Institute of Health Carlos III

Madrid, Spain

Institute of Health Carlos III

Madrid, Spain
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News Article | May 12, 2017

Immune cells, called macrophages, may rely on a compound to signal an attack to beat back attacks from parasitic worms, according to an international team of researchers, including Zissis C. Chroneos, associate professor of pediatrics, and microbiology and immunology at Penn State College of Medicine. The findings could lead to better drugs to fight common infections. It is estimated that parasitic worms infect hundreds of millions of people, mainly in the developing world. These roundworms and flatworms -- collectively known as helminths -- often infect the intestinal system, causing anemia and malnutrition. But worms can also infect other organs and systems, such as the lungs, urinary tract or bloodstream, causing a range of health problems. For example, the common worm infection schistosomiasis can lead to high blood pressure in lung arteries. Chroneos and his co-investigators studied a roundworm, called Nippostrongylus brasiliensis, that infects the lungs of rodents. A compound called interleukin 4, or IL-4, was used to activate large white blood cells -- macrophages -- to kill the parasite and promote healing in the lung tissue. The study, published in Science, helps to explain how this process works. The researchers discovered that IL-4 helps the outer layer of lung cells to boost production of the defense protein SP-A. This protein binds macrophages and enhances their ability to multiply and activate against the parasite. Chroneos discovered that the SP-A protein binds at a receptor called myosin 18A. IL-4 triggers the appearance, or expression, of the receptor on macrophages. "You cannot kill the worm if you don't have myosin 18A," Chroneos said. To test this, researchers in his lab developed antibodies to block the myosin 18A receptor. When it was blocked in mice, rats and human lung cells, the growth of macrophages against parasites was reduced. The findings have implications beyond the lungs, Chroneos said. The researchers found that the receptor myosin 18 also allows macrophages to bind to a different defense protein called C1q in the abdomen of mice. Macrophages from mouse liver, spleen and fat tissue expressed myosin 18A when exposed to the immune compound IL-4, which suggests that the receptor is important for fighting infections throughout the body. In the future, the new knowledge could be used to develop drugs against infections that trigger the IL-4 immune response. "Now that we know how this works, we can potentially use molecules that activate the myosin 18A pathway or the IL-4 pathway to kill the disease," Chroneos said. Other researchers on this project were Carlos M. Minutti, from the Complutense University of Madrid, the Instituto de Salud Carlos III, and the University of Edinburgh; Lucy H. Jackson-Jones, Johanna A. Knipper, Nicola Logan, Emma Rinqvist, David A. Ferenbach and Dietmar M. Zaiss, from the University of Edinburgh; Belén García-Fojeda and Cristina Casals from the Complutense University of Madrid and the Instituto de Salud Carlos III; Tara E. Sutherland from the University of Edinburgh and the University of Manchester; Raquel Guillamat-Prats and Antonio Artigas from the Instituto de Salud Carlos III and the Universitat Autònoma de Barcelona; Cordula Stamme from the University of Lu?beck; and Judith E. Allen from the University of Edinburgh and the University of Manchester. Minutti was recipient of fellowships from the Spanish Ministry of Science and Institute of Health Carlos III. This work was supported by the Spanish Ministry of Economy and Competitiveness, Institute of Health Carlos III, Medical Research Council UK, Wellcome Centre for Cell-Matrix Research, Medical Research Council, European Union, and National Institute of Health.

Abad R.,Institute of Health Carlos III | Debbag R.,Sanofi S.A. | Vazquez J.A.,Institute of Health Carlos III
Epidemiology and Infection | Year: 2014

Meningococcal serogroup W strains have been emerging throughout the current century with most of the isolates belonging to the sequence type (ST11)/electrophoretic type (ET37) clonal complex (ST11/E37 CC), particularly since the international outbreak following Hajj 2000. That outbreak appears to have triggered off that trend, contributing to the spread of W ST11/ET37 CC strains globally; however, local strains could be also responsible for increases in the percentage and/or incidence rates of this serogroup in some countries. More recently, unexpected increases in the percentage and incidence rate of W has been noticed in different countries located in the South Cone in Latin America, and W ST11/ET37 CC strains now appear as endemic in the region and an extensive immunization programme with tetravalent conjugate vaccine (covering serogroups A, C, Y and W) has been recently implemented in Chile. It is difficult to ascertain whether we are observing the emergence of W ST11 CC strains in different geographical areas or whether the Hajj 2000 strain is still spreading globally. Several aspects of the evolution of that situation are analysed in this paper, reviewing also the implications in immunization programmes. Closely related with the analysis of this potential evolution, it will be very interesting to monitor the evolution of serogroup W in the African meningitis belt after implementation of the extensive immunization programme with serogroup A conjugate vaccine that is currently underway. More data about carriers, transmission, clonal lineages, etc. are needed for taking decisions (target groups, outbreak control, defining the extent, etc.) to adapt the response strategy with potential interventions with broad coverage vaccines against the emergent serogroup W. Copyright © 2014 Cambridge University Press.

