parasitic diseases. Some sub-populations of migrants are also considered to be an under-immunised group and thus at risk of vaccine-preventable diseases. Providing high-risk migrants access to timely and efficacious screening and vaccination, and understanding how best to implement more integrated screening and vaccination programmes into European health systems ensuring linkage to care and treatment, is key to improving the health of migrants and their communities, alongside meeting national and regional targets for infection surveillance, control, and elimination. The European Centre for Disease Prevention and Control (ECDC) has responded to calls to action to improve migrant health and strengthen universal health coverage by developing evidence-based guidance for policy makers, public health experts, and front-line healthcare professionals on how to approach screening and vaccination in newly arrived migrants within the EU/EEA. In this Commentary, we provide a perspective towards developing efficacious screening and vaccination of newly arrived migrants, with a focus on defining implementation challenges and evidence gaps in high-migrant receiving EU/EEA countries. There is a need now to leverage the increasing momentum around migrant health to both strengthen the evidence-base and to advocate for universal access to health care for all migrants in the EU/ EEA, including undocumented migrants. This should include voluntary, confidential, and non-stigmatising screening and vaccination that should be free of charge and facilitate linkage to appropriate care and treatment.

Seasonal influenza is a common cause of hospital admission, especially in older people and those with comorbidities. The objective of this study was to determine influenza vaccine effectiveness (VE) in preventing intensive care admissions and shortening the length of stay (LOS) in hospitalized laboratory-confirmed influenza cases (HLCI) in Catalonia (Spain). A retrospective cohort study was carried out during the 2017–2018 season in HLCI aged ≥18 years from 14 public hospitals. Differences in means and proportions were assessed using a t-test or a chi-square test as necessary and the differences were quantified using standardized effect measures: Cohen’s d for quantitative and Cohen’s w for categorical variables. Adjusted influenza vaccine effectiveness in preventing severity was estimated by multivariate logistic regression where the adjusted VE = (1 − adjusted odds ratio) · 100%, adjustment was also made using the propensity score. We analyzed 1414 HLCI aged ≥18 years, 465 (33%) were vaccinated, of whom 437 (94%) were aged ≥60 years, 269 (57.8%) were male and 295 (63.4%) were positive for influenza type B. ICU admission was required in 214 (15.1%) cases. There were 141/1118 (12.6%) ICU admissions in patients aged ≥60 years and 73/296 (24.7%) in those aged &lt, 60 years (p &lt, 0.001). The mean LOS and ICU LOS did not differ significantly between vaccinated and unvaccinated patients. There were 52/465 (11.2%) ICU admissions in vaccinated cases vs. 162/949 (17.1%) in unvaccinated cases. Patients admitted to the ICU had a longer hospital LOS (mean: 22.4 [SD 20.3] days) than those who were not (mean: 11.1 [SD 14.4] days), p &lt, 0.001. Overall, vaccination was associated with a lower risk of ICU admission. Taking virus types A and B together, the estimated adjusted VE in preventing ICU admission was 31% (95% CI 1–52, p = 0.04). When stratified by viral type, the aVE was 40% for type A (95% CI -11–68, p = 0.09) and 25% for type B (95% CI -18–52, p = 0.21). Annual influenza vaccination may prevent ICU admission in cases of HLCI. A non-significantly shorter mean hospital stay was observed in vaccinated cases. Our results support the need to increase vaccination uptake and public perception of the benefits of influenza vaccination in groups at a higher risk of hospitalization and severe outcomes.

The COVID-19 pandemic has raised questions about the possible cross immunity resulting from common vaccination programs and SARS-CoV-2 infection. Therefore, the Spanish Obstetric Emergency group performed a multicenter prospective study on the vaccination status of Influenza and Tdap (diphtheria, tetanus and pertussis vaccine boost administered in adulthood) in consecutive cases of SARS-CoV-2 infection in a pregnancy cohort, in order to assess its possible association with the clinical presentation and severity of symptoms of SARS-CoV-2 infection, as well as to determine the factors that may affect vaccination adherence. A total of 1150 SARS-CoV-2 positive pregnant women from 78 Spanish hospitals were analyzed: 183 had not received either vaccine, 23 had been vaccinated for Influenza only, 529 for Tdap only and 415 received both vaccines. No association was observed between the vaccination status and the clinical presentation of SARS-CoV-2 infection and/or the severity of symptoms. However, a lower adherence to the administration of both vaccines was observed in the Latin-American subgroup. Based on the results above, we reinforce the importance of maternal vaccination programs in the actual pandemic. Health education campaigns should be specially targeted to groups less likely to participate in these programs, as well as for a future SARS-CoV-2 vaccination campaign., This research was supported by public funds obtained in competitive calls: Grant COV20/ 00021 from the Instituto de Salud Carlos III-Spanish Ministry of Health, and co-financed with Fondo Europeo de Desarrollo Regional (FEDER) funds

Background Pneumococcal nasopharyngeal colonization (PNC) generally precedes pneumococcal disease. The purpose of this study was to determine the prevalence of PNC and to identify the pneumococcal serotypes circulating among Bhutanese children under five years of age admitted with clinical pneumonia, before the introduction of pneumococcal conjugate vaccine (PCV13) in the country. We also aimed to contribute to the understanding of the interplay between PNC and viral co-infection among this population. Methods This was a prospective study conducted at the Jigme Dorji Wangchuck National Referral Hospital in Bhutan over 12 consecutive months. Children aged 2 to 59 months admitted with WHO-defined clinical pneumonia were eligible for recruitment. We collected blood for bacterial culture and molecular identification of S. pneumoniae, and nasopharyngeal washing for screening of respiratory viruses, and for the detection and capsular typing of S. pneumoniae by real-time polymerase chain reaction (RT-PCR). Results Overall, 189 children were recruited, and PNC was tested in 121 of them (64.0%). PNC was found in 76/121 children (62.8%) and S. pneumoniae was identified in blood (both by culture and RT-PCR) in a single child. Respiratory viruses were detected in a similar proportion among children with (62/70; 88.6%) and without PNC (36/40; 90.0%; p = 1.000), but rhinovirus detection was less common among children with PNC (20/70; 28.6% versus 19/40; 47.5%; p = 0.046). Capsular typing identified 30 different serotypes. Thirty-nine children (51.3%) were colonised with two to five different serotypes. A third of the children presented with serotypes considered highly invasive. Over half of the children (44/76; 57.9%) were carrying at least one serotype included in PCV13. Conclusions This study provides baseline information on the status of PNC among Bhutanese children admitted with clinical pneumonia prior to the introduction of PCV13, which is valuable to monitor its potential impact. PCV13 could theoretically have averted up to 58% of the pneumococcal infections among the children in this study, suggesting a future role for the vaccine to significantly reduce the burden associated with S. pneumoniae in Bhutan.

