Influenza A não H1N1 associada à insuficiência respiratória e à insuficiência renal aguda em paciente com fibrose cística previamente vacinado / Influenza A non-H1N1 associated with acute respiratory failure and acute renal failure in a previously vaccinated cystic fibrosis patient

RESUMO No período sazonal compreendido entre 2014 e 2015, a maior parte das infecções por influenza decorreu do vírus influenza A H3N2. Mais de dois terços dos vírus influenza A H3N2 circulante eram antigênica e geneticamente diferentes (drift) do componente A H3N2 da vacina da influenza sazonal 2014 - 2015 para os hemisférios norte e sul. O objetivo deste trabalho foi relatar um caso de infecção por influenza A sazonal não H1N1 ocorrido em junho de 2015 em um paciente adulto com fibrose cística com doença pulmonar grave, previamente vacinado com a vacina antigripal trivalente. O paciente evoluiu com insuficiências respiratória e renal (sem rabdomiólise), sendo submetido à ventilação mecânica e à hemodiálise. A evolução clínica foi positiva após 39 dias de permanência hospitalar. Ainda, o paciente permaneceu clinicamente estável após seguimento de 18 meses. Com os avanços recentes na medicina intensiva e no tratamento, a sobrevivência com uma doença pulmonar avançada na fibrose cística apresenta novas questões e problemas potenciais, que ainda estão sendo formulados.

ABSTRACT In the 2014 - 2015 season, most influenza infections were due to A (H3N2) viruses. More than two-thirds of circulating A (H3N2) viruses are antigenically and genetically different (drifted) from the A (H3N2) vaccine component of 2014 - 2015 northern and southern Hemisphere seasonal influenza vaccines. The purpose of this paper is to report a case of seasonal influenza A non-H1N1 infection that occurred in June 2015 in an adult cystic fibrosis patient with severe lung disease previously vaccinated with the anti-flu trivalent vaccine. The patient evolved to respiratory and renal failure (without rhabdomyolysis) and was placed under mechanical ventilation and hemodialysis. The clinical outcome was positive after 39 days of hospital stay. In addition, the patient was clinically stable after 18 months of follow-up. With the recent advances in critical care medicine and in cystic fibrosis treatment, survival with advanced pulmonary disease in cystic fibrosis presents new questions and potential problems, which are still being formulated.

Detección serológica de Brucella suis, virus de influenza y virus de la enfermedad de Aujeszky en criaderos porcinos familiares de menos de 100 madres en Argentina / Serological detection of Brucella suis, influenza virus and Aujeszky's disease virus in backyard and small swine holders in Argentina

Los criaderos porcinos de menos de 100 madres representan más del 99% de los de todo el país; sin embargo, existen escasos reportes sobre su situación sanitaria y productiva. Se recabó información productiva y se tomaron muestras para detectar anticuerpos contra Brucella suis (Bs), virus de la enfermedad de Aujeszky (VA) y virus de influenza (VI) en 68 establecimientos de menos de 100 madres ubicados en la región norte, centro y sur del país. El 80% de los establecimientos fueron positivos al VI H1 pandémico 2009, el 11% al H3 clúster 2, mientras que el 11,7% presentó anticuerpos contra el VA y el 6% contra Bs. Ninguno de los productores conocía los factores de riesgo para la transmisión de enfermedades del cerdo al humano. El 47% compra sus reproductores a pares o en ferias. En lo que respecta a normas de bioseguridad, solo el 16% de los establecimientos tenía cerco perimetral y el 37% de las granjas contaba con asesoramiento veterinario. Los resultados de este estudio demuestran que la caracterización productiva y el relevamiento sanitario son de suma importancia para mejorar la productividad y reducir el riesgo de transmisión de enfermedades. El conocimiento de la situación sanitaria y de los factores de riesgo es necesario para conseguir un mejor control y la erradicación de enfermedades en sistemas de baja tecnificación. Se deberían llevar a cabo estudios más representativos a nivel país para detectar los agentes circulantes y, sobre la base de esta información, implementar medidas de prevención y control.

