Analysis of antigen epitopes and molecular pathogenic characteristics of the 2009 H1N1 pandemic influenza A virus in China

In order to further predict the epidemic trend and develop vaccines for 2009 H1N1 virus, we monitored its epitopes and molecular pathogenic characteristics during the epidemic process. We also analyzed the similarity of antigenic and genetic characteristics among the novel 2009 H1N1, representative seasonal H1N1 strains, and vaccine strains. 2009 H1N1 isolates had high similarity of hemagglutinin (HA) antigenic sites with H1N1 viruses isolated before 1940 and up to 80.0% similarity with 1918 H1N1. The elderly people born before 1940 have relatively low 2009 H1N1 infection rate, which might be responsible for their previous infection with either 1918 H1N1 virus or an early progeny. Compared to seasonal H1N1 vaccine strains from 1999 to 2010, the HA, neuraminidase (NA), and nucleoprotein (NP) proteins of the isolates had highly conserved CTL epitopes (60.5-65.8%, 69.6-82.6%, and 76.7%, respectively). The seriousness and mortality rate of 2009 H1N1 infections were similar to seasonal influenza, which may be related to the molecular characteristics of low toxicity of 2009 H1N1 and cross-T-cell immunity, due to vaccination or exposure to seasonal H1N1 virus. Some strains of 2009 H1N1 acquired mutations at antigenic and glycosylation sites. It is of particular interest that Haishu/SWL110/10 and Beijing/SE2649/09, isolated after November 2009, gained a new glycosylation site at the position 179 of HA protein, near the RBD. Thus, in the future, vaccination with glycosylated 2009 H1N1 virus may prevent the seasonal epidemic caused by strains with glycosylation site mutation near the receptor binding domain (RBD).     

Pandemic influenza 2009 in Russia. Characteristics of the isolation and biological properties of viruses

Research Institute of Influenza, Ministry of Health and Social Development of Russia, Saint Petersburg The characteristics of the isolation of pandemic influenza A(H1N1)v viruses were studied on chick embryos (CE) and MDCK cell culture. The materials (nasal swabs and autopsies) were collected in different regions Russia in the period from 20 July to 30 December 2009. The paper gives the data of the antigenic analysis of isolates, their capacity to multiply in different species-specific and tissue cell cultures. The viruses isolated on CE were shown to have higher hemagglutination titers and to be more stable. Isolation from the autopsies was effective only on CE. All the test cell lines other than MDCK were insensitive to the isolated pandemic influenza strains. The antigenic analysis showed no significant antigenic drift of the viruses isolated during the first wave of the pandemic in the Russian Federation.     

Genetic variability of isolates of pandemic influenza virus A H1N1 isolated in Russia in 2009

In 14 isolates of pandemic influenza virus A H1N1 extracted from patients with influenza in 2009, complete nucleotide sequences of genome segments encoding surface proteins hemagglutinin and neuraminidase were determined. Phylogenetic analysis of these sequences showed their genetic similarity with the corresponding genes of other isolates of pandemic influenza virus A (H1N1) 2009 extracted in other countries, and the degree of homology for each gene was over 99%. Neuraminidase mutations known in the literature that lead to the stability of the virus to oseltamivir and other drugs of neuraminidase inhibitors were not recorded in the studied isolates. In four isolates from autopsy material, G155E mutation was found in hemagglutinin of the isolate A/Salekhard/01/2009 (H1N1). This mutation leads to increased viral replication in developing chick embryos. The frequency and nature of the nucleotide substitutions in the hemagglutinin and neuraminidase genes are determined.     

Yields of virus reassortants containing the HA gene of pandemic influenza 2009 virus

Keywords: influenza virus; reassortment; virus yield; gene constellation.     

Contribution of D I Ivanovsky Research Institute of Virology to monitoring influenza viruses during epidemics and 2009 pandemic in Russia

The data on monitoring influenza viruses in Russia are presented based on the research underway at Ivanovsky Research Institute of Virology since 1959. The Institute's priority in isolation and identification of influenza viruses during epidemics and 2009 pandemic is confirmed. Results of assessment of influenza vaccines and etiotropic preparations, development and introduction of new methods for diagnostics of influenza are discussed.     

