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Cited by 319Influenza Virus Research StudiesRespiratory viral infections researchVirology and Viral Diseases

Realities and enigmas of human viral influenza: pathogenesis, epidemiology and control.

HILLEMAN, M·2002·Vaccine
DOI 10.1016/s0264-410x(02)00254-2
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Abstract

Influenza A is a viral disease of global dimension, presenting with high morbidity and mortality in annual epidemics, and in pandemics which are of infrequent occurrence but which have very high attack rates. Influenza probes reveal a continuing battle for survival between host and parasite in which the host population updates the specificity of its pool of humoral immunity by contact with and response to infection with the most recent viruses which possess altered antigenic specificity in their hemagglutinin (HA) ligand. HA ligand binds the virus to the cell to bring about infection. Viral survival relies on escape from host immunity through antigenic alterations in nature which arise through genetic drift by point mutation principally of the HA gene, or through genetic shift by reassortment exchange of the HA ligand with that of viruses retained in avian species. Partial control of influenza is by use of killed whole, subunit, or possible live virus vaccines, all of which rely on worldwide surveillance to provide early detection of the altered immunologic specificity of the next virus to come. Future global surveillance may be aided by studies of sampled viral isolates in laboratories having capabilities for accelerated genetic sequencing and for automated rapid throughput analyses as well. Influenza vaccines of the future must be directed toward use of conserved group-specific viral antigens, such as are present in transitional proteins which are exposed during the fusion of virus to the host cell. Chemotherapy, though still primordial, must eventually provide the ultimate solution to vaccine failures. Probing the enigma of the severe influenza pandemic of 1918-1919 is an exciting contemporary venture in which genetic reconstruction of the viral genome from surviving archival RNA is being conducted with great success. Present evidence reveals successive recycling in pandemics, of only 3 of the 15 possible avian viral HAs. Pandemics are believed, conventionally, to be derived solely by rare events in which wild viruses of man acquire a new HA ligand of avian origin. There might be an alternative possibility involving a periodicity in selective control by the host population itself, in its receptivity or rejection at a particular time of particular reassortant viruses which might be created more frequently in nature than we are presently aware. This hypothesis, though remote, provides a different way to view and to probe the enigma of pandemic influenza.

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Crossref · 10.1016/s0264-410x(02)00254-2

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136 of 136 references verified0 citation errors · 0 not checkable

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  • The 1918 pandemic infected 50% of the world's population and resulted in approximately 40-50 million deaths worldwide.

    “It is considered the most devastating influenza pandemic ever recorded, infecting 50% of the world’s population and resulting in approximately 40–50 million deaths worldwide.”

    From Secondary bacterial infections associated with influenza pandemics (2017) · cites this paper as Hilleman, 2002

  • India alone suffered 7 million deaths during the 1918 pandemic.

    “India alone suffered 7 million deaths (Potter, 2001; Hilleman, 2002; Brundage, 2006; Michaelis et al., 2009).”

    From Secondary bacterial infections associated with influenza pandemics (2017) · cites this paper as Hilleman, 2002

  • The death toll in the United States during the 1957 pandemic was 69,800.

    “the death toll in the United States is accurately reported to have been 69, 800 (Klimov et al., 1999; Hilleman, 2002).”

    From Secondary bacterial infections associated with influenza pandemics (2017) · cites this paper as Hilleman, 2002

  • Overall 33,800 people died in the United States during the 1968-1969 pandemic, and the pandemic cost 3.9 billion dollars.

    “Overall 33,800 people died in the United States (Klimov et al., 1999) and the pandemic cost 3.9 billion dollars (Hilleman, 2002).”

    From Secondary bacterial infections associated with influenza pandemics (2017) · cites this paper as Hilleman, 2002

  • Influenza, as well as other upper respiratory tract viral infections, leads to a greater risk of infection from bacterial pathobionts and an increased likelihood of colonization with bacteria such as S. pneumoniae, H. influenzae, and S. aureus.

    “It has become clear that influenza, as well as other upper respiratory tract viral infections, leads not only to a greater risk of infection from bacterial pathobionts but also an increased likelihood that an individual may become colonized with bacteria such as S. pneumoniae, H. influenzae and S. aureus (Hament et al., 1999; Hilleman, 2002).”

    From Secondary bacterial infections associated with influenza pandemics (2017) · cites this paper as Hilleman, 2002

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Authors
HILLEMAN, M.
Affiliations
Merck & Co., Inc., Rahway, NJ, USA (United States) (US)
Corresponding author
HILLEMAN, M
Venue
Vaccine
Publisher
Elsevier BV
Published
2002-08
Volume
20
Issue
25-26
Pages
3068-3087
ISSN
0264-410X (ISSN-L)
DOI
10.1016/s0264-410x(02)00254-2
OpenAlex
W2049105549
Cited by
319
References
136
Citations by year
2026: 2 · 2025: 2 · 2024: 2 · 2023: 1 · 2022: 9 · 2021: 10 · 2020: 14 · 2019: 9 · 2018: 9 · 2017: 13 · 2016: 11 · 2015: 9 · 2014: 13 · 2013: 17 · 2012: 28
FWCI
8.29
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Vaccine (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Epidemiology › Influenza Virus Research Studies
  • Health Sciences › Medicine › Epidemiology › Respiratory viral infections research
  • Health Sciences › Medicine › Epidemiology › Virology and Viral Diseases
Keywords
influenza A virus, influenza pathogenesis, influenza epidemiology, influenza control, hemagglutinin, antigenic drift, antigenic shift, viral reassortment, avian influenza, influenza vaccination, global surveillance, viral genome reconstruction, antiviral therapy
MeSH terms
Adolescent, Adult, Aged, Animals, Antibodies, Viral, Antigens, Viral, Cell Line, Chickens, Child, Child, Preschool, Disease Outbreaks, Disease Reservoirs, Female, Forecasting, Health Policy, Humans, Infant, Influenza, Human, Influenza Vaccines, Male, Mammals, Middle Aged, Neuraminidase, Influenza A virus, Virulence, Virus Cultivation, Reassortant Viruses, Hemagglutinin Glycoproteins, Influenza Virus

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