Relacionamento entre bases de dados para vigilância da pandemia de influenza A(H1N1)pdm09, Brasil, 2009-2010 / Database linkage for surveillance of the influenza A(H1N1)pdm09 pandemic in Brazil, 2009-2010 / Relación entre bases de datos para la vigilancia de la pandemia de gripe A(H1N1)pdm09, Brasil, 2009-2010

Resumo: O objetivo deste estudo foi o de descrever, com base no relacionamento entre os sistemas de informação SINAN (Sistema de Informação de Agravos de Notificação) e SIM (Sistema de Informações sobre Mortalidade), o perfil epidemiológico dos casos notificados de influenza por novo subtipo viral que evoluíram para óbito, durante a pandemia da doença. Foram utilizados dados secundários de ambos os sistemas referentes aos anos de 2009 e 2010. O relacionamento identificou 5.973 óbitos de casos notificados como influenza pandêmica. Destes, 2.170 (36,33%) haviam sido classificados no SINAN como confirmados para a enfermidade; 215 (3,6%), como infecção por outro agente infeccioso; e 3.340 (55,92%), como descartados. Após o relacionamento, alguns casos, que, no SINAN, foram encerrados com evolução para óbito por influenza (n = 658) ou óbito por outras causas (n = 847), não foram encontrados no SIM. O relacionamento entre os bancos de dados pode aprimorar o sistema de vigilância e o dimensionamento da morbimortalidade. Recomendamos o fortalecimento da vigilância da influenza no país com o uso do relacionamento entre os sistemas de informação do Ministério da Saúde.

Abstract: Based on database linkage, the objective of this study was to describe the epidemiological profile of notified cases and deaths from the new viral subtype of influenza during the influenza pandemic. Secondary data were used from the SINAN (Information System for Notifiable Diseases) and SIM (Mortality Information System) for the years 2009 and 2010. Linkage identified 5,973 deaths of cases notified as pandemic influenza. Of these, 2,170 (36.33%) had been classified in the SINAN as confirmed pandemic influenza, 215 (3.6%) as due to other infectious agents, and 3,340 (55.92%) as ruled out. After linkage, some cases in the SINAN database that were closed as death from influenza (n = 658) or death from other causes (n = 847) could not be located in the SIM database. Database linkage can improve the surveillance system and monitoring of morbidity and mortality. We recommend strengthening influenza surveillance in Brazil using linkage of Ministry of Health databases.

Resumen: El objetivo de este estudio fue el de describir, a partir de la relación entre los sistemas de información, el perfil epidemiológico de los casos notificados y que evolucionaron hacia el óbito por gripe, debido a un nuevo subtipo viral durante la pandemia de gripe. Se utilizaron datos secundarios, años 2009 y 2010, del Sistema de Información sobre Enfermedades de Notificación Obligatoria (SINAN) y Sistema de Información sobre Mortalidad (SIM). La relación identificó 5.973 óbitos de casos notificados como gripe pandémica. De esos, 2.170 (36,33%) habían sido clasificados en el SINAN y confirmados como gripe pandémica, 215 (3,6%) como infección por otro agente infeccioso y 3.340 (55,92%) como descartados. Tras la relación, algunos casos en el SINAN que fueron cerrados con la evolución, donde el óbito por gripe (n = 658) u óbito por otras causas (n = 847) no se encontraron en el banco del SIM. La relación entre los bancos de datos puede perfeccionar el sistema de vigilancia y el dimensionamiento de la morbimortalidad. Recomendamos el fortalecimiento de la vigilancia de la gripe en el país con el uso de la relación entre los sistemas de información del Ministerio de la Salud.

Novel Influenza A (H1N1)-Associated Acute Necrotizing Encephalopathy: A Case Report

Several cases of acute necrotizing encephalopathy (ANE) with influenza A (H1N1) have been reported to date. The prognosis of ANE associated with H1N1 is variable; some cases resulted in severe neurologic complication, whereas other cases were fatal. Reports mostly focused on the diagnosis of ANE with H1N1 infection, rather than functional recovery. We report a case of ANE with H1N1 infection in a 4-year-old Korean girl who rapidly developed fever, seizure, and altered mentality, as well as had neurologic sequelae of ataxia, intentional tremor, strabismus, and dysarthria. Brain magnetic resonance imaging showed lesions in the bilateral thalami, pons, and left basal ganglia. To our knowledge, this is the first report of ANE caused by H1N1 infection and its long-term functional recovery in Korea.