African animal trypanosomiasis is caused by vector-transmitted parasites of the genus Trypanosoma. T. congolense and T. brucei brucei are predominant in Africa, T. evansi and T. vivax in America and Asia. They have in common an extracellular lifestyle and livestock tropism, which provokes huge economic losses in regions where vectors are endemic. There are licensed drugs to treat the infections, but adherence to treatment is poor and appearance of resistances common. Therefore, the availability of a prophylactic vaccine would represent a major breakthrough towards the management and control of the disease. Selection of the most appropriate antigens for its development is a bottleneck step, especially considering the limited resources allocated. Herein we propose a vaccine strategy based on multiple epitopes from multiple antigens to counteract the parasites&acute, biological complexity. Epitopes were identified by computer-assisted genome-wide screenings, considering sequence conservation criteria, antigens annotation and sub-cellular localization, high binding affinity to antigen presenting molecules, and lack of cross-reactivity to proteins in cattle and other breeding species. We ultimately provide 31 B-cell, 8 CD4 T-cell, and 15 CD8 T-cell epitope sequences from 30 distinct antigens for the prospective design of a genetic ensemble vaccine against the four trypanosome species responsible for African animal trypanosomiasis.

The lack of invasive pneumococcal disease (IPD) cost studies may underestimate the eect of pneumococcal polysaccharide conjugated vaccines (PCV). The objective of this study was to estimate the direct costs of hospitalized IPD cases. A prospective study was made in children aged

Background in 2016, WHO passed the Global Health Sector Strategy on Viral Hepatitis (GHSS), calling for its elimination by 2030. Two years later, Turkey approved a strategy to reach the WHO targets. This study reports new national prevalence data, breaks it down by subpopulation, and models scenarios to reach HCV elimination. Methods Literature was reviewed for estimates of HCV disease burden in Turkey. They were discussed with stakeholders and used as inputs to develop a disease burden model. the infected population was estimated by sequelae for the years 2015-2030. Three scenarios were developed to evaluate the disease burden in Turkey: a Base 2017 scenario, representing the current standard of care in Turkey; an increased treatment scenario, representing the impact of improved access to DAAs; and a WHO targets scenario, which meet the WHO GHSS viral hepatitis targets of a 65% reduction in mortality and 90% diagnosis rate of the infected population by 2030. Results At the beginning of 2017, 271,000 viremic infections were estimated. of these, 58,400 were diagnosed and 10,200 treated. Modelling results showed that, with the current treatment paradigm in Turkey, by 2030 the total number of viremic HCV infections would decline by 35%, while liver-related deaths, hepatocellular carcinoma (HCC), and decompensated cirrhosis would decrease by 10-25%. in the increased treatment scenario, by 2030 viremic HCV infections would decrease by 50%; liver-related deaths, HCC and decompensated cirrhosis would decrease by 45-70%. in the WHO targets scenario, HCV infections would decrease by 80%; sequelae would decrease by 80-85%. Data on disease burden in micro-elimination target subpopulations are largely unavailable. Conclusions To meet the WHO Global Health Sector Strategy targets for the elimination of HCV, Turkey needs to increase treatment. Better data are needed as well as countrywide access to DAAs., Gilead SciencesGilead Sciences, This publication has been supported by Gilead Sciences with financial support for some editorial services and administrative support to facilitate and coordinate the publication by arranging meetings. the funding body had no role in the study design, data collection, analysis, interpretation of data or in the writing of the manuscript. the content of the publication reflects the independent opinions of the authors and Gilead did not have any influence or control.

The aim was to analyse invasive pneumococcal disease (IPD) serotypes in children aged ⩽17 years according to clinical presentation and antimicrobial susceptibility. We conducted a prospective study (January 2012–June 2016). IPD cases were diagnosed by culture and/or real-time polymerase chain reaction (PCR). Demographic, microbiological and clinical data were analysed. Associations were assessed using the odds ratio (OR) and 95% confidence intervals (CI). Of the 253 cases, 34.4% were aged

Background: The objective of this study is to describe incidence and shifts of serotype and clonal distribution of invasive Streptococcus pneumoniae strains in four different age groups (65 years) during a period of intermediate PCV13 vaccination coverage (2011–2016) in Catalonia, Spain. Methods: We included all pneumococcal strains systematically sent to the Catalan support laboratory for molecular surveillance of invasive pneumococcal disease (IPD) located at Hospital Sant Joan de Deu, Barcelona. Two study periods were considered: 2011–13, early PCV13 vaccination period (EVP) and 2014–2016, late vaccination period (LVP). Results: A total of 2142 strains were included in the study. Five years after intermediate introduction of PCV13 in our population, a significant decrease of overall incidence of IPD in children 65 years. Results found when comparing both periods were consistent with IRRs observed year by year. In children 65 years the most frequently isolated serotypes were 3, 19A and 7F vs 3, 14 and 12F, respectively. Regarding clonal complexes (CCs) expressing mainly PCV13 serotypes, significant decreases of the proportions of CC306, CC191 and CC320 were observed, while CC156 showed a significant increase. As for CCs expressing mostly non-PCV13 serotypes, significant increases in ST989, CC53 and CC404 were showed. Conclusions: Despite low vaccine coverage in our setting a significant decrease of incidence of IPD was observed in children younger than 5 years. The modest indirect protection against vaccine serotypes causing IPD in elderly indicate the need for the inclusion of more serotypes in future high-valent PCV and vaccinating old adults should be considered. info:eu-repo/semantics/publishedVersion

Canine leishmaniosis is an important vector-borne zoonosis caused mainly by Leishmania infantum. Diagnosis and treatment of affected individuals can be particularly complex, hindering infection control in endemic areas. Methods to prevent canine leishmaniosis include the use of topical insecticides, prophylactic immunotherapy and vaccination. Four vaccines against canine leishmaniosis have been licensed since 2004, two in Brazil (Leishmune®, the production and marketing licence of which was withdrawn in 2014, and Leish-Tec®) and two in Europe (CaniLeish® and LetiFend®). After several years of marketing, doubts remain regarding vaccine efficacy and effectiveness, potential infectiousness of vaccinated and infected animals or the interference of vaccine-induced antibodies in L. infantum serological diagnosis. This review summarises the scientific evidence for each of the vaccines commercially approved for canine leishmaniosis, while discussing possible weaknesses of these studies. Furthermore, it raises the need to address important questions related to vaccination impact in Leishmania-endemic countries and the importance of post-marketing pharmacological surveillance.La leishmaniose canine est une importante zoonose à transmission vectorielle causée principalement par Leishmania infantum. Le diagnostic et le traitement des personnes atteintes peuvent être particulièrement complexes, entravant la lutte contre l’infection dans les zones d'endémie. Les méthodes de prévention de la leishmaniose canine comprennent l'utilisation d'insecticides topiques, l'immunothérapie prophylactique et la vaccination. Quatre vaccins contre la leishmaniose canine ont été homologués depuis 2004, deux au Brésil (Leishmune®, dont la licence de production et de commercialisation a été retirée en 2014 et Leish-Tec®) et deux en Europe (CaniLeish® et LetiFend®). Après plusieurs années de commercialisation, des doutes subsistent quant à l'efficacité et à l'effet du vaccin, au potentiel infectieux des animaux vaccinés et infectés ou à l'interférence des anticorps induits par le vaccin dans le diagnostic sérologique de L. infantum. Cette revue résume les données scientifiques de chacun des vaccins commercialement approuvés pour la leishmaniose canine, tout en discutant des possibles faiblesses de ces études. En outre, il soulève la nécessité de répondre à des questions importantes liées à l'impact de la vaccination dans les pays où la Leishmania est endémique et à l'importance de la surveillance pharmacologique post-marketing.

