Epidemiology of pandemic influenza A/H1N1 virus during 2009–2010 in Taiwan

Outbreak of swine-origin influenza A/H1N1 virus (pdmH1N1) occurred in 2009. Taiwanese authorities implemented nationwide vaccinations with pdmH1N1-specific inactivated vaccine as of November 2009. This study evaluates prevalence, HA phylogenetic relationship, and transmission dynamic of influenza A and B viruses in Taiwan in 2009–2010. Respiratory tract specimens were analyzed for influenza A and B viruses. The pdmH1N1 peaked in November 2009, was predominant from August 2009 to January 2010, then sharply dropped in February 2010. Significant prevalence peaks of influenza B in April–June of 2010 and H3N2 virus in July and August were observed. Highest percentage of pdmH1N1- and H3N2-positive cases appeared among 11–15-year-olds; influenza B-positive cases were dominant among those 6–10 years old. Maximum likelihood phylogenetic trees showed 11 unique clusters of pdmH1N1, seasonal H3N2 influenza A and B viruses, as well as transmission clusters and mixed infections of influenza strains in Taiwan. The 2009 pdmH1N1 virus was predominant in Taiwan from August 2009 to January 2010; seasonal H3N2 influenza A and B viruses exhibited small prevalence peaks after nationwide vaccinations. Phylogenetic evidence indicated transmission clusters and multiple independent clades of co-circulating influenza A and B strains in Taiwan.     

Are we ready for pandemic influenza H5N1?

Influenza is an important annual respiratory pathogen with the potential to cause infrequent pandemics with devastating consequences. The establishment of highly pathogenic avian influenza H5N1 as an endemic virus within duck and poultry populations in Asia increases the possibility of adaptation to humans and the threat of an emerging pandemic. Vaccines are the mainstay of prophylaxis against influenza, but there are technical and safety issues that must be overcome in the development of vaccines in order to combat avian influenza. Pandemic preparedness plans have been developed by national and international authorities but may be compromised by a lack of readily available interventions.     

Can influenza H1N1 vaccination lead to the membranous glomerulonephritis?

In 2009 winter, Influenza A (H1N1) monovalent split virus vaccine was used prevalently in the whole world as a result of the pandemic caused by Influenza (H1N1) virus. The vaccine's adverse effects were observed closely and vaccination has been found as safe in most studies. But some reports about immune response related diseases after influenza vaccinations are remarkable. The close relationship between membranous glomerulonephritis and antigens is known, particularly in seconder forms which occur after viral infections and vaccinations. So this case report is about a 56-year-old man, who developed membranous glomerulonephritis 23 days after the vaccination against Influenza A (H1N1) virus.     

A review of the dynamics and severity of the pandemic A(H1N1) influenza virus on Réunion Island, 2009

On Reunion Island, in response to the threat of emergence of the pandemic influenza A(H1N1)2009 virus, we implemented enhanced influenza surveillance from May 2009 onwards in order to detect the introduction of pandemic H1N1 influenza and to monitor its spread and impact on public health. The first 2009 pandemic influenza A(H1N1) virus was identified in Réunion on July 5, 2009, in a traveller returning from Australia; seasonal influenza B virus activity had already been detected. By the end of July, a sustained community pandemic virus transmission had been established. Pandemic H1N1 influenza activity peaked during week 35 (24–30 August 2009), 4 weeks after the beginning of the epidemic. The epidemic ended on week 38 and had lasted 9 weeks. During these 9 weeks, an estimated 66 915 persons who consulted a physician could have been infected by the influenza A(H1N1)2009 virus, giving a cumulative attack rate for consultants of 8.26%. Taking into account the people who did not consult, the total number of infected persons reached 104 067, giving a cumulative attack rate for symptomatics of 12.85%. The crude fatality rate (CFR) for influenza A(H1N1)2009 and the CFR for acute respiratory infection was 0.7/10 000 cases. Our data show that influenza pandemic did not have a health impact on overall mortality on Réunion Island. These findings demonstrate the value of an integrated epidemiological, virological and hospital surveillance programme to monitor the scope of an epidemic, identify circulating strains and provide some guidance to public health control measures.     

Oseltamivir-resistant 2009–2010 pandemic influenza A (H1N1) in an immunocompromised patient

Although neuraminidase inhibitors are active against most 2009–2010 pandemic influenza A (H1N1) swine-origin strains, sporadic cases of oseltamivir resistance have been described. Since April 2009, 54 cases of oseltamivir-resistant H1N1 swine-origin have been reported in the USA (http://www.cdc.gov/flu/weekly/; accessed 1 February 2010). Approximately 1.4% of tested isolates are oseltamivir resistant. We report a patient with an underlying hematological malignancy who was hospitalized with influenza A (H1N1) swine-origin and whose strain developed oseltamivir resistance during therapy.     

