ContextRespiratory viral infections are responsible for a large number of hospitalizations
in the United States each year.ObjectiveTo estimate annual influenza-associated hospitalizations in the United
States by hospital discharge category, discharge type, and age group.Design, Setting, and ParticipantsNational Hospital Discharge Survey (NHDS) data and World Health Organization
Collaborating Laboratories influenza surveillance data were used to estimate
annual average numbers of hospitalizations associated with the circulation
of influenza viruses from the 1979-1980 through the 2000-2001 seasons in the
United States using age-specific Poisson regression models.Main Outcome MeasuresWe estimated influenza-associated hospitalizations for primary and any
listed pneumonia and influenza and respiratory and circulatory hospitalizations.ResultsAnnual averages of 94 735 (range, 18 908-193 561) primary
and 133 900 (range, 30 757-271 529) any listed pneumonia and
influenza hospitalizations were associated with influenza virus infections.
Annual averages of 226 054 (range, 54 523-430 960) primary
and 294 128 (range, 86 494-544 909) any listed respiratory
and circulatory hospitalizations were associated with influenza virus infections.
Persons 85 years or older had the highest rates of influenza-associated primary
respiratory and circulatory hospitalizations (1194.9 per 100 000 persons).
Children younger than 5 years (107.9 primary respiratory and circulatory hospitalizations
per 100 000 persons) had rates similar to persons aged 50 through 64
years. Estimated rates of influenza-associated hospitalizations were highest
during seasons in which A(H3N2) viruses predominated, followed by B and A(H1N1)
seasons. After adjusting for the length of each influenza season, influenza-associated
primary pneumonia and influenza hospitalizations increased over time among
the elderly. There were no significant increases in influenza-associated primary
respiratory and circulatory hospitalizations after adjusting for the length
of the influenza season.ConclusionsSignificant numbers of influenza-associated hospitalizations in the
United States occur among the elderly, and the numbers of these hospitalizations
have increased substantially over the last 2 decades due in part to the aging
of the population. Children younger than 5 years had rates of influenza-associated
hospitalizations similar to those among individuals aged 50 through 64 years.
These findings highlight the need for improved influenza prevention efforts
for both young and older US residents.

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Influenza-associated hospitalizations in the United States.

Understanding the evolution of influenza A viruses in humans is important for surveillance and vaccine strain selection. We performed a phylogenetic analysis of 156 complete genomes of human H3N2 influenza A viruses collected between 1999 and 2004 from New York State, United States, and observed multiple co-circulating clades with different population frequencies. Strikingly, phylogenies inferred for individual gene segments revealed that multiple reassortment events had occurred among these clades, such that one clade of H3N2 viruses present at least since 2000 had provided the hemagglutinin gene for all those H3N2 viruses sampled after the 2002–2003 influenza season. This reassortment event was the likely progenitor of the antigenically variant influenza strains that caused the A/Fujian/411/2002-like epidemic of the 2003–2004 influenza season. However, despite sharing the same hemagglutinin, these phylogenetically distinct lineages of viruses continue to co-circulate in the same population. These data, derived from the first large-scale analysis of H3N2 viruses, convincingly demonstrate that multiple lineages can co-circulate, persist, and reassort in epidemiologically significant ways, and underscore the importance of genomic analyses for future influenza surveillance.

Whole-Genome Analysis of Human Influenza A Virus Reveals Multiple Persistent Lineages and Reassortment among Recent H3N2 Viruses

