Niños hospitalizados con influenza en un hospital pediátrico de Argentina durante 2019-2022: ¿qué ha cambiado luego de la pandemia por COVID-19? / Children with influenza admitted at a children's hospital in Argentina in the 2019­2022 period: What has changed after the COVID-19 pandemic?

Introducción. Durante 2020 y 2021, la circulación de los virus influenza se mantuvo por debajo de lo esperado en todo el mundo. En Argentina, en el año 2022 observamos una circulación ininterrumpida de influenza todo el año. Nuestros objetivos fueron describir los patrones de circulación y las características clínicas de niños internados con influenza. Población y métodos. Estudio retrospectivo, analítico, observacional. Se incluyeron todos los niños internados en un centro pediátrico con detección del virus influenza durante los años 2019-2022. Resultados. Se internaron 138 pacientes en 4 años; en 2019 se observó una tasa del 4,5/1000 egresos hospitalarios mientras que en 2022, fue del 15,1/1000. En 2020 y 2021 no hubo casos. En el 2019 la mayoría de los casos ocurrieron en invierno, la causa de la internación fue la infección respiratoria aguda baja (IRAB) en el 79 % y se detectó influenza A en el 92 % de los casos. En el 2022, la mayoría de los casos ocurrieron en primavera, el 62 % presentó IRAB y en el 56 % se detectó influenza A. Ambos períodos tuvieron similares frecuencias de vacunación y de comorbilidades. Conclusiones. En el 2022 se registraron más internaciones por influenza, lo que podría corresponder a que se realizaron métodos diagnósticos moleculares, que son más sensibles, y se observó un cambio en la estacionalidad con más casos en primavera. En 2019 predominó influenza A en infecciones del tracto respiratorio inferior, mientras que en el 2022 influenza A y B fueron similares, y hubo más formas extrapulmonares.

Introduction. During 2020 and 2021, the circulation of influenza virus remained below expectations worldwide. In Argentina, in 2022, we observed an uninterrupted circulation of influenza all year round. Our objectives were to describe the circulation patterns and clinical characteristics of hospitalized children with influenza. Population and methods. Retrospective, analytical, observational study. All children with influenza virus admitted to a children's hospital during the 2019­2022 period were included. Results. A total of 138 patients were admitted over 4 years; in 2019, the rate of hospital discharges was 4.5/1000, compared to 15.1/1000 in 2022. No cases were recorded in 2020 and 2021. In 2019, most cases were observed in the winter; in 79%, the cause was acute lower respiratory tract infection (ALRTI); influenza A was detected in 92%. In 2022, most cases occurred in the spring; 62% developed ALRTI; and influenza A was detected in 56%. Similar rates of vaccination and comorbidities were observed in both periods. Conclusions. In 2022, more hospitalizations due to influenza were recorded, which may have correlated with the use of more sensitive molecular diagnostic testing and a change in seasonality, with more cases observed in the spring. In 2019, influenza A predominated in lower respiratory tract infections, while in 2022, cases of influenza A and B were similar, with more extra-pulmonary forms.

Immunogenicity and safety of the quadrivalent inactivated split-virion influenza vaccine in populations aged ≥ 3 years: A phase 3, randomized, double-blind, non-inferiority clinical trial.

This study aimed to evaluate the immunogenicity non-inferiority and safety of the quadrivalent inactivated split-virion influenza vaccine in participants ≥ 3 years old. A total of 3,328 participants were enrolled. Participants 3-8 years old were administered one or two doses of the investigational vaccine or one dose of the control vaccine, whereas the other participants were administered only one dose of the investigational or control vaccine. The immunogenicity and occurrence of adverse events (AEs) after 30 days of full-course vaccination and serious adverse events (SAEs) within 6 months after full-course vaccination were assessed. The sero-conversion rates (SCRs) of anti-H1N1, H3N2, B(Y), and B(V) antibodies in the test group were 74.64%, 87.40%, 82.66%, and 78.89%, respectively, and their geometric mean titers were 1:250.13, 1:394.54, 1:200.84, and 1:94.91, respectively, which were non-inferior to those in the control group. The SCRs and sero-protection rates in the two-dose group of participants 3-8 years old were greater than those in the one-dose group. The incidences of total AEs and adverse reactions in the test group were 31.6% and 21.7%, respectively, which were close to those in the control group. In the two-dose group, the incidence of adverse reactions was considerably lower in the second dose (5.5%) than in the first dose (14.7%). Most AEs were grade 1 in severity, and no SAEs were recorded. The investigational vaccine had immunogenicity non-inferior to the control vaccine, and two doses were more effective than one dose in participants 3-8 years old, with a good overall safety.Trial registration: CTR20200715.