Farmers raising less than 100 sows represent more than 99% of swine producers in Argentina, although little is known about their sanitary status and productive characteristics in the country. Sanitary and productive information was obtained. Furthermore, samples for serological studies were taken to detect antibodies against Brucella suis (Bs), Aujeszky's disease virus (AV) and influenza virus (IV) in 68 backyard and small producers with less than 100 sows located in the north, central and south regions of Argentina. Antibodies against H1 pandemic were detected in 80% of the farms while 11%, 11.7% and 6.0% of the producers were positive to influenza H3 cluster 2, AV and Bs, respectively. None of the producers was aware of the risk factors concerning the transmission of diseases from pigs to humans. A percentage of 47% of them buy pigs for breeding from other farmers and markets. With regard to biosecurity measures, only 16% of the farms had perimeter fences. The results of this study demonstrate that productive characterization and disease surveys are important to improve productivity and to reduce the risk of disease transmission among animals and humans. The study of sanitary status and risk factors is necessary for better control and eradication of diseases in backyard or small producers. More representative studies at country level should be carried out to detect the pathogensthat circulate and, with this knowledge, to implement prevention and control measures.

Characterization of influenza outbreaks in Lebanon during the 2013/14 and 2014/15 seasons

Despite the significant burden of influenza outbreaks, active disease monitoring has been largely absent in the Middle East, including Lebanon. In this study we characterized influenza virus in 440 nasopharyngeal swabs collected from patients with acute respiratory infections during two influenza seasons in Lebanon. Influenza A[H3N2] was dominant in the 2013/14 season while the A[H1N1]pdm09 and B/Yamagata strains were most prevalent in the 2014/15 season. All tested isolates were susceptible to 4 neuraminidase inhibitors [oseltamivir, zanamivir, peramivir and laninamivir]. Genetic analysis of the haemagglutinin gene revealed multiple introductions of influenza viruses into Lebanon from different geographic sources during each season. Additionally, large data gaps were identified in the Middle East region, as indicated by the lack of current influenza sequences in the database from many countries in the region

Guia para a Rede Laboratorial de Vigilância de influenza no Brasil / Guide for the Influenza Surveillance Laboratory Network in Brazil

A gripe ou influenza é uma doença infectocontagiosa aguda do trato respiratório, de distribuição global, causada pelo vírus da influenza. Pessoas de todas as idades são susceptíveis a infecção por estes vírus, entretanto, idosos, crianças, gestantes e pessoas com algumas comorbidades (cardiopatas, pneumopatas, hipertensos, diabéticos, obesos mórbidos, entre outros) possuem um risco maior de desenvolver complicações devido à infecção por influenza, responsável por cerca de meio milhão de óbitos anuais em todo o mundo (WORLD HEALTH ORGANIZATION, 2014). Os vírus da influenza pertencem à família Orthomyxoviridae e possuem genoma de RNA segmentado. Há três tipos de vírus da influenza: A, B e C. O vírus da influenza do tipo C está frequentemente associado a infecções respiratórias brandas, com pouco impacto na saúde pública e não está relacionado com epidemias. Os vírus da influenza tipos A e B são responsáveis por epidemias anuais, sendo os vírus da influenza tipo A os responsáveis pelas grandes pandemias. Os vírus da influenza do tipo A são classificados em subtipos de acordo com as diferenças antigênicas das glicoproteínas de superfície, hemaglutinina (HA) e neuraminidase (NA). A proteína HA está associada ao reconhecimento e à infecção das células do trato respiratório, onde o vírus se multiplica; enquanto a proteína NA está envolvida na liberação das partículas virais da superfície das células infectadas (Figura 1). Até o momento, todos os 18 subtipos de HA e 11 de NA descritos foram identificados em aves (exceto H17 e 18, identificados em morcegos), alguns destes afetando também mamíferos (TONG et al., 2013). Entre estes, os subtipos A(H1N1) pdm09 e A(H3N2) circulam amplamente na população humana. Alguns vírus da influenza do tipo A de origem aviária também podem infectar humanos causando doença grave, como no caso do A(H5N1) e A(H7N9).