2009 pandemic characteristics and controlling experiences of influenza H1N1 virus 1 year after the inception in Hangzhou, China

This paper described the epidemiology and controlling experiences of influenza H1N1 in Hangzhou in the past 1 year. A total of 2,078 cases confirmed by real-time quantitative PCR till March 31, 2010, were analyzed by SPSS 12.0 software. During the early pandemic stage, a patient must be tested for H1N1 nucleic acid once he/she had influenza-like symptoms with the epidemiological history in 7 days, and be diagnosed if it was positive. But in the pandemic peak, we made efforts to identify and save severe cases combined with pneumonia or hypoxemia or respiratory failure or septic shock or multiple organ dysfunctions and failure. In general, the prevalence was 2.77/100,000 (2,078/7,510,844); severity rate, 10.44% (217/2,078); fatality rate, 0.48% (10/2,078). The carrier and secondary attack rate were 9.52% (58/612) and 8.66% (53/612), respectively. About 50% of serious cases and 100% of deaths had the basic underlying diseases: cardiovascular diseases, 13.66% (25/217); chronic lung disease, 12.02% (22/217); pregnant, 7.1% (13/217). Of all cases aged from 1 month to 89 years, 52.99% (1,435/2,708) were in the 10-29 years, with most of them distributed in downtown area. The timeline showed two epidemic peaks occurred in September and November 2009, respectively. Furthermore, the hemagglutinin gene remained 99% identical with the American and vaccine strains, but only 70% with the 1947-2008 Chinese strains. In conclusion, Hangzhou pandemic influenza H1N1 was caused by the highly conserved virus, with low prevalence, transmission, and mortality, because we took efficient controlling methods.     

Clinical and molecular characteristics of the 2009 pandemic influenza H1N1 infection with severe or fatal disease from 2009 to 2011 in Shenzhen,China

In the past 3 years, the 2009 pandemic influenza virus H1N1 (pH1N1) has led to many severe or fatal cases. The virus‐related factors that cause severe or fatal disease are not clear. The clinical and molecular characteristics of pH1N1 infections with severe or fatal disease were examined to understand the correlation between pH1N1 infection and disease severity. Since 2009, three pH1N1 influenza epidemic outbreaks have occurred in Shenzhen, China. One hundred forty‐six severe cases were confirmed in the first wave in 2009. In severe cases, a high proportion (49.3%) of patents displayed high fever (>39.0°C), and 73.2% of patients had pneumonia and tracheobronchitis. Seven fatal cases were recorded: three with viral encephalitis and four with respiratory failure. The results of sequencing and phylogenetic analysis showed that the viruses from fatal or severe cases were scattered throughout the phylogenetic tree. Four substitutions (D222G, D222N, D222E, and Q223R) were observed on the 220‐loop of the receptor‐binding sites of the HA gene. Both D222G and D222N were associated statistically with severe disease. The 2011 viruses had evolved into two distinct branches. Ten specific point mutations occurred in the 2011 virus. In summary, high fever, lower respiratory tract infections and serious complications were the main features of severe cases. Gene variation seemed not to be the main reason for severe disease. Vaccination is the effective mean to prevent infection and severe disease. J. Med. Virol. 85:405–412, 2013. © 2012 Wiley Periodicals, Inc.     

The epidemiology of seasonal influenza after the 2009 influenza pandemic in Africa: a systematic review

BackgroundInfluenza infection is a serious public health problem that causes an estimated 3 to 5 million cases and 250,000 deaths worldwide every year. The epidemiology of influenza is well-documented in high- and middle-income countries, however minimal effort had been made to understand the epidemiology, burden and seasonality of influenza in Africa. This study aims to assess the state of knowledge of seasonal influenza epidemiology in Africa and identify potential data gaps for policy formulation following the 2009 pandemic.MethodWe reviewed articles from Africa published into four databases namely: MEDLINE (PubMed), Google Scholar, Cochrane Library and Scientific Research Publishing from 2010 to 2019.ResultsWe screened titles and abstracts of 2070 studies of which 311 were selected for full content evaluation and 199 studies were considered. Selected articles varied substantially on the basis of the topics they addressed covering the field of influenza surveillance (n=80); influenza risk factors and co-morbidities (n=15); influenza burden (n=37); influenza vaccination (n=40); influenza and other respiratory pathogens (n=22) and influenza diagnosis (n=5).ConclusionSignificant progress has been made since the last pandemic in understanding the influenza epidemiology in Africa. However, efforts still remain for most countries to have sufficient data to allow countries to prioritize strategies for influenza prevention and control.     

