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BACKGROUND: Respiratory syncytial virus (RSV) is a highly infectious disease that poses a significant clinical and medical burden, as well as social disruption and economic costs, recognized by the World Health Organization as a public health issue. After several failed attempts to find preventive candidates (compounds, products, including vaccines), new alternatives might be available, one being nirsevimab, the first and only option approved for RSV prevention in neonates and infants during their first RSV season. The objective of this study was to develop a novel multi-criteria decision analysis (MCDA) framework for RSV antibody-based preventive alternatives and to use it to assess the value of nirsevimab vs. placebo as a systematic immunization approach to prevent RSV in neonates and infants during their first RSV season in Spain. METHODS: Based on a pre-established model called Vaccinex, an ad-hoc MCDA framework was created to reflect relevant attributes for the assessment of current and future antibody-based preventive measures for RSV. The estimated value of nirsevimab was obtained by means of an additive linear model combining weights and scores assigned by a multidisciplinary committee of 9 experts. A retest and three sensitivity analyses were conducted. RESULTS: Nirsevimab was evaluated through a novel framework with 26 criteria by the committee as a measure that adds value (positive final estimated value: 0.56 ± 0.11) to the current RSV scenario in Spain, by providing a high efficacy for prevention of neonates and infants. In addition, its implementation might generate cost savings in hospitalizations and to the healthcare system and increase the level of public health awareness among the general population, while reducing health inequities. CONCLUSIONS: Under a methodology with increasing use in the health field, nirsevimab has been evaluated as a measure which adds value for RSV prevention in neonates and infants during their first RSV season in Spain.
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Anticuerpos Monoclonales Humanizados , Infecciones por Virus Sincitial Respiratorio , Virus Sincitial Respiratorio Humano , Recién Nacido , Lactante , Humanos , Infecciones por Virus Sincitial Respiratorio/tratamiento farmacológico , Infecciones por Virus Sincitial Respiratorio/prevención & control , Antivirales , España , Técnicas de Apoyo para la DecisiónRESUMEN
To determine transmission rates for neonatal conjunctivitis causative microorganisms in Angola, we analyzed 312 endocervical and 255 conjunctival samples from mothers and newborns, respectively, during 2011-2012. Transmission rates were 50% for Chlamydia trachomatis and Neisseria gonorrhoeae and 10.5% for Mycoplasma genitalium. Possible pathogenic effects of M. genitalium in children's eyes are unknown.
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Infecciones Bacterianas del Ojo/epidemiología , Infecciones Bacterianas del Ojo/transmisión , Transmisión Vertical de Enfermedad Infecciosa , Angola/epidemiología , Chlamydia trachomatis/genética , Conjuntivitis Bacteriana/epidemiología , Conjuntivitis Bacteriana/historia , Conjuntivitis Bacteriana/microbiología , Conjuntivitis Bacteriana/transmisión , Infecciones Bacterianas del Ojo/historia , Infecciones Bacterianas del Ojo/microbiología , Femenino , Historia del Siglo XXI , Humanos , Recién Nacido , Mycoplasma genitalium/genética , Neisseria gonorrhoeae/genética , Prevalencia , Estudios ProspectivosRESUMEN
Seasonal influenza is an annual challenge for health-care systems, due to factors such as co-circulation of 2 influenza A subtypes jointly with 2 influenza B lineages; the antigenic drift of these virus, which eludes natural immunity, as well as immunity conferred by vaccination; together with influenza impact in terms of morbidity and mortality. Influenza vaccines have been available for more than 70 years and they have progressed in formulation, production and delivery route. Recommendations on vaccination are focused on those with a higher probability of severe disease, and have a progressively wider coverage, and classically based on inactivated vaccines, but with an increasing importance of attenuated live vaccines. More inactivated vaccines are becoming available, from adyuvanted and virosomal vaccines to intradermal delivery, cell-culture or quadrivalent. Overall vaccine effectiveness is about 65%, but varies depending on characteristics of vaccines, virus, population and the outcomes to be prevented, and ranges from less than 10% to almost 90%. Future challenges are formulations that confer more extensive and lasting protection, as well as increased vaccination coverage, especially in groups such as pregnant women and health-care professionals, as well as being extended to paediatrics.
