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*The Army was deeply involved in this research due to its experience of influenza in World War I, when thousands of troops were killed by the virus in a matter of months.<ref name= Knobler/>
*The Army was deeply involved in this research due to its experience of influenza in World War I, when thousands of troops were killed by the virus in a matter of months.<ref name= Knobler/>


==Etymology==
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The term influenza has its origins in 15th-century Italy, where the cause of the disease was ascribed to unfavourable astrological ''influences''.  Evolution in medical thought led to its modification to ''influenza del freddo'', meaning "influence of the cold." The word "influenza" was first attested in English in 1743 when it was borrowed during an outbreak of the disease in Europe.<ref name=Harper>{{cite web | last = Harper | first = D | title=Influenza | url=http://www.etymonline.com/index.php?search=influenza&searchmode=none  | publisher= Etymonlin}}</ref> Archaic terms for influenza include epidemic catarrh, grippe (from the French grippe, meaning flu; sometimes spelled "grip" or "gripe"), sweating sickness, and Spanish fever (particularly for the [[Spanish flu|1918 pandemic]] strain).<ref>{{cite web | last = Smith | first = P | title=Archaic Medical Terms | url= http://www.paul_smith.doctors.org.uk/ArchaicMedicalTerms.htm | accessdate = 2006-10-23}}</ref>
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:''See [[H5N1]] for the current [[epizootic]] (an [[epidemic]] in nonhumans) and panzootic (a disease affecting animals of many species especially over a wide area) of H5N1 influenza''
 
Wild [[fowl]] act as natural [[asymptomatic carrier]]s of Influenza A viruses. Prior to the current [[H5N1]] epizootic, strains of Influenza A virus had been demonstrated to be transmitted from wild fowl to only [[bird]]s, [[pig]]s, [[horse]]s, [[Pinniped|seal]]s, [[whale]]s and [[human]]s; and only between humans and pigs and between humans and domestic fowl; and not other pathways such as domestic fowl to horse. <ref>[http://www.nap.edu/books/0309095042/html/30.html NAP Books] National Academies Press Books - ''The Threat of Pandemic Influenza: Are We Ready? Workshop Summary (2005)'' - page 30</ref>
 
Wild aquatic birds are the natural hosts for a large variety of [[influenza]] A viruses. Occasionally viruses are transmitted from these birds to other species and may then cause devastating outbreaks in domestic poultry or give rise to human influenza [[pandemic]]s.<ref name=sobrino6>{{cite book |chapterurl=http://www.horizonpress.com/avir|author=Klenk et al|year=2008|chapter=Avian Influenza: Molecular Mechanisms of Pathogenesis and Host Range|title=Animal Viruses: Molecular Biology|publisher=Caister Academic Press|id=[http://www.horizonpress.com/avir ISBN 978-1-904455-22-6]}}</ref> <ref name=Kawaoka>{{cite book | author = Kawaoka Y (editor). | title = Influenza Virology: Current Topics | publisher = Caister Academic Press | year = 2006 | url=http://www.horizonpress.com/flu | id = [http://www.horizonpress.com/flu ISBN 978-1-904455-06-6 ]}}</ref>
 
