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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 storm]]s.<ref name="Patterson1"/> Indeed, symptoms in 1918 were so unusual that initially influenza was misdiagnosed as [[dengue]], [[cholera]], or [[typhoid]]. One observer wrote, "One of the most striking of the complications was hemorrhage from mucous membranes, especially from the nose, stomach, and intestine. Bleeding from the ears and [[petechia|petechial hemorrhages]] in the skin also occurred."<ref name=Knobler/> The majority of deaths were from [[bacterial pneumonia]], a [[secondary infection]] caused by influenza, but the virus also killed people directly, causing massive [[bleeding|hemorrhages]] and [[edema]] in the lung.<ref name="Taubenberger">{{cite journal | last = Taubenberger | first = J | coauthors = Reid A, Janczewski T, Fanning T | title = Integrating historical, clinical and molecular genetic data in order to explain the origin and virulence of the 1918 Spanish influenza virus | journal = Philos Trans R Soc Lond B Biol Sci | volume = 356 | issue = 1416 | pages = 1829–39 | year = 2001 | month=December 29 | pmid = 11779381 | url= http://www.journals.royalsoc.ac.uk/(3sud2455cjw1ut55yowx1d45)/app/home/contribution.asp?referrer=parent&backto=issue,3,22;journal,61,225;linkingpublicationresults,1:102022,1 | doi = 10.1098/rstb.2001.1020}}</ref>
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 storm]]s.<ref name="Patterson1"/> Indeed, symptoms in 1918 were so unusual that initially influenza was misdiagnosed as [[dengue]], [[cholera]], or [[typhoid]]. One observer wrote, "One of the most striking of the complications was hemorrhage from mucous membranes, especially from the nose, stomach, and intestine. Bleeding from the ears and [[petechia|petechial hemorrhages]] in the skin also occurred."<ref name=Knobler/> The majority of deaths were from [[bacterial pneumonia]], a [[secondary infection]] caused by influenza, but the virus also killed people directly, causing massive [[bleeding|hemorrhages]] and [[edema]] in the lung.<ref name="Taubenberger">{{cite journal | last = Taubenberger | first = J | coauthors = Reid A, Janczewski T, Fanning T | title = Integrating historical, clinical and molecular genetic data in order to explain the origin and virulence of the 1918 Spanish influenza virus | journal = Philos Trans R Soc Lond B Biol Sci | volume = 356 | issue = 1416 | pages = 1829–39 | year = 2001 | month=December 29 | pmid = 11779381 | url= http://www.journals.royalsoc.ac.uk/(3sud2455cjw1ut55yowx1d45)/app/home/contribution.asp?referrer=parent&backto=issue,3,22;journal,61,225;linkingpublicationresults,1:102022,1 | doi = 10.1098/rstb.2001.1020}}</ref>


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%.<ref name="Taubenberger"/><ref name=Knobler/> 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&nbsp;years old.<ref>{{cite journal | last = Simonsen | first = L | coauthors = Clarke M, Schonberger L, Arden N, Cox N, Fukuda K | title = Pandemic versus epidemic influenza mortality: a pattern of changing age distribution | journal = J Infect Dis | volume = 178 | issue = 1 | pages = 53–60 | year = 1998 | month=July | pmid = 9652423}}</ref> This is unusual since influenza is normally most deadly to the very young (under age 2) and the very old (over age 70), and may have been due to partial protection caused by exposure to a previous [[Influenza A virus subtype H2N2#Russian flu|Russian flu pandemic of 1889]].<ref name=hansen>O Hansen, 1923, ''Undersøkelser om influenzaens opptræden specielt i Bergen 1918–1922'' Skrifter utgit ved Klaus Hanssens Fond. Bergen: Medicinsk avdeling, Haukeland Sykehus, 1923: 3.</ref>
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%.<ref name="Taubenberger"/><ref name=Knobler/> 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&nbsp;years old. I highly agree with this statment hahaha
<ref>{{cite journal | last = Simonsen | first = L | coauthors = Clarke M, Schonberger L, Arden N, Cox N, Fukuda K | title = Pandemic versus epidemic influenza mortality: a pattern of changing age distribution | journal = J Infect Dis | volume = 178 | issue = 1 | pages = 53–60 | year = 1998 | month=July | pmid = 9652423}}</ref> This is unusual since influenza is normally most deadly to the very young (under age 2) and the very old (over age 70), and may have been due to partial protection caused by exposure to a previous [[Influenza A virus subtype H2N2#Russian flu|Russian flu pandemic of 1889]].<ref name=hansen>O Hansen, 1923, ''Undersøkelser om influenzaens opptræden specielt i Bergen 1918–1922'' Skrifter utgit ved Klaus Hanssens Fond. Bergen: Medicinsk avdeling, Haukeland Sykehus, 1923: 3.</ref>


== Origins of name ==
== Origins of name ==

Revision as of 01:46, 22 July 2009

Two American Red Cross nurses demonstrate treatment practices during the influenza pandemic of 1918.