The "Spanish" influenza pandemic of 1918-19 caused acute illness in 25-30 percent of the world's population and resulted in the death of up to an estimated 40 million people. Using fixed and frozen lung tissue of 1918 influenza victims, the complete genomic sequence of the 1918 influenza virus has been deduced. Sequence and phylogenetic analysis of the completed 1918 influenza virus genes shows them to be the most avian-like among the mammalian-adapted viruses. This finding supports the hypotheses that (1) the pandemic virus contains genes derived from avian-like influenza virus strains and that (2) the 1918 virus is the common ancestor of human and classical swine H1N1 influenza viruses. The relationship of the 1918 virus with avian influenza viruses is further supported by recent work in which the 1918 hemagglutinin (HA) protein crystal structure was resolved. Neither the 1918 hemagglutinin (HA) nor the neuraminidase (NA) genes possess mutations known to increase tissue tropicity that account for the virulence of other influenza virus strains like A/WSN/33 or the highly pathogenic avian influenza H5 or H7 viruses. Using reverse genetics approaches, influenza virus constructs containing the 1918 HA and NA on a modern human influenza virus background were lethal in mice. The complete 1918 virus was even more virulent in mice. The genotypic basis of this virulence has not yet been elucidated. The complete sequence of the non-structural (NS) gene segment of the 1918 virus was deduced and also tested for the hypothesis that enhanced virulence in 1918 could have been due to type I interferon inhibition by the NS1 protein. Results from these experiments suggest that in human cells the 1918 NS1 is a very effective interferon antagonist, but the 1918 NS1 gene does not have the amino acid change that correlates with virulence in the H5N1 virus strains identified in 1997 in Hong Kong. Sequence analysis of the 1918 pandemic influenza virus is allowing us to test hypotheses as to the origin and virulence of this strain. This information should help elucidate how pandemic influenza virus strains emerge and what genetic features contribute to virulence in humans.

https://www.jstor.org/stable/info/4598974

The Origin and Virulence of the 1918 “Spanish” Influenza Virus

The Spanish influenza pandemic of 1918-1919 caused acute illness in 25-30% of the world's population and resulted in the death of 40 million people. The complete genomic sequence of the 1918 influenza virus will be deduced using fixed and frozen tissues of 1918 influenza victims. Sequence and phylogenetic analyses of the complete 1918 haemagglutinin (HA) and neuraminidase (NA) genes show them to be the most avian-like of mammalian sequences and support the hypothesis that the pandemic virus contained surface protein-encoding genes derived from an avian influenza strain and that the 1918 virus is very similar to the common ancestor of human and classical swine H1N1 influenza strains. Neither the 1918 HA genes nor the NA genes possessed mutations that are known to increase tissue tropicity, which accounts for the virulence of other influenza strains such as A/WSN/33 or fowl plague viruses. The complete sequence of the nonstructural (NS) gene segment of the 1918 virus was deduced and tested for the hypothesis that the enhanced virulence in 1918 could have been due to type I interferon inhibition by the NS1 protein. The results from these experiments were inconclusive. Sequence analysis of the 1918 pandemic influenza virus is allowing us to test hypotheses as to the origin and virulence of this strain. This information should help to elucidate how pandemic influenza strains emerge and what genetic features contribute to their virulence.

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Integrating historical, clinical and molecular genetic data in order to explain the origin and virulence of the 1918 Spanish influenza virus

Annual outbreaks of influenza A infection are an ongoing public health threat and novel influenza strains can periodically emerge to which humans have little immunity, resulting in devastating pandemics. The 1918 pandemic killed at least 40 million people worldwide and pandemics in 1957 and 1968 caused hundreds of thousands of deaths. The influenza A virus is capable of enormous genetic variation, both by continuous, gradual mutation and by reassortment of genome segments between viruses. Both the 1957 and 1968 pandemic strains are thought to have originated as reassortants in which one or both human-adapted viral surface proteins were replaced by proteins from avian influenza strains. Analyses of the genes of the 1918 pandemic virus, however, indicate that this strain might have had a different origin. The haemagglutinin and nucleoprotein genome segments in particular are unlikely to have come directly from an avian source that is similar to those that are currently being sequenced. Determining whether a pandemic influenza virus can emerge by different mechanisms will affect the scope and focus of surveillance and prevention efforts.

Raymond A Strikes

Papers

Preparing for pandemic influenza: the need for enhanced surveillance