[The flu in its worse forms]. / La grippe sous ses pires facettes.

Influenza A and B infections are marred with variable morbidity and, in some cases, develop into severe or even fatal respiratory, circulatory and neurologic complications. Respiratory complications are most common and involve primary-Influenza pneumonia and pneumonia from bacterial or fungal superinfections. Nonrespiratory complications can affect several organs/systems, namely the heart (myocarditis, type 1 and 2 myocardial infarction) and the nervous system (stroke, encephalitis, Guillain-Barré Syndrome). This article provides an overview of the basic pathophysiological aspects of Influenza virus infection, reviews the main severe respiratory and nonrespiratory complications and discusses the different treatments with their respective indications, contraindications and limitations.

L'infection par les virus de la grippe de types A et B (influenza A et B) est grevée d'une morbidité variable, pouvant évoluer en diverses complications respiratoires, circulatoires et neurologiques sévères, voire fatales. Les complications pulmonaires sont les plus fréquentes et l'on distingue parmi elles les pneumonies dues au virus de celles par surinfection bactérienne ou fongique. Les complications extrapulmonaires, plus rares, peuvent toucher divers organes, dont le cœur (myocardite, infarctus du myocarde de types 1 et 2) et le système nerveux (AVC, encéphalite, syndrome de Guillain-Barré). Cet article aborde les aspects physiopatho logiques de base de la grippe, passe en revue les principales complications sévères pulmonaires et extrapulmonaires, et discute les indications, contre-indications et limites des différents traitements disponibles.

Neurological complications associated with influenza in season 2017/18 in Austria- a retrospective single center study.

BACKGROUND: Neurological complications associated with influenza (NCI) are rare events in adults with seasonal influenza. Information about the characteristics of neurological complications and the burden of disease has been limited to case reports, mainly during the pandemic 2009. Influenza-associated encephalopathy/encephalitis (IAE) is one of the most severe and frequently reported NCI, mostly caused by influenza A. Isolated case reports exist about NCI caused by influenza B. OBJECTIVES: The aim of this single center retrospective study is the better understanding of the frequency and the characteristics of NCI in adults in season 2017-2018, depending on the influenza subtype A or B. STUDY DESIGN: We reviewed 874 adult patients with laboratory confirmed influenza admitted to the Christian Doppler University Hospital Salzburg, Austria from December 2017 until March 2018 looking for NCI. RESULTS: 37 (4 %) of the 874 patients with confirmed influenza had NCI. 4 (11 %) had influenza A and 33 (89 %) had influenza B. IAE was the most frequent complication diagnosed in 24 (65 %) patients, of whom all but one had influenza B and 3 (13 %) had neurological residuals. Moreover 6 (16 %) had isolated epileptic seizures, 2 (5 %) had acute inflammatory demyelinating polyneuropathy (AIDP), and 5 (14 %) were classified as having infection-associated stroke. CONCLUSIONS: We report an incidence of 4 % for NCI and a high frequency of IAE caused by subtype B. Therefore, we recommend considering both influenza A and B as an etiologic factor of encephalopathy and other neurological disease in adults.

Vacunación frente a la gripe estacional en las personas mayores. Evaluación de la vacuna tetravalente. Informe de posicionamie / Seasonal flu vaccination for older people: Evaluation of the quadrivalent vaccine. Positioning repor