Influenza virus surveillance among young children in São Paulo, Brazil: the impact of vaccination

This study assessed the presence of influenza virus among young children and the coverage of vaccination from 2010 to 2012 in São Paulo, Brazil. Our results demonstrated a lower rate of influenza detection and a predominance of influenza B. A decrease of coverage vaccination through the surveillance periods was observed.

Influenza: evolución a cuatro años de la pandemia: Hospital Nacional Profesor Alejandro Posadas, Argentina / Influenza: A four-year evolution of the pandemic: Prof. Alejandro Posadas National Hospital, Argentina

En el Hospital Nacional Profesor Alejandro Posadas se estudiaron la incidencia de influenza, las características de casos y tipos y subtipos de virus circulantes de enero a agosto de 2013 inclusive, semanas epidemiológicas (SE) 1-35, y se compararon con los años 2009-2012. De fin de mayo a agosto inclusive de 2013 (SE 18 a 35) se observó un aumento del porcentaje de consulta por enfermedades respiratorias, enfermedad tipo influenza e internación por neumonía y se diagnosticaron 207 casos: 153 influenza A (FLU-A)(H1N1pdm09), 46 A(H3), ocho A(sin subtipificar). La mayor frecuencia fue en menores de 5 años, seguida por el grupo de 60 a 64.La chance de tener la enfermedad fue tres veces mayor en el grupo de 40-64 años versus 15-39 o > 64 años. La letalidad, que aumentó con la edad, fue de 7.2% y la chance de morir fue seis veces mayor en los > 64 años. El porcentaje de vacunación entre los casos fue11.6%. Ninguno de los fallecidos estaba vacunado. Luego de la pandemia de 2009 el porcentaje de consultas anuales disminuyó hasta 2012, con un aumento en el período invernal de 2013 de 52.0% con respecto a 2012. La circulación viral en 2013 fue más temprana que en los años anteriores. En 2009 y 2013 la mayor circulación fue FLU-A (H1N1pdm), en 2011 FLU-A(H3) y en 2010 y 2012 FLU-A(H3) y FLU-B.

As from January to August 2013, epidemiological weeks 1-35 (EW), Influenza incidence, case characteristics, types and subtypes of circulating influenza virus in the Nacional Profesor Alejandro Posadas Hospital were studied, and were compared to incidences during 2009-2012. From late May to the end of August 2013 (EW18-35), an increase was observed in the proportion of patients' visits for respiratory disease, influenza-like illness and hospitalizations due to pneumonia; of 207 cases diagnosed with influenza A virus, 153 were infected by H1N1pdm09, 46 by H3, and eight without subtype. The highest proportion of cases was found in children under five years of age, followed by the group 60-64.The chances of having the illness were three times greater among the group 40-64 years old compared to 15-39 or those older than 64. Mortality, which increased with age, was 7.2%, and the odds of death were six times higher among those older than 64. Vaccination rate among the cases was 11.6%. None of the fatal cases had received the vaccine. After the 2009 pandemic, the proportions of annual patients´ visits decreased until 2012; in 2013, an increase of 52.0% during the winter period compared to 2012. The viral circulation started earlier in 2013 compared to previous years. FLU-A(H1N1pdm) was the predominant circulating virus in 2009 and 2013, FLU-A(H3) in 2011, FLU-A(H3) and FLU-B in both 2010 and 2012.

BinaxNOW® - An immunochromatographic test for the diagnosis of human influenza viruses: Comparison with viral culture and polymerase chain reaction.

Purpose: A rapid test for influenza viruses (Binax NOW® ) was evaluated. Materials and Methods: In season-1, 35 respiratory samples were tested retrospectively; in season-2, 45 samples were tested prospectively [gold-standard: viral culture in season-1, culture+ reverse transcriptase-polymerase chain reaction (RT-PCR) in season-2]. Results: Sensitivity for Binax for influenza A was 59.3 and 0% in season-1 and -2, respectively. Sensitivity was low for influenza B (33.3% in season-1, 26.1% in season-2). Samples having low viral load were more likely to have a negative Binax test. Specificity of Binax was high (100 and 94.7% with influenza A and B, respectively). Conclusion: Sensitivity information provided in the kit insert does not always reflect post licensure performance in clinical settings.

