Pregnancy as a risk factor for severe influenza infection: an individual participant data meta-analysis

Background: WHO identifies pregnant women to be at increased risk for severe outcomes from influenza virus infections and recommends that they be prioritized for influenza vaccination. The evidence supporting this, however, is inconsistent. Ecologic studies in particular suggest more severe outcomes from influenza infection during pregnancy than studies based on individual patient data. Individual studies however may be underpowered and, as reported in a previous systematic review, confounding factors could not be adjusted for. We therefore conducted an individual participant data meta-analysis to assess the risk for severe outcomes of influenza infection in pregnant women while adjusting for other prognostic factors. Methods: We contacted authors of studies included in a recently published systematic review. We pooled the individual participant data of women of reproductive age and laboratory confirmation of influenza virus infection. We used a generalized linear mixed model and reported odds ratios (OR) and 95% confidence intervals (CI). Results: A total of 33 datasets with data on 186,656 individuals were available, including 36,498 eligible women of reproductive age and known pregnancy status. In the multivariable model, pregnancy was associated with a 7 times higher risk of hospital admission (OR 6.80, 95%CI 6.02–7.68), among patients receiving medical care as in- or outpatients, pregnancy was associated with a lower risk of admission to intensive care units (ICU; OR 0.57, 95%CI 0.48–0.69), and was not significantly associated with death (OR 1.00, 95%CI 0.75–1.34). Conclusions: Our study found a higher risk of influenza associated hospitalization among pregnant women as compared to non-pregnant women. We did not find a higher mortality rate or higher likelihood of ICU admission among pregnant women who sought medical care. However, this study did not address whether a true community based cohort of pregnant women is at higher risk of influenza associated complications.Fil: Mertz, Dominik. Mc Master University; CanadáFil: Lo, Calvin Ka Fung. Mc Master University; CanadáFil: Lytvyn, Lyubov. Mc Master University; CanadáFil: Ortiz, Justin R.. Organizacion Mundial de la Salud; ArgentinaFil: Loeb, Mark. Mc Master University; CanadáFil: Ang, Li Wei. Ministry of Health; SingapurFil: Anlikumar, Mehta Asmita. Amrita Vishwa Vidyapeetham; IndiaFil: Bonmarin, Isabelle. Santé publique; FranciaFil: Borja Aburto, Victor Hugo. Instituto Mexicano del Seguro Social; MéxicoFil: Burgmann, Heinz. Medical University Vienna; AustriaFil: Carratalà, Jordi. Universidad de Barcelona; España. Instituto de Investigación Biomédica de Bellvitge; España. Spanish Network for Research in Infectious Diseases; EspañaFil: Chowell, Gerardo. Georgia State University; Estados Unidos. National Institutes of Health; Estados UnidosFil: Cilloniz, Catia. Universidad de Barcelona; España. Instituto de Investigaciones Biomédicas August Pi i Sunyer; EspañaFil: Cohen, Jessica. Centers for Disease Control and Prevention; Estados UnidosFil: Cutter, Jeffery. Ministry of Health; SingapurFil: Filleul, Laurent. Santé publique; Francia. French National Public Health Agency; FranciaFil: Garg, Shikha. Centers for Disease Control and Prevention; Estados UnidosFil: Geis, Steffen. London School of Hygiene and Tropical Medicine; Reino UnidoFil: Helferty, Melissa. Public Health Agency; CanadáFil: Huang, Wan Ting. Taiwan Centers for Disease Control; ChinaFil: Jain, Seema. Centers for Disease Control and Prevention; Estados UnidosFil: Sevic, Biljana Joves. Institute for Pulmonary Diseases of Vojvodina; SerbiaFil: Kelly, Paul. Australian Capital Territory Health Directorate; Australia. Australian National University Medical School; AustraliaFil: Kusznierz, Gabriela. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorios e Instituto de Salud "Dr. C. G. Malbran". Instituto Nacional de Enfermedades Respiratorias; ArgentinaFil: Lehners, Nicola. Ruprecht Karls Universitat Heidelberg; AlemaniaFil: Lenzi, Luana. Universidade Federal do Paraná; BrasilFil: Ling, Ivan T.. Sir Charles Gairdner Hospital; AustraliaFil: Mitchell, Robyn. Public Health Agency; CanadáFil: Mulrennan, Siobhain A.. Sir Charles Gairdner Hospital; Canadá. University of Western Australia; AustraliaFil: Nishioka, Sergio A.. Ministerio de Salud de Brasil; BrasilFil: Norton, Robert. Townsville Hospital; AustraliaFil: Oh, Won Sup. Kangwon National University School of Medicine; Corea del SurFil: Orellano, Pablo Wenceslao. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