The 1918 flu pandemic (commonly referred to as the Spanish flu) was an influenza pandemic that spread to nearly every part of the world. It was caused by an unusually virulent and deadly influenza A virus strain of subtype H1N1. Historical and epidemiological data are inadequate to identify the geographic origin of the virus.[1] Most of its victims were healthy young adults, in contrast to most influenza outbreaks which predominantly affect juvenile, elderly, or otherwise weakened patients. The flu pandemic has also been implicated in the sudden outbreak of encephalitis lethargica in the 1920s.[2]

The pandemic lasted from March 1918 to June 1920,[3] spreading even to the Arctic and remote Pacific islands. It is estimated that anywhere from 50 to 100 million people were killed worldwide,[4][5] or the approximate equivalent of one third of the population of Europe.[6][7][8] An estimated 500 million people, one third of the world's population (approximately 1.6 billion at the time), became infected.[5]

Scientists have used tissue samples from frozen victims to reproduce the virus for study. Given the strain's extreme virulence there has been controversy regarding the wisdom of such research. Among the conclusions of this research is that the virus kills via a cytokine storm (overreaction of the body's immune system) which explains its unusually severe nature and the concentrated age profile of its victims. The strong immune systems of young adults ravaged the body, whereas the weaker immune systems of children and middle-aged adults caused fewer deaths.

Mortality

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).[9]
Three pandemic waves: weekly combined influenza and pneumonia mortality, United Kingdom, 1918–1919[10]

The global mortality rate from the 1918/1919 pandemic is not known, but it is estimated that 10% to 20% of those who were infected died. With about a third of the world population infected, this case-fatality ratio means that 3% to 6% of the entire global population died.[11] Influenza may have killed as many as 25 million in its first 25 weeks. Older estimates say it killed 40–50 million people[4] while current estimates say 50 million to 100 million people worldwide were killed.[12] This pandemic has been described as "the greatest medical holocaust in history" and may have killed more people than the Black Death.[13]

As many as 17 million died in India, about 5% of India's population at the time.[14] In Japan, 23 million persons were affected, and 390,000 died.[15] In the U.S., about 28% of the population suffered, and 500,000 to 675,000 died.[16] In Britain as many as 250,000 died; in France more than 400,000.[17] In Canada approximately 50,000 died.[18] Entire villages perished in Alaska[19] and southern Africa.[which?] Ras Tafari (the future Haile Selassie) was one of the first Ethiopians who contracted influenza but survived,[20] although many of his subjects did not; estimates for the fatalities in the capital city, Addis Ababa, range from 5,000 to 10,000, with some experts opining that the number was even higher,[21] while in British Somaliland one official there estimated that 7% of the native population died from influenza.[22] In Australia an estimated 12,000 people died and in the Fiji Islands, 14% of the population died during only two weeks, and in Western Samoa 22%.

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.[4] Indeed, symptoms in 1918 were so unusual that initially influenza was misdiagnosed as dengue, cholera, or typhoid. One observer wrote, "One of the most striking of the complications was hemorrhage from mucous membranes, especially from the nose, stomach, and intestine. Bleeding from the ears and petechial hemorrhages in the skin also occurred."[12] 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.[9]

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%.[9][12] 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. I highly agree with this statment hahaha

[23] This is unusual since influenza is normally most deadly to the very young (under age 2) and the very old (over age 70), and may have been due to partial protection caused by exposure to a previous Russian flu pandemic of 1889.[24]

Origins of name

Although the first cases of the disease were registered in the continental US and the rest of Europe long before getting to Spain, the 1918 Flu received its nickname "Spanish Flu" because Spain, a neutral country in WWI, had no special censorship for news against the disease and its consequences. Hence the most reliable news came from Spain, giving the false impression that Spain was the most—if not the only—affected zone.[25]

History

While World War I did not cause the flu, the close troop quarters and massive troop movements hastened the pandemic, and increased transmission augmented mutation and may have increased the lethality of the virus. Some researchers speculate that the soldiers' immune systems were weakened by malnourishment, and the stresses of combat and chemical attacks, increasing their susceptibility to the disease.[26] Price-Smith has made the controversial argument that the virus helped tip the balance of power in the latter days of the war towards the Allied cause. Specifically, he provides data that the viral waves hit the Central Powers before they hit the Allied powers, and that both morbidity and mortality in Germany and Austria were considerably higher than in Britain and France.[27]

A large factor of worldwide flu occurrence was increased travel. Modern transportation systems made it easier for soldiers, sailors, and civilian travelers to spread the disease quickly to communities worldwide.

