Impact of H5N8 duck and chicken viral isolates on the immunological profile of vaccinated specific pathogen free chickens

Nowadays, there is a global concern about outbreaks caused by the highly pathogenic avian influenza virus H5N8 clade 2.3.4.4 which caused devastating losses in the poultry industry sector. This clade was subdivided into two waves: clade 2.3.4.4A from 2014 to 2015 and clade 2.3.4.4b from 2016 until now. In this literature we aimed to evaluate the efficacy of recently used inactivated commercial avian influenza vaccines against two new Egyptian highly pathogenic avian influenza virus H5N8 isolates of clade 2.3.4.4b, A/chicken/Egypt/1526v/2020/H5N8 (H5N8-CH) and A/Duck/Egypt/Qalubia321/2021 (H5N8-D). Three-week-old specific pathogen free chickens were vaccinated with eight types of the most recently used inactivated avian influenza vaccines containing homologous and heterologous virus to the circulating H5N8 isolates. All specific pathogen free chicken groups were bled weekly post vaccination for antibody analysis using two H5N8 isolates of chicken and duck origin as antigen in hemagglutination inhibition test. Also, all vaccinated chicken groups were challenged 4 weeks post vaccination against the H5N8 duck isolate with a dose of 109 EID50/0.1 mL per chicken to measure the protection percentage of the commercial vaccines used. The results showed that vaccines with homologous and heterologous virus showed variable degrees of accepted protection percentage ranged from 90percent to 100percent, thus it was concluded that not only the genetic and antigenic match of the vaccine strains with the circulating highly pathogenic avian influenza viruses influences vaccine efficiency; other factors, such as manufacturing procedures, adjuvant, antigen content, vaccine dose and administration factors could affect vaccine efficacy, therefore, further vaccine development studies are needed to improve the percentage of protection and prevention of viral shedding against local highly pathogenic avian influenza H5 viruses in Egypt(AU)

En la actualidad, existe una preocupación mundial por los brotes causados por el virus de la gripe aviar altamente patógena H5N8 clado 2.3.4.4 que causó pérdidas devastadoras en el sector de la industria avícola. Este clado se subdividió en dos oleadas: clado 2.3.4.4A de 2014 a 2015 y clado 2.3.4.4b de 2016 hasta ahora. En el presente trabajo, dos aislamientos egipcios de la gripe aviar altamente patógena H5N8 del clado 2.3.4.4b, A/chicken/Egypt/1526v/2020/H5N8 (H5N8_CH) y A/Duck/Egypt/Qalubia321/2021 (H5N8_D), se utilizaron para evaluar la eficacia de vacunas comerciales inactivadas contra la gripe aviar de reciente utilización. Pollos libres de patógenos específicos de tres semanas de edad fueron vacunados con ocho vacunas inactivadas contra la influenza aviar, de uso reciente, que contenían virus homólogos y heterólogos a los aislamientos circulantes de H5N8. Todos los grupos de pollos libres de patógenos específicos fueron sangrados semanalmente tras la vacunación para el análisis de anticuerpos; dos virus H5N8 aislados de pollo y pato se utilizaron como antígeno en la prueba de inhibición de la hemaglutinación. Además, todos los grupos de pollos vacunados fueron retados 4 semanas después de la vacunación con el virus H5N8 aislado de pato, con una dosis de 109 EID50/0,1 mL por pollo, para medir el porcentaje de protección de las vacunas comerciales utilizadas. Los resultados mostraron que las vacunas con virus homólogos y heterólogos presentaron grados variables de aceptada protección, la que osciló entre el 90 por ciento y el 100 por ciento, por lo que se concluyó que no sólo la coincidencia genética y antigénica de las cepas vacunales con los virus circulantes de la influenza aviar altamente patógena influye en la eficacia de la vacuna; otros factores, como los procedimientos de fabricación, el adyuvante, el contenido en antígenos, la dosis de la vacuna y los factores de administración podrían afectar a la eficacia de la vacuna, por lo que es necesario seguir estudiando el desarrollo de vacunas para mejorar la protección y la prevención de la excreción viral contra los virus H5 de la influenza aviar altamente patógena locales en Egipto(AU)

Efficacy of some avian influenza H5 vaccines against local highly pathogenic avian influenza viruses subtype H5N8 isolated in 2018 and 2020 in Egypt