People in China are frequently infected by influenza viruses in specific seasons, causing a large burden of disease. Influenza viruses have distinct phenotypes depending on the season. Therefore, vaccines that can effectively prevent the infection of various influenza virus phenotypes need to be developed. The quadrivalent inactivated split-virion influenza vaccine is effective against four influenza virus phenotypes. In this trial, the immunogenicity and safety of the quadrivalent inactivated split-virion influenza vaccine (investigational vaccine) developed by Dalian Aleph Biomedical Co., Ltd. were evaluated. A total of 3,328 participants ≥ 3 years old were included. Participants 3­8 years old were further divided based on the presence or absence of a history of influenza vaccination. Those participants without a vaccination history were administered one or two doses of the investigational vaccine or one dose of a marketed quadrivalent influenza vaccine (control vaccine), and those participants with a vaccination history were administered one dose of the investigational or control vaccine. This study showed for the first time that the immunogenicity and safety of the investigational vaccine were not inferior to those of the control vaccine and that the two-dose procedure induced a good immune effect in the 3­8-year-old group. In conclusion, administration of the investigational vaccine can prevent seasonal influenza in populations aged ≥ 3 years.

Serological studies of influenza infection among population in southern region of Kazakhstan during the 2018-2021 epidemic season.

Objective: To conduct serological studies of influenza infection rate during an epidemic. METHODS: The retrospective study was conducted at the Research and Production Centre for Microbiology and Virology, Almaty, Kazakhstan, and comprised data, including blood samples, from patients with symptoms of acute respiratory viral infection, bronchitis and pneumonia during 2018-21 from various healthcare institutions in the Almaty region. Serological tests on blood serums were carried out sing haem agglutination inhibition assay and enzyme-linked immunosorbent assay. Data was analysed using Graph Pad Prism 9. RESULTS: Of the 779 blood samples, 392(50.3%) came from women and 387(49.7%) from men. The overall age range was 0-80 years. Serological analyses using haem agglutination inhibition assay showed the presence of anti-hemagglutinins against pandemic A(H1N1)pdm09 virus in 292(37.5%) samples, influenza A/H3N2 virus in 340(43.6%) and type B virus in 53(6.8%). Antibodies against two subtypes of influenza A virus and type B virus were simultaneously identified in 25(3.2%) cases, whereas against influenza A (H1N1+H3N2) viruses in 69(8.9%). In enzyme-linked immunosorbent assay, antibodies against influenza A/H1N1pdm virus were detected in 108(13.9%) cases, against A/H3N2 virus in 105(13.5%) and type B virus in 65(8.3%). Antibodies simultaneously against two subtypes of influenza A virus were identified in 46(5.9%) of blood serums, and against influenza A and B viruses in 60(7.7%). Conclusion: Co-circulation of influenza A and B viruses was observed, confirming the role of influenza viruses in the epidemic process.

Use of oral fluids for efficient monitoring of influenza viruses in swine herds in Colombia

Background: Influenza A virus (IAV) surveillance in swine is critical not only due to the direct impact of the disease in the pork industry but also because IAV are prone to interspecies transmission (from human to pigs and vice versa); therefore, its monitoring is fundamental from a public and animal health perspective. Several diagnostic techniques have been used to detect IAV infection from nasal samples in swine, while samples of oral fluids (OF) are in use as novel alternatives for pathogen detection. The OF allow for efficient and feasible low-cost disease detection at the herd level, with low risk of stress for the animals. Objective: To describe a surveillance strategy of IAV at the herd level during respiratory disease outbreaks in swine farms at tropical settings using porcine oral fluids. Methods: An active surveillance strategy was conducted in several farms with past records of respiratory disease. The IAV detection was conducted in five purposively selected swine farms from years 2014 to 2017. We investigated a total of 18 respiratory outbreaks of the disease. Swine OF were collected for IAV testing. An OF sample is described as a pen-based specimen collected from a group of >20 pigs per pen and/or per barn (stall-housed individually with close contact among them). The IAV infection was investigated in OF by rRT-PCR testing and confirmed by viral isolation in cell culture Results: We found 107 (7.4%) positives to IAV by rRT-PCR from a total of 1,444 OF samples tested. Additionally, 9 IAV isolates were all further identified as H1 subtype. Conclusions: Our results demonstrate that OF can be easily implemented as a novel, user-friendly, welfare-friendly, accurate and cost-effective sampling method for active surveillance and monitoring of IAV infections in swine farms in tropical settings.