A retrospective evaluation of critically ill patients infected with H1N1 influenza A virus in Bursa,Turkey, during the 2009–2010 pandemic

Background

H1N1 influenza A virus infections were first reported in April 2009 and spread rapidly, resulting in mortality worldwide. The aim of this study was to evaluate patients with H1N1 infection treated in the intensive care unit (ICU) in Bursa, Turkey.

Methods

Demographic characteristics, clinical features, and outcome relating to H1N1 infection were retrospectively analysed in patients treated in the ICU.

Results

Twenty-three cases of H1N1 infection were treated in the ICU. The mean age of patients was 37 years range: (17–82). Fifteen patients were female (65.2%). The mean Acute Physiology and Chronic Health Evaluation (APACHE) II score was 19 range: (5–39). The most common symptoms were dyspnea (73.9%), fever (69.6%), and cough (60.9%). Mechanical ventilation was required for all patients. Oseltamivir and antibiotics were administered to all patients. Six (26.1%) patients died. APACHE II scores were higher in the deceased 28.5 range: [16–39] vs. 14 range: [5–28] in survivors; p = 0.013).

Conclusion

When compared to the literature, the demographic, epidemiological, and clinical characteristics were similar in the cases we encountered. The mortality rate was high despite the use of appropriate treatment. We believe that the high mortality is related to higher APACHE II scores. The H1N1 virus should be considered in community acquired pneumonia, especially in younger patients presenting with severe pneumonia.     

Genetic characterization of H5N1 avian influenza viruses isolated in southern China during the 2003–04 avian influenza outbreaks

Summary. The recent H5N1 avian influenza outbreaks in Asia spread over more than 8 countries. It has caused enormous economic loss and grand challenges for the public health. During these breakouts we isolated three strains of H5N1 Avian Influenza Virus (AIV) from chickens and one from duck in different farms of Southern China. We completely sequenced these four AIVs. Molecular characterization demonstrated that these strains retain the reported H5N1 AIV sequence properties relevant to virus virulence and host adaptation. Phylogeny results demonstrated that three of these isolates (except A/Chicken/Guangdong/174/04) were closely linked to other H5N1 AIVs isolated from the recent H5N1 outbreaks in Asia. Six of 8 segments (except PA and M) of A/Chicken/Guangdong/174/04 also shares a close linkage to other H5N1 AIVs isolated from the recent H5N1 outbreaks. However, the PA gene of A/Chicken/Guangdong/174/04 and another H5N1 strain forms a distinct subgroup along with an H6N1 AIV, and the M gene of A/Chicken/Guangdong/174/04 shows a close linkage to some H5N1 AIVs from aquatic species in China. Our findings suggest that a new genotype of AIV (in addition to previous reported ones) was present during the 2003–04 Asian bird flu outbreaks and that continuing virus surveillance of AIVs be conducted to monitor the evolutionary paths of the A/Chicken/Guangdong/174/04-like AIVs.     

Will the next human influenza pandemic be caused by the virus of the avian flu A/H5N1? Arguments pro and counter

In 1997, the avian influenza A subtype H5N1 that caused big outbreaks of fowl pest in mass poultry farming had emerged in Hong Kong. Its spread throughout Eurasia had given rise to concerns in terms of the possible imminence of the next human influenza pandemic. In this article, epidemiological and virological arguments supporting or declining this fear are outlined and discussed with regard to viral infectivity and pathogenicity.     

Panvax(®): a monovalent inactivated unadjuvanted vaccine against pandemic influenza A (H1N1) 2009

Panvax(?) (CSL Biotherapies, Parkville, Australia) is one of a number of pandemic influenza A (H1N1) 2009 (pH1N1) vaccines fast-tracked for production, clinical trials and licensure in response to the emergence of the novel pH1N1 strain in early-mid-2009. Unexpectedly good immunogenicity following a single 15-μg dose was demonstrated in expedited clinical trials in adults and children. This facilitated early licensure and then rapid rollout for population immunization from October 2009. The vaccine's safety profile in the Australian population has been excellent.     