an individual participant data meta-analysis

Background The impact of neuraminidase inhibitors (NAIs) on influenza-related pneumonia (IRP) is not established. Our objective was to investigate the association between NAI treatment and IRP incidence and outcomes in patients hospitalised with A(H1N1)pdm09 virus infection. Methods A worldwide meta- analysis of individual participant data from 20 634 hospitalised patients with laboratory-confirmed A(H1N1)pdm09 (n = 20 021) or clinically diagnosed (n = 613) ‘pandemic influenza’. The primary outcome was radiologically confirmed IRP. Odds ratios (OR) were estimated using generalised linear mixed modelling, adjusting for NAI treatment propensity, antibiotics and corticosteroids. Results Of 20 634 included participants, 5978 (29·0%) had IRP; conversely, 3349 (16·2%) had confirmed the absence of radiographic pneumonia (the comparator). Early NAI treatment (within 2 days of symptom onset) versus no NAI was not significantly associated with IRP [adj. OR 0·83 (95% CI 0·64–1·06; P = 0·136)]. Among the 5978 patients with IRP, early NAI treatment versus none did not impact on mortality [adj. OR = 0·72 (0·44–1·17; P = 0·180)] or likelihood of requiring ventilatory support [adj. OR = 1·17 (0·71–1·92; P = 0·537)], but early treatment versus later significantly reduced mortality [adj. OR = 0·70 (0·55–0·88; P = 0·003)] and likelihood of requiring ventilatory support [adj. OR = 0·68 (0·54–0·85; P = 0·001)]. Conclusions Early NAI treatment of patients hospitalised with A(H1N1)pdm09 virus infection versus no treatment did not reduce the likelihood of IRP. However, in patients who developed IRP, early NAI treatment versus later reduced the likelihood of mortality and needing ventilatory support

Impact of neuraminidase inhibitors on influenza A(H1N1)pdm09‐related pneumonia: an individual participant data meta‐analysis

BACKGROUND: The impact of neuraminidase inhibitors (NAIs) on influenza‐related pneumonia (IRP) is not established. Our objective was to investigate the association between NAI treatment and IRP incidence and outcomes in patients hospitalised with A(H1N1)pdm09 virus infection. METHODS: A worldwide meta‐analysis of individual participant data from 20 634 hospitalised patients with laboratory‐confirmed A(H1N1)pdm09 (n = 20 021) or clinically diagnosed (n = 613) ‘pandemic influenza’. The primary outcome was radiologically confirmed IRP. Odds ratios (OR) were estimated using generalised linear mixed modelling, adjusting for NAI treatment propensity, antibiotics and corticosteroids. RESULTS: Of 20 634 included participants, 5978 (29·0%) had IRP; conversely, 3349 (16·2%) had confirmed the absence of radiographic pneumonia (the comparator). Early NAI treatment (within 2 days of symptom onset) versus no NAI was not significantly associated with IRP [adj. OR 0·83 (95% CI 0·64–1·06; P = 0·136)]. Among the 5978 patients with IRP, early NAI treatment versus none did not impact on mortality [adj. OR = 0·72 (0·44–1·17; P = 0·180)] or likelihood of requiring ventilatory support [adj. OR = 1·17 (0·71–1·92; P = 0·537)], but early treatment versus later significantly reduced mortality [adj. OR = 0·70 (0·55–0·88; P = 0·003)] and likelihood of requiring ventilatory support [adj. OR = 0·68 (0·54–0·85; P = 0·001)]. CONCLUSIONS: Early NAI treatment of patients hospitalised with A(H1N1)pdm09 virus infection versus no treatment did not reduce the likelihood of IRP. However, in patients who developed IRP, early NAI treatment versus later reduced the likelihood of mortality and needing ventilatory support

Neuraminidase Inhibitors and Hospital Length of Stay: A Meta-analysis of Individual Participant Data to Determine Treatment Effectiveness Among Patients Hospitalized With Nonfatal 2009 Pandemic Influenza A(H1N1) Virus Infection

© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: [email protected]. BACKGROUND: The effect of neuraminidase inhibitor (NAI) treatment on length of stay (LoS) in patients hospitalized with influenza is unclear. METHODS: We conducted a one-stage individual participant data (IPD) meta-analysis exploring the association between NAI treatment and LoS in patients hospitalized with 2009 influenza A(H1N1) virus (A[H1N1]pdm09) infection. Using mixed-effects negative binomial regression and adjusting for the propensity to receive NAI, antibiotic, and corticosteroid treatment, we calculated incidence rate ratios (IRRs) and 95% confidence intervals (CIs). Patients with a LoS o

Acute respiratory infection by adenoviruses in children hospitalized in Santa Fe

Fil: Rusznierz, Gabriela F. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Respiratorias; Argentina.Fil: Cociglio, Raquel. Hospital de Niños “Orlando Alassia”; Argentina.Fil: Pierini, Judith. Hospital “J.B. Iturraspe”; Argentina.Fil: Malatini, María I. Hospital “J.B. Iturraspe”; Argentina.Fil: Walker, Analía. Clínica de Niños Rafaela, Santa Fe; Argentina.Fil: Millán Alejandra. Hospital de Niños “Orlando Alassia”; Argentina.RESUMEN Introducción. Los adenovirus (Ads), son agentes etiológicos importantes de la infección respiratoria aguda (IRA). El Ad7 se asocia con las manifestaciones clínicas de mayor gravedad. Objetivos. Describir los aspectos clínicos y epidemiológicos de las IRA por Ads en niños hospitalizados en la Provincia de Santa Fe, durante el período 1998-2001. Población, material y métodos. Se evaluaron 31 historias clínicas de pacientes hospitalizados con diagnóstico de IRA en hospitales de Santa Fe y se registraron datos demográficos, clínicos, radiológicos y de tratamiento. La infección por Ads se documentó mediante inmunofluorescencia indirecta. Los Ads se aislaron en células Hep-2, a partir de aspirados nasofaríngeos y se caracterizaron por PCR. Resultados. Se encontró un predominio de adenovirus subespecie B:1 (25/29), de los cuales 24 fueron Ad7. El Ad7 se asoció a neumonías mientras que Ads de las especies C (3/29) y D (1/29) encontrados en baja proporción se relacionaron con cuadros leves de bronquitis y catarro de vías aéreas superiores. Los niños menores de 1 año fueron el grupo más comunmente afectado. La estadía hospitalaria y el tratamiento con oxígeno fue mayor de 8 días en 17/ 31 y 14/22, respectivamente. Once niños desarrollaron neumonías graves, que requirieron cuidados intensivos y asistencia respiratoria (4/11). Dos casos desarrollaron miocarditis y uno hepatitis. La mortalidad fue del 9,7% (3/31) asociada a Ad7. Conclusión. Este estudio aporta un mejor conocimiento acerca de la clínica y los serotipos de los adenovirus causantes de IRA en niños, más prevalentes en una provincia del interior del país. La edad temprana de los niños, las estadías hospitalarias prolongadas y la gravedad del cuadro clínico hacen necesario implementar estrategias de control y prevención. (EN) SUMMARY Introduction. Adenovirus are (Ads) an important etiologic agent of acute respiratory infections (ARI). Ad7 has been associated with clinical manifestations of most considerable severity. Objective. The aim of this study was to describe the clinical and epidemiologic aspects of the ARI by Ads in hospitalized patients in Santa Fe, Argentina during 1998-2001. Population, material and methods. We conducted a retrospective study. Medical charts of 31 patients with ARI admitted in hospitals in Santa Fe were examined. Demographic information, as well as the radiographic and clinical outcome, were captured on special forms. Infections by Ads were documented by indirect immunonofluorescence. Ads were isolated in Hep2-cell cultures from nasopharyngeal aspirates. The molecular characterization was performed by PCR. Results. During the study period there was a predominance of subspecies B:1 (25/29), 24 was Ad7. The Ad7 was associated with pneumonia whereas the adenovirus species C(3/29) y D (1/29) were associated with mild bronchitis and upper respiratory tract catarrh. Children less than one year of age were the most common age group affected. The duration of oxygen treatment and hospital stay was 8 days in the 14/22 y 17/31 of the children studied, respectively. Eleven of thirty-one children developed a severe pneumonia, requiring intensive care and mechanical respiratory assistance (4/11). Two cases developed miocarditis and hepatitis. Among all cases included the mortality was 9.7% (3/31) associated with Ad7. Conclusions. This study contributes to have better information on the clinical picture, and about the most common serotypes of adenovirus causing ARI in children in a province from Argentine. The early age of the infection onset, extended hospital stay and the severity of the infection, emphasize the need for implementation of both strategies of control and prevention