Commercial inactivated avian influenza H5 vaccine is used as an essential control strategy for avian influenza disease in Egypt. Since the initial outbreaks of highly pathogenic avian influenza H5N8, the virus has diverged with new genotypes and variant viruses continuing to emerge which mainly stand behind vaccination failure. In the present work, four different commercial avian influenza vaccines were inoculated in specific pathogenic free chickens for assessing its efficacy against local highly pathogenic avian influenza H5N8 virus isolated in 2018 and 2020. Two hundred and forty specific pathogenic free chickens were clustered into four groups; each group was inoculated with the corresponding vaccine (60 specific pathogenic free chickens/vaccine). Sixty specific pathogenic free chicks were kept as control unvaccinated group. Sera collected from vaccinated chicken groups at 3rd and 4th week post vaccination were examined for calculating neutralizing antibodies using heterologous highly pathogenic avian influenza H5N8 2018 and 2020. At 4th week post vaccination, vaccinated chickens were challenged; moreover, oropharyngeal swabs were collected from challenged vaccinated chickens to calculate the viral shedding. Our findings revealed the groups vaccinated with vaccine code no 1 and 2 that contains two vaccine strains (H5N1 and H5N8) of local origin exhibited the highest hemagglutination inhibition titer, protection (percent) and reduction in viral shedding titer when examined by highly pathogenic avian influenza H5N8 2018 while, vaccine code no 3 induced lower antibody response, protection (percent) and reduction in viral shedding, but still within satisfactory level when compared to previous groups. When highly pathogenic avian influenza H5N8 2020 was used, it was found the seroconversion rate, protection (percent) and mean titer of reduction of viral shedding decreased in comparison to those recorded for highly pathogenic avian influenza H5N8 2018. Vaccine code no 4 was impotent to either highly pathogenic avian influenza 2018 or 2020. Accordingly, it was recommended to update vaccine strain according to epidemiological condition and used the predominant circulating strain isolate in challenge test(AU)

La vacuna comercial inactivada H5 se utiliza como estrategia esencial de control de la enfermedad de la gripe aviar en Egipto. Desde los brotes iniciales de la gripe aviar altamente patógena H5N8, el virus ha variado al aparecer continuamente nuevos genotipos y variantes virales, que son los principales responsables del fracaso de la vacunación. En el presente trabajo, cuatro vacunas comerciales diferentes contra la gripe aviar se inocularon en pollos libres de patógenos específicos para evaluar su eficacia contra cepas del virus local de la gripe aviar altamente patógeno H5N8 aisladas en 2018 y 2020. Se agruparon 240 pollos pollos libres de patógenos específicos en cuatro grupos, cada uno fue inoculado con la vacuna correspondiente (60 pollos pollos libres de patógenos específicos/vacuna). Sesenta pollos SPF se mantuvieron como grupo control sin vacunar. Los sueros de los pollos vacunados recogidos en la 3ª y 4ª semana después de la vacunación se examinaron para calcular los anticuerpos neutralizantes contra la gripe aviar heteróloga H5N8 2018 y 2020. En la cuarta semana después de la vacunación, los pollos vacunados fueron retados; además, se recogieron hisopados orofaríngeos de los pollos vacunados retados para calcular la diseminación viral. Nuestros resultados revelaron que los grupos vacunados con las vacunas con códigos nº 1 y 2, que contienen dos cepas vacunales (H5N1 y H5N8) de origen local, mostraron el mayor título de inhibición de la hemaglutinación, protección (por ciento) y reducción del título de excreción viral cuando se evaluaron contra la gripe aviar altamente patógena H5N8 2018, mientras que la vacuna con código nº 3 indujo menor respuesta de anticuerpos, protección (por ciento) y reducción de la excreción viral, pero todavía dentro de un nivel satisfactorio en comparación con los grupos anteriores. Al utilizar la vacuna contra la gripe aviar altamente patógena H5N8 2020, se observó que la tasa de seronconversión, la protección (por ciento) y el título medio de reducción de la excreción viral disminuyeron en comparación con los registrados para la gripe aviar altamente patógena H5N8 2018. La vacuna con código nº 4 no fue potente para la gripe aviar altamente patógena de 2018 o de 2020. Por consiguiente, se recomendó actualizar la cepa de la vacuna de acuerdo con las condiciones epidemiológicas y utilizar el aislamiento de la cepa circulante predominante en la prueba de reto(AU)

Characterization of a monoclonal antibody against the hemagglutinin stem of H7N9 subtype avian influenza virus / 生物工程学报

The conserved hemagglutinin (HA) stem region of avian influenza virus (AIV) is an important target for designing broad-spectrum vaccines, therapeutic antibodies and diagnostic reagents. Previously, we obtained a monoclonal antibody (mAb) (5D3-1B5) which was reactive with the HA stem epitope (aa 428-452) of H7N9 subtype AIV. To systematically characterize the mAb, we determined the antibody titers, including the HA-binding IgG, hemagglutination-inhibition (HI) and virus neutralizing (VN) titers. In addition, the antigenic epitope recognized by the antibody as well as the sequence and structure of the antibody variable region (VR) were also determined. Moreover, we evaluated the cross-reactivity of the antibody with influenza virus strains of different subtypes. The results showed that the 5D3-1B5 antibody had undetectable HI and VN activities against H7N9 virus, whereas it exhibited strong reactivity with the HA protein. Using the peptide-based enzyme-linked immunosorbent assay and biopanning with a phage-displayed random peptide library, a motif with the core sequence (431W-433Y-437L) in the C-helix domain in the HA stem was identified as the epitope recognized by 5D3-1B5. Moreover, the mAb failed to react with the mutant H7N9 virus which contains mutations in the epitope. The VR of the antibody was sequenced and the complementarity determining regions in the VR of the light and heavy chains were determined. Structural modeling and molecular docking analysis of the VR verified specific binding between the antibody and the C-helix domain of the HA stem. Notably, 5D3-1B5 showed a broad cross-reactivity with influenza virus strains of different subtypes belonging to groups 1 and 2. In conclusion, 5D3-1B5 antibody is a promising candidate in terms of the development of broad-spectrum virus diagnostic reagents and therapeutic antibodies. Our findings also provided new information for understanding the epitope characteristics of the HA protein of H7N9 subtype AIV.