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Vacunas contra la Influenza/inmunología , Gripe Humana/prevención & control , Potencia de la Vacuna , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Animales , Variación Antigénica , Niño , Preescolar , Brotes de Enfermedades/prevención & control , Femenino , Predicción , Humanos , Esquemas de Inmunización , Lactante , Virus de la Influenza A/inmunología , Virus de la Influenza B/inmunología , Vacunas contra la Influenza/clasificación , Gripe Humana/epidemiología , Masculino , Persona de Mediana Edad , Guías de Práctica Clínica como Asunto , Embarazo , Vacunas Atenuadas , Vacunas de Productos Inactivados , Vacunas de Virosoma , Adulto Joven , ZoonosisRESUMEN
After the COVID-19 pandemic, the omicron variant of the SARS-CoV-2 virus became the dominant lineage in Spain in 2022. Although it possesses a milder pathogenicity than previous variants, it still poses a high risk of causing severe COVID-19 for immunocompromised populations. A systematic review was conducted to assess the burden of COVID-19 in Spain among immunocompromised patients during the omicron predominance (1/04/2022-1/04/2023), using PubMed, Cochrane Library, and EPICOVIDEHA between May and July 2023. The search retrieved 217 articles, of which a total of 5 were included. Upon analysis, it was observed that immunocompromised patients during the omicron lineage predominance continue to exhibit higher rates of hospitalizations, ICU admissions, and mortality compared to the general population affected by COVID-19. Although the pandemic has ended, the risk persists for immunocompromised individuals.
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SARS-CoV-2 reinfections have been frequent, even among those vaccinated. The aim of this study is to know if hybrid immunity (infection + vaccination) is affected by the moment of vaccination and number of doses received. We conducted a retrospective study in 746 patients with a history of COVID-19 reinfection and recovered the dates of infection and reinfection and vaccination status (date and number of doses). To assess differences in the time to reinfection(tRI) between unvaccinated, vaccinated before 6 months, and later; and comparing one, two or three doses (incomplete, complete and booster regime) we performed the log-rank test of the cumulative incidence calculated as 1 minus the Kaplan-Meier estimator. Also, an adjusted Cox-regression was performed to evaluate the risk of reinfection in all groups. The tRI was significantly higher in those vaccinated vs. non-vaccinated (p < 0.001). However, an early incomplete regime protects similar time than not receiving a vaccine. Vaccination before 6 months after infection showed a lower tRI compared to those vaccinated later with the same regime (adj-p < 0.001). Actually, early vaccination with complete and booster regimes provided lower length of protection compared to vaccinating later with incomplete and complete regime, respectively. Vaccination with complete and booster regimes significantly increases the tRI (adj-p < 0.001). Vaccination increases the time it takes for a person to become reinfected with SARS-CoV-2. Increasing the time from infection to vaccination increases the time in which a person could be reinfected and reduces the risk of reinfection, especially in complete and booster regimes. Those results emphasize the role of vaccines and boosters during the pandemic and can guide strategies on future vaccination policy.
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COVID-19 , Humanos , COVID-19/epidemiología , COVID-19/prevención & control , SARS-CoV-2 , Reinfección/epidemiología , Reinfección/prevención & control , Estudios Retrospectivos , VacunaciónRESUMEN
INTRODUCTION: The Raise Awareness of Influenza Strategies in Europe (RAISE) group gathered information about the healthcare burden of influenza (hospitalizations, intensive care unit [ICU] admissions, and excess deaths), surveillance systems, and the vaccine coverage rate (VCR) in older adults in 18 European countries and Israel. AREAS COVERED: Published medical literature and official medical documentation on the influenza disease burden in the participating countries were reviewed from 2010/11 until the 2022/23 influenza seasons. Information on the framework for monitoring the disease burden and the provision for ensuring older adults had access to vaccination in their respective countries was provided. Data on influenza VCR in older adults were collected for the 2019/20 to 2022/23 influenza seasons. Data are reported descriptively. EXPERT OPINION: Influenza presents a significant healthcare burden in older adults. Reporting outcomes across participating countries is heterogeneous, highlighting the need for standardized approaches. Although older adults receive free influenza vaccination, vaccine uptake is highly variable among countries. Moreover, hospitalization rates remain high even in countries reporting a high VCR. Increased awareness and education on the burden of disease and the broader use of improved influenza vaccines for older adults may help reduce the disease burden on this population.