Acute respiratory infection by adenoviruses in children hospitalized in Santa Fe

Fil: Rusznierz, Gabriela F. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Respiratorias; Argentina.Fil: Cociglio, Raquel. Hospital de Niños “Orlando Alassia”; Argentina.Fil: Pierini, Judith. Hospital “J.B. Iturraspe”; Argentina.Fil: Malatini, María I. Hospital “J.B. Iturraspe”; Argentina.Fil: Walker, Analía. Clínica de Niños Rafaela, Santa Fe; Argentina.Fil: Millán Alejandra. Hospital de Niños “Orlando Alassia”; Argentina.RESUMEN Introducción. Los adenovirus (Ads), son agentes etiológicos importantes de la infección respiratoria aguda (IRA). El Ad7 se asocia con las manifestaciones clínicas de mayor gravedad. Objetivos. Describir los aspectos clínicos y epidemiológicos de las IRA por Ads en niños hospitalizados en la Provincia de Santa Fe, durante el período 1998-2001. Población, material y métodos. Se evaluaron 31 historias clínicas de pacientes hospitalizados con diagnóstico de IRA en hospitales de Santa Fe y se registraron datos demográficos, clínicos, radiológicos y de tratamiento. La infección por Ads se documentó mediante inmunofluorescencia indirecta. Los Ads se aislaron en células Hep-2, a partir de aspirados nasofaríngeos y se caracterizaron por PCR. Resultados. Se encontró un predominio de adenovirus subespecie B:1 (25/29), de los cuales 24 fueron Ad7. El Ad7 se asoció a neumonías mientras que Ads de las especies C (3/29) y D (1/29) encontrados en baja proporción se relacionaron con cuadros leves de bronquitis y catarro de vías aéreas superiores. Los niños menores de 1 año fueron el grupo más comunmente afectado. La estadía hospitalaria y el tratamiento con oxígeno fue mayor de 8 días en 17/ 31 y 14/22, respectivamente. Once niños desarrollaron neumonías graves, que requirieron cuidados intensivos y asistencia respiratoria (4/11). Dos casos desarrollaron miocarditis y uno hepatitis. La mortalidad fue del 9,7% (3/31) asociada a Ad7. Conclusión. Este estudio aporta un mejor conocimiento acerca de la clínica y los serotipos de los adenovirus causantes de IRA en niños, más prevalentes en una provincia del interior del país. La edad temprana de los niños, las estadías hospitalarias prolongadas y la gravedad del cuadro clínico hacen necesario implementar estrategias de control y prevención. (EN) SUMMARY Introduction. Adenovirus are (Ads) an important etiologic agent of acute respiratory infections (ARI). Ad7 has been associated with clinical manifestations of most considerable severity. Objective. The aim of this study was to describe the clinical and epidemiologic aspects of the ARI by Ads in hospitalized patients in Santa Fe, Argentina during 1998-2001. Population, material and methods. We conducted a retrospective study. Medical charts of 31 patients with ARI admitted in hospitals in Santa Fe were examined. Demographic information, as well as the radiographic and clinical outcome, were captured on special forms. Infections by Ads were documented by indirect immunonofluorescence. Ads were isolated in Hep2-cell cultures from nasopharyngeal aspirates. The molecular characterization was performed by PCR. Results. During the study period there was a predominance of subspecies B:1 (25/29), 24 was Ad7. The Ad7 was associated with pneumonia whereas the adenovirus species C(3/29) y D (1/29) were associated with mild bronchitis and upper respiratory tract catarrh. Children less than one year of age were the most common age group affected. The duration of oxygen treatment and hospital stay was 8 days in the 14/22 y 17/31 of the children studied, respectively. Eleven of thirty-one children developed a severe pneumonia, requiring intensive care and mechanical respiratory assistance (4/11). Two cases developed miocarditis and hepatitis. Among all cases included the mortality was 9.7% (3/31) associated with Ad7. Conclusions. This study contributes to have better information on the clinical picture, and about the most common serotypes of adenovirus causing ARI in children in a province from Argentine. The early age of the infection onset, extended hospital stay and the severity of the infection, emphasize the need for implementation of both strategies of control and prevention

Efecto de las epidemias de influenza sobre la mortalidad en Santa Fe, Argentina, en 1992-1999