Objective The Plan of Information on Acute Respiratory Infections in Catalonia (PIDIRAC) included the surveillance of severe hospitalized cases of laboratory-confirmed influenza (SHCLCI) in 2009. The objective of this study was to determine the clinical, epidemiological and virological features of SHCLCI recorded in 12 sentinel hospitals during five influenza seasons. Results From a sample of SHCLCI recorded during the 5 influenza epidemics seasons from 2010–2011 to 2014–2015, Cases were confirmed by PCR and/or viral isolation in cell cultures from respiratory samples. A total of 1400 SHCLCI were recorded, 33% required ICU admission and 12% died. The median age of cases was 61 years (range 0–101 years); 70.5% were unvaccinated; 80.4% received antiviral treatment (in 79.6 and 24% of cases within 48 h after hospital admission and the onset of symptoms, respectively); influenza virus A [37.9% A (H1N1)pdm09, 29.3% A (H3N2)] was identified in 87.7% of cases. Surveillance of SHCLCI provides an estimate of the severity of seasonal influenza epidemics and the identification and characterization of at-risk groups in order to facilitate preventive measures such as vaccination and early antiviral treatment. Electronic supplementary material The online version of this article (10.1186/s13104-018-3349-y) contains supplementary material, which is available to authorized users.

Antonio Miguel,1 Luis Sendra,1 Verónica Noé,2 Carles J Ciudad,2 Francisco Dasí,3,4 David Hervas,5 María José Herrero,1,6 Salvador F Aliño17 1Department of Pharmacology, Faculty of Medicine, University of Valencia, 2Department of Biochemistry and Molecular Biology, Faculty of Pharmacy, University of Barcelona, 3Research University Hospital of Valencia, INCLIVA Health Research Institute, 4Department of Physiology, Faculty of Medicine, University of Valencia Foundation, 5Biostatistics Unit, 6Pharmacogenetics Unit, Instituto de Investigación Sanitaria La Fe (IIS La Fe), 7Clinical Pharmacology Unit, ACM Hospital Universitario y Politécnico La Fe, Valencia, Spain Abstract: The antitumor response after therapeutic vaccination has a limited effect and seems to be related to the presence of T regulatory cells (Treg), which express the immunoregulatory molecules CTLA4 and Foxp3. The blockage of CTLA4 using antibodies has shown an effective antitumor response conducing to the approval of the human anti-CTLA4 antibody ipilimumab by the US Food and Drug Administration. On the other hand, Foxp3 is crucial for Treg development. For this reason, it is an attractive target for cancer treatment. This study aims to evaluate whether combining therapeutic vaccination with CTLA4 or Foxp3 gene silencing enhances the antitumor response. First, the “in vitro” cell entrance and gene silencing efficacy of two tools, 2'-O-methyl phosphorotioate-modified oligonucleotides (2'-OMe-PS-ASOs) and polypurine reverse Hoogsteen hairpins (PPRHs), were evaluated in EL4 cells and cultured primary lymphocytes. Following B16 tumor transplant, C57BL6 mice were vaccinated with irradiated B16 tumor cells engineered to produce granulocyte-macrophage colony-stimulating factor (GM-CSF) and were intraperitoneally treated with CTLA4 and Foxp3 2'-OMe-PS-ASO before and after vaccination. Tumor growth, mice survival, and CTLA4 and Foxp3 expression in blood cells were measured. The following results were obtained: 1) only 2'-OMe-PS-ASO reached gene silencing efficacy “in vitro”; 2) an improved survival effect was achieved combining both therapeutic vaccine and Foxp3 antisense or CTLA4 antisense oligonucleotides (50% and 20%, respectively); 3) The blood CD4+CD25+Foxp3+ (Treg) and CD4+CTLA4+ cell counts were higher in mice that developed tumor on the day of sacrifice. Our data showed that tumor cell vaccine combined with Foxp3 or CTLA4 gene silencing can increase the efficacy of therapeutic antitumor vaccination. Keywords: gene silencing, antitumor vaccine, Treg, antisense oligonucleotide, cancer immunotherapy

Objectives: The aim of this study was to assess direct health costs in children with pertussis aged 0–9 years who were vaccinated, partially vaccinated, and unvaccinated during childhood, and to assess the association between pertussis costs and pertussis vaccination in Catalonia (Spain) in 2012–2013. Methods: Direct healthcare costs included pertussis treatment, pertussis detection, and preventive chemotherapy of contacts. Pertussis patients were considered vaccinated when they had received 4–5 doses, and unvaccinated or partially vaccinated when they had received 0–3 doses of vaccine. The Chi square test and the odds ratios were used to compare percentages and the t test was used to compare mean pertussis costs in different groups, considering a p

Model animal; COVID-19; Recerca preclínica Modelo animal; COVID-19; Investigación preclínica Animal model; COVID-19; Pre-clinical research Many milestones in medical history rest on animal modeling of human diseases. The SARS-CoV-2 pandemic has evoked a tremendous investigative effort primarily centered on clinical studies. However, several animal SARS-CoV-2/COVID-19 models have been developed and pre-clinical findings aimed at supporting clinical evidence rapidly emerge. In this review, we characterize the existing animal models exposing their relevance and limitations as well as outline their utility in COVID-19 drug and vaccine development. Concurrently, we summarize the status of clinical trial research and discuss the novel tactics utilized in the largest multi-center trials aiming to accelerate generation of reliable results that may subsequently shape COVID-19 clinical treatment practices. We also highlight areas of improvement for animal studies in order to elevate their translational utility. In pandemics, to optimize the use of strained resources in a short time-frame, optimizing and strengthening the synergy between the preclinical and clinical domains is pivotal.

