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Concept: Influenza pandemic

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In the United States, annual vaccination against seasonal influenza is recommended for all persons aged ≥6 months (1). During each influenza season since 2004-05, CDC has estimated the effectiveness of seasonal influenza vaccine to prevent laboratory-confirmed influenza associated with medically attended acute respiratory illness (ARI). This report uses data from 4,562 children and adults enrolled in the U.S. Influenza Vaccine Effectiveness Network (U.S. Flu VE Network) during November 2, 2017-February 3, 2018. During this period, overall adjusted vaccine effectiveness (VE) against influenza A and influenza B virus infection associated with medically attended ARI was 36% (95% confidence interval [CI] = 27%-44%). Most (69%) influenza infections were caused by A(H3N2) viruses. VE was estimated to be 25% (CI = 13% to 36%) against illness caused by influenza A(H3N2) virus, 67% (CI = 54%-76%) against A(H1N1)pdm09 viruses, and 42% (CI = 25%-56%) against influenza B viruses. These early VE estimates underscore the need for ongoing influenza prevention and treatment measures. CDC continues to recommend influenza vaccination because the vaccine can still prevent some infections with currently circulating influenza viruses, which are expected to continue circulating for several weeks. Even with current vaccine effectiveness estimates, vaccination will still prevent influenza illness, including thousands of hospitalizations and deaths. Persons aged ≥6 months who have not yet been vaccinated this season should be vaccinated.

Concepts: Immune system, Infectious disease, Virus, Vaccine, Vaccination, Influenza, Influenza pandemic, Influenza vaccine

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Highly pathogenic avian H5N1 influenza A viruses occasionally infect humans, but currently do not transmit efficiently among humans. The viral haemagglutinin (HA) protein is a known host-range determinant as it mediates virus binding to host-specific cellular receptors. Here we assess the molecular changes in HA that would allow a virus possessing subtype H5 HA to be transmissible among mammals. We identified a reassortant H5 HA/H1N1 virus-comprising H5 HA (from an H5N1 virus) with four mutations and the remaining seven gene segments from a 2009 pandemic H1N1 virus-that was capable of droplet transmission in a ferret model. The transmissible H5 reassortant virus preferentially recognized human-type receptors, replicated efficiently in ferrets, caused lung lesions and weight loss, but was not highly pathogenic and did not cause mortality. These results indicate that H5 HA can convert to an HA that supports efficient viral transmission in mammals; however, we do not know whether the four mutations in the H5 HA identified here would render a wholly avian H5N1 virus transmissible. The genetic origin of the remaining seven viral gene segments may also critically contribute to transmissibility in mammals. Nevertheless, as H5N1 viruses continue to evolve and infect humans, receptor-binding variants of H5N1 viruses with pandemic potential, including avian-human reassortant viruses as tested here, may emerge. Our findings emphasize the need to prepare for potential pandemics caused by influenza viruses possessing H5 HA, and will help individuals conducting surveillance in regions with circulating H5N1 viruses to recognize key residues that predict the pandemic potential of isolates, which will inform the development, production and distribution of effective countermeasures.

Concepts: Virus, Influenza, Avian influenza, Influenza pandemic, Transmission and infection of H5N1, Pandemic, 2009 flu pandemic, Influenza A virus subtype H5N1

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The avian H7N9 influenza outbreak in 2013 resulted from an unprecedented incidence of influenza transmission to humans from infected poultry. The majority of human H7N9 isolates contained a hemagglutinin (HA) mutation (Q226L) that has previously been associated with a switch in receptor specificity from avian-type (NeuAcα2-3Gal) to human-type (NeuAcα2-6Gal), as documented for the avian progenitors of the 1957 (H2N2) and 1968 (H3N2) human influenza pandemic viruses. While this raised concern that the H7N9 virus was adapting to humans, the mutation was not sufficient to switch the receptor specificity of H7N9, and has not resulted in sustained transmission in humans. To determine if the H7 HA was capable of acquiring human-type receptor specificity, we conducted mutation analyses. Remarkably, three amino acid mutations conferred a switch in specificity for human-type receptors that resembled the specificity of the 2009 human H1 pandemic virus, and promoted binding to human trachea epithelial cells.

Concepts: DNA, Protein, Influenza, Avian influenza, Influenza pandemic, Transmission and infection of H5N1, Pandemic, Human flu

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For centuries, novel strains of influenza have emerged to produce human pandemics, causing widespread illness, death, and disruption. There have been four influenza pandemics in the past hundred years. During this time, globalization processes, alongside advances in medicine and epidemiology, have altered the way these pandemics are experienced. Drawing on international case studies, this paper provides a review of the impact of past influenza pandemics, while examining the evolution of our understanding of, and response to, these viruses. This review argues that pandemic influenza is in part a consequence of human development, and highlights the importance of considering outbreaks within the context of shifting global landscapes. While progress in infectious disease prevention, control, and treatment has improved our ability to respond to such outbreaks, globalization processes relating to human behaviour, demographics, and mobility have increased the threat of pandemic emergence and accelerated global disease transmission. Preparedness planning must continue to evolve to keep pace with this heightened risk. Herein, we look to the past for insights on the pandemic experience, underlining both progress and persisting challenges. However, given the uncertain timing and severity of future pandemics, we emphasize the need for flexible policies capable of responding to change as such emergencies develop.