[[H5N1]] has been shown to be transmitted to tigers, leopards, and domestic cats that were fed uncooked domestic fowl (chickens) with the virus. [[H3N8]] viruses from [[horse]]s have crossed over and caused outbreaks in [[dog]]s. Laboratory mice have been infected successfully with a variety of avian flu genotypes. <ref>[http://www.nap.edu/books/0309095042/html/82.html NAP Books] National Academies Press Books - ''The Threat of Pandemic Influenza: Are We Ready? Workshop Summary (2005)'' - page 82 - "Interestingly, recombinant influenza viruses containing the 1918 HA and NA and up to three additional genes derived from the 1918 virus (the other genes being derived from the A/WSN/33 virus) were all highly virulent in mice (Tumpey et al., 2004). Furthermore, expression microarray analysis performed on whole lung tissue of mice infected with the 1918 HA/ NA recombinant showed increased upregulation of genes involved in apoptosis, tissue injury, and oxidative damage (Kash et al., 2004). These findings were unusual because the viruses with the 1918 genes had not been adapted to mice. The completion of the sequence of the entire genome of the 1918 virus and the reconstruction and characterization of viruses with 1918 genes under appropriate biosafety conditions will shed more light on these findings and should allow a definitive examination of this explanation. Antigenic analysis of recombinant viruses possessing the 1918 HA and NA by hemagglutination inhibition tests using ferret and chicken antisera suggested a close relationship with the A/swine/Iowa/30 virus and H1N1 viruses isolated in the 1930s (Tumpey et al., 2004), further supporting data of Shope from the 1930s (Shope, 1936). Interestingly, when mice were immunized with different [[H1N1]] virus strains, challenge studies using the 1918-like viruses revealed partial protection by this treatment, suggesting that current vaccination strategies are adequate against a 1918-like virus (Tumpey et al., 2004)."</ref>
 
Influenza A viruses spread in the air and in [[manure]] and survives longer in cold weather.  It can also be transmitted by contaminated feed, water, equipment and clothing; however, there is no evidence that the virus can survive in well-cooked meat. Symptoms in animals vary, but virulent [[strain (biology)|strain]]s can cause death within a few days.
 
"Highly pathogenic avian influenza virus is on every top ten list available for potential agricultural bioweapon agents". <ref>[http://www.nap.edu/books/0309095042/html/285.html NAP Books] National Academies Press Books - ''The Threat of Pandemic Influenza: Are We Ready? Workshop Summary (2005)'' - page 285 - "As of October 2001, the potential for use of infectious agents, such as anthrax, as weapons has been firmly established. It has been suggested that attacks on a nation’s agriculture might be a preferred form of terrorism or economic disruption that would not have the attendant stigma of infecting and causing disease in humans. Highly pathogenic avian influenza virus is on every top ten list available for potential agricultural bioweapon agents, generally following foot and mouth disease virus and Newcastle disease virus at or near the top of the list. Rapid detection techniques for bioweapon agents are a critical need for the first-responder community, on a par with vaccine and antiviral development in preventing spread of disease."</ref>
 
Avian influenza viruses that the [[OIE]] and others test for in order to control poultry disease include: [[H5N1]], [[H7N2]], [[H1N7]], [[H7N3]], [[H13N6]], [[H5N9]], [[H11N6]], [[H3N8]], [[H9N2]], [[H5N2]], [[H4N8]], [[H10N7]], [[H2N2]], [[H8N4]], [[H14N5]], [[H6N5]], [[H12N5]] and others.
 
;Known outbreaks of highly pathogenic flu in poultry 1959-2003<ref>[http://www.who.int/csr/don/2004_03_02/en/ WHO] Avian influenza A(H5N1)- update 31: Situation (poultry) in Asia: need for a long-term response, comparison with previous outbreaks - Known outbreaks of highly pathogenic flu in poultry 1959-2003. </ref>
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Revision as of 14:25, 29 October 2014

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Historical Perspective

  • The symptoms of human influenza were clearly described by Hippocrates roughly 2400 years ago.[1][2]
  • Since then, the virus has caused numerous pandemics.
  • Historical data on influenza are difficult to interpret, because the symptoms can be similar to those of other diseases, such as diphtheria, pneumonic plague, typhoid fever, dengue, or typhus.
  • The first convincing record of an influenza pandemic was of an outbreak in 1580, which began in Asia and spread to Europe via Africa.
  • In Rome over 8,000 people were killed, and several Spanish cities were almost wiped out.
  • Pandemics continued sporadically throughout the 17th and 18th centuries, with the pandemic of 1830–1833 being particularly widespread; it infected approximately a quarter of the people exposed.[3]
The difference between the influenza mortality age-distributions of the 1918 epidemic and normal epidemics. Deaths per 100,000 persons in each age group, United States, for the interpandemic years 1911–1917 (dashed line) and the pandemic year 1918 (solid line).[4]