Respiratory viruses in acute respiratory tract infections in Western India.

OBJECTIVE: To study the circulation pattern of respiratory viruses in out patients department (OPD) and hospitalized children with acute respiratory tract infection. METHODS: Nasopharyngeal aspirates were collected from 385 children with acute respiratory tract infections attending the OPD (n=199, 51.7%) and admitted to pediatric ward (n=186, 43.2%). Specimens were screened for seven respiratory viruses by immunofluoresence test (IFT) using Respiratory panel 1 screening and identification kit. RESULTS: Viral antigens were detected in 57 (28.6%) and 86 (46.2%) patients from OPD and admitted cases respectively, giving an overall positivity of 143 (37.1%) for respiratory viruses. Of the six respiratory viruses, the most common was respiratory syncytial virus (RSV) in 100 (26%) patients, followed by influenza viruses in 21 (5.4%), parainfluenza in 8 (2.07%), adenovirus in 3 (0.8%). One patient had mixed infection of RSV and adenovirus. RSV was most frequently detected in the hospitalized children (39.8%). CONCLUSION: RSV appeared to be the most common respiratory viral infection in the age group 0-1 year causing hospitalization.

EMRO NICs participate in composition of influenza virus vaccines, 2008-2009

During the last three years [2005-2007], National Influenza Centre [NIC], Egypt isolated a total of 109 influenza viruses out of 3,979 specimens collected [a positivity rate of 2.7 %]. The predominant influenza virus strain was Flu B [N=95, 87.2%]. Influenza A [H3N2] constitued 11% [12 isolates] and influenza A [H1N1] constituted 1.8% [2 isolates only]. The NIC, Morocco, isolated influenza viruses in 98 [8.8%] out of 1,120 specimens tested. Isolated viruses included 64 [65.3%] isolates of influenza A [H3N2], 27 [27.6%] of A [H1N1] and 7 [7.1%] of Flu B. The NIC, Oman isolated 11 influenza viruses out of 195 specimens [5.6% positivity rate]: 7 [63.6%] were influenza B and 4 [36.4%] were influenza A [H3N2]

Co-infection between influenza virus and flagellated bacteria

Tripsina é necessária na ativação da clivagem do vírus influenza A in vitro. Esta clivagem é importante para entrada do vírus na célula por endocitose mediada pelo receptor celular. Bactérias presentes no trato respiratório são fontes de proteases que podem contribuir na replicação do vírus influenza in vivo. Entre 47 amostras coletadas de cavalos, suínos e humanos, a influenza foi isolada e confirmada em 13 que estavam co-infectadas com bactéria flagelada: Stenotrophomonas maltophilia desde o início destes experimentos. Apesar do tratamento das amostras com antibióticos, as bactérias resistiram em diversas delas (48.39%). A protease (elastase), secretada pela Stenotrophomonas maltophilia, desenvolveu papel decisivo na potencialização da infecção pelo vírus influenza. Essa atividade proteolítica foi detectada pelo teste de ágar-caseína. Amostras positivas para o vírus influenza isolado em animais, bem como em humanos tiveram potencialização da infectividade (ECP) em células MDCK e NCI-H292, sempre que a Stenotrophomonas maltophilia esteve presente. Os referidos microorganismos, bactéria e vírus foram observados ultra-estruturalmente. Esses achados in vitro demonstram como complicações respiratórias podem ocorrer in vivo, através da contribuição de protease microbiana, provocando aumento da inflamação ou destruição dos inibidores celulares de proteases endógenas, nos hospedeiros susceptíveis à influenza.

Isolation and identification of influenza virus strains circulating in Thailand in 2001.