Objetivos. Descubrir el efecto de las epidemias de influenza sobre la mortalidad y determinar el criterio más apropiado para predecir la magnitud de ésta, a fin de brindar un método que alerte precozmente de la gravedad de una epidemia de influenza. Métodos. El estudio se realizó en La Capital, departamento de la provincia de Santa Fe, Argentina, durante el período de 1992-1999. Para lograr el primer objetivo se llevó a cabo un análisis retrospectivo de los datos de mortalidad por neumonía e influenza en personas mayores de 65 años, utilizando el método autorregresivo integrado de promedios móviles (ARIMA, por el inglés auto-regressive integrated moving averages). Con él se determinó el exceso de mortalidad atribuible a las epidemias de influenza. A fin de alcanzar el segundo objetivo, se efectuó un análisis de regresión para estudiar la relación entre la morbilidad semanal por influenza y la mortalidad mensual por neumonía o influenza en personas mayores de 65 años. La morbilidad se expresó mediante tres medidas resumen calculadas a partir del número de casos notificados durante las primeras 35 semanas epidemiológicas del año (ocho primeros meses calendario): la suma total de los casos notificados semanalmente, su desviación estándar y su número en la semana invernal en que hubo más casos. En este análisis se incluyeron el tipo y el subtipo de influenza. Estos cuatro parámetros (el tipo y subtipo de influenza, junto con una de las tres medidas resumen) se compararon entre sí con respecto a su poder para explicar la mortalidad registrada durante los primeros ocho meses del año. Resultados. Se produjeron epidemias en la estación invernal de 1993, 1995, 1999 y en la primavera de 1997, estaciones en las que se identificó un exceso de muertes asociado a la circulación de una cepa predominante del virus de la influenza de tipo A, la H3N2. Este patrón de exceso de mortalidad es típico de cepas de la influenza del tipo A (H3N2). Durante los inviernos de 1994, 1996 y 1998 no se produjeron epidemias a pesar de haber estado en circulación el virus de la influenza de tipo A (H3N2). En las estaciones invernales relacionadas con la circulación de cepas de la influenza de los tipos A (H1N1) (1992) y B (1997), cuyos patrones suelen asociarse a una baja mortalidad, tampoco se detectó un exceso de muertes. Conclusiones. El número de casos de influenza semanales notificados durante el pico de la estación invernal resulta el mejor parámetro para estimar el impacto de la influenza sobre el número de defunciones

[Human Metapneumovirus (hMPV) associated to severe bronchial asthmatic crisis]

Human Metapneumovirus (hMPV) is a recently reported agent of acute infection in the respiratory tract. It has been found in children as well as in young adults and elders. The clinical manifestations produced by hMPV are indistinguishable from those by common respiratory virus, and can evolve from asymptomatic infection into severe pneumonia. On the other hand, some authors have described cases of bronchial asthma exacerbation associated with hMPV infection. In this work we report a case of a child who presented a severe bronchial asthmatic crisis with a suspected viral associated infection. Immunofluorescence tests yielded negative results for sincitial respiratory virus, adenovirus, a-b influenza virus and parainfluenza 1, 2, 3, virus. In an attempt to detect the presence of hMPV, a RT-PCR was carried out to amplify sequences from both N and F genes. Using this approach, a positive result for hMPV was obtained. To our knowledge, this is the first description of a case of asthma exacerbation associated to hMPV in our region. In addition, these results are similar to previous reports where it was hypothesized that, like RSV, hMPV can trigger a respiratory chronic disease as asthma

[Human Metapneumovirus (hMPV) associated to severe bronchial asthmatic crisis]

Human Metapneumovirus (hMPV) is a recently reported agent of acute infection in the respiratory tract. It has been found in children as well as in young adults and elders. The clinical manifestations produced by hMPV are indistinguishable from those by common respiratory virus, and can evolve from asymptomatic infection into severe pneumonia. On the other hand, some authors have described cases of bronchial asthma exacerbation associated with hMPV infection. In this work we report a case of a child who presented a severe bronchial asthmatic crisis with a suspected viral associated infection. Immunofluorescence tests yielded negative results for sincitial respiratory virus, adenovirus, a-b influenza virus and parainfluenza 1, 2, 3, virus. In an attempt to detect the presence of hMPV, a RT-PCR was carried out to amplify sequences from both N and F genes. Using this approach, a positive result for hMPV was obtained. To our knowledge, this is the first description of a case of asthma exacerbation associated to hMPV in our region. In addition, these results are similar to previous reports where it was hypothesized that, like RSV, hMPV can trigger a respiratory chronic disease as asthma