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COVID-19 , Hospitalización , Vacunas contra la Influenza , Gripe Humana , Cobertura de Vacunación , Humanos , Gripe Humana/prevención & control , Gripe Humana/epidemiología , Anciano , Israel/epidemiología , Europa (Continente)/epidemiología , Cobertura de Vacunación/estadística & datos numéricos , Vacunas contra la Influenza/administración & dosificación , COVID-19/prevención & control , COVID-19/epidemiología , Hospitalización/estadística & datos numéricos , Anciano de 80 o más AñosRESUMEN
Cell counts of leukocytes subpopulations are demonstrating to have an important value in predicting outcome in severe infections. We evaluated here the render of leukogram counts to predict outcome in patients with ventilator-associated pneumonia (VAP) caused by Staphylococcus aureus. Data from patients admitted to the ICU of Hospital Clínico Universitario de Valladolid from 2006 to 2011 with diagnosis of VAP caused by S. aureus were retrospectively collected for the study (n = 44). Leukocyte counts were collected at ICU admission and also at VAP diagnosis. Our results showed that nonsurvivors had significant lower eosinophil counts at VAP diagnosis. Multivariate Cox regression analysis performed by the Wald test for forward selection showed that eosinophil increments from ICU admission to VAP diagnosis and total eosinophil counts at VAP diagnosis were protective factors against mortality in the first 28 days following diagnosis: (HR [CI 95%], P): (0.996 [0.993-0.999], 0.010); (0.370 [0.180-0.750], 0.006). Patients with eosinophil counts <30 cells/mm(3) at diagnosis died earlier. Eosinophil counts identified survivors: (AUROC [CI 95%], P): (0.701 [0.519-0.882], 0.042). Eosinophil behaves as a protective cell in patients with VAP caused by S. aureus.
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Eosinófilos/fisiología , Neumonía Estafilocócica/sangre , Neumonía Asociada al Ventilador/sangre , Neumonía Asociada al Ventilador/mortalidad , Anciano , Área Bajo la Curva , Cuidados Críticos , Farmacorresistencia Bacteriana , Eosinófilos/microbiología , Femenino , Humanos , Unidades de Cuidados Intensivos , Masculino , Persona de Mediana Edad , Neumonía Estafilocócica/mortalidad , Neumonía Asociada al Ventilador/microbiología , Modelos de Riesgos Proporcionales , Análisis de Regresión , Staphylococcus aureus , Resultado del TratamientoRESUMEN
Objective: Antibodies elicited by seasonal influenza vaccines mainly target the head of hemagglutinin (HA). However, antibodies against the stalk domain are cross-reactive and have been proven to play a role in reducing influenza disease severity. We investigated the induction of HA stalk-specific antibodies after seasonal influenza vaccination, considering the age of the cohorts. Methods: A total of 166 individuals were recruited during the 2018 influenza vaccine campaign (IVC) and divided into groups: <50 (n = 14), 50-64 (n = 34), 65-79 (n = 61), and ≥80 (n = 57) years old. Stalk-specific antibodies were quantified by ELISA at day 0 and day 28 using recombinant viruses (cH6/1 and cH14/3) containing an HA head domain (H6 or H14) from wild bird origin with a stalk domain from human H1 or H3, respectively. The geometric mean titer (GMT) and the fold rise (GMFR) were calculated, and differences were assessed using ANOVA adjusted by the false discovery rate (FDR) and the Wilcoxon tests (p <0.05). Results: All age groups elicited some level of increase in anti-stalk antibodies after receiving the influenza vaccine, except for the ≥80-year-old cohort. Additionally, <65-year-old vaccinees had higher group 1 antibody titers versus group 2 before and after vaccination. Similarly, vaccinees within the <50-year-old group showed a higher increase in anti-stalk antibody titers when compared to older individuals (≥80 years old), especially for group 1 anti-stalk antibodies. Conclusion: Seasonal influenza vaccines can the induction of cross-reactive anti-stalk antibodies against group 1 and group 2 HAs. However, low responses were observed in older groups, highlighting the impact of immunosenescence in adequate humoral immune responses.