Emergence of H274Y oseltamivir-resistant A(H1N1) influenza viruses in Japan during the 2008–2009 season

BackgroundA substantial increase in oseltamivir-resistant A(H1N1) influenza viruses was reported in Europe in late 2007.ObjectivesTo monitor the antiviral susceptibility profile of human A(H1N1) influenza viruses in Japan during the 2007–2008 and 2008–2009 seasons.Study designViruses were obtained from respiratory samples of patients with influenza collected in Japan between December 2007 and April 2008 (n = 1046) and between December 2008 and April 2009 (n = 1789). Oseltamivir resistance was determined by an H274Y-specific real-time PCR cycling probe assay and a neuraminidase inhibition assay. Amantadine resistance was assessed by sequencing the M2 gene. Sequencing of the hemagglutinin and NA genes was performed to infer phylogenetic relationships between different strains.ResultsThree of 687 (0.4%) A(H1N1) viruses from the 2007–2008 season and 745 of 745 (100%) viruses from the 2008–2009 season carried the NA–H274Y substitution and demonstrated a >300-fold reduction in oseltamivir susceptibility. All oseltamivir-resistant viruses from the 2008–2009 season possessed an A193T substitution in the receptor-binding domain of the hemagglutinin. Amantadine resistance was detected in 431 of 687 (62.7%) and 0 of 745 (0.0%) of the A(H1N1) viruses from the 2007–2008 and 2008–2009 seasons, respectively.ConclusionsA dramatic surge in oseltamivir-resistant A(H1N1) viruses possessing the NA–H274Y substitution was detected in Japan during the 2008–2009 season. The emergence of oseltamivir-resistant viruses was facilitated by mutations in the viral genome. Intensified surveillance, including phenotypic assays and sequencing of the hemagglutinin, neuraminidase, and M2 gene would allow monitoring of the spread and evolution of drug-resistant influenza virus variants.     

Characterization of a reassortant H11N9 subtype avian influenza virus isolated from bean goose along the East Asian–Australian flyway

During the surveillance of avian influenza viruses in the Dongxi Lake wetland of Hubei in 2015–2016, an H11N9 avian influenza virus was isolated from a bean goose (Anser fabalis). Phylogenetic analysis showed that the HA gene of this isolate belongs to the North American lineage; however, the NA and the internal genes of the isolate were generated from the Eurasian lineage. This strain had reduced pathogenicity in mice and was capable of replication in the mouse lung without prior adaptation. This is the first report detecting H11N9 subtype influenza virus from migratory birds in central China. These findings highlight the transmission of avian influenza virus along the East Asian–Australian flyway and the need for continuing surveillance in central China.     

Postreassortment changes in a model system: HA–NA adjustment in an H3N2 avian–human reassortant influenza virus

Summary. In our previous studies we described the postreassortment changes in the hemagglutinin (HA) of H2N1, H3N1, H4N1 and H13N1 influenza A virus reassortants with HAs derived from avian viruses and low-functional neuraminidase (NA) of a human parent virus A/USSR/90/77 (H1N1). The changes involved amino acid substitutions that increased the negative local charge in the vicinity of the receptor-binding pocket and decreased the affinity of HA to sialic acid receptors. In the present report we describe the studies performed with H3N2 reassortant viruses having HA of A/Duck/Ukraine/1/63 (H3N8) virus and NA of A/Aichi/2/68 (H3N2) virus. Amino acid changes in the HA gene registered in virus variants selected in the course of serial passages resulted in a decrease in the affinity to sialic acid-containing substrates and cell receptors. However, the decrease was less expressed than in the reassortants containing the low-functional NA of N1 subtype described in our earlier studies, and the amino acid changes were not necessarily associated with an increase of negative charge. In one passage variant an amino acid substitution in NA was detected. The relevance of these results for the evolution of the H3N2 virus of the 1968 pandemic is discussed.     

Response of BALB/c mice to a monovalent influenza A （H1N1） 2009 split vaccine

The novel influenza A (H1N1) 2009 virus has emerged to cause the first pandemic of the twenty-first century. Disease outbreaks caused by the influenza A (H1N1) virus have prompted concerns about the potential for a pandemic and have driven the development of vaccines against this subtype of influenza A. In this study, we developed a monovalent influenza A (H1N1) split vaccine and evaluated its effects in BALB/c mice. Mice were immunized subcutaneously with 2 doses of the vaccine containing hemagglutinin (HA) alone or HA plus an aluminum hydroxide (Al(OH)₃) adjuvant. Immunization with varying doses of HA (3.75, 7.5, 15, 30, 45 or 60 µg) was performed to induce the production of neutralizing antibodies. The vaccine elicited strong hemagglutination inhibition (HI) and microneutralization, and addition of the adjuvant augmented the antibody response. A preliminary safety evaluation showed that the vaccine was not toxic at large doses (0.5 ml containing 60 µg HA+600 µg Al(OH)₃ or 60 µg HA). Moreover, the vaccine was found to be safe at a dose of 120 µg HA+1200 µg Al(OH)₃ or 120 µg HA in 1.0 ml in rats. In conclusion, the present study provides support for the clinical evaluation of influenza A (H1N1) vaccination as a public health intervention to mitigate a possible pandemic. Additionally, our findings support the further evaluation of the vaccine used in this study in primates or humans.