Evaluation of pregnancy as a risk factor in the outcomes of influenza A (H1N1)/2009 in women of childbearing age / Avaliação da gestação como fator de risco nos desfechos da influenza A (H1N1)/2009 em mulheres em idade fértil

The aim of this study was to verify whether pregnancy was a risk factor for death in influenza A (H1N1)/2009 infection. We compared the case-fatality rates for pandemic influenza among non-pregnant women of childbearing age and pregnant women, besides investigating other factors that differentiated the groups in relation to the outcomes. The data were collected from the National Information System on Diseases of Notification (SINAN), of the Ministry of Health. The study used cases with laboratory confirmation and included 1,861 women from 10 to 49 years of age, of whom 352 were pregnant. The case-fatality rate during the 2009 pandemic was 4.5 percent for pregnant women and 6.4 percent for non-pregnant women (p = 0.197). Logistic regression did not show an association between pregnancy and death (OR = 0.7; 95 percentCI: 0.41-1.21). However, there were significant differences between the two groups in relation to mean age, treatment with oseltamivir, schooling, and presence of other risk factors.

O objetivo deste estudo foi verificar se a gestação esteve associada como fator de risco para o óbito na infecção por Influenza A (H1N1)/2009. Comparou-se a letalidade da influenza pandêmica entre mulheres em idade fértil e gestantes, realizando ainda a busca por outros fatores que diferenciem os grupos em relação aos desfechos. Os dados foram coletados no Sistema de Informação de Agravos de Notificação (SINAN), do Ministério da Saúde. Foram utilizados os casos confirmados laboratorialmente, sendo incluídas 1.861 mulheres com idades entre 10 e 49 anos, das quais 352 eram gestantes. A taxa de letalidade observada durante a pandemia de 2009 foi de 4,5 por cento para as gestantes e 6,4 por cento para as não gestantes (p = 0,197). O resultado da regressão logística não evidenciou associação entre a presença de gestação e o óbito (OR = 0,7; IC95 por cento: 0,41-1,21). No entanto, houve diferenças significativas entre os dois grupos em relação à idade média, ao tratamento com oseltamivir, à escolaridade e à presença de outros fatores de risco.

Recurrent Plastic Bronchitis in a Child with 2009 Influenza A (H1N1) and Influenza B Virus Infection

Plastic bronchitis is an uncommon disorder characterized by the formation of bronchial casts. It is associated with congenital heart disease or pulmonary disease. In children with underlying conditions such as allergy or asthma, influenza can cause severe plastic bronchitis resulting in respiratory failure. A review of the literature showed nine cases of plastic bronchitis with H1N1 including this case. We report a case of a child with recurrent plastic bronchitis with eosinophilic cast associated with influenza B infection, who had recovered from plastic bronchitis associated with an influenza A (H1N1) virus infection 5 months previously. To the best of our knowledge, this is the first case of recurrent plastic bronchitis related to influenza viral infection. If patients with influenza virus infection manifest acute respiratory distress with total lung atelectasis, clinicians should consider plastic bronchitis and early bronchoscopy should be intervened. In addition, management for underlying disease may prevent from recurrence of plastic bronchitis.

Recombination analysis of full-length genomic sequences of novel influenza virus A/H1N1 in 2009 pandemic / 第二军医大学学报

Objective: To analyze the recombination of full-length genomic sequences of novel influenza virus A/H1N1 in 2009 pandemic. Methods: The full-length sequences of the novel A/H1N1 and reference sequences were downloaded from NCBI database. MEGA4.0 software was used to connect, align sequences, and analyze the similarity between the full-length sequences of the novel virus and each of the reference strains. Recombination was analyzed by Simplot software (version 3.5.1). Results: Simplot analysis indicated that the PB1 genes (polymerase B1, PB1) of the novel A/H1N1 viruses might evolve from human H3N2 virus (identity: 93.7%); the PB2 genes (polymerase B2, PB2) and the PA genes (polymerase A, PA) might evolve from avian H5N1 viruses (identity: 89.0%, 89.9%, respectively); the HA genes (hemagglutinin, HA), the NP genes (nucleoprotein, NP) and the NS genes (non-structural protein, NS) showed high similarities with those of swine H1N1 viruses isolated in North America (identity: 91.7%, 93.1%, and 93.1%, respectively); and the NA genes (neuraminidase, NA) and the MP genes (matrix protein, MP) might evolve from European swine H1N1 viruses (identity: 90.5%, 95.5%, respectively). The full-length sequence of the novel A/H1N1 viruses had a highest similarities with swine H1N1 viruses isolated in North America (identity: 83.9%). Conclusion: The novel influenza virus A/H1N1 is a recombinant virus evolving from human H3N2 viruses, swine H1N1 from North America, swine H1N1 from Europe, and swine H5N1 from Asia.