The Eurasian genes of the 2009 pandemic influenza virus: an integrative perspective on their conveyance to and assimilation in America

Abstract

The formation of pandemic influenza genotypes varied phylogeographically and ecophylogenetically throughout their fully recognized recent 100-years natural history, involving consistently avian plus human genes, and at times swine genes. The last four traceable pandemic strains (PSs) included two American H1N1 viruses with genomes predominantly containing swine genes, of which at least one genome originated from both America and Eurasia; and two non-H1N1 Asian viruses with genomes entirely originating from Asia, and having no swine genes. This study explores whether there is a particular interhemispheric system underlying such divergence, and its properties. Unlike the assumption that transport of live pigs from Eurasia to America facilitated the formation of the 2009 H1N1 PS in America, it is suggested that conveyance of Eurasian swine genes to America, and their assimilation therein, took place through a distinct, perfectly natural ecophylogenetic machinery. The latter conjunctively involves, foremost, a native Asian duck–swine–man interface, a Holarctic chain of certain migratory Anas ducks, a native American turkey–swine–man interface, and two specific clades of American influenza A viruses. Likewise, the described machinery could have readily given rise to the 1918 H1N1, and, presumably, earlier American PSs, altogether constituting private cases of a much broader, self-sustained, permanent phylogeographic system.     

Antigenic and biological characteristics of influenza virus A strains isolated in 1985

The antigenic structure of hemagglutinin of influenza A virus (H3N2) strains isolated in 1985 was studied using a series of monoclonal antibody to A/Dunedin/4/73/A (H3N2) and A/Bangkok/1/79/A (H3N2), and biological and physico-chemical properties of these strains were compared with those of influenza A (H3N2) virus of 1983 and reference A (H3N2) of 1979-1984 (the rate of adsorption on chick erythrocytes and eluting activity, thermostability of hemagglutinin and neuraminidase, sensitivity to nonionic detergents, sensitivity to remantadine, analysis of virion polypeptide composition). A high degree of heterogeneity of the 1985 strain population of influenza A (H3N2) virus was revealed both in the antigenic structure of hemagglutinin and in all the biological and physico-chemical parameters tested. It was suggested that the A/Caen/1/84 strain originated not from A/Philippines/2/82 but directly from A/Texas/1/77.     

Spontaneous pneumomediastinum complicating pneumonia in children infected with the 2009 pandemic influenza A (HINI) virus

We report two occurrences of spontaneous pneumomediastinum (SPM) complicating pneumonia in Japanese children infected with the novel influenza A (HINI) virus (IV). General practitioners especially should suspect possible SPM when examining and treating children with the novel influenza accompanied by status asthmaticus or wheezing. The presented patients illustrate the specific clinical and radiological signs associated with SPM complicating pneumonia in children infected with A(HINI)v.     

First influenza season after the 2009 pandemic influenza: characteristics of intensive care unit admissions in adults and children in Vall d'Hebron Hospital

To assess potential differences in epidemiology and management of patients admitted with influenza infection in the intensive care unit (ICU) during the first post-pandemic influenza period. Observational prospective study comparing September 2009–January 2010 with September 2010–January 2011. Variables captured: demographics, co-morbidities, physiological parameters, outcomes and management. Analysis was performed using SPSS v. 13.0; significance was set at p 0.5. Data from 53 patients, 38 adults (age, median 41.5 years; interquartile range (IQR) 32.8–51.3) and 15 children (age, median 2 years, IQR 0.5–9) are presented. Vaccination rates were 0% and 4.3% during the first and second periods, respectively. Differences postpandemic were: 100% of episodes developed after December compared with 16.7% in the 2009 season. Younger children were affected (median age 0.8 years (IQR 0.3–4.8) vs 7 years (IQR 1.25–11.5), p 0.05) and influenza B caused 8.7% of ICU admissions. Influenza A (H1N1) 2009 and respiratory syncytial virus epidemics occurred simultaneously (42.8% of children) and bacterial co-infections doubled (from 10% to 21.7%); the prevalence of co-infections (viral or bacterial) increased from 10% to 39.1% (OR 5.8, 95% CI 1.3–24.8). Respiratory syndromes without chest X-ray opacities reflecting exacerbation of asthma or chronic obstructive pulmonary disease, bronchitis or bronchiolitis increased (from 6.9% to 39.1%, p <0.05) and pneumonia decreased (from 83.3% to 56.5%, p <0.05). Primary viral pneumonia predominated among ICU admissions. Postpandemic ICU influenza developed later, with some cases of influenza B, more frequent bacterial and viral co-infections and more patients with severe acute respiratory infection with normal chest X-ray. Increasing vaccination rates among risk-group individuals is warranted to prevent ICU admission and death.