Antecedentes: La vigilancia del Virus Influenza A (IAV) en los cerdos es fundamental debido al impacto directo de la enfermedad en la industria porcina, pero también porque los IAV son propensos de transmisión entre especies (humanos a cerdos y viceversa), y por lo tanto su monitoreo es crítico desde las perspectivas de salud pública y animal. Actualmente existen varias técnicas de diagnóstico disponibles para detectar la infección por IAV a partir de muestras nasales en cerdos, sin embargo, se han implementado otras muestras como los fluidos orales (OF) como nuevas alternativas para la detección de patógenos. El OF permite una detección eficiente y factible de enfermedades a menor costo a nivel de rebaño, con menor riesgo de estrés para los animales. Objetivo: Describir una estrategia de vigilancia de IAV a nivel de hato por medio de fluidos orales porcinos durante brotes de enfermedades respiratorias en granjas porcinas en entornos tropicales. Métodos: Se llevó a cabo una estrategia de vigilancia activa en cinco granjas porcinas seleccionadas con antecedentes de enfermedades respiratorias. Se recolectaron OF porcinos para la prueba de IAV. Una muestra de OF se describió como una muestra grupal recolectada de un grupo de >20 cerdos por corral y/o por establo (si estaban alojados individualmente, pero tenían un contacto cercano entre ellos). La infección por IAV se investigó probando OF mediante rRT-PCR y la confirmación mediante aislamiento viral en cultivo celular. Resultados: La detección de IAV se llevó a cabo en cinco granjas seleccionadas intencionalmente entre 2014- 2017. Investigamos un total de 18 eventos de brotes de enfermedades respiratorias. Del total de 1.444 OF muestras analizadas, encontramos 107 (7,4%) positivos a IAV mediante rRT-PCR. Además, solo se obtuvieron 9 aislamientos de IAV y todos se identificaron además como subtipo H1. Conclusiones: Los resultados de nuestro estudio demostraron cómo la OF puede implementarse fácilmente como un método de muestreo novedoso, fácil de usar, amigable con el bienestar animal, preciso y rentable para la vigilancia activa y el monitoreo de infecciones por IAV en granjas porcinas en entornos tropicales.

Antecedentes: A vigilância do vírus Influenza A (IAV) em suínos é crítica devido ao impacto direto da doença na indústria de suínos, mas também porque os IAV são propensos a transmissão interespécies (de humanos para porcos e vice-versa) e, portanto, seu monitoramento é crítico do ponto de vista da saúde pública e animal. Atualmente, existem várias técnicas de diagnóstico disponíveis para detectar a infecção por IAV em amostras nasais de suínos, no entanto, outras amostras, como fluidos orais (OF), têm sido implementadas como novas alternativas para a detecção de patógenos. O OF permite uma detecção eficiente e viável de doenças com menor custo em nível de rebanho, com menor risco de estresse para os animais. Objetivo: Descrever uma estratégia de vigilância de IAV em nível de rebanho durante surtos de doenças respiratórias em granjas de suínos em ambientes tropicais por meio de fluidos orais suínos. Métodos: A estratégia de vigilância ativa foi conduzida em cinco granjas de suínos selecionadas com histórico de doenças respiratórias. Suínos OF foram coletados para teste de IAV. Uma amostra OF foi descrita como um espécime baseado em curral coletado de um grupo de >20 porcos por curral e/ou por celeiro (se eles foram alojados individualmente, mas tendo contato próximo entre eles). A infecção IAV foi investigada testando OF por rRT-PCR e confirmada por isolamento em cultura de células. Resultados: A detecção do IAV foi realizada em cinco fazendas selecionadas propositalmente entre 2014-2017. Nós investigamos um total de 18 eventos de surto de doença respiratória. Do total de 1.444 amostras de OF testadas, encontramos 107 (7,4%) positivas para IAV por rRT-PCR. Além disso, apenas 9 isolados de IAV foram obtidos, e todos foram posteriormente identificados como subtipo H1. Conclusão: Os resultados de nosso estudo demonstraram como o OF pode ser facilmente implementado como um método de amostragem novo, amigável, amigável com o bem-estar, preciso e de baixo custo para vigilância ativa e monitoramento de infecções IAV em fazendas de suínos em ambientes tropicais.

Estratégia protetora de ventilação mecânica na síndrome respiratória aguda grave por influenza: revisão sistemática / Protective mechanical ventilation strategy in severe acute respiratory syndrome by influenza: a systematic review

Objetivo: Avaliar se a estratégia protetora de ventilação mecânica na síndrome do desconforto respiratório agudo (SDRA) por Influenza é capaz de reduzir o tempo de ventilação mecânica e aumentar a sobrevida. Métodos: A busca foi realizada nas bases de dados Pubmed, Embase, Cochrane, Lilacs, Medline, Scopus, Web of Science, Science Direct, Cinahl e SAGE, entre 2009 e 2019. Buscou-se por ensaios clínicos controlados e randomizados, estudos analíticos com grupo controle: coorte prospectiva ou controle histórico. A população estudada foi de indivíduos adultos com diagnóstico de síndrome respiratória aguda grave por Influenza, que receberam estratégia protetora de ventilação com baixos volumes correntes e/ou manobra de recrutamento alveolar comparada com qualquer outra estratégia. Resultados: A busca resultou em 445 referências; apenas 1 artigo preencheu os critérios de elegibilidade. O estudo incluído trouxe que o uso de baixos volumes traz benefícios para os pacientes com SDRA de etiologias virais, como menor tempo de ventilação mecânica, de internação em UTI e hospitalar. Conclusão: A escassez de artigos sobre a estratégia de ventilação protetora em SDRA secundário à infecção por Influenza não permite concluir se essa estratégia é capaz de reduzir o tempo de ventilação e/ou melhorar a sobrevida nessa população. A literatura carece de mais estudos que permitam conclusões robustas.