Aiken L.H.,University of Pennsylvania | Sloane D.M.,University of Pennsylvania | Bruyneel L.,Catholic University of Leuven | Van Den Heede K.,Catholic University of Leuven | And 14 more authors.
The Lancet | Year: 2014

Background Austerity measures and health-system redesign to minimise hospital expenditures risk adversely affecting patient outcomes. The RN4CAST study was designed to inform decision making about nursing, one of the largest components of hospital operating expenses. We aimed to assess whether differences in patient to nurse ratios and nurses' educational qualifications in nine of the 12 RN4CAST countries with similar patient discharge data were associated with variation in hospital mortality after common surgical procedures. Methods For this observational study, we obtained discharge data for 422 730 patients aged 50 years or older who underwent common surgeries in 300 hospitals in nine European countries. Administrative data were coded with a standard protocol (variants of the ninth or tenth versions of the International Classification of Diseases) to estimate 30 day in-hospital mortality by use of risk adjustment measures including age, sex, admission type, 43 dummy variables suggesting surgery type, and 17 dummy variables suggesting comorbidities present at admission. Surveys of 26 516 nurses practising in study hospitals were used to measure nurse staffing and nurse education. We used generalised estimating equations to assess the effects of nursing factors on the likelihood of surgical patients dying within 30 days of admission, before and after adjusting for other hospital and patient characteristics. Findings An increase in a nurses' workload by one patient increased the likelihood of an inpatient dying within 30 days of admission by 7% (odds ratio 1·068, 95% CI 1·031- 1·106), and every 10% increase in bachelor's degree nurses was associated with a decrease in this likelihood by 7% (0·929, 0·886- 0·973). These associations imply that patients in hospitals in which 60% of nurses had bachelor's degrees and nurses cared for an average of six patients would have almost 30% lower mortality than patients in hospitals in which only 30% of nurses had bachelor's degrees and nurses cared for an average of eight patients. Interpretation Nurse staffing cuts to save money might adversely affect patient outcomes. An increased emphasis on bachelor's education for nurses could reduce preventable hospital deaths. Funding European Union's Seventh Framework Programme, National Institute of Nursing Research, National Institutes of Health, the Norwegian Nurses Organisation and the Norwegian Knowledge Centre for the Health Services, Swedish Association of Health Professionals, the regional agreement on medical training and clinical research between Stockholm County Council and Karolinska Institutet, Committee for Health and Caring Sciences and Strategic Research Program in Care Sciences at Karolinska Institutet, Spanish Ministry of Science and Innovation.

Savulescu C.,Centers for Disease Control and Prevention | Savulescu C.,Institute of Health Carlos III | Valenciano M.,EpiConcept | de Mateo S.,Institute of Health Carlos III | Larrauri A.,Institute of Health Carlos III
Vaccine | Year: 2010

We conducted a case-control and screening method studies to estimate influenza vaccine effectiveness (IVE) in the age group ≥65 years, based on the Spanish Influenza Sentinel Surveillance System (SISSS). Cases (influenza laboratory-confirmed) were compared to influenza-negative ILI patients (test-negative) and patients without ILI since the beginning of the season (non-ILI). For the screening method, cases' vaccination coverage was compared to the vaccination coverage of the GPs' catchment population. The results suggested a protective effect of the vaccine against laboratory-confirmed influenza in elderly in 2008-2009. The screening method and the test-negative control designs enable estimating IVE using exclusively SISSS data. © 2010 Elsevier Ltd. All rights reserved.