A broadly neutralizing human monoclonal antibody against the hemagglutinin of avian influenza virus H7N9 / 中华医学杂志(英文版)

BACKGROUND@#The new emerging avian influenza A H7N9 virus, causing severe human infection with a mortality rate of around 41%. This study aims to provide a novel treatment option for the prevention and control of H7N9.@*METHODS@#H7 hemagglutinin (HA)-specific B cells were isolated from peripheral blood plasma cells of the patients previously infected by H7N9 in Jiangsu Province, China. The human monoclonal antibodies (mAbs) were generated by amplification and cloning of these HA-specific B cells. First, all human mAbs were screened for binding activity by enzyme-linked immunosorbent assay. Then, those mAbs, exhibiting potent affinity to recognize H7 HAs were further evaluated by hemagglutination-inhibiting (HAI) and microneutralization in vitro assays. Finally, the lead mAb candidate was selected and tested against the lethal challenge of the H7N9 virus using murine models.@*RESULTS@#The mAb 6-137 was able to recognize a panel of H7 HAs with high affinity but not HA of other subtypes, including H1N1 and H3N2. The mAb 6-137 can efficiently inhibit the HA activity in the inactivated H7N9 virus and neutralize 100 tissue culture infectious dose 50 (TCID50) of H7N9 virus (influenza A/Nanjing/1/2013) in vitro, with neutralizing activity as low as 78 ng/mL. In addition, the mAb 6-137 protected the mice against the lethal challenge of H7N9 prophylactically and therapeutically.@*CONCLUSION@#The mAb 6-137 could be an effective antibody as a prophylactic or therapeutic biological treatment for the H7N9 exposure or infection.

Questions and answers / Preguntas y respuestas

In which country did the first epidemic caused by the avian flu virus, known as severe acute respiratory syndrome (SARS) emerged.

¿En qué país surgió la primera epidemia causada por el virus de la gripe aviar, conocida como síndrome respiratorio agudo severo (SARS)

Molecular diagnosis of avian viruses in grassland passerines and captive yellow cardinals Gubernatrix cristata in Brazil / Diagnóstico molecular de vírus aviários em passeriformes campestres e cardeais-amarelos Gubernatrix cristata cativos no Brasil

Avian influenza viruses (AIVs), Newcastle disease virus (NDV), West Nile virus (WNV), adenovirus (AV) and herpesvirus (HV) play an important role in the health of human and animal populations. However, knowledge of the prevalence of these viruses in wild birds is restricted to some groups (e.g. shorebirds) or regions worldwide. Information on grassland birds of South America, which is essential for their conservation, is scarce. The objectives of the present study were to evaluate occurrences of AIV, NDV, WNV, AV and HV for the first time in a bird community of a unique protected area in southern Brazil, which is home for the critically endangered yellow cardinal (Gubernatrix cristata), and captive yellow cardinals from fauna maintainers of the Brazilian Captive Program of the Yellow Cardinal. Passerine species of wild life were caught, identified and samples (swabs) were collected from the oropharynx and cloaca of 64 passerines of 26 species (including 3 yellow cardinals) and 30 yellow cardinals of captive, for molecular diagnosis. The samples were subjected to RNA and DNA extraction and the real-time polymerase chain reaction (RT-PCR) for AIV, NDV and WNV and nested PCR for AV and HV. One yellow cardinal of captive presented a positive result for AV, this result is important for planning, managing natural attributes and making decisions in relation to integrated conservation of threatened species. This is the first report of AV in yellow cardinal and epidemiological investigation of viruses in wild passerines of the Pampa biome, in Rio Grande do Sul, Brazil.(AU)