Hisashi Shoji,1,* Daniel A Vázquez-Sánchez,1,* Aida Gonzalez-Diaz,1,2 Meritxell Cubero,1,2 Fe Tubau,1,2 Salud Santos,2,3 Dolores García-Somoza,1,2 Josefina Liñares,1,2 José Yuste,2,4 Sara Martí,1,2 Carmen Ardanuy1,2 1Microbiology Department, Hospital Universitari de Bellvitge, IDIBELL, University of Barcelona, Barcelona, Spain; 2CIBER de Enfermedades Respiratorias, ISCIII, Madrid, Spain; 3Respiratory Medicine Department, Hospital Universitari de Bellvitge, IDIBELL, University of Barcelona, Barcelona, Spain; 4Pneumococcal Reference Laboratory, Centro Nacional de Microbiología, ISCIII, Madrid, Spain *These authors contributed equally to this work Background: Streptococcus pneumoniae is an important pathogen in chronic obstructive pulmonary disease (COPD). We aimed at showing the recent changes in the epidemiology of pneumococcal diseases in patients with COPD, especially after the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13).Methods: From 2013 to 2016, strains causing invasive pneumococcal disease (IPD), non-bacteremic pneumococcal pneumonia (non-BPP), and acute exacerbation of COPD (AE-COPD) were prospectively included. Antimicrobial susceptibility testing, serotyping, and genotyping were analyzed.Results: We collected 345 pneumococci from 286 COPD patients (57 IPD, 78 non-BPP, and 210 AE-COPD). The most frequent serotypes were serotypes 3 (14.0%), 8 (14.0%), and 12F (8.8%) in IPD; serotypes 3 (16.7%), 11A (9%), 9L/N (7.7%), and 23A (7.7%) in non-BPP; and serotypes 11A (11%), nontypeable (11%), and 6C (10%) in AE-COPD. Resistance rates were highest among AE-COPD strains. Penicillin resistance was associated with serotypes 11A (CC156) and 19A (CC320 and CC230). Compared with previous studies, fluoroquinolone resistance in AE-COPD increased (9.5%), PCV13 serotypes decreased (31.6%, 26.9%, and 16.7% for IPD, non-BPP, and AE-COPD, respectively), and serotype 11A-CC156 in AE-COPD and serotype 8 in IPD increased.Conclusion: The epidemiology of pneumococcal disease in COPD changed after the introduction of PCV13 in children. Increases in the highly invasive serotype 8 among patients with IPD and in serotype 11A-CC156 among patients with AE-COPD could compromise the ability of current PCVs to prevent diseases. Vaccines with a greater coverage could improve the benefits of adult vaccination. Keywords: Streptococcus pneumoniae, pneumococcal conjugate vaccine, chronic obstructive pulmonary disease, invasive pneumococcal disease

Pneumococcal pneumonia is a serious cause of morbidity and mortality in the elderly, but investigation of the etiological agent of community-acquired pneumonia (CAP) is not possible in most hospitalized patients. The aim of this study was to estimate the effect of pneumococcal polysaccharide vaccination (PPSV23) in preventing CAP hospitalization and reducing the risk of intensive care unit admission (ICU) and fatal outcomes in hospitalized people aged ≥65 years. We made a multicenter case-control study in 20 Spanish hospitals during 2013–2014 and 2014–2015. We selected patients aged ≥65 years hospitalized with a diagnosis of pneumonia and controls matched by sex, age and date of hospitalization. Multivariate analysis was performed using conditional logistic regression to estimate vaccine effectiveness and unconditional logistic regression to evaluate the reduction in the risk of severe and fatal outcomes. 1895 cases and 1895 controls were included; 13.7% of cases and 14.4% of controls had received PPSV23 in the last five years. The effectiveness of PPSV23 in preventing CAP hospitalization was 15.2% (95% CI -3.1–30.3). The benefit of PPSV23 in avoiding ICU admission or death was 28.1% (95% CI -14.3–56.9) in all patients, 30.9% (95% CI -32.2–67.4) in immunocompetent patients and 26.9% (95% CI -38.6–64.8) in immunocompromised patients. In conclusion, PPSV23 showed a modest trend to avoidance of hospitalizations due to CAP and to the prevention of death or ICU admission in elderly patients hospitalized with a diagnosis of CAP., This study was funded by the National Plan of I+D+I 2008-2011 and ISCIII-Subdirección General de Evaluación y Fomento de la Investigación (Project PI12/02079) and cofounded by FEDER and the Catalan Agency for the Management of Grants for University Research (AGAUR Grant number 2014/ SGR 1403).

Background: Currently, no vaccine against Pseudomonas is available. IC43 is a new, recombinant, protein (OprF/I)-based vaccine against the opportunistic pathogen, Pseudomonas aeruginosa, a major cause of serious hospital-acquired infections. IC43 has proven immunogenicity and tolerability in healthy volunteers, patients with burns, and patients with chronic lung diseases. In order to assess the immunogenicity and safety of IC43 in patients who are most at risk of acquiring Pseudomonas infections, it was evaluated in mechanically ventilated ICU patients. Methods: We conducted a randomized, placebo-controlled, partially blinded study in mechanically ventilated ICU patients. The immunogenicity of IC43 at day 14 was determined as the primary endpoint, and safety, efficacy against P. aeruginosa infections, and all-cause mortality were evaluated as secondary endpoints. Vaccinations (100 μg or 200 μg IC43 with adjuvant, or 100 μg IC43 without adjuvant, or placebo) were given twice in a 7-day interval and patients were followed up for 90 days. Results: Higher OprF/I IgG antibody titers were seen at day 14 for all IC43 groups versus placebo (P < 0.0001). Seroconversion (≥4-fold increase in OprF/I IgG titer from days 0 to 14) was highest with 100 μg IC43 without adjuvant (80.6%). There were no significant differences in P. aeruginosa infection rates, with a low rate of invasive infections (pneumonia or bacteremia) in the IC43 groups (11.2-14.0%). Serious adverse events (SAEs) considered possibly related to therapy were reported by 2 patients (1.9%) in the group of 100 μg IC43 with adjuvant. Both SAEs resolved and no deaths were related to study treatment. Local tolerability symptoms were mild and rare (, SCOPUS: ar.j, info:eu-repo/semantics/published

A prospective laboratory-based multicenter study that collected all adult invasive pneumococcal disease (IPD) episodes from 6 Spanish hospitals before (2008-2009) and after (2012-2013). The 13-valent pneumococcal conjugate vaccine (PCV13) licensure was conducted in order to analyze the impact of PCV13 introduction for children on adult IPD. A total of 1558 IPD episodes were detected. The incidence of IPD decreased significantly in the second period by -33.9% (95% CI, -40.3% to -26.8%). IPD due to PCV7 serotypes (-52.7%; 95% CI, -64.2% to -37.5%) and to PCV13 additional serotypes (-55.0% 95% CI, -62.0% to -46.7%) significantly decreased whereas IPD due to non-PCV13 serotypes remained stable (1.0% 95% CI, -12.9% to 17.2%). IPD due to all PCV13 additional serotypes significantly declined with the exception of serotype 3 (-11.3%; 95%CI -35.0% to 21.1%). IPD due to two non-PCV13 serotypes varied: serotype 6C that rose (301.6%; 95%CI, 92.7% to 733.3%, p

Supplemental Digital Content is available in the text, The impact of the investigational human immunodeficiency virus type 1 (HIV-1) F4/AS01B vaccine on HIV-1 viral load (VL) was evaluated in antiretroviral therapy (ART)-naive HIV-1 infected adults. This phase IIb, observer-blind study (NCT01218113), included ART-naive HIV-1 infected adults aged 18 to 55 years. Participants were randomized to receive 2 (F4/AS01B_2 group, N = 64) or 3 (F4/AS01B_3 group, N = 62) doses of F4/AS01B or placebo (control group, N = 64) at weeks 0, 4, and 28. Efficacy (HIV-1 VL, CD4+ T-cell count, ART initiation, and HIV-related clinical events), safety, and immunogenicity (antibody and T-cell responses) were evaluated during 48 weeks. At week 48, based on a mixed model, no statistically significant difference in HIV-1 VL change from baseline was demonstrated between F4/AS01B_2 and control group (0.073 log10 copies/mL [97.5% confidence interval (CI): −0.088; 0.235]), or F4/AS01B_3 and control group (−0.096 log10 copies/mL [97.5% CI: −0.257; 0.065]). No differences between groups were observed in HIV-1 VL change, CD4+ T-cell count, ART initiation, or HIV-related clinical events at intermediate timepoints. Among F4/AS01B recipients, the most frequent solicited symptoms were pain at injection site (252/300 doses), fatigue (137/300 doses), myalgia (105/300 doses), and headache (90/300 doses). Twelve serious adverse events were reported in 6 participants; 1 was considered vaccine-related (F4/AS01B_2 group: angioedema). F4/AS01B induced polyfunctional F4-specific CD4+ T-cells, but had no significant impact on F4-specific CD8+ T-cell and anti-F4 antibody levels. F4/AS01B had a clinically acceptable safety profile, induced F4-specific CD4+ T-cell responses, but did not reduce HIV-1 VL, impact CD4+ T-cells count, delay ART initiation, or prevent HIV-1 related clinical events.