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Vacunas contra la Influenza , Gripe Humana , Humanos , Anciano , Persona de Mediana Edad , Anciano de 80 o más Años , Hemaglutininas , Formación de Anticuerpos , Gripe Humana/prevención & control , AnticuerposRESUMEN
The inï¬uenza virus has accompanied humans since time immemorial, in the form of annual epidemics and occasional pandemics. It is a respiratory infection with multiple repercussions on people's lives at an individual and social level, as well as representing a signiï¬cant burden on the health system. This Consensus Document arises from the collaboration of various Spanish scientiï¬c societies involved in inï¬uenza virus infection. The conclusions drawn are based on the highest quality evidence available in the scientiï¬c literature and, failing that, on the opinion of the experts convened. The Consensus Document addresses the clinical, microbiological, therapeutic, and preventive aspects (with respect to the prevention of transmission and in relation to vaccination) of inï¬uenza, for both adult and pediatric populations. This Consensus Document aims to help facilitate the clinical, microbiological, and preventive approach to inï¬uenza virus infection and, consequently, to reduce its important consequences on the morbidity and mortality of the population.
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Enfermedades Transmisibles , Gripe Humana , Orthomyxoviridae , Niño , Adulto , Humanos , Gripe Humana/diagnóstico , Gripe Humana/prevención & control , Salud Pública , Medicina Comunitaria , VacunologíaRESUMEN
Community-acquired pneumonia represents the third-highest cause of mortality in industrialized countries and the first due to infection. Although guidelines for the approach to this infection model are widely implemented in international health schemes, information continually emerges that generates controversy or requires updating its management. This paper reviews the most important issues in the approach to this process, such as an aetiologic update using new molecular platforms or imaging techniques, including the diagnostic stewardship in different clinical settings. It also reviews both the Intensive Care Unit admission criteria and those of clinical stability to discharge. An update in antibiotic, in oxygen, or steroidal therapy is presented. It also analyzes the management out-of-hospital in CAP requiring hospitalization, the main factors for readmission, and an approach to therapeutic failure or rescue. Finally, the main strategies for prevention and vaccination in both immunocompetent and immunocompromised hosts are reviewed.
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Conventional clinical parameters are not sensitive or specific enough for detecting ongoing disease activity in the Systemic Lupus Erythematosus (SLE). Measurement of cytokines in urine is an encouraging approach to detection of early flares in this disease. Here we have profiled 27 different cytokines, chemokines and celular growth factors in the urine of 48 patients previously diagnosed of SLE as potential biomarkers of disease activity. Correlation analysis with Bonferroni correction showed that MCP-1 was the only immune mediator which levels in urine correlated directly with the SLE Disease Activity Index 2000 (SLEDAI-2K) score (correlation coefficient, p): MCP-1 (0.45,0.003). MCP-1 correlated inversely with levels of C3 complement protein in serum (-0.50,0.001). MCP-1 showed significant higher levels in patients with severe disease activity in comparison with those exhibiting mild activity. Levels of this chemokine were also higher in patients with severe disease activity in comparison with patients with inactive disease and healthy controls. Areas under receiver operating characteristic curves (AUROC) for detection of severe disease (SLEDAI⩾8) was as follows for MCP-1: [AUROC, (IC95%), p]: [0.81 (0.65-0.96) 0.003]. In addition, MCP-1 showed a good result in the AUROC analysis for detecting renal involvement [0.70 (0.52-0.87) 0.050]. When correlation analysis were repeated excluding those patients with active renal disease (n=14), levels of MCP-1 in urine kept on showing a significant positive association with SLEDAI-2K score. In conclusion, multiplex-based cytokine profiling in urine demonstrated the superiority of MCP-1 over a wide range of cytokines as biomarker of disease activity in SLE.