Os vírus da gripe aviária (VGA), vírus da doença de Newcastle (VDN), vírus do Nilo Ocidental (VNO), adenovírus (AV) e herpesvírus (HV) desempenham um papel importante na saúde das populações humana e animal. No entanto, o conhecimento da prevalência desses vírus em aves selvagens é restrito a alguns grupos (por exemplo, aves limícolas) ou regiões em todo o mundo. As informações sobre as aves campestres da América do Sul, essenciais para a sua conservação, são escassas. Os objetivos do presente estudo foram avaliar a ocorrência de VGA, VDN, VNO, AV e HV pela primeira vez em uma comunidade de aves de uma área única protegida no Sul do Brasil, que abriga o cardeal-amarelo (Gubernatrix cristata) criticamente ameaçado de extinção e em cardeais-amarelos de cativeiro dos mantenedores de fauna do Programa Brasileiro de Cativeiro do Cardeal-amarelo. Espécies de passeriformes silvestres foram capturadas, identificadas e amostras (swabs) foram coletadas da orofaringe e cloaca de 64 passeriformes de 26 espécies (incluindo 3 cardeais-amarelos) e 30 cardeais-amarelos de cativeiro, para diagnóstico molecular. As amostras foram submetidas à extração de RNA e DNA e à reação em cadeia da polimerase em tempo real (RT-PCR) para VGA, VDN e VNO e nested PCR para AV e HV. Um cardeal-amarelo de cativeiro apresentou resultado positivo para AV, este resultado é importante para o planejamento, manejo dos atributos naturais e tomada de decisões em relação à conservação integrada de espécies ameaçadas. Este é o primeiro relato de AV em cardeal-amarelo e de investigação epidemiológica de vírus em passeriformes silvestres do bioma Pampa, no Rio Grande do Sul, Brasil.(AU)

Avian influenza A (H7N9) virus: from low pathogenic to highly pathogenic / 医学前沿

The avian influenza A (H7N9) virus is a zoonotic virus that is closely associated with live poultry markets. It has caused infections in humans in China since 2013. Five waves of the H7N9 influenza epidemic occurred in China between March 2013 and September 2017. H7N9 with low-pathogenicity dominated in the first four waves, whereas highly pathogenic H7N9 influenza emerged in poultry and spread to humans during the fifth wave, causing wide concern. Specialists and officials from China and other countries responded quickly, controlled the epidemic well thus far, and characterized the virus by using new technologies and surveillance tools that were made possible by their preparedness efforts. Here, we review the characteristics of the H7N9 viruses that were identified while controlling the spread of the disease. It was summarized and discussed from the perspectives of molecular epidemiology, clinical features, virulence and pathogenesis, receptor binding, T-cell responses, monoclonal antibody development, vaccine development, and disease burden. These data provide tools for minimizing the future threat of H7N9 and other emerging and re-emerging viruses, such as SARS-CoV-2.

Influenza A/H1N1 e COVID-19 no Brasil: impactos e diferenças epidemiológicas / Influenza A/H1N1 and COVID-19 in Brazil: epidemiological impacts and diferences / Influenza A/H1N1 y COVID-19 en Brasil: impactos epidemiológicos y diferencias

Justificativa e Objetivos: Em 2009, o Brasil enfrentou a pandemia de influenza A/H1N1pdm09 que infectou, pelo menos, 50 mil pessoas. Em 2020, enfrenta outra pandemia causada pelo vírus SARS-Cov-2 (COVID-19). Por se tratar de uma doença nova, há muita especulação sobre a mesma, assim como comparação com outros cenários, muitas vezes com base em informações falsas. Este estudo compara os impactos e diferenças epidemiológicas da Influenza A/H1N1 e COVID-19 no Brasil. Métodos: Estudo quantitativo, descritivo, epidemiológico, de base documental, cujos dados foram coletados nas plataformas de informação do Ministério da Saúde do Brasil e da Organização Mundial da Saúde, além de artigos científicos. Os dados sobre Influenza A/H1N1 referem-se ao ano de 2009 e os de COVID-19 ao período de março a 30 de abril de 2020. Resultados: Constata-se que no Brasil, em apenas dois meses, o número de casos da COVID-19 (85.380) já ultrapassou o total de casos de influenza A/H1N1pdm09 (50.482) ocorridos em todo o ano de 2009 e provocou o triplo de óbitos. Portanto, a COVID-19 apresenta-se de forma mais severa, dada as proporções alcançadas em letalidade, pela falta de vacina e tratamento específico dos casos. Conclusão: A pandemia da COVID-19 é mais impactante para o Brasil que a pandemia da influenza A/H1N1pdm09.(AU)

Background and Objectives: In 2009, Brazil faced the influenza A/H1N1pdm09 pandemic that infected at least 50 thousand people. In 2020, it faces another pandemic caused by the SARS-Cov-2 virus (COVID-19). Because it is a new disease, there is much speculation about it and comparison with other scenarios, often based on fake news. This study compares the impacts and epidemiological differences of Influenza A / H1N1 and COVID-19 in Brazil. Methods: Quantitative, descriptive, epidemiological study, based on documents, whose data were collected on the information platforms of the Ministry of Health of Brazil and the World Health Organization, in addition to scientific articles. The data on Influenza A/H1N1 refer to the year 2009 and the data on COVID-19 to the period from March to April 30, 2020. Results: It appears that in Brazil, in just two months the number of cases of COVID-19 (85,380) has already exceeded the total cases of influenza A/H1N1pdm09 (50,482) that occurred in the whole year of 2009 and caused a triple of deaths. Therefore, COVID-19 presents itself more severely, given the proportions reached in lethality, due to the lack of vaccine and specific treatment of cases. Conclusion: The COVID-19 pandemic is more impactful for Brazil than the influenza A/H1N1pdm09 pandemic.(AU)