The National Plan for the Elimination of Rubella was implemented in Spain in 2008 using the logistics of the National Plan for the Elimination of Measles that have been employed since year 2000. Molecular characterization of rubella virus (RUBV) is important for disease surveillance and for monitoring elimination of the disease throughout the world. We describe the first complete series of data regarding the circulation of RUBV genotypes in Spain. The 739-nucleotide fragment designated by the WHO for RUBV genotyping was sequenced in 88 selected cases collected from 1998 to 2014. Five genotypes were identified: 1E, 2B, 1J, 1I, and 1a. Genotype 1E was predominant between 1998 and 2003 but was replaced by genotype 2B, which was detected in sporadic cases in 2004, 2006, 2008, 2012, 2013 and 2014. There was an outbreak of genotype 2B in Algeciras (Andalusia) in 2008. Genotype 1J caused an outbreak in Madrid in 2004/2005 and sporadic cases in 2005 and 2007. Genotype 1I was found to have infected an immune-suppressed patient with neurological symptoms in 2008. Finally, vaccine strain RA 27/3 was detected in three sporadic cases, two of them immune-suppressed and without a recent history of vaccination. This suggests that during these years there were a series of imported sporadic cases and outbreaks, confirming the findings of epidemiological data analysis. The importation sources were generally consistent with our geographic and cultural ties, mainly with Europe (genotypes 1E, 2B, 1I) and Latin America (1J). This work has received financial support from the fellowship for Ph.D. Study by Republic of Panama and Acuerdo de Encomienda de Gestión entre la Dirección General de Salud Pública del Ministerio de Sanidad y Consumo y el Instituto de Salud Carlos III. N° expediente: DGVI-1429/05-3, and Fondo de Investigación Sanitaria, Instituto de Salud Carlos III (IP12/02006). Also, has been developed under the Project FIS PI12/02006 funded by the Strategic Action on Health of the Instituto de Salud Carlos III. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Sí

BACKGROUND: Maternal group B streptococcal (GBS) vaccines under development hold promise to prevent GBS disease in young infants. Sub-Saharan Africa has the highest estimated disease burden, although data on incidence and circulating strains are limited. We described invasive bacterial disease (IBD) trends among infants /=0.12 mug/mL) associated with penicillin-binding protein (PBP) 2x substitution G398A. Epidemiologic and molecular data suggest this is a well-established clone. CONCLUSION: A notable young infant GBS disease burden persisted despite improvements in overall maternal and neonatal health. We report an established strain with pbp2x point mutation, a first-step mutation associated with reduced penicillin susceptibility within a well-known virulent lineage in rural Mozambique. Our findings further underscores the need for non-antibiotic GBS prevention strategies.

From the first day of imprisonment, prisoners are exposed to and expose other prisoners to various communicable diseases, many of which are vaccine-preventable. The risk of acquiring these diseases during the prison sentence exceeds that of the general population. This excess risk may be explained by various causes; some due to the structural and logistical problems of prisons and others to habitual or acquired behaviors during imprisonment. Prison is, for many inmates, an opportunity to access health care, and is therefore an ideal opportunity to update adult vaccination schedules. The traditional idea that prisons are intended to ensure public safety should be complemented by the contribution they can make in improving community health, providing a more comprehensive vision of safety that includes public health.

The aim of this study was to study the serotypes and clonal diversity of pneumococci causing invasive pneumococcal disease in Catalonia, Spain, in the era of 13-valent pneumococcal conjugate vaccine (PCV13). In our region, this vaccine is only available in the private market and it is estimated a PCV13 vaccine coverage around 55% in children. A total of 1551 pneumococcal invasive isolates received between 2010 and 2013 in the Molecular Microbiology Department at Hospital Sant Joan de Déu, Barcelona, were included. Fifty-two serotypes and 249 clonal types—defined by MLST—were identified. The most common serotypes were serotype 1 (n = 182; 11.7%), 3 (n = 145; 9.3%), 19A (n = 137; 8.8%) and 7F (n = 122; 7.9%). Serotype 14 was the third most frequent serotype in children < 2 years (15 of 159 isolates). PCV7 serotypes maintained their proportion along the period of study, 16.6% in 2010 to 13.4% in 2013, whereas there was a significant proportional decrease in PCV13 serotypes, 65.3% in 2010 to 48.9% in 2013 (p

Background Published influenza vaccination coverage in health care workers (HCW) are calculated using two sources: self-report and vaccination records. The objective of this study was to determine whether self-report is a good proxy for recorded vaccination in HCW, as the degree of the relationship is not known, and whether vaccine behaviour influences self-reporting. Methods A cross-sectional study was conducted using a self-administered survey during September 2010. Considering the vaccination record as the gold standard of vaccination, the properties of self-report as a proxy of the record (sensitivity, specificity, positive predictive value, negative predictive value) were calculated. Concordance between the vaccination campaigns studied (2007–2010) was made using the Kappa index, and discordance was analyzed using McNemar’s test. Results 248 HCW responded. The 95% confidence intervals of coverage according to the vaccination record and to self-report overlapped, except for 2007, and the Kappa index showed a substantial concordance, except for 2007. McNemar’s test suggested that differences between discordant cases were not due to chance and it was found that the proportion of unvaccinated discordant cases was higher than that of vaccinated discordant cases. Conclusions In our study population, self-reported influenza vaccination coverage in HCW in the previous two years is a good proxy of the vaccination record. However, vaccination behaviour influences the self-report and explains a trend to overestimate coverage in self-reporting compared to the vaccination record. The sources of coverage should be taken into account whenever comparisons are made.

