Concept: Avian influenza
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.
Increased risk of noninfluenza respiratory virus infections associated with receipt of inactivated influenza vaccine.
- Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
- Published almost 9 years ago
We randomized 115 children to trivalent inactivated influenza vaccine (TIV) or placebo. Over the following 9 months, TIV recipients had an increased risk of virologically-confirmed non-influenza infections (relative risk: 4.40; 95% confidence interval: 1.31-14.8). Being protected against influenza, TIV recipients may lack temporary non-specific immunity that protected against other respiratory viruses.
A perfect storm: Impact of genomic variation and serial vaccination on low influenza vaccine effectiveness during the 2014-15 season
- Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
- Published almost 5 years ago
The 2014-15 influenza season was distinguished by an A(H3N2) epidemic of antigenically-drifted virus and vaccine containing identical components to 2013-14. We report 2014-15 vaccine effectiveness (VE) estimates from Canada and explore contributing agent-host factors.
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.
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.
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.
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.
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 188.8.131.52, which has been found almost exclusively in Egypt.We analyzed 226 HA and 92 NA sequences with an emphasis on the H5N1 184.108.40.206 strains in Egypt using a Bayesian discrete phylogeography approach. This allowed modeling of virus dispersion between Egyptian governorates including the most likely origin.
The worldwide spread of a novel influenza A (H1N1) virus in 2009 showed that influenza remains a significant health threat, even for individuals in the prime of life. This paper focuses on the unusually high young adult mortality observed during the Spanish flu pandemic of 1918. Using historical records from Canada and the U.S., we report a peak of mortality at the exact age of 28 during the pandemic and argue that this increased mortality resulted from an early life exposure to influenza during the previous Russian flu pandemic of 1889-90. We posit that in specific instances, development of immunological memory to an influenza virus strain in early life may lead to a dysregulated immune response to antigenically novel strains encountered in later life, thereby increasing the risk of death. Exposure during critical periods of development could also create holes in the T cell repertoire and impair fetal maturation in general, thereby increasing mortality from infectious diseases later in life. Knowledge of the age-pattern of susceptibility to mortality from influenza could improve crisis management during future influenza pandemics.
Disparities in influenza mortality and transmission related to sociodemographic factors within Chicago in the pandemic of 1918
- Proceedings of the National Academy of Sciences of the United States of America
- Published over 4 years ago
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.