Evolutionary characteristics of polymerase PA, PB1, and PB2 genes of novel influenza virus A/H1N1 in 2009 pandemic / 第二军医大学学报

Objective: To elucidate the evolutionary characteristics of polymerase PA, PB1, and PB2 genes of the novel influenza virus A/H1N1 in 2009 pandemic. Methods: The sequences of the PA, PB1, and PB2 genes of the novel H1N1 strains in 2009 pandemic, and the reference sequences of human, swine, and avian influenza viruses isolated during different years at different locations were retrieved from NCBI. Molecular Evolutionary Genetics Analysis version 4.0 (MEGA4.0) software was employed to align and blunt nucleotide sequences, construct phylogenetic tree, deduce and align PB2 protein sequences, and the results were compared between the novel A/H1N1 and each of the reference strains. Results: The sequences of the PA, PB1, and PB2 genes of 2009 novel A/H1N1 strains isolated from different locations shared a high homology and clustered in a unique new clade, and were close to the swine influenza viruses. The PA, PB1, and PB2 genes of the novel H1N1 viruses had a high similarity with the corresponding sequences of a human H1N1 strain isolated in Iowa State of USA in 2005 (A/Iowa/CEID23/2005/H1N1). Alignments of the deduced protein sequences showed that the 627th amino acid of PB2 of the novel H1N1 strains and A/Iowa/CEID23/2005/H1N1 were glutamic acid (Glu), which was the same as that in the avian influenza virus in Iowa State of USA in 2005 (DQ889682), and was different from those of the reference sequences of human A/H1N1 strains isolated from 1918 to 2008, which were lysine (Lys). Conclusion: The 2009 novel A/H1N1 virus might be originated from the human A/H1N1 strains isolated in 2005 in Iowa State of America (A/Iowa/CEID23/2005/H1N1), and the polymerase gene of the novel H1N1 virus might re-assort with avian A influenza virus.

Genetic characteristics and deduced protein variation of nonstructural protein of novel influenza virus A/H1N1 in 2009 pandemic / 第二军医大学学报

Objective: To elucidate the genetic characteristics and deduced protein variation of nonstructural protein (NS) gene of the novel influenza virus A/H1N1 in 2009 pandemic. Methods: The sequence of NS gene of A/H1N1 viruses isolated in North America, Europe, and Asia during 1930-2009 were downloaded from NCBI database. MEGA4.0 software and NJ method were used for sequence alignment, protein sequence alignment, and the phylogenetic tree construction. Results: The NS genes of novel influenza virus A/H1N1 in 2009 pandemic were originated from A/swine/H1N1 virus of 2005-2007; they shared a high homology of 97.5%-97.6%. There was an obvious evolutionary relationship between the NS genes of novel A/H1N1 virus and those of the influenza A/swine/H1N1 viruses isolated in North America from 1930 to 2007. No obvious changes were found in the amino acid sites for the antagonistic function of NS1 against the host antiviral capacity among these viruses. Conclusion: The NS gene of novel influenza virus A/H1N1 in 2009 pandemic might evolve from swine A/H1N1 influenza viruses isolated in the United States. The antagonistic function of NS1 against the host antiviral capacity is not changed.

Molecular evolutionary analysis of matrix protein and nucleoprotein genes of novel influenza virus A/H1N1 in 2009 pandemic / 第二军医大学学报

Objective: To analyze evolutionary characteristics of the matrix protein (M) and nucleoprotein (NP) genes of influenza virus A/H1N1 in 2009 pandemic. Methods: The M and NP genes of A/H1N1 viruses were downloaded from NCBI database. MEGA4.0 software and NJ method were used for sequence alignment, protein sequence alignment, and the phylogenetic tree construction. Meanwhile, Epi Info software was used to analyze the linear trend of evolutionary distance of the M and NP genes of human H1N1 strains isolated during 1918 to 2009. Results: The M and NP gene sequences were similar among the novel A/H1N1 viruses, but different from those of the previous influenza H1N1 viruses. Using reference sequences of human H1N1 strains isolated during 1918 to 2008, we found that changes in evolutionary distances of the M genes between novel A/H1N1 strains and each of the reference A/H1N1 strains increased with increasing year intervals (Ptrend = 0.001). Compared with the amino acid sequence of M2 protein of reference human A/H1N1 virus strains isolated during 1918 to 2008, the novel A/H1N1 viruses had the amino acid substitutions at 6 sites: 11, 43, 54, 57, 77, and 78. Compared with swine and avian A/H1N1, the novel A/H1N1 virus only had the amino acid substitutions at 43 and 77. Conclusion: The NP gene of novel A/H1N1 virus, which is routinely considered as a conserved sequence, is different from those of the previously isolated human H1N1 influenza viruses; the related mechanisms and consequences on viral activity remain to be elucidated. The substitution to threonine at 11 and 43 amino acids of M2 protein might contribute to amantadine resistance of the novel H1N1 virus pandemic in 2009.