Local influenza surveillance plays an important role in preparing for, and responding to, epidemics and pandemics. Between January and December 2001, the National Institute of Health of Thailand collected a total of 711 throat swab specimens from outpatients affected with acute respiratory symptoms from several centers throughout Thailand, of which 374 were virus-positive. Of these, 338 (90.4%) were positive for influenza virus by immunofluorescence testing. By hemagglutination-inhibition (HI) testing, 155 of the type A viruses were found to be subtype H1N1 strains closely related to A/New Caledonia/20/99, and 70 were subtype H3N2 A/Moscow/ 10/99-like viruses. For type B, the isolates were antigenically B/Sichuan/379/9-like by HI, although a number of the strains could be shown to be more closely related to earlier influenza B strains by genetic analysis. The strains circulating in Thailand were antigenically similar to strains isolated worldwide during the same period and to strains recommended by the WHO for inclusion in the vaccines for use in 2001-2002.

Vigilancia sistemática de virus influenza, respiratorio sincicial, parainfluenza y adenovirus en niños ambulatorios con infecciones respiratorias agudas / Systematic surveillance of influenza, syncytial respiratory, parainfluenza and adenovirus in ambulatory children with acute respiratory infections

Background: The efficacy of influenza vaccination programs depends on the antigenic similitude between vaccine and the influenza virus circulating in the community. Therefore the surveillance of clinical activity and antigenic features of influenza virus is of utmost importance. Aim: To perform a systematic surveillance of clinical activity and antigenic characteristics of influenza virus. Material and methods: Since 1996 and during the cold months (may to september), 20 samples of upper respiratory secretions per week, were obtained from children with acute respiratory infections consulting to the emergency room of a public hospital. Using indirect immunofluorescence and cellular cultures, the presence of influenza, syncytial respiratory, parainfluenza and adenovirus was assessed. The weekly number of consultations in the emergency room and the number of hospital discharges due to acute respiratory infections, were registered. Results: Influenza and syncytial respiratory were the predominant virus detected since 1996. In 1996 and 1998, the weekly detection of influenza virus followed a single seasonal curve. The maximal weekly positively results reached 85 and 80 percent of the obtained samples, respectively. During 1997, two curves of influenza virus activity were observed, but none reached more than 50 percent of weekly positive samples. The demand for outpatient care evolved in parallel to the weekly detection of influenza virus. The hospital discharges due to acute respiratory infections paralleled the syncytial respiratory virus detection rates. Conclusions: This surveillance model is effective for the detection of influenza and other virus responsible for acute respiratory infections and their relationship with the demand for health care during the cold months

Evaluation of WHO monoclonal antibody kit for diagnosis of acute respiratory viral infections.

In 1990 and 1991, six laboratories located in the WHO Western Pacific Region (WPR) and South East Asian Region (SEAR) were selected, based on their experience in the immunofluorescence antibody technique (IFAT), to participate in the evaluation of a WHO monoclonal antibody (Mab) kit to detect respiratory syncytial (RS) virus, influenza A virus, influenza B virus, parainfluenza virus and adenovirus. Despite differences in the initial standardization procedures, the WHO monoclonal antibodies were found to be of high quality, sensitivity and specificity when tested on clinical specimens. The constant supply of affordable high quality reagents from WHO would enable their use in clinical virological laboratories in the developing countries as well as promote the utilization of IFAT as an adjunct to cell culture isolation in the diagnosis of acute respiratory viral infections.

Actividad del virus de influenza humana en Medellín, Colombia, 1990-1993

Para determinar el virus de influenza en Medellín y contribuir al programa de la Organización Mundial de la Salud (OMS), sobre la investigación de esta enfermedad, se realizó entre 1990-1993 un estudio serológico y virológico en población sana y en pacientes con infección respiratoria aguda (IRA), respectivamente. En 1991 y 1992 se detectó un aumento en el porcentaje de individuos con anticuerpos contra el virus A/Taiwan/1/86 (H1N1). Este porcentaje disminuyó en el año 1993, pero en este mismo año se presentó el mayor número de individuos con anticuerpos contra otras dos cepas del mismo tipo viral: A/Sichuan/2/87 (HGRX -97) y A/Shangai/16/89 (H3N2). También en los primeros meses de 1993 se encontró un porcentaje de individuos sanos con anticuerpos contra el virus A/Beijing/353/89 (H3N2), algo no detectado en el año anterior. Igualmente en el mes de enero de 1993 se aisló un virus A/Beijing/353/89, semejante al que circuló en Estados Unidos en 1992 y 1993. Para el virus de influenza tipo B, no se hallaron anticuerpos contra las cepas estudiadas: B/Victoria/2/87 y B/Panamá/45/90. No se descarta la posibilidad de que haya circulado otra cepa B diferente, que no pudo ser detectado. También se incluyó la búsqueda de anticuerpos contra virus de influenza humana, en cerdos post-infección respiratoria aguda; los resultados fueron negativos. El presente estudio nos muestra la circulación reciente, en muestro medio,de varias cepas de influenza tipo A