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Quimiocina CCL2/orina , Lupus Eritematoso Sistémico/orina , Adulto , Biomarcadores/orina , Femenino , Humanos , MasculinoRESUMEN
INTRODUCTION: Gene expression profiling in the first weeks of treatment of patients with chronic hepatitis C may contribute to better evaluate the response to interferon-based therapy. The objective of this study was to evaluate the gene expression profiles of early responders and non-responders before, and after 12 weeks of treatment with peginterferon alfa and ribavirin. METHODS: Gene expression profiles were analysed in 12 patients with chronic hepatitis C, and scheduled for treatment with peginterferon alpha and ribavirin. RESULTS: Of the 12 patients studied, six showed a complete early virological response, while six failed to control viremia. In early responders, treatment with peginterferon and ribavirin induced an increased expression of a larger number of interferon-induced genes (ISG15, IFI6, IFI44L, IFI27, MX1, OASL, IRF7, IFIT3, IFITM1, EIF2AK2, HERC5 and APOBEC3) than in non-responders (ISG15, IFI44L, IFI27, IRF7, USP18) in the first twelve weeks of treatment (P<0.05). In both groups, there were changes in the levels of certain genes poorly described in the treatment of hepatitis C so far. CONCLUSIONS: The gene expression profiles described in this study provide a new insight to understanding the pathogenesis of the disease and treatment effect. The more marked effect of the treatment on the expression of interferon-response genes observed in early responders could explain their better control of viral load.
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Antivirales/uso terapéutico , Perfilación de la Expresión Génica , Hepacivirus/genética , Hepatitis C Crónica/genética , Interferón-alfa/uso terapéutico , Polietilenglicoles/uso terapéutico , Ribavirina/uso terapéutico , Viremia/genética , Adulto , Consumo de Bebidas Alcohólicas/genética , Antivirales/farmacología , Quimioterapia Combinada , Femenino , Genotipo , Hepacivirus/efectos de los fármacos , Hepacivirus/aislamiento & purificación , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/virología , Humanos , Interferón alfa-2 , Interferón-alfa/administración & dosificación , Interferón-alfa/farmacología , Interferones , Interleucinas/genética , Masculino , Persona de Mediana Edad , Polietilenglicoles/administración & dosificación , Polietilenglicoles/farmacología , Estudios Prospectivos , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/farmacología , Proteínas Recombinantes/uso terapéutico , Ribavirina/administración & dosificación , Ribavirina/farmacología , Factores de Tiempo , Viremia/tratamiento farmacológico , Viremia/virologíaRESUMEN
Pandemic dynamics and health care responses are markedly different during the COVID-19 pandemic than in earlier outbreaks. Compared with established infectious disease such as influenza, we currently know relatively little about the origin, reservoir, cross-species transmission and evolution of SARS-CoV-2. Health care services, drug availability, laboratory testing, research capacity and global governance are more advanced than during 20th century pandemics, although COVID-19 has highlighted significant gaps. The risk of zoonotic transmission and an associated new pandemic is rising substantially. COVID-19 vaccine development has been done at unprecedented speed, with the usual sequential steps done in parallel. The pandemic has illustrated the feasibility of this approach and the benefits of a globally coordinated response and infrastructure. Some of the COVID-19 vaccines recently developed or currently in development might offer flexibility or sufficiently broad protection to swiftly respond to antigenic drift or emergence of new coronaviruses. Yet many challenges remain, including the large-scale production of sufficient quantity of vaccines, delivery of vaccines to all countries and ensuring vaccination of relevant age groups. This wide vaccine technology approach will be best employed in tandem with active surveillance for emerging variants or new pathogens using antigen mapping, metagenomics and next generation sequencing.