Streptococcus pneumoniae is the leading cause of vaccine-preventable deaths globally. The objective of this study was to determine the distribution and clonal type variability of three potential vaccine antigens: Pneumococcal serine-rich repeat protein (PsrP), Pilus-1, and Pneumococcal choline binding protein A (PcpA) among pneumococcal isolates from children with invasive pneumococcal disease and healthy nasopharyngeal carriers. We studied by Real-Time PCR a total of 458 invasive pneumococcal isolates and 89 nasopharyngeal pneumococcal isolates among children (total = 547 strains) collected in Barcelona, Spain, from January 2004 to July 2010. pcpA, psrP and pilus-1 were detected in 92.8%, 51.7% and 14.4% of invasive isolates and in 92.1%, 48.3% and 18% of carrier isolates, respectively. Within individual serotypes the prevalence of psrP and pilus-1 was highly dependent on the clonal type. pcpA was highly prevalent in all strains with the exception of those belonging to serotype 3 (33.3% in serotype 3 isolates vs. 95.1% in other serotypes; P

SUMMARYSocioeconomic factors and the patterns of use of health services associated with influenza and pneumococcal vaccination were studied in people aged ⩾65 years admitted to three general hospitals in Spain between 2005 and 2007. The following data were collected: age, sex, risk of pneumonia, educational level, social class, type of household, physician visits, length of time with the same general practitioner, and influenza and pneumococcal vaccination (23vPPV). Associations between variables were assessed using multivariate logistic regression analysis. In total, 1702 patients were included; 59·9% had received 23vPPV and 65·6% influenza vaccine. Older age (OR 1·04,PP=0·003) and influenza vaccination during the last year (OR 6·64,PP=0·005), older age (OR 1·02,P=0·009), moderate risk of pneumonia (OR 1·58,P=0·001), living with a partner (OR 1·52,P=0·015) and frequent physician visits during the last year (1–6 annuals visits (OR 2·65,P6 visits (OR 3·83,P

STUDY OBJECTIVES—The objective of this study was to evaluate the effectiveness of a mass vaccination programme carried out in Catalonia (Spain) in the last quarter of 1997 in response to an upsurge of serogroup C meningococcal disease (SCMD). DESIGN—Vaccination coverage in the 18 month to 19 years age group was investigated by means of a specific vaccination register. Vaccination effectiveness was calculated using the prospective cohort method. Cases of SCMD were identified on the basis of compulsory reporting and microbiological notification by hospital laboratories. Vaccination histories were investigated in all cases. Unadjusted and age adjusted vaccination effectiveness referred to the time of vaccination and the corresponding 95% confidence intervals (CI) were estimated at 6, 12, 18 and 24 months of follow up. SETTING—All population aged 18 months to 19 years of Catalonia. MAIN RESULTS—A total of seven cases of SCMD were detected at six months of follow up (one in the vaccinated cohort), 12 cases at 12 months (one in the vaccinated cohort), 19 cases at 18 months (two in the vaccinated cohort) and 24 at 24 months (two in the vaccinated cohort). The age adjusted effectiveness was 84% (95%CI 30, 97) at six months, 92% (95%CI 63, 98) at 12 months, 92% (95% CI 71, 98) at 18 months and 94% (95%CI 78, 98) at 24 months. In the target population, cases have been reduced by more than two thirds (68%) two years after the vaccination programme. In the total population the reduction was 43%. CONCLUSION—Vaccination effectiveness has been high in Catalonia, with a dramatic reduction in disease incidence in the vaccinated cohort accompanied by a relevant reduction in the overall population. Given that vaccination coverage was only 54.6%, it may be supposed that this vaccination effectiveness is attributable, in part, to the herd immunity conferred by the vaccine. Keywords: serogroup C; meningococcal disease; vaccination; mass campaign

Background The Hepatitis B virus (HBV) infection is a major cause of liver disease and liver cancer worldwide according to the World Health Organization. Following acute HBV infection, 1-5% of infected healthy adults and up to 90% of infected infants become chronic carriers and have an increased risk of cirrhosis and primary hepatocellular carcinoma. The aim of this study was to investigate the relationship between the reduction in acute hepatitis B incidence and the universal vaccination programme in preadolescents in Catalonia (Spain), taking population changes into account, and to construct a model to forecast the future incidence of cases that permits the best preventive strategy to be adopted. Methods Reported acute hepatitis B incidence in Catalonia according to age, gender, vaccination coverage, percentage of immigrants and the year of report of cases was analysed. A statistical analysis was made using three models: generalized linear models (GLM) with Poisson or negative binomial distribution and a generalized additive model (GAM). Results The higher the vaccination coverage, the lower the reported incidence of hepatitis B (p 70%, the reduction in incidence was 2-fold higher than in groups with a coverage Conclusions The results of the adjusted models in this study confirm that the global incidence of hepatitis B has declined in Catalonia after the introduction of the universal preadolescent vaccination programme, but the incidence increased in male immigrants of working age. Given the potential severity of hepatitis B for the health of individuals and for the community, universal vaccination programmes should continue and programmes in risk groups, especially immigrants, should be strengthened.

Estudis de control de casos; Pneumònia; Vacunació i immunització Estudios de casos y controles; Neumonía; Vacunación e inmunización Case-control studies; Pneumonia; Vaccination and immunization Background The 13-valent pneumococcal conjugate vaccine (PCV13) was licensed based on the results of immunogenicity studies and correlates of protection derived from randomized clinical trials of the 7-valent conjugate pneumococcal vaccine. We assessed the vaccination effectiveness (VE) of the PCV13 in preventing invasive pneumococcal disease (IPD) in children aged 7–59 months in a population with suboptimal vaccination coverage of 55%. Methods The study was carried out in children with IPD admitted to three hospitals in Barcelona (Spain) and controls matched by hospital, age, sex, date of hospitalization and underlying disease. Information on the vaccination status was obtained from written medical records. Conditional logistic regression was made to estimate the adjusted VE and 95% confidence intervals (CI). Results 169 cases and 645 controls were included. The overall VE of ≥1 doses of PCV13 in preventing IPD due to vaccine serotypes was 75.8% (95% CI, 54.1–87.2) and 90% (95% CI, 63.9–97.2) when ≥2 doses before 12 months, two doses on or after 12 months or one dose on or after 24 months, were administered. The VE of ≥1 doses was 89% (95% CI, 42.7–97.9) against serotype 1 and 86.0% (95% CI, 51.2–99.7) against serotype 19A. Serotype 3 showed a non-statistically significant effectiveness (25.9%; 95% CI, -65.3 to 66.8). Conclusions The effectiveness of ≥1 doses of PCV13 in preventing IPD caused by all PCV13 serotypes in children aged 7–59 months was good and, except for serotype 3, the effectiveness of ≥1 doses against the most frequent PCV13 serotypes causing IPD was high when considered individually. This work was supported by the Plan Nacional I+D+I, ISCIII – Subdirección General de Evaluación y Fomento de la Investigación Sanitaria (Projects PI 11/02081, PI 11/2345) and cofounded by Fondo Europeo de Desarrollo Regional (FEDER) and AGAUR (Grant 2014 SGR 1403).