La gripe es un importante problema de salud pública, particularmente en las personas susceptibles de presentar complicaciones asociadas, personas mayores, niños menores de 2 años, enfermos crónicos, inmunocomprometidos y embarazadas. Pero, además, la gripe tiene un gran impacto sanitario con un aumento de la demanda asistencial y un espectacular aumento de las visitas ambulatorias, sobrecargando los servicios de urgencias y hospitalarios. Durante los brotes epidémicos, las tasas de hospitalización de las personas mayores de 65 años son máximas y la mortalidad notificada por gripe en la temporada 2017/2018 ha sido de 960 defunciones. La vacunación antigripal estacional es el método con una mayor relación coste-efectividad de prevención primaria de la gripe, reduciendo las enfermedades respiratorias relacionadas, el número de visitas a las consultas médicas, el número de hospitalizaciones y muertes en personas de alto riesgo y el absentismo laboral en adultos. En los últimos años la gripe B ha recibido escasa atención en la literatura científica y, sin embargo, en períodos interepidémicos, la gripe B puede ser una de las principales causas de epidemias de gripe estacional, causando una considerable morbimortalidad y un aumento de costes. La vacuna tetravalente, a diferencia de la trivalente, obtiene una protección inmunológica frente al segundo linaje de la gripe B y, de acuerdo con una revisión crítica de la literatura científica, proporciona una protección más amplia sin afectar a la inmunogenicidad de las otras 3 cepas vacunales comunes a las vacunas trivalente y tetravalente. La vacuna tetravalente es coste-efectiva al disminuir el número de casos de gripe y siempre es una intervención rentable, con un importante ahorro de coste para el sistema de salud y para la sociedad, disminuyendo las tasas de hospitalización y de mortalidad asociadas a las complicaciones de la gripe

Influenza is a significant health problem, particularly in those persons susceptible to having associated complications, older people, children less than 2 years, patients with chronic diseases, immunocompromised patients, and pregnant women. But influenza also has a large impact on the health system, with an increase in the healthcare demand and a spectacular increase in outpatient visits, overloading the emergency and hospital services. During epidemic outbreaks, the hospital admission rates of people over 65 years are at a maximum, and the mortality notified for the 2017/2018 influenza season was 960 deaths. The seasonal anti-influenza vaccine is the method with a better cost-effective ratio of primary prevention of influenza, reducing associated respiratory diseases, the number of hospital admissions, and deaths in high risk individuals, as well as work absenteeism in adults. In the last few years, influenza B has received little attention in the scientific literature, although in the periods between epidemics influenza B can be one of the main causes of seasonal epidemics, causing considerable morbidity and mortality and an increase in costs. The quadrivalent vaccine has a second-line immunological protection against influenza B, and according to a critical review of the scientific literature, it provides wider protection without affecting immunogenicity of the other three vaccine strains common to the trivalent and tetravalent vaccine. The quadrivalent vaccine is cost-effective in reducing the number of influenza cases, and is always a worthwhile intervention, with a significant cost saving for the health system and for society, by reducing the hospital admission rates and mortality associated with the complications of influenza

Does Vitamin D Deficiency Affect the Immunogenic Responses to Influenza Vaccination? A Systematic Review and Meta-Analysis.

Influenza virus infection is a major global public health problem, and the efficacy of influenza vaccination is not satisfactory. Vitamin D is involved in many immune-mediated inflammatory processes. The impact of vitamin D levels on the immunogenic response to influenza vaccination is not clear. We performed a comprehensive literature search and systematic review of studies that investigated vitamin D and influenza vaccination. Data pertaining to study population, vaccine components, vitamin D levels, and immunogenic response were analyzed. Nine studies, with a combined study population of 2367 patients, were included in the systematic review. Four studies were included in the meta-analysis to investigate the influence of vitamin D deficiency (VDD) on the seroprotection (SP) rates and seroconversion (SC) rates following influenza vaccination. We found no significant association between vitamin D level and the immunogenic response to influenza vaccination. However, strain-specific differences may exist. We observed lower SP rates of influenza A virus subtype H3N2 (A/H3N2) and B strain in VDD patients than patients with normal vitamin D levels (A/H3N2: 71.8% vs. 80.1%, odds ratio (OR): 0.63, 95% confidence interval (CI): 0.43-0.91, p = 0.01; B strain: 69.6% vs. 76.4%, OR: 0.68, 95% CI: 0.5-0.93, p = 0.01). However, the SP rates of A/H1N1 and SC rates of all three strains were not significantly different in VDD and control groups. In conclusion, no association was observed between VDD and immunogenic response to influenza vaccination.

Bronquitis obliterante secundaria a neumonía por virus Influenzae B y sobreinfección por Staphylococcus aureus / Bronchitis obliterans due to Influenza B pneumonia complicated with Staphylococcus aureus infection

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Comparative epidemiology of influenza A and B viral infection in a subtropical region: a 7-year surveillance in Okinawa, Japan.