Justificación y Objetivos: En 2009, Brasil se enfrentó a la pandemia de influenza A / H1N1pdm09 que infectó al menos a 50,000 personas. En 2020, se enfrenta a otra pandemia causada por el virus SARS-Cov-2 (COVID-19). Como se trata de una enfermedad nueva, se especula mucho y se compara con otros escenarios, a menudo basados en información falsa. Este estudio compara los impactos y las diferencias epidemiológicas de la Influenza A / H1N1 y COVID-19 en Brasil. Métodos: Estudio epidemiológico cuantitativo, descriptivo, basado en documentos, cuyos datos fueron recolectados en las plataformas de información del Ministerio de Salud de Brasil y de la Organización Mundial de la Salud, además de artículos científicos. Los datos sobre Influenza A / H1N1 se refieren al año 2009 y los datos sobre COVID-19 al período de marzo al 30 de abril de 2020. Resultados: Parece que en Brasil, en solo dos meses, el número de casos de COVID-19 (85,380) ya excedió el número total de casos de influenza A / H1N1pdm09 (50,482) que ocurrieron en todo el año de 2009 y causaron un triple de muertes. Por lo tanto, COVID-19 se presenta más severamente, dadas las proporciones alcanzadas en la letalidad, debido a la falta de vacuna y al tratamiento específico de los casos. Conclusión: La pandemia de COVID-19 es más impactante para Brasil que la pandemia de influenza A / H1N1pdm09.(AU)

Una revisión sistemática de los patógenos virales y bacterianos de aves silvestres en Chile / A systematic revision of viral and bacterial pathogens of free-ranging wild birds in Chile

Resumen El conocimiento acerca de agentes patógenos presentes en aves silvestres es crucial para la apropiada prevención de eventos de transmisión que puedan afectar a la salud pública y animal. Esta revisión sistemática organiza toda la información disponible acerca de los patógenos virales y bacterianos de las aves silvestres chilenas, determina qué patógenos y órdenes de aves han recibido atención reciente por parte de la comunidad científica local, evalúa cambios en la frecuencia de publicación de artículos e identifica brechas en el conocimiento respecto a estos patógenos. Un total de 35 artículos revisados por pares han sido publicados desde enero de 1941 hasta abril de 2019. Agentes virales fueron evaluados en 11 estudios, mientras que 24 concernieron a bacterias. Los artículos científicos se han publicado mayormente de forma discontinua en años previos al 2006. Salmonella spp. e influenza aviar han sido los patógenos más estudiados con 10 y 8 estudios, respectivamente. Las regiones de Los Ríos y Valparaíso concentran el mayor número de estudios y no se ha realizado investigación en las regiones de O'Higgins, Maule y Aysén. En general, la información acerca de patógenos en aves silvestres es escasa, por lo que es necesario incrementar los esfuerzos para identificar patógenos portados por reservorios aviares y evaluar el riesgo potencial que pueden representar para la conservación de fauna silvestre, producción animal y el sistema de salud pública en Chile.

Abstract Knowledge about pathogenic agents present in wild birds is pivotal to properly prevent transmission events that might threaten public and animal health. This systematic review organizes all information available about viral and bacterial pathogens of Chilean wild birds, determines which pathogens and avian orders have received attention from the local scientific community, evaluates changes in the frequency of article publication, and identifies gaps in knowledge regarding these pathogens. A total of 35 peer-reviewed publications have been published from January 1941 through April 2019. Viral agents were evaluated in 11 studies, while 24 involved bacteria. Article publication has been mostly discontinuous in years prior to 2006. Salmonella spp. and avian influenza have been the most studied pathogens with 10 and 8 studies, respectively. Los Ríos and Valparaíso regions concentrate the highest number of studies and no research has been carried out in O'Higgins, Maule, and Aysén regions. Overall, information about pathogens in wild birds is scarce, highlighting the need for increased effort to identify pathogens being carried by avian reservoirs and evaluate the potential threat that they might pose for wildlife conservation, animal production, and the public health system in Chile.

As Repercussões Históricas da Pandemia da Gripe Influenza A (H1N1) no Brasil / Las Repercusiones Históricas de la Pandemia de Gripe de la Influenza a (h1n1) de Brasil / The Historical Repercussions of the Influenza Pandemic a (h1n1) in Brazil

Introdução: A pandemia da gripe influenza A (H1N1) ocorrida em 2009 foi considerada a primeira do Século XXI com importantes consequências para a saúde pública mundial. Objetivo: Analisar as repercussões da pandemia da gripe influenza A (H1N1) no Brasil. Método: Trata-se de um estudo histórico-social, cujas fontes diretas utilizadas foram documentos escritos. Discussão e Resultados: As estratégias empreendidas evidenciadas foram implementadas pelo Ministério da Saúde para conter o avanço da doença no país. Entre essas a Carta Aberta, a Nota Técnica sobre Emergência de Saúde Pública de Importância Internacional e o Plano Brasileiro de Preparação para Enfrentamento de uma Pandemia de Influenza. Considerações Finais: Evidenciamos que as autoridades de saúde investiram na luta contra a pandemia no contexto das recomendações da Organização Mundial da Saúde e das demandas de saúde da população brasileira frente aos desafios provocados pela gripe influenza A (H1N1).