BACKGROUND: Studies have shown a slight excess risk in Guillain-Barré syndrome (GBS) incidence associated with A(H1N1)pdm09 vaccination campaign and seasonal trivalent influenza vaccine immunisations in 2009-2010. We aimed to assess the incidence of GBS as a potential adverse effect of A(H1N1)pdm09 vaccination. METHODS: A neurologist-led network, active at the neurology departments of ten general hospitals serving an adult population of 4.68 million, conducted GBS surveillance in Spain in 2009-2011. The network, established in 1996, carried out a retrospective and a prospective study to estimate monthly alarm thresholds in GBS incidence and tested them in 1998-1999 in a pilot study. Such incidence thresholds additionally to observation of GBS cases with immunisation antecedent in the 42 days prior to clinical onset were taken as alarm signals for 2009-2011, since November 2009 onwards. For purpose of surveillance, in 2009 we updated both the available centres and the populations served by the network. We also did a retrospective countrywide review of hospital-discharged patients having ICD-9-CM code 357.0 (acute infective polyneuritis) as their principal diagnosis from January 2009 to December 2011. RESULTS: Among 141 confirmed of 148 notified cases of GBS or Miller-Fisher syndrome, Brighton 1-2 criteria in 96 %, not a single patient was identified with clinical onset during the 42-day time interval following A(H1N1)pdm09 vaccination. In contrast, seven cases were seen during a similar period after seasonal campaigns. Monthly incidence figures did not, however, exceed the upper 95 % CI limit of expected incidence. A retrospective countrywide review of the registry of hospital-discharged patients having ICD-9-CM code 357.0 (acute infective polyneuritis) as their principal diagnosis did not suggest higher admission rates in critical months across the period December 2009-February 2010. CONCLUSIONS: Despite limited power and underlying reporting bias in 2010-2011, an increase in GBS incidence over background GBS, associated with A(H1N1)pdm09 monovalent or trivalent influenza immunisations, appears unlikely Sí

Background Although routine vaccination is a major tool in the primary prevention of some infectious diseases, there is some reluctance in a proportion of the population. Negative parental perceptions of vaccination are an important barrier to paediatric vaccination. The aim of this study was to investigate parental knowledge of paediatric vaccines and vaccination in Catalonia. Methods A retrospective, cross-sectional study was carried out in children aged < 3 years recruited by random sampling from municipal districts of all health regions of Catalonia. The total sample was 630 children. Parents completed a standard questionnaire for each child, which included vaccination coverage and knowledge about vaccination. The level of knowledge of vaccination was scored according to parental answers. Results An association was observed between greater vaccination coverage of the 4:4:4:3:1 schedule (defined as: 4 DTPa/w doses, 4 Hib doses, 4 OPV doses, 3 MenC doses and 1 MMR dose) and maternal age >30 years (OR: 2.30; 95% CI: 1.20–4.43) and with a knowledge of vaccination score greater than the mean (OR: 0.45; 95% CI: 0.28–0.72). The score increased with maternal educational level and in parents of vaccinated children. A total of 20.47% of parents stated that vaccines could have undesirable consequences for their children. Of these, 23.26% had no specific information and 17.83% stated that vaccines can cause adverse reactions and the same percentage stated that vaccines cause allergies and asthma. Conclusion Higher vaccination coverage is associated with older maternal age and greater knowledge of vaccination. Vaccination coverage could be raised by improving information on vaccines and vaccination.

Meningococcal disease causes considerable morbidity and has a high case-fatality rate. In the United Kingdom, the meningococcal quadrivalent vaccine is recommended for travelers visiting the meningitis belt of Africa. We analyzed 302 responses to a cross-sectional study conducted in 2010 of travelers who had visited the meningitis belt recently or were shortly due to travel there. Using the results of an online questionnaire, we assessed knowledge and understanding of meningococcal disease and likelihood of uptake of meningococcal immunization before travel. Meningococcal vaccine uptake was 30.1%. Although global scores in the questionnaire did not correlate with vaccine uptake, knowledge of the meningitis belt and knowledge of certain key symptoms or signs were statistically associated with high vaccine uptake. We conclude that improved education of travelers may improve vaccine uptake before travel to the meningitis belt in Africa.

Background Completion of multiple dose vaccine schedules is crucial to ensure a protective immune response, and maximise vaccine cost-effectiveness. While barriers and facilitators to vaccine uptake have recently been reviewed, there is no comprehensive review of factors influencing subsequent adherence or completion, which is key to achieving vaccine effectiveness. This study identifies and summarises the literature on factors affecting completion of multi-dose vaccine schedules by adolescents. Methods Ten online databases and four websites were searched (February 2014). Studies with analysis of factors predicting completion of multi-dose vaccines were included. Study participants within 9–19 years of age were included in the review. The defined outcome was completion of the vaccine series within 1 year among those who received the first dose. Results Overall, 6159 abstracts were screened, and 502 full texts were reviewed. Sixty one studies were eligible for this review. All except two were set in high-income countries. Included studies evaluated human papillomavirus vaccine, hepatitis A, hepatitis B, and varicella vaccines. Reported vaccine completion rates, among those who initiated vaccination, ranged from 27 % to over 90 %. Minority racial or ethnic groups and inadequate health insurance coverage were risk factors for low completion, irrespective of initiation rates. Parental healthcare seeking behaviour was positively associated with completion. Vaccine delivery in schools was associated with higher completion than delivery in the community or health facilities. Gender, prior healthcare use and socio-economic status rarely remained significant risks or protective factors in multivariate analysis. Conclusions Almost all studies investigating factors affecting completion have been carried out in developed countries and investigate a limited range of variables. Increased understanding of barriers to completion in adolescents will be invaluable to future new vaccine introductions and the further development of an adolescent health platform. PROSPERO reg# CRD42014006765. Electronic supplementary material The online version of this article (doi:10.1186/s12889-016-2845-z) contains supplementary material, which is available to authorized users.

Background Influenza vaccination coverage remains low among health care workers (HCWs) in many health facilities. This study describes the social network defined by HCWs’ conversations around an influenza vaccination campaign in order to describe the role played by vaccination behavior and other HCW characteristics in the configuration of the links among subjects. Methods This study used cross-sectional data from 235 HCWs interviewed after the 2010/2011 influenza vaccination campaign at the Hospital Clinic of Barcelona (HCB), Spain. The study asked: “Who did you talk to or share some activity with respect to the seasonal vaccination campaign?” Variables studied included sociodemographic characteristics and reported conversations among HCWs during the influenza campaign. Exponential random graph models (ERGM) were used to assess the role of shared characteristics (homophily) and individual characteristics in the social network around the influenza vaccination campaign. Results Links were more likely between HCWs who shared the same professional category (OR 3.13, 95% CI = 2.61–3.75), sex (OR 1.34, 95% CI = 1.09–1.62), age (OR 0.7, 95% CI = 0.63–0.78 per decade of difference), and department (OR 11.35, 95% CI = 8.17–15.64), but not between HCWs who shared the same vaccination behavior (OR 1.02, 95% CI = 0.86–1.22). Older (OR 1.26, 95% CI = 1.14–1.39 per extra decade of HCW) and vaccinated (OR 1.32, 95% CI = 1.09–1.62) HCWs were more likely to be named. Conclusions This study finds that there is no homophily by vaccination status in whom HCWs speak to or interact with about a workplace vaccination promotion campaign. This result highlights the relevance of social network analysis in the planning of health promotion interventions. Electronic supplementary material The online version of this article (doi:10.1186/s13012-016-0522-3) contains supplementary material, which is available to authorized users.