Genetic characterization of neuraminidase gene of novel influenza virus A/H1N1 in 2009 pandemic / 第二军医大学学报

Objective: To investigate the genetic characterization (evolution, antigenicity, enzymatically active site, and glycosylation site) of the neuraminidase (NA) gene of the novel influenza virus A/H1N1 in 2009 pandemic. Methods: Genetic evolution and amino acid substitutions of the 43 NA gene sequences of influenza virus A of different years were retrieved from GenBank and were analyzed by using MEGA 4.0 software. Results: The new A/H1N1 influenza virus strains and avian H5N1 influenza virus strains had similar antigen sites of the NA genes, sharing a homology of 85%. Amino acid residues at the enzymatically active site of the NA genes were strictly conserved in all influenza virus strains, but the glycosylation sites varied. Conclusion: The NA genes of novel H1N1 influenza viruses may originate from avian H5N1 influenza virus endemic in Asia. The new H1N1 influenza viruses may respond well to the neuraminidase inhibitor treatment.

Evolution analysis of hemagglutinin gene of novel influenza virus A/H1N1 in 2009 pandemic / 第二军医大学学报

Objective: To investigate the evolutionary relationship of the hemagglutinin (HA) gene of novel influenza virus A/H1N1 in 2009 pandemic with the HA genes of A/H1N1 viruses isolated in different parts of the world previously. Methods: The sequences of the HA gene of the novel A/H1N1 strain and the reference sequences of human, swine, and avian influenza A viruses were retrieved from NCBI. MEGA 4.0 software was employed to align, blunt nucleotide sequences, and construct phylogenetic tree. The deduced amino acid sequences of the HA genes of novel influenza virus A/H1N1 were compared with those of the A/H1N1 isolates in North America, Europe, and Asia. Results: Phylogenetic tree of the HA genes of A/H1N1 strains worldwide showed that the HA genes of novel influenza virus A/H1N1 in 2009 shared a high homology with those of the 7 human A/H1N1 influenza viruses isolated in North America during 1976 to 2007, and shared a low homology with those of the human influenza viruses A/H1N1 isolated in Europe and Asia. Phylogenetic tree of the HA gene between different species showed that the HA genes of novel influenza virus A/H1N1 in 2009 had a close evolutionary relationship with those of the two swine A/H1N1 strains isolated in 1998 and 2007 in North America, but a distant evolutionary relationship with those of swine and avian A/H1N1 isolated in Europe and Asia. Alignment of amino acid at important antigenic sites showed that the HA gene of the novel A/H1N1 strains shared important antigen sites with the swine A/H1N1 influenza viruses isolated in North America, and did not share with the swine A/H1N1 influenza viruses isolated in Europe and Asia or the human A/H1N1 influenza vaccine strains. Conclusion: The HA genes of the novel influenza virus A/H1N1 might originate from swine A/H1N1 influenza viruses in North America after a long time evolution and the reassortment with fragments of human A/H1N1 in the area, and the current A/human/H1N1 influenza vaccine may not be effective for the novel A/H1N1 virus.

Epidemic situation of emerging influenza virus A/H1N1 in 2009 pandemic and the prevention/control measures / 第二军医大学学报

Since the first reported case of swine influenza A in Mexico, a total of 15 510 cases have been confirmed in 53 countries by May 29, 2009. On April 29, 2009, the World Health Organization (WHO) raised its pandemic alert from grade 4 to grade 5. The virus is described as a new subtype of A/H1N1 and is not detected in pigs or humans previously. The virus is sensitive to oseltamivir and zanamivir, but resistant to amantadine and rimantadine. The genetics of the virus are so novel that humans are unlikely to have much immunity to it. The virus can transmit from human to human; therefore it is necessary to enforce quarantine measure for close contactors because the virus transmits during latency. Precaution methods like covering noses and mouths with a tissue when coughing or sneezing can reduce the transmission opportunity. Hands should be washed frequently with soap, especially after coughing or sneezing. Public places with ventilation conditions, personal health behavior and health condition are critical for the prevention and control of this epidemic.