Spanish Flu Pandemic

  • The most famous and lethal outbreak was the so-called Spanish flu pandemic (type A influenza, H1N1 subtype), which lasted from 1918 to 1919.
  • Older estimates say it killed 40–50 million people[5] while current estimates say 50 million to 100 million people worldwide were killed.[6]
  • This pandemic has been described as "the greatest medical holocaust in history" and may have killed as many people as the Black Death.[3]
  • This huge death toll was caused by an extremely high infection rate of up to 50% and the extreme severity of the symptoms, suspected to be caused by cytokine storms.[5]
  • Indeed, symptoms in 1918 were so unusual that initially influenza was misdiagnosed as dengue, cholera, or typhoid.
  • The majority of deaths were from bacterial pneumonia, a secondary infection caused by influenza, but the virus also killed people directly, causing massive hemorrhages and edema in the lung.[4]
  • The Spanish flu pandemic was truly global, spreading even to the Arctic and remote Pacific islands.
  • The unusually severe disease killed between 2 and 20% of those infected, as opposed to the more usual flu epidemic mortality rate of 0.1%.[4][6]
  • Another unusual feature of this pandemic was that it mostly killed young adults, with 99% of pandemic influenza deaths occurring in people under 65, and more than half in young adults 20 to 40 years old.[7]
  • This is unusual since influenza is normally most deadly to the very young (under age 2) and the very old (over age 70).
  • The total mortality of the 1918–1919 pandemic is not known, but it is estimated that 2.5% to 5% of the world's population was killed. As many as 25 million may have been killed in the first 25 weeks; in contrast, HIV/AIDS has killed 25 million in its first 25 years.[6]

Known Flu Pandemics[8][3]
Name of pandemic Date Deaths Subtype involved Pandemic Severity Index
Asiatic (Russian) Flu 1889–1890 1 million possibly H2N2 ?
Spanish Flu 1918–1920 40 million H1N1 5
Asian Flu 1957–1958 1 to 1.5 million H2N2 2
Hong Kong Flu 1968–1969 0.75 to 1 million H3N2 2

Other Flu Pandemics

  • Later flu pandemics were not so devastating.
  • They included the following:
  • Even these smaller outbreaks killed millions of people.
  • In later pandemics antibiotics were available to control secondary infections and this may have helped reduce mortality compared to the Spanish Flu of 1918.[4]
  • Although there were scares in New Jersey in 1976 (with the Swine Flu), world wide in 1977 (with the Russian Flu), and in Hong Kong and other Asian countries in 1997 (with H5N1 avian influenza), there have been no major pandemics since the 1968 Hong Kong Flu.
  • Immunity to previous pandemic influenza strains and vaccination may have limited the spread of the virus and may have helped prevent further pandemics.[8]

Influenza Virus

Flu Vaccine

  • The first significant step towards preventing influenza was the development in 1944 of a killed-virus vaccine for influenza by Thomas Francis, Jr.. This built on work by Frank Macfarlane Burnet, who showed that the virus lost virulence when it was cultured in fertilized hen's eggs.[11]
  • Application of this observation by Francis allowed his group of researchers at the University of Michigan to develop the first flu vaccine, with support from the U.S. Army.[12]
  • The Army was deeply involved in this research due to its experience of influenza in World War I, when thousands of troops were killed by the virus in a matter of months.[6]

Year Area Affected Species Subtype
1959 Scotland chicken H5N1
1963 England turkey H7N3
1966 Ontario (Canada) turkey H5N9
1976 Victoria (Australia) chicken H7N7
1979 Germany chicken H7N7
1979 England turkey H7N7
1983 Pennsylvania (USA)* chicken,turkey H5N2
1983 Ireland turkey H5N8
1985 Victoria (Australia) chicken H7N7
1991 England turkey H5N1
1992 Victoria (Australia) chicken H7N3
1994 Queensland (Australia) chicken H7N3
1994 Mexico* chicken H5N2
1994 Pakistan* chicken H7N3
1997 New South Wales (Australia) chicken H7N4
1997 Hong Kong (China)* chicken H5N1
1997 Italy chicken H5N2
1999 Italy* turkey H7N1
2002 Hong Kong (China) chicken H5N1
2002 Chile chicken H7N3
2003 Netherlands* chicken H7N7

*Outbreaks with significant spread to numerous farms, resulting in great economic losses. Most other outbreaks involved little or no spread from the initially infected farms.