Evaluation of immunogenicity of trivalent split-vinus influenza vaccine among elderly populations / 预防医学

Objective@#To investigate immune responses to influenza virus infections and the immunogenicity of trivalent split-virus influenza vaccine among elderly populations in Jiangbei District, Ningbo City, so as to provide the support for promoting influenza vaccination among elderly populations.@*Methods@#The elderly populations at ages of 60 years and older were recruited in Jiangbei District of Ningbo City from September to November, 2020, and the participants were assigned to the vaccination group and the control group according to vaccination intention. The titers of haemagglutination inhibition ( HI ) antibodies against influenza viruses A ( H1N1 and H3N2 ) and BV were measured using the micro HI test prior to vaccination and 30 days post-vaccination, and the protective rate, geometric mean titer ( GMT ) and seroconversion rate of antibodies were analyzed before and after vaccination.@*Results@#There were 290 participants in the vaccination group, including 132 men (45.52% ), and 290 controls, including 132 men ( 45.52% ). There were no significant differences between the vaccination group and the control group in terms of the protective rate or GMT of antibodies against influenza viruses A ( H1N1 and H3N2 ) and BV prior to vaccination ( P>0.05 ). Following vaccination, the protective rates of antibodies against influenza viruses A ( H1N1 and H3N2 ) and BV were 98.62%, 94.14% and 88.28%, and the GMT of antibodies against influenza viruses A ( H1N1 and H3N2 ) and BV increased by 9.26, 6.19 and 10.09 folds, while the seroconversion rates of antibodies against influenza viruses A ( H1N1 and H3N2 ) and BV were 78.62%, 68.28% and 71.38%, respectively. The protective rates, GMT and seroconversion rates of antibodies against influenza viruses A ( H1N1 and H3N2 ) and BV were all significantly greater in the vaccination group than in the control group post-vaccination ( P<0.05 ). A lower increase was seen in the GMT of antibodies against the influenza virus BV among residents at ages of 80 years and older (increase by 7.91 folds) than among residents at ages of 70 to 79 years ( increase by 12.53 folds ) and 60 to 69 years (increase by 13.32 folds) in the vaccination group post-vaccination ( P<0.05 ), and the seroconversion rate of antibodies against the influenza virus BV was significantly lower in residents at ages of 80 years and older ( 62.57% ) than in those at ages of 70 to 79 years ( 83.33% ) ( P<0.05 ), while the positive conversion rate of antibodies against the influenza virus A ( H3N2 ) was significantly lower in residents at ages of 80 years and older ( 62.57% ) than in those at ages of 60 to 69 years ( 91.30% ) ( P<0.05 ).@*Conclusions@#Low-level immune responses are detected to antibodies against influenza virus A ( H3N2 ) and BV among elderly populations in Jiangbei District of Ningbo City, and trivalent split-virus influenza vaccine shows a high immunogenicity among elder populations. An emphases on improvements in coverage of influenza vaccination among elderly populations at ages of 60 to 69 years, and development of influenza vaccines with a higher protective efficacy for residents at ages of 80 years and older are recommended.

Rapid Molecular Point of Care Testing for Detection of Influenza A, B Viruses and Respiratory Syncytial Virus Versus Multiplex PCR

@#Introduction: Rapid detection of influenza viruses and respiratory syncytial virus (RSV) can be achieved by having rapid molecular point of care tests (POCTs). This expedites the diagnosis attributed by having similar clinical presentations leading to facilitation of precision medicine and reduction of antimicrobial resistance. The growing number of POCTs foster the need to ensure that these POCTs have satisfactory and reliable performance. With that the aim of this study is to evaluate the performance of rapid molecular POCT regarded as ‘X’ for the detection of Influenza viruses and RSV in comparison to multiplex PCR. Methods: A laboratory-based study was conducted from January to December 2020 which involved analysis of 116 nasopharyngeal swabs, tested using POCT X and multiplex PCR as a method of reference. The performance analysis incorporated the sensitivity, specificity, positive and negative predicted values determination. The cycle threshold values were reviewed for discordant results. Results: The POCT X demonstrated sensitivity of 88.57% with 100% specificity for Influenza A virus, and 85.71% of sensitivity with 100% specificity for influenza B virus detection. Meanwhile it revealed 100% sensitivity and specificity for RSV detection. There were ten specimens demonstrating discordant results whereby viruses were not detected by POCT X, however detected by multiplex PCR. The POCT X was not able to detect eight (12.9%) and two (16.7%) influenza A and B viruses respectively. Conclusion: The overall performance of POCT X was corresponded to multiplex PCR. This best served as a steadfast ancillary test for influenza and RSV infection.

Corrigendum: Key Determinants of Cell-Mediated Immune Responses: A Randomized Trial of High Dose Vs. Standard Dose Split-Virus Influenza Vaccine in Older Adults.

[This corrects the article DOI: 10.3389/fragi.2021.649110.].

Understanding the outcomes of COVID-19 - does the current model of an acute respiratory infection really fit?