Comparative evaluation of a simple and sensitive assay for detection of orthomyxo and paramyxoviruses

Studies were done to evaluate comparatively the traditional HA assay and a more recently introduced lectin-neuraminidase (LN) methodologyin search of a simple and sensitive assay for virus detection during laboratorial diagnosis. The results proved the value of LN assay as a sensitive methodologyfor detection of virus particles, presenting results at least equal to those obtained by HA (hemagglutination) assay, with significant values of accumulated frequencies for LN/HA factors (ratios between LN and HA titers) higher than two. The accumulated values of frequencies for LN/HA factors as high as four were very significant, 72.7 (per cent) for influenzavirus and 60.7 (per cent) for Newcastle disease virus (NDV), moreover accumulated frequencies for LN/HA factors even as high as 32 were due to influenzavirus (45.4 per cent) and NDV (7.2 per cent) samples. After the storage period, most of those concentraded samples that even did not present HA titers could be detected through LN assay, demonstrating a lower threshold for virus detection

Myxo and paramyxovirus surface structures: antigenic and functional studies

Amostras de vírus da Doença de Newcastle (cepas SO-93, B1 e La Sota) e da Influenza (cepa A/PR/8/34 (H1N1) foram analisadas especificamente quanto à presença de carboidratos específicos, de comprovada importância no processamento das atividades biológicas virais. As amostras virais foram concentradas por sedimentaçäo, avaliadas quanto ao seu teor proteico e título hemaglutinante e, entäo, estudadas quanto aos seus resíduos carboidratos. O estudo realizado com uso de lectinas e açúcar específico (inibidor de Concanavalina A) revelou a importância e especificidade do caráter carboidratado de estruturas peptídicas de superfície viral, o que pode ser observado através da inibiçäo do aparecimento das linhas de precipitaçäo entre Concanavalina A e soro específico para vírus da Doença de Newcastle

Detección de antígenos virales en lactantes con infección respiratoria aguda baja / Viral antigens in nasopharingeal exudates from infants with acute lower respiratory tract infections

Con el propósito de medir la frecuencia con que se aíslan determinados antígenos virales, en niños con infecciones respiratorias agudas bajas graves (IRAB), se realizaron ensayos de inmunofluorescencia (IF) para antígenos de virus sincicial respiratorio (VSR), adenovirus (ADV), virus parainfluenza 1, 2 y 3 (VPI), virus influenza a y b (VIa y VIb) en las secreciones nasofaríngeas de 660 niños menores de 24 meses que cumplían con criterios clínicos y radiológicos de IRAB grave comúnmente aceptados. En 322 casos (48,8%) se obtubvieron resultados positivos. Los antígenos más frecuentemente identificados fueron los de VSR (56,2%) y ADV (26,7%). La letalidad en niños con IRAB e IF positiva fue 9,9% y 6,2% en aquellos con IF negativa (p NS). En 24 de 32 (75%) pacientes fallecidos con IF positivas, el antígeno identificado correspondía a ADV, siendo el riesgo de morir en estos casos significativamente mayor que en el de pacientes portadores de otros antígenos o ninguno (Z crítico -1,65. Z calculado -1,178). La apnea fue la principal manifestación clínica en 46 pacientes, todos menores de 3 meses y 19 con reacciones de inmunofluorescencia positivas que, con una sola excepción, correspondían a antígenos de VSR