In a pooled analysis of data collected from invasive pneumococcal disease surveillance databases, Daniel Feikin and colleagues examine serotype replacement after the introduction of 7-valent pneumococcal conjugate vaccine (PCV7) into national immunization programs. Please see later in the article for the Editors' Summary, Background Vaccine-serotype (VT) invasive pneumococcal disease (IPD) rates declined substantially following introduction of 7-valent pneumococcal conjugate vaccine (PCV7) into national immunization programs. Increases in non-vaccine-serotype (NVT) IPD rates occurred in some sites, presumably representing serotype replacement. We used a standardized approach to describe serotype-specific IPD changes among multiple sites after PCV7 introduction. Methods and Findings Of 32 IPD surveillance datasets received, we identified 21 eligible databases with rate data ≥2 years before and ≥1 year after PCV7 introduction. Expected annual rates of IPD absent PCV7 introduction were estimated by extrapolation using either Poisson regression modeling of pre-PCV7 rates or averaging pre-PCV7 rates. To estimate whether changes in rates had occurred following PCV7 introduction, we calculated site specific rate ratios by dividing observed by expected IPD rates for each post-PCV7 year. We calculated summary rate ratios (RRs) using random effects meta-analysis. For children, Editors’ Summary Background Pneumococcal disease–a major cause of illness and death in children and adults worldwide–is caused by Streptococcus pneumoniae, a bacterium that often colonizes the nose and throat harmlessly. Unfortunately, S. pneumoniae occasionally spreads into the lungs, bloodstream, or covering of the brain, where it causes pneumonia, septicemia, and meningitis, respectively. These invasive pneumococcal diseases (IPDs) can usually be successfully treated with antibiotics but can be fatal. Consequently, it is better to avoid infection through vaccination. Vaccination primes the immune system to recognize and attack disease-causing organisms (pathogens) rapidly and effectively by exposing it to weakened or dead pathogens or to pathogen molecules that it recognizes as foreign (antigens). Because there are more than 90 S. pneumoniae variants or “serotypes,” each characterized by a different antigenic polysaccharide (complex sugar) coat, vaccines that protect against S. pneumoniae have to include multiple serotypes. Thus, the pneumococcal conjugate vaccine PCV7, which was introduced into the US infant immunization regimen in 2000, contains polysaccharides from the seven S. pneumoniae serotypes mainly responsible for IPD in the US at that time. Why Was This Study Done? Vaccination with PCV7 was subsequently introduced in several other high- and middle-income countries, and IPD caused by the serotypes included in the vaccine declined substantially in children and in adults (because of reduced bacterial transmission and herd protection) in the US and virtually all these countries. However, increases in IPD caused by non-vaccine serotypes occurred in some settings, presumably because of “serotype replacement.” PCV7 prevents both IPD caused by the serotypes it contains and carriage of these serotypes. Consequently, after vaccination, previously less common, non-vaccine serotypes can colonize the nose and throat, some of which can cause IPD. In July 2010, a World Health Organization expert consultation on serotype replacement called for a comprehensive analysis of the magnitude and variability of pneumococcal serotype replacement following PCV7 use to help guide the introduction of PCVs in low-income countries, where most pneumococcal deaths occur. In this pooled analysis of data from multiple surveillance sites, the researchers investigate serotype-specific changes in IPD after PCV7 introduction using a standardized approach. What Did the Researchers Do and Find? The researchers identified 21 databases that had data about the rate of IPD for at least 2 years before and 1 year after PCV7 introduction. They estimated whether changes in IPD rates had occurred after PCV7 introduction by calculating site-specific rate ratios–the observed IPD rate for each post-PCV7 year divided by the expected IPD rate in the absence of PCV7 extrapolated from the pre-PCV7 rate. Finally, they used a statistical approach (random effects meta-analysis) to estimate summary (pooled) rate ratios. For children under 5 years old, the overall number of observed cases of IPD in the first year after the introduction of PCV7 was about half the expected number; this reduction in IPD continued through year 7 after PCV7 introduction. Notably, the rate of IPD caused by the S. pneumonia serotypes in PCV7 decreased every year, but the rate of IPD caused by non-vaccine serotypes increased annually. By year 7, the number of cases of IPD caused by non-vaccine serotypes was 3-fold higher than expected, but was still smaller than the decrease in vaccine serotypes, thereby leading to the decrease in overall IPD. Finally, smaller decreases in overall IPD also occurred among adults but occurred later than in children 2 years or more after PCV7 introduction. What Do These Findings Mean? These findings show that consistent, rapid, and sustained decreases in overall IPD and in IPD caused by serotypes included in PCV7 occurred in children and thus support the use of PCVs. The small increases in IPD caused by non-vaccine serotypes that these findings reveal are likely to be the result of serotype replacement, but changes in antibiotic use and other factors may also be involved. These findings have several important limitations, however. For example, PCV7 is no longer made and extrapolation of these results to newer PCV10 and PCV13 formulations should be done cautiously. On the other hand, many of the serotypes causing serotype replacement after PCV7 are included in these higher valency vaccines. Moreover, because the data analyzed in this study mainly came from high-income countries, these findings may not be generalizable to low-income countries. Nevertheless, based on their analysis, the researchers make recommendations for the collection and analysis of IPD surveillance data that should allow valid interpretations of the effect of PCVs on IPD to be made, an important requisite for making sound policy decisions about vaccination against pneumococcal disease. Additional Information Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001517. The US Centers for Disease Control and Prevention provides information for patients and health professionals on all aspects of pneumococcal disease and pneumococcal vaccination, including personal stories Public Health England provides information on pneumococcal disease and on pneumococcal vaccines The World Health Organization also provides information on pneumococcal vaccines The not-for-profit Immunization Action Coalition has information on pneumococcal disease, including personal stories MedlinePlus has links to further information about pneumococcal infections (in English and Spanish) The International Vaccine Access Center at Johns Hopkins Bloomberg School of Public Health has more information on introduction of pneumococcal conjugate vaccines in low-income countries

Background: A main criterion to identify malaria vaccine candidates is the proof that acquired immunity against them is associated with protection from disease. The age of the studied individuals, heterogeneous malaria exposure, and assumption of the maintenance of a baseline immune response can confound these associations. Methods: Immunoglobulin G/immunoglobulin M (IgG/ IgM) levels were measured by Luminex(R) in Mozambican children monitored for clinical malaria from birth until 3 years of age, together with functional antibodies. Studied candidates were pre-erythrocytic and erythrocytic antigens, including EBAs/PfRhs, MSPs, DBLs, and novel antigens merely or not previously studied in malaria-exposed populations. Cox regression models were estimated at 9 and 24 months of age, accounting for heterogeneous malaria exposure or limiting follow-up according to the antibody's decay. Results: Associations of antibody responses with higher clinical malaria risk were avoided when accounting for heterogeneous malaria exposure or when limiting the follow-up time in the analyses. Associations with reduced risk of clinical malaria were found only at 24 months old, but not younger children, for IgG breadth and levels of IgG targeting EBA140III-V, CyRPA, DBL5epsilon and DBL3x, together with C1q-fixation activity by antibodies targeting MSP119. Conclusions: Malaria protection correlates were identified, only in children aged 24 months old when accounting for heterogeneous malaria exposure. These results highlight the relevance of considering age and malaria exposure, as well as the importance of not assuming the maintenance of a baseline immune response throughout the follow-up. Results may be misleading if these factors are not considered.