Although coronavirus disease 2019 (COVID-19) is regarded as an acute, resolving infection followed by the development of protective immunity, recent systematic literature review documents evidence for often highly prolonged shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in respiratory and faecal samples, periodic recurrence of PCR positivity in a substantial proportion of individuals and increasingly documented instances of reinfection associated with a lack of protective immunity. This pattern of infection is quite distinct from the acute/resolving nature of other human pathogenic respiratory viruses, such as influenza A virus and respiratory syncytial virus. Prolonged shedding of SARS-CoV-2 furthermore occurs irrespective of disease severity or development of virus-neutralizing antibodies. SARS-CoV-2 possesses an intensely structured RNA genome, an attribute shared with other human and veterinary coronaviruses and with other mammalian RNA viruses such as hepatitis C virus. These are capable of long-term persistence, possibly through poorly understood RNA structure-mediated effects on innate and adaptive host immune responses. The assumption that resolution of COVID-19 and the appearance of anti-SARS-CoV-2 IgG antibodies represents virus clearance and protection from reinfection, implicit for example in the susceptible-infected-recovered (SIR) model used for epidemic prediction, should be rigorously re-evaluated.

Key Determinants of Cell-Mediated Immune Responses: A Randomized Trial of High Dose Vs. Standard Dose Split-Virus Influenza Vaccine in Older Adults.

BACKGROUND: Efforts to improve influenza vaccine effectiveness in older adults have resulted in some successes, such as the introduction of high-dose split-virus influenza vaccine (HD-SVV), yet studies of cell-mediated immune responses to these vaccines remain limited. We have shown that the activity of the cytolytic mediator, granzyme B (GrB), in peripheral blood mononuclear cells (PBMC) challenged with influenza A/H3N2 virus, correlates with protection against influenza following standard dose vaccination (SD-SVV) in older adults. Further, the interferon-γ (IFNγ) to interleukin-10 (IL-10) ratio can be a correlate of protection depending on the timing of vaccination relative to exposure to influenza. METHODS: In a double-blind trial (ClinicalTrials.gov NCT02297542) older adults (≥65 years, n=582) were randomized to receive SD-SVV or HD-SVV (Fluzone®) from 2014/15 to 2017/18. Young adults (20-40 years, n=79) received SD-SVV. At 0, 4, 10 and 20 weeks post-vaccination, serum antibody titers, IFNγ, IL-10, and inducible GrB (iGrB) were measured in ex vivo influenza virus-challenged PBMC. iGrB is defined as the fold change in GrB activity from baseline levels (bGrB) in circulating T cells. Responses of older adults were compared to younger controls, while specifically for older adults we analyzed effects of age, sex, cytomegalovirus (CMV) serostatus, frailty, and vaccine dose. RESULTS: Prior to vaccination, younger adults produced significantly higher IFNγ, IL-10 and iGrB levels, but with no difference in the IFNγ:IL-10 ratio. Relative to SD-SVV recipients, older HD-SVV recipients exhibited significantly lower IFNγ:IL-10 ratios at 4 weeks post-vaccination. In contrast, IFNγ and iGrB levels were higher in younger SD vs. older SD or HD recipients; only the HD group showed a significant IFNγ response to vaccination compared to the SD groups while all three groups showed a significant iGrB response to vaccination. In a regression analysis, female sex and HD-SVV were associated with higher IL-10 levels, while SD-SVV was associated with lower iGrB levels. Prior season influenza vaccination showed a decline in iGrB levels but an increase in IFNγ and IL-10 levels, which correlated with influenza A/H3N2 hemagglutination inhibition antibody titers. CONCLUSIONS: Overall, HD-SVV amplified the IL-10 response consistent with enhanced antibody responses, with little effect on the iGrB response relative to SD-SVV in either younger or older adults. These results suggest that enhanced protection with HD-SVV is largely antibody-mediated.

Caracterización clínica y epidemiológica de infección asociada a atención en salud por virus influenza en pacientes críticos / Clinical and epidemiological characterization of healthcare acquired influenza in critical ill patients

Resumen Introduccion: Las infecciones asociadas a atencion de salud (IAAS) aumentan la morbilidad y mortalidad. Durante 2014, en Hospital Clinico Red de Salud UC Christus (RS-UCCH) se estimo que 15% de las infecciones virales respiratorias fueron adquiridas durante la atencion de salud, siendo mas frecuente el virus influenza. Objetivos: Caracterizacion clinico-epidemiologica de IAAS por influenza en pacientes hospitalizados en unidades de pacientes criticos (UPC) y cuidados especiales. Material y Metodos: Estudio descriptivo. Se incluyeron pacientes en UPC y cuidados especiales con IAAS influenza entre 2014 y 2017 en RS-UCCH. IAAS por influenza se definio como: inicio de sintomas y/o RPC-TR positiva para virus influenza ≥ 48 h de ingreso hospitalario, sin sintomatologia respiratoria o estudio negativo previo. Resultados: Se identificaron 22 pacientes, edad mediana 74 anos. La influenza fue adquirida en promedio al dia 13; el 77% fue por influenza A y el 27% presento coinfeccion respiratoria. Trece (59%) estaban hospitalizados en UPC, dos (15%) por problemas pulmonares. El 86% tenia co-morbilidad y el 50% descompensacion de ella. No estaba vacunado 59%; la letalidad observada fue 18%. Conclusiones: IAAS por influenza ocurrio en pacientes cronicos, de mayor edad y no vacunados. Es primordial educar en prevencion de IAAS y mantener altas coberturas de vacunacion.