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COVID-19 , Pandemias , Vacunas contra la COVID-19 , Humanos , Pandemias/prevención & control , SARS-CoV-2RESUMEN
INTRODUCTION: Pandemic A/H1N1/2009 influenza causes severe lower respiratory complications in rare cases. The association between host immune responses and clinical outcome in severe cases is unknown. METHODS: We utilized gene expression, cytokine profiles and generation of antibody responses following hospitalization in 19 critically ill patients with primary pandemic A/H1N1/2009 influenza pneumonia for identifying host immune responses associated with clinical outcome. Ingenuity pathway analysis 8.5 (IPA) (Ingenuity Systems, Redwood City, CA) was used to select, annotate and visualize genes by function and pathway (gene ontology). IPA analysis identified those canonical pathways differentially expressed (P < 0.05) between comparison groups. Hierarchical clustering of those genes differentially expressed between groups by IPA analysis was performed using BRB-Array Tools v.3.8.1. RESULTS: The majority of patients were characterized by the presence of comorbidities and the absence of immunosuppressive conditions. pH1N1 specific antibody production was observed around day 9 from disease onset and defined an early period of innate immune response and a late period of adaptive immune response to the virus. The most severe patients (n = 12) showed persistence of viral secretion. Seven of the most severe patients died. During the late phase, the most severe patient group had impaired expression of a number of genes participating in adaptive immune responses when compared to less severe patients. These genes were involved in antigen presentation, B-cell development, T-helper cell differentiation, CD28, granzyme B signaling, apoptosis and protein ubiquitination. Patients with the poorest outcomes were characterized by proinflammatory hypercytokinemia, along with elevated levels of immunosuppressory cytokines (interleukin (IL)-10 and IL-1ra) in serum. CONCLUSIONS: Our findings suggest an impaired development of adaptive immunity in the most severe cases of pandemic influenza, leading to an unremitting cycle of viral replication and innate cytokine-chemokine release. Interruption of this deleterious cycle may improve disease outcome.
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Inmunidad Adaptativa/genética , Subtipo H1N1 del Virus de la Influenza A/inmunología , Gripe Humana/genética , Gripe Humana/inmunología , Pandemias , Índice de Severidad de la Enfermedad , Inmunidad Adaptativa/inmunología , Adulto , Regulación hacia Abajo/genética , Regulación hacia Abajo/inmunología , Femenino , Perfilación de la Expresión Génica/métodos , Humanos , Subtipo H1N1 del Virus de la Influenza A/genética , Gripe Humana/epidemiología , Masculino , Persona de Mediana EdadRESUMEN
Suboptimal vaccine effectiveness against seasonal influenza is a significant public health concern, partly explained by antigenic differences between vaccine viruses and viruses circulating in the environment. Haemagglutinin mutations within vaccine viruses acquired during serial passage in eggs have been identified as a source of antigenic variation between vaccine and circulating viruses. This study retrospectively compared the antigenic similarity of circulating influenza isolates with egg- and cell-propagated reference viruses to assess any observable trends over a 16-year period. Using annual and interim reports published by the Worldwide Influenza Centre, London, for the 2002-2003 to 2017-2018 influenza seasons, we assessed the proportions of circulating viruses which showed antigenic similarity to reference viruses by season. Egg-propagated reference viruses were well matched against circulating viruses for A/H1N1 and B/Yamagata. However, A/H3N2 and B/Victoria cell-propagated reference viruses appeared to be more antigenically similar to circulating A/H3N2 and B/Victoria viruses than egg-propagated reference viruses. These data support the possibility that A/H3N2 and B/Victoria viruses are relatively more prone to egg-adaptive mutation. Cell-propagated A/H3N2 and B/Victoria reference viruses were more antigenically similar to circulating A/H3N2 and B/Victoria viruses over a 16-year period than were egg-propagated reference viruses.