Concepts: Epidemiology, Disease, Infectious disease, Influenza, Avian influenza, Influenza pandemic, Pandemic, Pandemic Severity Index

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Assessment of the effect of influenza on populations, including risk of infection, illness if infected, illness severity, and consultation rates, is essential to inform future control and prevention. We aimed to compare the community burden and severity of seasonal and pandemic influenza across different age groups and study years and gain insight into the extent to which traditional surveillance underestimates this burden.

Concepts: Infectious disease, Influenza, Avian influenza, Influenza pandemic, Transmission and infection of H5N1, Pandemic, Influenza vaccine, World Health Organization

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In preparing for influenza pandemics, public health agencies stockpile critical medical resources. Determining appropriate quantities and locations for such resources can be challenging, given the considerable uncertainty in the timing and severity of future pandemics. We introduce a method for optimizing stockpiles of mechanical ventilators, which are critical for treating hospitalized influenza patients in respiratory failure. As a case study, we consider the US state of Texas during mild, moderate, and severe pandemics. Optimal allocations prioritize local over central storage, even though the latter can be deployed adaptively, on the basis of real-time needs. This prioritization stems from high geographic correlations and the slightly lower treatment success assumed for centrally stockpiled ventilators. We developed our model and analysis in collaboration with academic researchers and a state public health agency and incorporated it into a Web-based decision-support tool for pandemic preparedness and response.

Concepts: Public health, Influenza, Avian influenza, Influenza pandemic, U.S. state, Pandemic, World Health Organization, Texas

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To the Editor: Avian-origin influenza A (H7N9) viruses emerged as human pathogens in China in 2013 and have caused 137 cases and 45 deaths to date.(1) These viruses have acquired mutations that could facilitate infection in mammals,(2) which could pose a pandemic threat if the viruses become readily transmissible in humans. Vaccines are a key defense against pandemics, but candidate vaccines featuring H7 hemagglutinins (HA) have been poorly immunogenic.(3) We have previously described the development, manufacture, and efficacy in mice of an A/Anhui/1/13 (H7N9) viruslike particle (VLP) vaccine produced in insect cells with the use of recombinant baculovirus. This vaccine . . .

Concepts: Immune system, Microbiology, Vaccine, Vaccination, Influenza, Influenza pandemic, Pandemic, Influenza vaccine

180

Influenza A H5N1 has killed millions of birds and raises serious public health concern because of its potential to spread to humans and cause a global pandemic. While the early focus was in Asia, recent evidence suggests that Egypt is a new epicenter for the disease. This includes characterization of a variant clade 2.2.1.1, which has been found almost exclusively in Egypt.We analyzed 226 HA and 92 NA sequences with an emphasis on the H5N1 2.2.1.1 strains in Egypt using a Bayesian discrete phylogeography approach. This allowed modeling of virus dispersion between Egyptian governorates including the most likely origin.

Concepts: Public health, Epidemiology, Influenza, Avian influenza, Influenza pandemic, Pandemic, 2009 flu pandemic, Egypt

176

Social factors have been shown to create differential burden of influenza across different geographic areas. We explored the relationship between potential aggregate-level social determinants and mortality during the 1918 influenza pandemic in Chicago using a historical dataset of 7,971 influenza and pneumonia deaths. Census tract-level social factors, including rates of illiteracy, homeownership, population, and unemployment, were assessed as predictors of pandemic mortality in Chicago. Poisson models fit with generalized estimating equations (GEEs) were used to estimate the association between social factors and the risk of influenza and pneumonia mortality. The Poisson model showed that influenza and pneumonia mortality increased, on average, by 32.2% for every 10% increase in illiteracy rate adjusted for population density, homeownership, unemployment, and age. We also found a significant association between transmissibility and population density, illiteracy, and unemployment but not homeownership. Lastly, analysis of the point locations of reported influenza and pneumonia deaths revealed fine-scale spatiotemporal clustering. This study shows that living in census tracts with higher illiteracy rates increased the risk of influenza and pneumonia mortality during the 1918 influenza pandemic in Chicago. Our observation that disparities in structural determinants of neighborhood-level health lead to disparities in influenza incidence in this pandemic suggests that disparities and their determinants should remain targets of research and control in future pandemics.

Concepts: Demography, Population, Influenza, Avian influenza, Influenza pandemic, Pandemic, 1918 flu pandemic

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