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*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.<ref>{{cite journal | last = Kendall | first = H | title = Vaccine Innovation: Lessons from World War II | url= http://docstore.ingenta.com/cgi-bin/ds_deliver/1/u/d/ISIS/32620254.1/pal/jphp/2006/00000027/00000001/art00005/FB2494BF0313967611615398189A7A906334373166.pdf?link=http://www.ingentaconnect.com/error/delivery&format=pdf | journal = Journal of Public Health Policy | volume = 27 | issue = 1 | pages = 38–57 | year = 2006}}</ref>  
*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.<ref>{{cite journal | last = Kendall | first = H | title = Vaccine Innovation: Lessons from World War II | url= http://docstore.ingenta.com/cgi-bin/ds_deliver/1/u/d/ISIS/32620254.1/pal/jphp/2006/00000027/00000001/art00005/FB2494BF0313967611615398189A7A906334373166.pdf?link=http://www.ingentaconnect.com/error/delivery&format=pdf | journal = Journal of Public Health Policy | volume = 27 | issue = 1 | pages = 38–57 | year = 2006}}</ref>  
*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/>
===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 [[pandemic]]s.<ref> [http://www.cdc.gov/ncidod/EID/vol12no01/05-0979.htm CDC] ARTICLE ''1918 Influenza: the Mother of All Pandemics'' by Jeffery K. Taubenberger published January 2006</ref>
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.<ref> [http://www.sciencedaily.com/releases/2006/10/061026185115.htm Science Daily] article ''New Study Has Important Implications For Flu Surveillance'' published  October 27, 2006</ref>


==References==
==References==

Revision as of 14:36, 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][9]
Name of pandemic Date Deaths Case fatality rate Subtype involved Pandemic Severity Index
1889–1890 Flu Pandemic
(Asiatic or Russian Flu)[10] 		1889–1890 1 million 0.15% possibly H3N8
or H2N2		 N/A
1918 Flu Pandemic
(Spanish flu)[11] 		1918–1920 20 to 100 million 2% H1N1 5
Asian Flu 1957–1958 1 to 1.5 million 0.13% H2N2 2
Hong Kong Flu 1968–1969 0.75 to 1 million <0.1% H3N2 2
Russian flu 1977–1978 no accurate count N/A H1N1 N/A
2009 Flu Pandemic[12] 2009–2010 105,700-395,600[13] 0.03% H1N1 N/A

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.[16]
  • 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.[17]
  • 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]

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 (19 August 2002). "Realities and enigmas of human viral influenza: pathogenesis, epidemiology and control". Vaccine. 20 (25–26): 3068–87. doi:10.1016/S0264-410X(02)00254-2. PMID 12163258.
  9. ↑ "Ten things you need to know about pandemic influenza". World Health Organization. 14 October 2005. Archived from the original on 23 September 2009. Retrieved 26 September 2009.
  10. ↑ Valleron AJ, Cori A, Valtat S, Meurisse S, Carrat F, Boëlle PY (May 2010). "Transmissibility and geographic spread of the 1889 influenza pandemic". Proc. Natl. Acad. Sci. U.S.A. 107 (19): 8778–81. Bibcode:2010PNAS..107.8778V. doi:10.1073/pnas.1000886107. PMC 2889325. PMID 20421481.
  11. ↑ Mills CE, Robins JM, Lipsitch M (December 2004). "Transmissibility of 1918 pandemic influenza". Nature. 432 (7019): 904–6. Bibcode:2004Natur.432..904M. doi:10.1038/nature03063. PMID 15602562.
  12. ↑ Donaldson LJ; Rutter PD; Ellis BM; et al. (2009). "Mortality from pandemic A/H1N1 2009 influenza in England: public health surveillance study". BMJ. 339: b5213. doi:10.1136/bmj.b5213. PMC 2791802. PMID 20007665. Unknown parameter |author-separator= ignored (help)
  13. ↑ Dawood, Fatimah S (26 June 2012). "Estimated global mortality associated with the first 12 months of 2009 pandemic influenza A H1N1 virus circulation: a modelling study". The Lancet Infectious Diseases. 12 (9): 687–95. doi:10.1016/S1473-3099(12)70121-4. PMID 22738893. Retrieved 19 March 2014. Unknown parameter |coauthors= ignored (help)
  14. ↑ 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)
  15. ↑ Smith, W (1933). "A virus obtained from influenza patients". Lancet. 2: 66–68. Unknown parameter |coauthors= ignored (help)
  16. ↑ Sir Frank Macfarlane Burnet: Biography The Nobel Foundation. Accessed 22 Oct 06
  17. ↑ Kendall, H (2006). "Vaccine Innovation: Lessons from World War II" (PDF). Journal of Public Health Policy. 27 (1): 38–57.

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