BACKGROUND: The epidemic patterns of influenza B infection and their association with climate conditions are not well understood. Influenza surveillance in Okinawa is important for clarifying transmission patterns in both temperate and tropical regions. Using surveillance data, collected over 7 years in the subtropical region of Japan, this study aims to characterize the epidemic patterns of influenza B infection and its association with ambient temperature and relative humidity, in a parallel comparison with influenza A. METHODS: From January 2007 until March 2014, two individual influenza surveillance datasets were collected from external sources. The first dataset, included weekly rapid antigen test (RAT) results from four representative general hospitals, located in the capital city of Okinawa. A nation-wide surveillance of influenza, diagnosed by RAT results and/or influenza-like illness symptoms, included the age distribution of affected patients and was used as the second dataset. To analyze the association between infection and local climate conditions, ambient temperature and relative humidity during the study period were retrieved from the Japanese Meteorological Agency website. RESULTS: Although influenza A maintained high number of infections from December through March, epidemics of influenza B infection were observed annually from March through July. The only observed exception was 2010, when the pandemic strain of 2009 dominated. During influenza B outbreaks, influenza patients aged 5 to 9 years old and 10 to 14 years old more frequently visited sentinel sites. Although both ambient temperature and relative humidity are inversely associated with influenza A infection, influenza B infection was found to be directly associated with high relative humidity. CONCLUSION: Further studies are needed to elucidate the complex epidemiology of influenza B and its relationship with influenza A. In the subtropical setting of Okinawa, epidemics of influenza B infection occur from March to July following the influenza A epidemic, and primarily affect school-age children. These findings help to define unknown aspects of influenza B and can inform healthcare decisions for patients located outside temperate regions.

Severe influenza in children: incidence and risk factors.

INTRODUCTION: The identification of factors that can predispose to the development of severe influenza is essential to enable the implementation of optimal prevention and control measures for vulnerable populations. AREAS COVERED: Unfortunately, data in the pediatric age group remain difficult to interpret. However, epidemiological data seem to suggest that the most severe influenza cases, those who are hospitalized, those who are admitted to the intensive care unit, and those who died, occur in children in the first 2 years of life and in school age patients. Expert commentary: Immaturity of the immune system, and in particular of the mechanisms that usually recognize influenza viruses and activate cytokine and chemokine responses to reduce viral replication, might explain the high hospitalization rate observed in the youngest patients. Some underlying chronic conditions favour the development of the severe cases, sometime leading to death, although both admission to the intensive care unit and death can occur in otherwise healthy subjects.

Production of Influenza Virus HA1 Harboring Native-Like Epitopes by Pichia pastoris.

The outbreak of the H5N1 highly pathogenic avian influenza which exhibits high variation had brought a serious threat to the safety of humanity. To overcome this high variation, hemagglutinin-based recombinant subunit vaccine with rational design has been considered as a substitute for traditional virion-based vaccine development. Here, we expressed HA1 part of the hemagglutinin protein using the Pichia pastoris expression system and attained a high yield of about 120 mg/L through the use of fed-batch scalable fermentation. HA1 protein in the culture supernatant was purified using two-step ion-exchange chromatography. The resultant HA1 protein was homogeneous in solution in a glycosylated form, as confirmed by endoglycosidase H treatment. Sedimentation velocity tests, silver staining of protein gels, and immunoblotting were used for verification. The native HA1 reacted well with conformational, cross-genotype, neutralizing monoclonal antibodies, whereas a loss of binding activity was noted with the denatured HA1 form. Moreover, the murine anti-HA1 serum exhibited a virus-capture capability in the hemagglutination inhibition assay, which suggests that HA1 harbors native-like epitopes. In conclusion, soluble HA1 was efficiently expressed and purified in this study. The functional glycosylated protein will be an alternative for the development of recombinant protein-based influenza vaccine.