1979: "More than 400 harbor seals, most of them immature, died along the New England coast between December 1979 and October 1980 of acute pneumonia associated with influenza virus, A/Seal/Mass/1/180 (H7N7)." [13]

1995: "[V]accinated birds can develop asymptomatic infections that allow virus to spread, mutate, and recombine (ProMED-mail, 2004j). Intensive surveillance is required to detect these “silent epidemics” in time to curtail them. In Mexico, for example, mass vaccination of chickens against epidemic H5N2 influenza in 1995 has had to continue in order to control a persistent and evolving virus (Lee et al., 2004)." [14]

1997: "Influenza A viruses normally seen in one species sometimes can cross over and cause illness in another species. For example, until 1997, only H1N1 viruses circulated widely in the U.S. pig population. However, in 1997, H3N2 viruses from humans were introduced into the pig population and caused widespread disease among pigs. Most recently, H3N8 viruses from horses have crossed over and caused outbreaks in dogs." [15]

2000: "In California, poultry producers kept their knowledge of a recent H6N2 avian influenza outbreak to themselves due to their fear of public rejection of poultry products; meanwhile, the disease spread across the western United States and has since become endemic." [16]

2003: In Netherlands H7N7 influenza virus infection broke out in poultry on several farms. [17]

2004: In North America, the presence of avian influenza strain H7N3 was confirmed at several poultry farms in British Columbia in February 2004. As of April 2004, 18 farms had been quarantined to halt the spread of the virus. [18]

2005: Tens of millions of birds died of H5N1 influenza and hundreds of millions of birds were culled to protect humans from H5N1. H5N1 is endemic in birds in southeast Asia and represents a long term pandemic threat.

2006: H5N1 spreads across the globe killing hundreds of millions of birds and over 100 people causing a significant H5N1 impact from both actual deaths and predicted possible deaths.

Evolution

See also: Punctuated equilibrium

Taubenberger says:

"All influenza A pandemics since [the Spanish flu pandemic], and indeed almost all cases of influenza A worldwide (excepting human infections from avian viruses such as H5N1 and H7N7), have been caused by descendants of the 1918 virus, including "drifted" H1N1 viruses and reassorted H2N2 and H3N2 viruses. The latter are composed of key genes from the 1918 virus, updated by subsequently incorporated avian influenza genes that code for novel surface proteins, making the 1918 virus indeed the "mother" of all pandemics.[19]

Researchers from the National Institutes of Health used data from the Influenza Genome Sequencing Project and concluded that during the ten-year period examined most of the time the hemagglutinin gene in H3N2 showed no significant excess of mutations in the antigenic regions while an increasing variety of strains accumulated. This resulted in one of the variants eventually achieving higher fitness, becoming dominant, and in a brief interval of rapid Darwinian evolution rapidly sweeping through the human population and eliminating most other variants.[20]