There insufficient information regarding access and participation of immigrant women in Spain in sexual and reproductive health programs. Recent studies show their lower participation rate in gynecological cancer screening programs; however, little is known about the participation in other sexual and reproductive health programs by immigrant women living in rural areas with high population dispersion. The objective of this study is to explore the perceptions of midwives who provide these services regarding immigrant women's access and participation in sexual and reproductive health programs offered in a rural area. A qualitative study was performed, within a larger ethnographic study about rural primary care, with data collection based on in-depth interviews and field notes. Participants were the midwives in primary care serving 13 rural basic health zones (BHZ) of Segovia, a region of Spain with high population dispersion. An interview script was designed to collect information about midwives' perceptions on immigrant women's access to and use of the healthcare services that they provide. Interviews were recorded and transcribed with participant informed consent. Data were analyzed based on the qualitative content analysis approach and triangulation of results with fieldwork notes. Midwives perceive that immigrants in general, and immigrant women in particular, underuse family planning services. This underutilization is associated with cultural differences and gender inequality. They also believe that the number of voluntary pregnancy interruptions among immigrant women is elevated and identify childbearing and childrearing-related tasks and the language barrier as obstacles to immigrant women accessing the available prenatal and postnatal healthcare services. Immigrant women's underutilization of midwifery services may be linked to the greater number of unintended pregnancies, pregnancy terminations, and the delay in the first prenatal visit, as discerned by midwives. Future research should involve samples of immigrant women themselves, to provide a deeper understanding of the current knowledge, attitudes, and practices of the immigrant population regarding reproductive and sexual health to provide better health services.

Abad R.,Institute of Health Carlos III | Biolchi A.,Novartis | Moschioni M.,Novartis | Giuliani M.M.,Novartis | And 2 more authors.
Clinical and Vaccine Immunology | Year: 2015

A new vaccine (the 4CMenB 4-component protein vaccine [Bexsero], which includes PorA, factor H-binding protein [fHbp], neisserial heparin-binding antigen [NHBA], and Neisseria adhesin A [NadA]) against serogroup B meningococci has recently been approved for use in people older than age 2 months in Europe, Australia, and Canada. Preapproval clinical efficacy studies are not feasible for invasive meningococcal disease because its incidence is low/very low, and the serum bactericidal antibody (SBA) titer (or the human SBA [hSBA] titer when human complement is used in the assay) has been used as a surrogate marker of protection. However, the hSBA assay cannot be used on a large scale, and therefore, a meningococcal antigen typing system (MATS) was developed. MATS combines conventional PorA genotyping with an enzyme-linked immunosorbent assay (ELISA) that quantifies both the expression and the cross-reactivity of antigenic variants. The assay has been used to evaluate the potential of the 4CMenB meningococcal group B vaccine to cover group B strains in several countries. Some recent data suggest that MATS is a conservative predictor of strain coverage. We used pooled sera from adolescents and infants to test by the hSBA assay 10 meningococcal group B strains isolated in Spain that were negative for the 3 antigens (n = 9) or that had very low levels of the 3 antigens (n = 1) by MATS. We found that all strains were killed by sera from adolescents and that 5 of the 10 strains were also killed, although at a low titer, by sera from infants. Our data confirm that MATS underestimates vaccine coverage. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Savulescu C.,Institute of Health Carlos III
Euro surveillance : bulletin européen sur les maladies transmissibles = European communicable disease bulletin | Year: 2011

We present preliminary results of a case-control study to estimate influenza vaccine effectiveness in Spain, from week 50 of 2010 to week 6 of 2011. The adjusted effectiveness of the vaccine in preventing laboratory-confirmed influenza due to any type of influenza virus was 50% (95% CI: -6 to 77%) for the trivalent seasonal vaccine and 72% (95% CI: 7 to 92%) for both trivalent seasonal and monovalent pandemic vaccines, suggesting a protective effect of seasonal vaccination lower than that reported for the previous season.

Sizaire V.,Institute of Health Carlos III
Euro surveillance : bulletin Européen sur les maladies transmissibles = European communicable disease bulletin | Year: 2014

In Spain, whole cell pertussis vaccination started in 1975, with three doses before the age of 6-7 months. Doses at 15-18 months and 4-6 years were introduced in 1996 and 2001, respectively. Spain switched to an acellular vaccine in 2005. From 1998 to 2009, pertussis incidence rates remained ≤1.5 cases/100,000 inhabitants but increased from 2010 to 7.5 cases/100,000 in 2012. Data from 1998 to 2012 were analysed to assess disease trends and susceptible populations. We defined four epidemic periods: 1998-2001 (reference), 2002-05, 2006-09 and 2010-12. In 2002-05, the incidence rate increased in individuals aged 15-49 years (IRR: 1.41 (95% CI: 1.11-1.78)) and ≥50 years (IRR: 2.78 (95% CI: 1.78-4.33)) and in 2006-09 increased also in infants aged <3 months (IRR: 1.83 (95% CI: 1.60-2.09)). In 2010-12, the incidence rate increased notably in all age groups, with IRRs ranging between 2.5 (95% CI: 2.3-2.8) in 5-9 year-olds and 36.0 (95% CI: 19.4-66.8) in 20-29 year-olds. These results, consistent with the country's vaccination history, suggest a progressive accumulation of susceptible individuals due to waning immunity after years of low incidence. Further vaccination strategies should be assessed and implemented to prevent pertussis in pre-vaccinated infants, in whom the disease is more severe.