Impacto del virus gripal tipo B y divergencia con la cepa B incluida en la vacuna antigripal en España / Burden of influenza virus type B and mismatch with the flu vaccine in Spain

Introducción. Dos linajes de virus tipo B llevan co-circulando desde los años 80. Las divergencias antigénicas entre ellos son importantes y conduce a la falta de reactividad cruzada. Dado el impacto en la carga de enfermedad debida al virus gripal B, la mala previsión a la hora de estimar cuál de los dos linajes de virus B circulará en la temporada, y la consecuente falta de inmunidad en caso de incluir la cepa equivocada, hace que la disponibilidad de las vacunas cuadrivalentes se presenten como muy útiles. El objetivo del presente artículo es analizar las últimas temporadas gripales en España para valorar la carga de enfermedad, divergencia entre la cepa vacunal B y la circulante en el desarrollo de cada epidemia estacional. Material y métodos. Revisión de todos los informes emitidos por el Sistema de Vigilancia de Gripe en España desde la temporada 2003-2004 hasta la 2012-2013. Resultados. A lo largo de las últimas temporadas gripales, aunque el tipo A ha estado mayoritariamente presente, la circulación del virus gripal B en cada temporada ha sido identificada, siendo incluso co-dominante en alguna de ellas. En un alto número de temporadas la divergencia entre la cepa vacunal y el linaje de la cepa circulante ha quedado constatada. Conclusiones. El efecto protector de la vacuna antigripal ha variado en función del tipo/subtipo de virus gripal estudiado. La efectividad de la vacuna antigripal frente a la infección por virus de la gripe B ha variado enormemente en función de la temporada analizada (AU)

Introduction. Since the 80s two lineages of type B viruses are co - circulating in the world. Antigenic differences between them are important and it leads to lack of cross-reactivity. The impact on the burden of disease due to influenza B virus, poor foresight in estimating which of the two lineages of B viruses circulate in the season, and the consequent lack of immunity in case of including the wrong strain make that the availability of the quadrivalent vaccine is very useful. The aim of this paper is to analyze the past influenza seasons in Spain to assess the burden of disease, divergence between the vaccine strain and the circulating B and viral characteristics associated with type B in each seasonal epidemic. Material and methods. Review of all reports issued by the Influenza Surveillance System in Spain since the 2003-2004 season to 2012-2013. Results. Over the past influenza seasons, although type A was present mostly, circulation of influenza B virus in each season was observed, even being co - dominant in some of them. In a high number of seasons the divergence between the vaccine strain and the circulating strain lineage has been observed Conclusions. The protective effect of influenza vaccine has varied depending on the type / subtype of influenza virus studied. The vaccine effectiveness against influenza infection by influenza B virus has varied greatly depending on the season analyzed (AU)

Actividad antiviral de un extracto acuoso del alga roja Laurencia obtusa frente a virus influenza A y B / Antiviral activity of an aqueous extract from the red alga Laurencia obtusa against influenza A and B viruses

Introducción: la terapia antiviral frente a las infecciones provocadas por virus influenza se basa en empleo de inhibidores de las proteínas M2 y neuraminidasa (NA). Sin embargo, la emergencia de cepas estacionales resistentes a ambos grupos de fármacos motiva la búsqueda de nuevos fármacos anti-influenza. Los extractos de algas pueden ser utilizados como fuente para la obtención de estos compuestos, teniendo en cuenta la diversidad de metabolitos descrita en estos organismos. Objetivo: evaluar la actividad antiviral in vitro de un extracto acuoso del alga roja Laurencia obtusa frente a virus influenza A (H1N1), A (H3N2) e influenza B. Métodos: se evaluó la citotoxicidad en células MDCK, mediante cálculo de la viabilidad celular, en presencia de concentraciones crecientes del extracto. Los efectos sobre la replicación viral se cuantificaron mediante determinación de los niveles de la hemaglutinina (HA) y de la inhibición del efecto citopático (ECP). El índice selectivo (IS) se calculó a partir de la relación IS=CC50/CE 50. Resultados: el extracto acuoso de Laurencia obtusa posee actividad antiviral in vitro frente a virus influenza B, A (H3N2) y A (H1N1) con valores de IS de 7,73; 11,79 y 12,95; respectivamente. Conclusiones: Laurencia obtusa inhibe la replicación de virus influenza de elevada importancia clínica. La realización de ensayos secundarios de caracterización de la actividad biológica, así como de caracterización molecular del extracto, podrían permitir el desarrollo de novedosos compuestos antivirales. Este trabajo constituye el primer informe de actividad inhibitoria de esta especie de macroalga frente a virus influenza(AU)