Background: Healthcare-associated infections (HAIs) increase morbidity and mortality. During 2014, at the Hospital Clinico Red de Salud UC Christus (RS-UCCH) it was estimated that 15% of respiratory viral infections were acquired during hospitalization and influenza A was more frequent. Aims: Clinical and epidemiological characterization of HAIs due to influenza virus in patients hospitalized in critical care units (CCU) and special care. Methods: Descriptive study. We included patients hospitalized in CCU and special care with hospital acquired influenza during 2014-2017. HAI due to influenza was defined as: symptom onset and/or positive influenza PCR after ≥ 48 hours of hospital admission, without previous respiratory symptoms or previous negative influenza test study. Results: 22 patients were identified, median age was 74 years. Influenza was acquired average on day 13. Influenza A was detected in 77% and 27% had respiratory co-infection. Thirteen (59%) were hospitalized in CCU, only 2 (15%) due to lung problems. Comorbidity was present in 86% and decompensation in 50%. Only 41% received influenza vaccine. The associated lethality was 18%. Conclusions: HAI due to influenza occurred in chronic, older and unvaccinated patients. Education about HAIs and continuous high vaccination coverage must be reinforced.

Infecção pelo vírus influenza A em suínos no sul de Moçambique / Influenza A virus infection in pigs in southern Mozambique

A influenza suína (IS) é uma doença aguda e altamente contagiosa do trato respiratório de suínos, causada pelo vírus influenza A (VIA). A doença provoca perdas econômicas na suinocultura e também, tem importância na saúde pública devido ao seu potencial zoonótico. O objetivo deste trabalho foi relatar a infecção pelo VIA em suínos de Moçambique e realizar a caracterização anatomopatológica e imuno-histoquímica (IHQ) das lesões pulmonares associadas. Pulmões de 457 suínos abatidos foram avaliados e coletados 38 (8,3%) pulmões de suínos com áreas de consolidação pulmonar em um abatedouro na cidade da Matola, no Sul de Moçambique. As áreas de consolidação em cada lobo pulmonar foram classificadas em 4 graus de acordo com a extensão da lesão. Amostras de pulmões com consolidação foram submetidas ao exame histopatológico e IHQ para a detecção de antígenos do VIA, Circovírus suíno tipo 2 (PCV2) e Mycoplasma hyopneumoniae. Os pulmões coletados apresentaram áreas multifocais ou coalescentes de consolidação pulmonar, frequentemente, observadas nos lobos craniais, mediais e acessório. Estas lesões acometiam principalmente um ou três lobos pulmonares e as lesões de grau 1 e 2 foram as mais frequentes. As principais lesões histopatológicas observadas foram bronquiolite necrotizante (23/38), infiltrado de neutrófilos nos alvéolos (24/38), hiperplasia de pneumócitos tipo II (26/38), hiperplasia de tecido linfoide peribronquiolar (28/38), e pneumonia intersticial mononuclear (29/38). No exame de IHQ, antígenos do VIA foram detectados em 84.3% (32/38) dos pulmões com pneumonia, e a nucleoproteína do vírus foi visualizada, no núcleo de células epiteliais de brônquios e bronquíolos e em macrófagos alveolares. Suínos positivos para o VIA na IHQ eram provenientes do distrito de Matutuine (5/32), distrito da Moamba (2/32), distrito de Namaacha (21/32), distrito de Boane (3/32) e Cidade da Matola (1/32). Todas as amostras foram negativas para PCV2 e Mycoplasma hyopneumoniae pelo exame de IHQ. Os resultados demonstram que o VIA está presente e é causa de pneumonia em suínos em Moçambique.(AU)