Introduction: The Influenza Pandemic type A(H1N1), which occured in 2009, was considered the first of the twenty-first century with important consequences for all the public health systems around the world. Objective: To analyze the implications of the influenza pandemic A H1N1 on the public health system in Brazil. Method: qualitative research, with a socio-historical approach based on direct sources which consisted of written documents. Discussion and Results: The evidenced strategies were implemented by the Ministry of Health to contain the progress of the disease in the country. Among these strategies were an Open Letter, a Technical Note on Public Health Emergency of International Concern e and the Brazilian Preparation Plan for Coping with Pandemic Influenza. Final Considerations: It has been demonstrated that the Health Authorities invested in the fight against the Pandemic, meeting the recommendations of the World Health Organization as well as the health demands of the Brazilian population in the face of the challenges which the H1N1 epidemic represented.

Introducción: La Pandemia de Influenza tipo A (H1N1) ocurrió en 2009, fue considerada la primera del Siglo XXI con importantes consecuencias para la salud pública mundial. Objetivo: Analizar las implicaciones de la pandemia de gripe influenza A H1N1 en Brasil. Método: Investigación cualitativa, con abordaje histórico-social, dónde utilizaron como fuentes directas documentos escritos. Discusión Resultados: El Ministerio de la Salud implementó las estrategias emprendidas evidenciadas para contener el progreso de la enfermedad en el país. Entre ellas está la Carta Abierta, la Nota Técnica sobre Emergencia de Salud Pública de Importancia Internacional y el Plan Brasileño para el Enfrentamiento de una Pandemia de Influenza. Consideraciones finales: Podemos evidenciar que las autoridades de salud invirtieron en la lucha contra la Pandemia estando en concordancia con las ecomendaciones de la Organización Mundial de la Salud y de las demandas de salud de la población brasileña frente a los desafíos que impuso la epidemia H1N1.

Evaluation of Immune Responses and Histopathological Effects against Gamma Irradiated Avian Influenza (Sub type H9N2) Vaccine on Broiler Chicken

Abstract Vaccination is a good strategy for the prevention of avian influenza virus. In this research Gamma Irradiated Avian Influenza (Sub type H9N2) Vaccine (GAIV) was prepared by 30 kGy irradiation and used for vaccination of broiler chickens. The purpose was a comparison of immune responses in the two routes of administration for the GAIV vaccine; intranasal and subcutaneously, use of Montanide ISA70 and Trehalose accompanied with irradiated vaccine and compare with formalin vaccine. The Influenza Virus A/Chicken/IRN/Ghazvin/2001/H9N2 was irradiated and used for vaccine formulation, and formalin inactivated AIV was used as conventional vaccine. Chickens were vaccinated by GAIV with and without Trehalose, GAIV and formalin vaccines with ISA70, two routes of administration were intranasal and subcutaneously. All the vaccinated chickens showed a significant increase in antibody titration. The most significant increase of antibody titration was in irradiated vaccine plus Trehalose groups intranasal and subcutaneously. After the first and second intranasal vaccination, the amount of IFN-gamma increased in the irradiated vaccine plus Trehalose group compared to other groups. However, most of the vaccinated groups did not show any significant increase of IFN-α concentration. Histopathological examination revealed lymphocyte infiltration (++), foci dispersed of hemorrhage and edema in intranasal vaccination groups and in addition to these, thickening of alveolar septa was observed in the injection groups. GAIV vaccine can be a good candidate for vaccine preparation, and Trehalose as a stabilizer protects viral antigenic proteins, also makes more absorbance of antigen by the inhalation route. In vaccinated chickens the ulcers in injected vaccines were lower than intranasal vaccines.

Hospitalizaciones y mortalidad asociada a influenza, Honduras. 2011-2015 / Hospitalizations and deaths associated with Influenza, Honduras. 2011-2015

La carga de enfermedad por influenza está bien documentada en países de clima templado, pero hasta la fecha en Honduras solo se ha realizado un estudio, siendo este el segundo con respecto a la carga médica asociada a influenza. Objetivo: Estimar el número de hospitalizaciones y defunciones, debidos a la influenza, como causante de las infecciones respiratorias agudas en la población. Material yMétodos: Se realizó un estudio descriptivo retrospectivo. Seutilizó tres fuentes de datos secundarias:registros de todos los egresos hospitalarios, resultados de detección viral por influenza y proyecciones de población por grupos de edad. Se estimó la tasa de incidencia y su intervalo de confianza al 95%, combinando las tres fuentes de datos. Resultados: Las hospitalizaciones en las infecciones respiratorias agudas graves (IRAG) J09-J18 asociadas a influenza en el 2011-2015 son mayores en los menores de cinco años, en donde las hospitalizaciones son mayores en los años 2013 con 68.2 (IC 95%: 64.2-72.1) casos por 100, 000 habitantes. En el periodo 2011-2015. Las tasas de incidencia en las defunciones de IRAG asociadas a influenza1.Doctor(a) en medicina y cirugía.2.Doctor(a) en Pediatría3.Nivel Básico de Epidemiologia de Campo del FETP4.MSc.Epidemiólogo del FETP, coordinador de las enfermedades Transmisibles de la unidad devigilancia de la salud, Secretaria de Salud de HondurasAutor de correspondencia: Hommer Mejía, homams2003@yahool.comRecibido: Aprobado: (J09-J18) fueron mayores en el año 2014 con 1 caso (IC 95%: 0.4-1.6) por 100 000 habitantes. La circulación por influenza comenzó a incrementarse a partir de agosto del 2011 luego en los años 2012-2015 con picos altos durante los meses de octubre y noviembre. Conclusión: La carga médica asociada a influenza representa un impacto para los servicios de salud de Honduras, siendo los grupos de población en edades extremas, los que más hospitalizaciones y muertes presentaron. Se sugiere promover la vacunación contra influenza con la composición de cepas circulantes en el país y en temporada apropiada, enfatizando en los grupos más vulnerables de la población...(AU)