Introduction: antiviral therapy against infections caused by influenza viruses is based on the use of inhibitors of M2 protein and neuraminidase (NA). However, the emergence of seasonal strains resistant to both drug groups has led to the search for new anti-influenza medications. Extracts from algae may be used as a source of compounds, considering the diversity of metabolites described for these organisms. Objective: evaluate the in vitro antiviral activity of an aqueous extract from the red alga Laurencia obtusa against influenza A (H1N1), A (H3N2) and B viruses. Methods: cytotoxicity was evaluated in MDCK cells by cell viability estimation in the presence of growing concentrations of the extract. The effects over viral replication were quantified by determining hemagglutinin (HA) levels and inhibition of the cytopathic effect (CPE). The selective index (SI) was estimated by SI=CC50/CE50. Results: the aqueous extract of Laurencia obtusa showed in vitro antiviral activity against influenza B, A (H3N2) and A (H1N1) viruses with SI values of 7.73, 11.79 and 12.95, respectively. Conclusions: Laurencia obtusa inhibits the replication of influenza viruses, a fact of great clinical importance. Secondary assays to characterize the biological activity and molecular composition of the extract may lead to the development of novel antiviral compounds. The present paper is the first report on the inhibitory activity of this macroalga species against influenza viruses(AU)

Estatus con alteraciones periictales en resonancia magnética cerebral versus encefalitis / Status with periictal changes in cerebral magnetic resonance versus encephalitis

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Gaseous nitric oxide reduces influenza infectivity in vitro.

Gaseous nitric oxide (gNO) is an approved vasodilator drug for inhalation up to a maximum dose of 80 ppm. While gNO has been shown, in vitro, to be an effective antibacterial agent (at 160 ppm), NO-donor compounds have been shown to inhibit a variety of viruses at varying stages of replication. This research was done in order to determine whether gNO at 80 or 160 ppm possesses an antiviral effect on influenza viruses. Three strains of influenza (A and B) were exposed to gNO for up to 180 min, before and after infection of MDCK cells. In search for possible mechanism of antiviral action, Neuraminidase (NA) inhibition assay of H1N1 that was exposed to gNO was performed. Results show that when virions were exposed to gNO prior to infection a complete inhibition of infectivity was achieved for all three strains. Post infection exposure of influenza with gNO resulted in about 30% inhibition of infectivity. Further testing showed that when eliminating the pH effect by exposing a dried virus to gNO, 90% inhibition was found after 2h exposure. NA activity, of whole dried H1N1 virus, was found to be inhibited by gNO (80%). These results suggest that 80 and 160 ppm gNO have a time dependent antiviral effect on influenza strains of viruses during various stages of cellular infection, which are not due to concomitant changes in pH in the surrounding milieu. Viral NA inhibition by gNO was shown and may be responsible for this antiviral effect.

Detección de resistencia al oseltamivir en las cepas gripales humanas tipo A (H1N1) en la temporada epidémica 2007-2008 / No disponible

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Reversible splenial lesion in influenza virus encephalopathy.

We describe a rare case of clinically mild, influenza-associated encephalopathy with a reversible splenial lesion. A 12-year-old Japanese girl presented with fever and headache, followed by muscle weakness and somnolence. Magnetic resonance imaging on day 4 of her illness showed a solitary lesion of the splenium of the corpus callosum that was most prominently visualized on diffusion-weighted images. The patient was diagnosed with influenza B-associated encephalopathy. Her neurologic signs had completely recovered by day 6, and the splenial abnormalities disappeared on day 11. A review of the literature identified four additional pediatric cases of this type of influenza-associated encephalopathy: three and one were caused by influenza A and B viruses, respectively. Common features include prompt and complete recovery from clinical and radiologic abnormalities, a relatively older age (> or = 5 years), and a higher incidence among the Japanese. To better understand the pathophysiology of this encephalopathy, we examined interleukin-6, tumor necrosis factor-alpha, and soluble tumor necrosis factor receptor 1 levels in serum and cerebrospinal fluid from this patient. The results did not reveal any elevations of these cytokines in the sera or cerebrospinal fluid, suggesting that this condition is not mediated by augmented cytokine responses.