References

  1. ↑ Martin, P (2006). "2,500-year evolution of the term epidemic". Emerg Infect Dis. 12 (6). PMID 16707055. Unknown parameter |coauthors= ignored (help); Unknown parameter |month= ignored (help)
  2. ↑ Hippocrates (400 BCE). "Of the Epidemics". Retrieved 2006-10-18. Unknown parameter |coauthors= ignored (help); Check date values in: |date= (help)
  3. ↑ 3.0 3.1 3.2 Potter, CW (2006). "A History of Influenza". J Appl Microbiol. 91 (4): 572–579. PMID 11576290. Unknown parameter |month= ignored (help)
  4. ↑ 4.0 4.1 4.2 4.3 Taubenberger, J (2006). "1918 Influenza: the mother of all pandemics". Emerg Infect Dis. 12 (1): 15–22. PMID 16494711. Unknown parameter |coauthors= ignored (help)
  5. ↑ 5.0 5.1 Patterson, KD (1991). "The geography and mortality of the 1918 influenza pandemic". Bull Hist Med. 65 (1): 4–21. PMID 2021692. Unknown parameter |month= ignored (help); Unknown parameter |coauthors= ignored (help)
  6. ↑ 6.0 6.1 6.2 6.3 Knobler S, Mack A, Mahmoud A, Lemon S (ed.). "1: The Story of Influenza". The Threat of Pandemic Influenza: Are We Ready? Workshop Summary (2005). Washington, D.C.: The National Academies Press. pp. 60–61.
  7. ↑ Simonsen, L (1998). "Pandemic versus epidemic influenza mortality: a pattern of changing age distribution". J Infect Dis. 178 (1): 53–60. PMID 9652423. Unknown parameter |month= ignored (help); Unknown parameter |coauthors= ignored (help)
  8. ↑ 8.0 8.1 Hilleman, M (2002). "Realities and enigmas of human viral influenza: pathogenesis, epidemiology and control". Vaccine. 20 (25–26): 3068–87. PMID 12163258. Unknown parameter |month= ignored (help)
  9. ↑ Shimizu, K (1997). "History of influenza epidemics and discovery of influenza virus". Nippon Rinsho. 55 (10): 2505–201. PMID 9360364. Unknown parameter |month= ignored (help)
  10. ↑ Smith, W (1933). "A virus obtained from influenza patients". Lancet. 2: 66–68. Unknown parameter |coauthors= ignored (help)
  11. ↑ Sir Frank Macfarlane Burnet: Biography The Nobel Foundation. Accessed 22 Oct 06
  12. ↑ Kendall, H (2006). "Vaccine Innovation: Lessons from World War II" (PDF). Journal of Public Health Policy. 27 (1): 38–57.
  13. ↑ NCBI - NLM - NIH National Center for Biotechnology Information (part of) U.S. National Library of Medicine (part of) National Institutes of Health (part of) US Government - Science. 1982 Feb 26;215(4536):1129-31. - Mass mortality of harbor seals: pneumonia associated with influenza A virus. - "More than 400 harbor seals, most of them immature, died along the New England coast between December 1979 and October 1980 of acute pneumonia associated with influenza virus, A/Seal/Mass/1/180 (H7N7). The virus has avian characteristics, replicates principally in mammals, and causes mild respiratory disease in experimentally infected seals. Concurrent infection with a previously undescribed mycoplasma or adverse environmental conditions may have triggered the epizootic. The similarities between this epizootic and other seal mortalities in the past suggest that these events may be linked by common biological and environmental factors."
  14. ↑ NAP Books National Academies Press Books - The Threat of Pandemic Influenza: Are We Ready? Workshop Summary (2005) - page 15 - "Unlike most other affected countries, Indonesia also instituted mass vaccination of healthy domestic birds against H5N1, followed by routine vaccination (China has a similar policy; other Asian countries are considering it [ProMED-mail, 2004j]) (Soebandrio, 2004). This is a risky strategy, because vaccinated birds can develop asymptomatic infections that allow virus to spread, mutate, and recombine (ProMED-mail, 2004j). Intensive surveillance is required to detect these “silent epidemics” in time to curtail them. In Mexico, for example, mass vaccination of chickens against epidemic H5N2 influenza in 1995 has had to continue in order to control a persistent and evolving virus (Lee et al., 2004)."
  15. ↑ CDC Centers for Disease Control and Prevention - Transmission of Influenza A Viruses Between Animals and People
  16. ↑ NAP Books National Academies Press Books - The Threat of Pandemic Influenza: Are We Ready? Workshop Summary (2005) - page 27.
  17. ↑ BBC News Early bird flu warning for Dutch - 6 November 2005
  18. ↑ CDC detailed analysis Human Illness from Avian Influenza H7N3, British Columbia
  19. ↑ CDC ARTICLE 1918 Influenza: the Mother of All Pandemics by Jeffery K. Taubenberger published January 2006
  20. ↑ Science Daily article New Study Has Important Implications For Flu Surveillance published October 27, 2006

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