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Vacunas contra la Influenza , Gripe Humana/epidemiología , Humanos , Subtipo H1N1 del Virus de la Influenza A/genética , Subtipo H3N2 del Virus de la Influenza A/genética , Subtipo H3N2 del Virus de la Influenza A/inmunología , Virus de la Influenza B , Londres , Estudios Retrospectivos , Estaciones del AñoRESUMEN
PURPOSE: Quadrivalent influenza vaccine (QIV) includes the same strains as trivalent influenza vaccine (TIV) plus an additional B strain of the other B lineage. The aim of the study was to analyse the public health and economic impact of replacing TIV with QIV in different scenarios in Spain. METHODS: A dynamic transmission model was developed to estimate the number of influenza B cases prevented under TIV and QIV strategies (<65 years (high risk) and ≥65 years). This model considers cross-protective immunity induced by different lineages of influenza B. The output of the transmission model was used as input for a decision tree model that estimated the economic impact of switching TIV to QIV. The models were populated with Spanish data whenever possible. Deterministic univariate and probabilistic multivariate sensitivity analyses were performed. RESULTS: Replacing TIV with QIV in all eligible patients with current vaccine coverage in Spain may have prevented 138,707 influenza B cases per season and, therefore avoided 10,748 outpatient visits, 3,179 hospitalizations and 192 deaths. The replacement could save 532,768 in outpatient visit costs, 13 million in hospitalization costs, and 3 million in costs of influenza-related deaths per year. An additional 5 million costs associated with productivity loss could be saved per year, from the societal perspective. The budget impact from societal perspective would be 6.5 million, and the incremental cost-effectiveness ratio (ICER) 1,527 per quality-adjusted life year (QALY). Sensitivity analyses showed robust results. In additional scenarios, QIV also showed an impact at public health level reducing influenza B related cases, outpatient visits, hospitalizations and deaths. CONCLUSIONS: Our results show public health and economic benefits for influenza prevention with QIV. It would be an efficient intervention for the Spanish National Health Service with major health benefits especially in the population ≥65-year.
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Vacunas contra la Influenza/economía , Gripe Humana/economía , Vacunación/economía , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Costo de Enfermedad , Análisis Costo-Beneficio , Humanos , Lactante , Vacunas contra la Influenza/uso terapéutico , Gripe Humana/epidemiología , Gripe Humana/prevención & control , Persona de Mediana Edad , Salud Pública , España , Adulto JovenRESUMEN
Seasonal influenza causes significant morbidity and mortality in people aged ≥65 years. Antiviral treatment can reduce complications and disease severity. The objective of this study was to investigate the effect of antiviral treatment in patients aged ≥65 years hospitalized with confirmed influenza in preventing intensive care unit (ICU) admission or death. A retrospective cohort study was carried out in 20 hospitals from seven Spanish regions during 2013-2015 in patients aged ≥65 years. Hospitalized cases of laboratory-confirmed influenza were selected. To assess the association between antiviral treatment and ICU admission or death, the adjusted odds ratios (aOR) and their 95% confidence intervals (CI) were calculated using multivariate logistic regression. We included 715 hospitalized patients, of whom 640 (87.9%) received antiviral treatment, 77 (10.8%) required ICU admission and 66 (9.2%) died. In the 64-74 years age group, receipt of antiviral treatment ≤48â¯h (aOR 0.20; 95% CI 0.04-0.89), 3-4 days (aOR 0.23; 95% CI 0.05-0.92) and 5-7 days (aOR 0.24; 95% CI 0.03-0.91) after clinical symptom onset was associated with reduced mortality. Receipt of treatment >7 days after symptom onset was not associated with reduced mortality. No association of antiviral treatment with reduced mortality was observed in the >74 years age group or with the prevention of ICU admission in any age group. Antiviral treatment had a protective effect in avoiding death in patients aged 65-74 years hospitalized due to influenza when administered ≤48â¯h after symptom onset and when no more than 7 days had elapsed.