Swine influenza (SI) is an acute and highly contagious disease of the respiratory tract of pigs caused by influenza A virus (IAV). The disease causes economic losses in swine production and is of great public importance for its zoonotic potential. The aim of the present study was to report IAV infection in pigs from Mozambique and characterize the anatomopathological and immunohistochemical features of associated lung lesions. Lungs from 457 slaughtered pigs were subjected to gross evaluation and 38 (8.3%) lungs with cranioventral consolidation were collected from a slaughterhouse in Matola City, southern Mozambique. Areas of consolidation in each lung lobe were classified in 4 grades according to the lesion extension. Samples with consolidated lung tissue were examined for histopathology and immunohistochemistry (IHC) for the presence of IAV, Porcine circovirus type 2 (PCV2) and Mycoplasma hyopneumoniae antigens. The lungs had multifocal to coalescing areas of consolidation observed most frequently in the cranial, middle, and accessory lobes. The lesions involved mainly one or three pulmonary lobes and grade 1 and 2 lesions were the most frequent. The main histopathological findings were necrotizing bronchiolitis (23/38), alveolar neutrophil infiltration (24/38), type II pneumocytes hyperplasia (26/38), peribronchiolar lymphoid tissue hyperplasia (28/38) and interstitial mononuclear cells infiltrate (29/38). Immunohistochemistry revealed positive staining in 84.3% (32/38) of the samples and IAV nucleoprotein was present in the nucleus of bronchial and bronchiolar epithelial cells and alveolar macrophages. Positive IHC pigs were from Matutuine district (5/32), Moamba district (2/32), Namaacha district (21/32), Boane district (3/32) and Matola city (1/32). All lung samples were immunohistochemically negative for PCV2 and Mycoplasma hyopneumoniae. These results demonstrate that IAV is a cause of pneumonia in pigs in Mozambique.(AU)

Patients with influenza A (H1N1)pdm09 admitted to the ICU. Impact of the recommendations of the SEMICYUC. / Pacientes con gripe por el virus influenza A (H1N1)pdm09 ingresados en la UCI. Impacto de las recomendaciones de la SEMICYUC.

OBJECTIVES: To evaluate the impact of the recommendations of the SEMICYUC (2012) on severe influenza A. DESIGN: A prospective multicenter observational study was carried out. SETTING: ICU. PATIENTS: Patients infected with severe influenza A (H1N1) from the GETGAG/SEMICYUC registry. INTERVENTIONS: Analysis of 2 groups according to the epidemic period of the diagnosis (2009-2011; 2013-2015). VARIABLES: Demographic, temporal, comorbidities, severity, treatments, mortality, late diagnosis and place of acquisition. RESULTS: A total of 2,205 patients were included, 1,337 (60.6%) in the first period and 868 (39.4%) in the second one. Age and severity on admission were significantly greater in the second period, as well as co-infection. With regard to the impact of the recommendations, in the second period the diagnosis was established earlier (70.8 vs. 61.1%, P<.001), without changes in the start of treatment. Patients received less corticosteroid treatment (39.7 vs. 44.9%, P<.05), more NIMV was used (47.4 vs. 33.2%, P<.001) and more vaccination was made (11.1 vs. 1.7%, P<.001), without changes in mortality (24.2 vs. 20.7%). A decrease in nosocomial infection was also noted (9.8 vs. 16%, P<.001). Patients needed less MV with more days of ventilation, more vasopressor drug use and more ventral decubitus. CONCLUSIONS: The management of patients with severe influenza A (H1N1) has changed over the years, though without changes in mortality. The recommendations of the SEMICYUC (2012) have allowed earlier diagnosis and improved corticosteroid use. Pending challenges are the delay in treatment, the vaccination rate and the use of NIMV.

Functional role of Hsp60 as a positive regulator of human viral infection progression.

Heat shock proteins (Hsps) are a family of proteins highly conserved in evolution. Members of the Hsp family are mainly responsible for proper protein folding, however they perform many other functions in living organisms. Hsp60 is a molecular chaperone that is present in mitochondria and cytosol of eukaryotic cells, as well as on their surface. It is also found in the extracellular space and in the peripheral blood. Apart from its role in assisting protein folding in cooperation with Hsp10, Hsp60 contributes to regulation of apoptosis, as well as participates in modulation of the immune system activity. Hsp60 may favor oncogenesis by promoting survival or growth of some tumor cell types. Hsp60 is a subject of medical research due to its role in pathogenesis of certain tumors and infectious diseases. In this review we discuss mechanisms by which Hsp60 promotes development and progression of infections caused by three human viruses: hepatitis B virus (HBV), human immunodeficiency virus (HIV) and influenza A virus.

Sex bias in mouse humoral immune response to influenza vaccine depends on the vaccine type.

The study explored influence of biological sex on development of humoral immune response to seasonal trivalent whole inactivated virus (WIV) and split virus (SV) influenza vaccines in outbred Swiss mouse model. To this end, mice of both sexes were immunized with WIV (WIV mice) and SV vaccines (SV mice) and examined for specific antibody response. Irrespective of sex, total IgG and neutralizing antibody responses to distinct virus strains were weaker in SV than in WIV mice. In WIV mice of both sexes, irrespective of strain specificity, IgG isotype response was dominated by IgG2a antibodies, while in SV mice nearly equal representation of IgG2a and IgG1 antibodies was found. The analyses of sex differences showed higher titers of H1N1-specific and both H1N1- and H3N2-specific total IgG and neutralizing antibodies in female WIV and SV mice, respectively. Additionally, sexual dimorphism in IgG subclass profile depended on vaccine type. Specifically, compared with males, in females WIV shifted IgG2a/IgG1 antibody ratio towards IgG2a isotype on the account of weaker IgG1 response, whereas in SV mice, irrespective of virus strain, IgG2a and IgG1 isotypes were equally represented in both sexes. These findings indicate the vaccine type-dependent sex bias in antibody response to inactivated influenza vaccines.