Sanchez S.,Institute of Health Carlos III | Llorente M.T.,Institute of Health Carlos III | Echeita M.A.,Institute of Health Carlos III | Herrera-Leon S.,Institute of Health Carlos III
PLoS ONE | Year: 2015

Escherichia coli serogroups O5, O15, O26, O45, O55, O76, O91, O103, O104, O111, O113, O118, O121, O123, O128, O145, O146, O157, O165, O172, and O177 are the O-antigen forms of the most clinically relevant Shiga toxin-producing E. coli (STEC) serotypes. In this study, three multiplex PCR assays able to specifically detect these 21 serogroups were developed and validated. For this purpose, the O-antigen gene clusters of E. coli O5 and O76 were fully sequenced, their associated genes were identified on the basis of homology, and serogroup-specific primers were designed. After preliminary evaluation, these two primer pairs were proven to be highly specific and suitable for the development of PCR assays for O5 and O76 serogroup identification. Specific primers were also designed for serogroups O15, O45, O55, O91, O104, O113, O118, O123, O128, O146, O157, O165, O172, and O177 based on previously published sequences, and previously published specific primers for serogroups O26, O103, O111, O121, and O145 were also included. These 21 primer pairs were shown to be specific for their target serogroup when tested against E. coli type strains representing 169 known O-antigen forms of E. coli and Shigella and therefore suitable for being used in PCR assays for serogroup identification. In order to validate the three multiplex PCR assays, 22 E. coli strains belonging to the 21 covered serogroups and 18 E. coli strains belonging to other serogroups were screened in a double-blind test and their sensitivity was determined as 1 ng chromosomal DNA. The PCR assays developed in this study could be a faster, simpler, and less expensive strategy for serotyping of the most clinically relevant STEC strains in both clinical microbiology and public health laboratories, and so their development could benefit for clinical diagnosis, epidemiological investigations, surveillance, and control of STEC infections. © 2015 Sánchez et al.

Physicians of the Spanish Influenza Sentinel Surveillance System report and systematically swab patients attended to their practices for influenza-like illness (ILI). Within the surveillance system, some Spanish regions also participated in an observational study aiming at estimating influenza vaccine effectiveness (cycEVA study). During the season 2009-2010, we estimated pandemic influenza vaccine effectiveness using both the influenza surveillance data and the cycEVA study. We conducted two case-control studies using the test-negative design, between weeks 48/2009 and 8/2010 of the pandemic season. The surveillance-based study included all swabbed patients in the sentinel surveillance system. The cycEVA study included swabbed patients from seven Spanish regions. Cases were laboratory-confirmed pandemic influenza A(H1N1)2009. Controls were ILI patients testing negative for any type of influenza. Variables collected in both studies included demographic data, vaccination status, laboratory results, chronic conditions, and pregnancy. Additionally, cycEVA questionnaire collected data on previous influenza vaccination, smoking, functional status, hospitalisations, visits to the general practitioners, and obesity. We used logistic regression to calculate adjusted odds ratios (OR), computing pandemic influenza vaccine effectiveness as (1-OR)*100. We included 331 cases and 995 controls in the surveillance-based study and 85 cases and 351 controls in the cycEVA study. We detected nine (2.7%) and two (2.4%) vaccine failures in the surveillance-based and cycEVA studies, respectively. Adjusting for variables collected in surveillance database and swabbing month, pandemic influenza vaccine effectiveness was 62% (95% confidence interval (CI): -5; 87). The cycEVA vaccine effectiveness was 64% (95%CI: -225; 96) when adjusting for common variables with the surveillance system and 75% (95%CI: -293; 98) adjusting for all variables collected. Point estimates of the pandemic influenza vaccine effectiveness suggested a protective effect of the pandemic vaccine against laboratory-confirmed influenza A(H1N1)2009 in the season 2009-2010. Both studies were limited by the low vaccine coverage and the late start of the vaccination campaign. Routine influenza surveillance provides reliable estimates and could be used for influenza vaccine effectiveness studies in future seasons taken into account the surveillance system limitations.

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