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Antivirales/uso terapéutico , Gripe Humana/tratamiento farmacológico , Oseltamivir/uso terapéutico , Corticoesteroides/uso terapéutico , Anciano , Femenino , Hospitalización , Humanos , Gripe Humana/mortalidad , Unidades de Cuidados Intensivos , Masculino , Estudios Retrospectivos , Tiempo de Tratamiento , Resultado del TratamientoRESUMEN
INTRODUCTION: Influenza is associated with significant morbidity and mortality worldwide. Whilst vaccination is key for the prevention of influenza infection, there are many factors which may contribute to reduced vaccine effectiveness, including antigenic evolution via both antigenic drift and egg-adaptations. Due to the currently dissociated and indirect evidence supporting both the occurrence of these two phenomena in the egg-based manufacturing process and their effects on vaccine effectiveness, this topic remains a subject of debate. OBJECTIVE: To review the evidence and level of agreement in expert opinion supporting a mechanistic basis for reduced vaccine effectiveness due to egg-based manufacturing, using an expert consensus-based methodology and literature reviews. METHODS: Ten European influenza specialists were recruited to the expert panel. The overall research question was deconstructed into four component principles, which were examined in series using a novel, online, two-stage assessment of proportional group awareness and consensus. The first stage independently generated a list of supporting references for each component principle via literature searches and expert assessments. In the second stage, a summary of each reference was circulated amongst the experts, who rated their agreement that each reference supported the component principle on a 5-point Likert scale. Finally, the panel were asked if they agreed that, as a whole, the evidence supported a mechanistic basis for reduced vaccine effectiveness due to egg-based manufacturing. RESULTS: All component principles were reported to have a majority of strong or very strong supporting evidence (70-90%). CONCLUSIONS: On reviewing the evidence for all component principles, experts unanimously agreed that there is a mechanistic basis for reduced vaccine effectiveness resulting from candidate influenza virus variation due to egg-based manufacturing, particularly in the influenza A/H3N2 strain. Experts pointed to surveillance, candidate vaccine virus selection and manufacturing stages involving eggs as the most likely to impact vaccine effectiveness.
Asunto(s)
Vacunas contra la Influenza , Gripe Humana , Consenso , Humanos , Subtipo H3N2 del Virus de la Influenza A , Gripe Humana/prevención & control , VacunaciónRESUMEN
INTRODUCTION: Human host immune response following infection with the new variant of A/H1N1 pandemic influenza virus (nvH1N1) is poorly understood. We utilize here systemic cytokine and antibody levels in evaluating differences in early immune response in both mild and severe patients infected with nvH1N1. METHODS: We profiled 29 cytokines and chemokines and evaluated the haemagglutination inhibition activity as quantitative and qualitative measurements of host immune responses in serum obtained during the first five days after symptoms onset, in two cohorts of nvH1N1 infected patients. Severe patients required hospitalization (n = 20), due to respiratory insufficiency (10 of them were admitted to the intensive care unit), while mild patients had exclusively flu-like symptoms (n = 15). A group of healthy donors was included as control (n = 15). Differences in levels of mediators between groups were assessed by using the non parametric U-Mann Whitney test. Association between variables was determined by calculating the Spearman correlation coefficient. Viral load was performed in serum by using real-time PCR targeting the neuraminidase gene. RESULTS: Increased levels of innate-immunity mediators (IP-10, MCP-1, MIP-1beta), and the absence of anti-nvH1N1 antibodies, characterized the early response to nvH1N1 infection in both hospitalized and mild patients. High systemic levels of type-II interferon (IFN-gamma) and also of a group of mediators involved in the development of T-helper 17 (IL-8, IL-9, IL-17, IL-6) and T-helper 1 (TNF-alpha, IL-15, IL-12p70) responses were exclusively found in hospitalized patients. IL-15, IL-12p70, IL-6 constituted a hallmark of critical illness in our study. A significant inverse association was found between IL-6, IL-8 and PaO2 in critical patients. CONCLUSIONS: While infection with the nvH1N1 induces a typical innate response in both mild and severe patients, severe disease with respiratory involvement is characterized by early secretion of Th17 and Th1 cytokines usually associated with cell mediated immunity but also commonly linked to the pathogenesis of autoimmune/inflammatory diseases. The exact role of Th1 and Th17 mediators in the evolution of nvH1N1 mild and severe disease merits further investigation as to the detrimental or beneficial role these cytokines play in severe illness.