Reporte de caso por infección de virus Influenza A H1N1: hallazgos de autopsia / Case report of Influenza virus H1N1 infection: autopsy findings

La influenza continúa siendo una causa importante de muerte en las Américas; en nuestro país al igual que en otros países del continente, hay circulación viral sostenida del virus Influenza A H1N1pdm09, este reporte describe los hallazgos histopatológicos más relevantes, encontrados en femenina de 32 años de edad, con antecedentes de anemia drepanocítica; que falleció tres días después de inicio de síntomas respiratorios. La autopsia estableció como causa de muerte neumonía, daño alveolar difuso (DAD), edema, hemorragia, membranas hialinas y colonias bacterianas secundarias a infección por virus Influenza AH1N1pdm09. Este reporte destaca la importancia que el médico forense realice una labor integrativa, de los hallazgos macro y microscópicos y exámenes complementarios de la autopsia en el contexto epidemiológico y clínico en el que se dan los decesos...(AU)

Encefalitis hemorrágica por influenza A H1N1: presentación de un caso y revisión de la literatura / H1N1 influenza hemorrhage encephalitis: presentation of a case and review of the literature

RESUMEN Las complicaciones neurológicas asociadas a los virus respiratorios (en especial la influenza) son descritas de manera poco frecuente. Particularmente el virus influenza A subtipo H1N1 tiene escasos reportes, la mayoría proviene de niños y adultos jóvenes. Presentamos el caso del adulto mayor con un cuadro infeccioso respiratorio y múltiples complicaciones sistémicas graves a su cuadro primario, quien durante la estancia hospitalaria presentó un cuadro encefalopático, con características clínicas y radiológicas muy sugestivas de encefalitis hemorrágica debido a su agente primario infeccioso, en este caso influenza A H1N1.

SUMMARY Neurological complications associated with respiratory viruses such as influenza, are described infrequently. Particularly influenza A(H1N1) has few descriptions most of which come from children and young adults. We present the case of the elderly with respiratory infectious picture and multiple serious systemic complications to your primary table, who during the hospital stay has a encephalopathic box with suggestive clinical and radiologic features of hemorrhagic encephalitis due to its infectious primary agent in this case influenza A H1N1.

Distinctive Responses in an In Vitro Human Dendritic Cell-Based System upon Stimulation with Different Influenza Vaccine Formulations.

Vaccine development relies on testing vaccine candidates in animal models. However, results from animals cannot always be translated to humans. Alternative ways to screen vaccine candidates before clinical trials are therefore desirable. Dendritic cells (DCs) are the main orchestrators of the immune system and the link between innate and adaptive responses. Their activation by vaccines is an essential step in vaccine-induced immune responses. We have systematically evaluated the suitability of two different human DC-based systems, namely the DC-cell line MUTZ-3 and primary monocyte-derived DCs (Mo-DCs) to screen immunopotentiating properties of vaccine candidates. Two different influenza vaccine formulations, whole inactivated virus (WIV) and subunit (SU), were used as model antigens as they represent a high immunogenic and low immunogenic vaccine, respectively. MUTZ-3 cells were restricted in their ability to respond to different stimuli. In contrast, Mo-DCs readily responded to WIV and SU in a vaccine-specific way. WIV stimulation elicited a more vigorous induction of activation markers, immune response-related genes and secretion of cytokines involved in antiviral responses than the SU vaccine. Furthermore, Mo-DCs differentiated from freshly isolated and freeze/thawed peripheral blood mononuclear cells (PBMCs) showed a similar capacity to respond to different vaccines. Taken together, we identified human PBMC-derived Mo-DCs as a suitable platform to evaluate vaccine-induced immune responses. Importantly, we show that fresh and frozen PBMCs can be used indistinctly, which strongly facilitates the routine use of this system. In vitro vaccine pre-screening using human Mo-DCs is thus a promising approach for evaluating the immunopotentiating capacities of new vaccine formulations that have not yet been tested in humans.

Antiviral drug review: a guide to clinicians

Over the past forty years, there has been a great advance in antiviral infections treatment. The discovery of acyclovir in 1977 paved the way to new antiviral drugs. Other nucleoside analogues such as valacyclovir, penciclovir, famciclovir, ganciclovir, valganciclovir, cidofovir and foscarnet were made available, as well as neuraminidase inhibitors. Also, drugs for the treatment of viral hepatitis and patients with HIV/AIDS have not only increased life quality and expectancy, but also decreased the incidence of some viral infections. Antiviral drugs are important tools to the clinician, especially when treating patients with impaired immunological and clinical condition. Aiming to restore health and prevent further adverse events, the clinician must be aware of the best antiviral drug available, its proper route of administration and dosage. The aim of this review is to present the antiviral drugs currently available, focusing on treatment of common viral infections in clinical practice. A brief description of the mechanisms of action and prescription of antiviral drugs is presented, using the data available from evidence-based medicine.