Pacientes con Influenza A subtipo H3N2 y soporte ventilatorio durante el brote estacional en una central de emergencias en Argentina / Patients with Influenza A Subtype H3N2 and Ventilatory Support During A Seasonal Outbreak in an Emergency Department in Argentina

Objetivo: Describir las características de los pacientes con Influenza A subtipo H3N2 y requerimiento de soporte ventilatorio durante el brote del 2017, así como la evolución y los resultados clínicos. Materiales y métodos: Cohorte retrospectiva. Se incluyeron todos los pacientes con diagnóstico confirmado de H3N2 durante el mes de junio 2017 con requerimientos de asistencia respiratoria mecánica invasivo, no invasivo, terapia de alto flujo por cánula nasal y/o presión continua en la vía aérea que consultaron a la central de emergencias. Resultados: Se incluyeron 34 pacientes, 52.9% hombres, media de edad 81 (DE 10) años. Las principales comorbilidades de los pacientes al ingreso fueron: 73.5% hipertensión arterial, 44.1% enfermedad pulmonar obstructiva crónica y 76.5% insuficiencia cardíaca congestiva. La media del score de Charlson fue de 6 (DE 2), la mediana de APACHE II fue de 17 (IIC 14-20) y la de SOFA al día 1 de 5 (IIC 3-7). Al ingreso, 23 pacientes requirieron ventilación no invasiva, 5 presión continua en la vía aérea, 4 asistencia respiratoria mecánica invasiva y 2 terapia de alto flujo. Se registró un 47.8% (IC95% 26.8-69.4) de falla de la ventilación no invasiva y finalmente el 38.2% fueron intubados y ventilados mecánicamente. La mortalidad hospitalaria fue de 52.9% (IC95% 35.1-70.2). Conclusiones: se observó una alta mortalidad en una población añosa y comórbida durante el brote de H3N2. La mayoría realizó una prueba de ventilación no invasiva al ingreso, un alto porcentaje falló. El cuadro inicial pudo ser interpretado como enfermedad pulmonar obstructiva crónica reagudizada y/o insuficiencia cardíaca congestiva.

Patients with Influenza A Subtype H3N2 and Ventilatory Support During A Seasonal Outbreak in an Emergency Department in Argentina / Pacientes con Influenza A subtipo H3N2 y soporte ventilatorio durante el brote estacional en una central de emergencias en Argentina

Objective: To describe the characteristics of patients with influenza A subtype H3N2 requiring ventilatory support during the 2017 outbreak, as well as the evolution of the disease and clinical results. Materials and Methods: Retrospective cohort. We included all patients admitted to the Emergency Department with confirmed diagnosis of H3N2 during June 2017, requiring invasive or noninvasive mechanical respiratory assistance, high-flow nasal cannula treatment or continuous airway pressure. Results: 34 patients were included; 52.9% men, mean age 81 years (Standard Deviation [SD] 10). Main comorbidities of patients on admission were: 73.5% hypertension, 44.1% chronic obstructive pulmonary disease and 76.5% congestive heart failure. The mean Charlson Index score was 6 (SD 2), the APACHE II median (Acute Physiology and Chronic Health Evaluation II) was 17 (IQR 14-20) and the SOFA median (Sequential Organ Failure Assessment) on day 1 was 5 (IQR 3-7). On admission, 23 patients required noninvasive ventilation, 5 continuous positive airway pressure, 4 invasive mechanical ventilation and 2 high-flow nasal cannula therapy. The rate of noninvasive ventilation failure was 47.8% (95% CI [confidence interval] 26.8-69.4) and finally 38.2% of patients were intubated and mechanically ventilated. Hospital mortality was 52.9% (95% CI 35.1-70.2). Conclusions: A high mortality rate was observed among elderly patients with comorbidities during the H3N2 outbreak. Most patients underwent a noninvasive ventilation trial on admission, however a high percentage failed. The initial condition could have been interpreted as acute chronic obstructive pulmonary disease or congestive heart failure.