Role of swine as host and a mixing vessel in evolution of 2009 novel influenza virus A/H1N1 / 第二军医大学学报

Several epidemic influenza viruses leading to worldwide periodical pandemics all result from the genetic reassortment of different influenza viruses. The novel 2009 A/H1N1 virus is a reassortment virus evolved from swine influenza virus A/H1N1, avian influenza virus H5N1, and human influenza virus A/H1N1. The 8 fragmente genes of the novel A/H1N1 virus had their own evolutionary characteristics. All the pandemic viruses in humans originate from avian influenza viruses and are transferred into humans after reassortment processes in pigs. Pigs as middle host and a mixing vessel of influenza A virus play an important role in the evolution of the 2009 novel A/H1N1 virus. More attention should be paid on the role of swine in the prevention and control of novel H1N1 virus epidemics in future.

Epidemiologic Characteristics of Pandemic H1N1 Influenza in 2009: An Observational Study at a Single Emergency Department

PURPOSE: This study was designed to determine the epidemiological and clinical characteristics of patients suspected or confirmed with to be infected by the pandemic 2009 H1N1 virus in one emergency medical center. METHODS: This was a prospective observational study. It was conducted between September 1 and November 30, 2009 in one tertiary academic emergency department. We recorded clinical and epidemiologic features of patients infected by the pandemic 2009 H1N1 virus. A follow-up telephone survey was done to determine the final outcome of infection. This survey was conducted by ED personnel 1 week after the initial visit. Multivariate logistic regression analysis was done for the association between disposition or H1N1 influenza diagnosis and potential predictors. RESULTS: During the study period, a total 5,317 patients visited the influenza clinical center of our emergency department. Among them, 1,472 patients (27.7%) were confirmed as influenza A by RT-PCR methods. Among RT-PCR positive patients, 90 (1.7%) were admitted to the ward and 7 to the intensive care unit. Five patients needed mechanical ventilation and one patient was diagnosed as ARDS; the ARDS patient fully recovered. There was no mortality caused by H1N1. The median age of confirmed patients was 9 years (range, 1 month~81 years); 825 patients (56.1%) were male. Incident rates for common symptoms were: fever (92.8%), cough (84.1%), and rhinorrhea (44.0%) by. A total of 40.3% (593/1472) patients were of pre-school age (range, 1 month~7 years, median 4 years). In young patients, clinical characteristics were similar to those of adults. Male, young age, contact history, lack of seasonal influenza vaccination, chronic renal failure, malignancy, and pregnancy were significantly associated with a confirmed diagnosis of H1N1. Hypertension, chronic renal failure, malignancy, neurologic disease, dyspnea, seizure, vomiting, and chest pain were also associated with risk of admission to the hospital. CONCLUSION: Surveillance of H1N1 virus cases shows that the majority of those infected have a mild illness. The 2009 H1N1 virus is common among individuals of pre-school age. Few H1N1-related severe illnesses occur in young individuals.

Role of swine as host and a mixing vessel in evolution of 2009 novel influenza virus A/H1N1 / 第二军医大学学报

Several epidemic influenza viruses leading to worldwide periodical pandemics all result from the genetic reassortment of different influenza viruses.The novel 2009 A/H1N1 virus is a reassortment virus evolved from swine influenza virus A/H1N1,avian influenza virus H5N1,and human influenza virus A/H1N1.The 8 fragmente genes of the novel A/H1N1 virus had their own evolutionary characteristics.All the pandemic viruses in humans originate from avian influenza viruses and are transferred into humans after reassortment processes in pigs.Pigs as middle host and a mixing vessel of influenza A virus play an important role in the evolution of the 2009 novel A/H1N1 virus.More attention should be paid on the role of swine in the prevention and control of novel H1N1 virus epidemics in future.

Epidemic situation of emerging influenza virus A/H1N1 in 2009 pandemic and the prevention/control measures / 第二军医大学学报

Since the first reported case of swine influenza A in Mexico,a total of 15 510 cases have been confirmed in 53 countries by May 29,2009.On April 29,2009,the World Health Organization(WHO)raised its pandemic alert from grade 4 to grade 5.The virus is described as a new subtype of A/H1N1 and is not detected in pigs or humans previously.The virus is sensitive to oseltamivir and zanamivir,but resistant to amantadine and rimantadine.The genetics of the virus are so novel that humans are unlikely to have much immunity to it.The virus can transmit from human to human;therefore it is necessary to enforce quarantine measure for close contactors because the virus transmits during latency.Precaution methods like covering noses and mouths with a tissue when coughing or sneezing can reduce the transmission opportunity.Hands should be washed frequently with soap,especially after coughing or sneezing.Public places with ventilation conditions,personal health behavior and health condition are critical for the prevention and control of this epidemic.