Características clínicas de pacientes pediátricos internados por Influenza A: comparación de dos subtipos virales (H1N1) y (H3N2) / Clinical characteristics of pediatric patients hospitalized due to Influenza A: comparison of two viral subtypes (H1N1 and H3N2)

Influenza is a respiratory disease ocasionated by influenza virus A and B. Is a disease with high morbi-mortality world-wide. Influenza produces an acute febrile respiratory illness with cough, headache and myalgias for 3-4 days, with simptoms that may persist for as long as 2 weeks. There are three types of influenza virsuses: A, B and C, of whom the type a has a higher ability to originate pandemias and is subclassified according to their surface antigens: hemaglutinine (H) and neuraminidase (N). Of the capacity of mutation that has the influenza virus and the consequent expression of different proteins, can modify its virulence. The transmission route is through direct contact with secretetory repirations. The transmission route is through direct contact with secretetory repirations. The incubation period is scant, between 12-72 hs. The aim of this study was to compare the clinical characteristics demographicals and evolutive of pediatric patients hospitalized because by Influenze A: subtypes H1N1 (pdm2009) and H3N2. An observative study was performed, retrospective, using data of hospitalizations of children during the years 2016 and 2017 with influenza A confirmed by laboratory. The study also, aimed to evaluate if the viral subtype constitutes a factor of risk, independent for complicated hospitalization (admission to intensive care and/or development of complications) in hospitalized children. The results obtained in the study are detailed in the paper. In conclusion, both viral subtypes affected mainly to children with risk factors. The viral subtype H1N1 was related with higher severety in hospitalized children. is of most importance to perform preventive works, specially in vulnerable groups, offering a good cover of immunizations. The clinical parameters arae commented (AU)

Aspectos clínicos de la infección por influenza en el Hospital Metropolitano de Quito, Ecuador, entre noviembre de 2017 y febrero 2018 / Clinical aspects of influenza infection at the Metropolitan Hospital of Quito, Ecuador, between November 2017 and February 2018

Introducción: la influenza es altamente contagiosa. Sus manifestaciones sintomáticas son variables; 10% presenta síntomas severos que pueden deberse a factores propios del huésped o a la cepa del virus. Objetivo: describir el perfil clínico del brote de influenza en un hospital privado de Quito-Ecuador. Materiales y métodos: estudio retrospectivo observacional en pacientes con influenza atendidos en los Servicios de Emergencia y Hospitalización del Hospital Metropolitano de Quito. Resultados: se registraron 422 casos de influenza. El síntoma más frecuente fue la tos (83%). 69,1% recibió oseltamivir, 26,5% fue tratado con oseltamivir y antibioticoterapia. 203 pacientes fueron hospitalizados (48,1%), de ellos 46,8% fueron menores de 5 años, 60% requirió aporte de oxígeno, la complicación más frecuente fue la neumonía (38,9%), 9 ingresaron a cuidados intensivos y 4 fallecieron. Conclusión: la influenza causa altas tasas de morbilidad y graves complicaciones.

Abstract: Background: Influenza is highly contagious. It presents variable clinical manifestations. 10% presents severe symptoms that can be due to factors associated with the infected individual as well as the virus strain. Objective: To describe clinical characteristics of influenza outbreak in a private hospital in Quito-Ecuador. Materials and methods: Retrospective observational study of patients with influenza who were admitted to Emergency and Hospitalization of Hospital Metropolitano of Quito. Results: 422 influenza cases were identified. The most frequent symptom was cough (83%). 69.1% was treated with oseltamivir and 26.5% with oseltamivir and antibiotics. 203 patients were hospitalized (48.1%), of which 46.8% were children less than 5 years of age. 60% required oxygen, the most frequent complication was pneumonia (38.9%). 9 patients were admitted to intensive care unit. 4 patients died. Conclusions: Influenza causes high morbidity rates and severe complications. Key words: influenza, complications, hospitalization

High expression and immunogenicity analysis of HA globular head domain of H5 subtype avian influenza virus produced in Pichia pastoris / 生物工程学报

To evaluate the immunogenicity of HA globular head domain of H5 subtype influenza virus (H5HA), the gene of H5HA was optimized and the recombinant pPICZaA-H5HA expressing vector was constructed and transfected into Pichia pastoris. The expression of the recombinant H5HA was confirmed by SDS-PAGE and Western blotting and the results demonstrated that the recombinant H5HA (37 kDa) was highly expressed in Pichia pastoris with concentration of 0.2 mg/mL in medium. The recombinant H5HA was concentrated and purified using Ni-NTA affinity chromatography. The immunogenicity of H5HA was evaluated by immunizing eight groups of chicken through intranasal or intramuscular injection with different doses of purified H5HA combined with different adjuvants, respectively. The results showed that the recombinant H5HA could induce high level IgG (HI titer was 1:64 and neutralizing antibody titer was 1:218) and the optimal dosage of the recombinant H5HA was 50 μg combined with oil. In addition, intramuscular injection was better than nasal immunization. This study provided a theoretical support for subunit vaccine development.