Geographic sources

Some scholars have theorized that the flu probably originated in the Far East.[28] Dr. C. Hannoun, leading expert of the 1918 flu for the Institut Pasteur noticed that the former virus was likely to have come from China, mutated in the United States near Boston, and spread to Brest (France), Europe's battlefields, Europe, and the world using Allied soldiers and sailors as main spreaders.[29] C. Hannoun also designated several other theories, such as Spain, Kansas, and Brest, as being possible but not likely.

Historian Alfred W. Crosby observed that the flu seems to have originated in Kansas.[30] Political scientist Andrew Price-Smith published data from the Austrian archives suggesting that the influenza had earlier origins, beginning in Austria in the spring of 1917.[31] Popular writer John Barry echoed Crosby in proposing that Haskell County, Kansas was the location of the first outbreak of flu.[32] In the United States the disease was first observed at Fort Riley, Kansas, United States, on March 4, 1918,[33] and Queens, New York, on March 11, 1918. In August 1918, a more virulent strain appeared simultaneously in Brest, France, in Freetown, Sierra Leone, and in the U.S. at Boston, Massachusetts. The Allies of World War I came to call it the Spanish flu, primarily because the pandemic received greater press attention after it moved from France to Spain in November 1918. Spain was not involved in the war and had not imposed wartime censorship.[34]

Investigative work by a British team, led by virologist John Oxford[35] of St Bartholomew's Hospital and the Royal London Hospital, has suggested that a principal British troop staging camp in Étaples, France was at the center of the 1918 flu pandemic, or was the location of a significant precursor virus.[36]

Patterns of fatality

The influenza strain was unusual in that this pandemic killed many young adults and otherwise healthy victims; typical influenzas kill mostly weak individuals, such as infants (aged 0–2 years), the elderly, and the immunocompromised. Older adults may have had some immunity from the earlier Russian flu pandemic of 1889.[24] Another oddity was that the outbreak was widespread in summer and fall (in the Northern Hemisphere); influenza is usually worse in winter.[37]

In fast-progressing cases, mortality was primarily from pneumonia, by virus-induced pulmonary consolidation. Slower-progressing cases featured secondary bacterial pneumonias, and there may have been neural involvement that led to mental disorders in some cases. Some deaths resulted from malnourishment and even animal attacks in overwhelmed communities.[38]

Deadly second wave

The second wave of the 1918 pandemic was much deadlier than the first. During the first wave, which began in early March, the epidemic resembled typical flu epidemics. Those at the most risk were the sick and elderly, and younger, healthier people recovered easily. But in August, when the second wave began in France, Sierra Leone and the United States,[39] the virus had mutated to a much more deadly form. This has been attributed to the circumstances of the First World War.[40] In civilian life evolutionary pressures favor a mild strain: those who get really sick stay home, but those mildly ill continue with their lives, go to work and go shopping, preferentially spreading the mild strain. In the trenches the evolutionary pressures were reversed: soldiers with a mild strain remained where they were, while the severely ill were sent on crowded trains to crowded field hospitals, spreading the deadlier virus. So the second wave began and flu quickly spread around the world again.[41] It was the same flu, in that those who recovered from first-wave infections were immune, but it was far more deadly, and the most vulnerable people were those like the soldiers in the trenches—young, otherwise healthy, adults.[42] Consequently, during modern pandemics, health officials pay attention when the virus reaches places with social upheaval, looking for deadlier strains of the virus.[41]

Devastated communities

Chart of deaths in major cities

Even in areas where mortality was low, so many people were incapacitated that much of everyday life stopped. Some communities closed all stores or required customers to leave their orders outside the store. There were many reports of places where the health-care workers could not tend the sick nor the grave-diggers bury the dead because they too were ill. Mass graves were dug by steam shovel and bodies buried without coffins in many places.[43] Several Pacific island territories were particularly hard-hit. The pandemic reached them from New Zealand, which was too slow to implement measures to prevent ships carrying the flu from leaving its ports. From New Zealand the flu reached Tonga (killing 8% of the population), Nauru (16%) and Fiji (5%, 9000 people). Worst affected was Western Samoa, a territory then under New Zealand military administration. A crippling 90% of the population was infected; 30% of adult men, 22% of adult women and 10% of children were killed. By contrast, the flu was kept away from American Samoa by a commander who imposed a blockade.[44] The mortality rate in New Zealand itself was 5%.[45]

Less affected areas

In Japan, 257,363 deaths were attributed to influenza by July 1919, giving an estimated 0.425% mortality rate, much lower than nearly all other Asian countries for which data are available. The Japanese government severely restricted maritime travel to and from the home islands when the pandemic struck.

In the Pacific, American Samoa[46] and the French colony of New Caledonia[47] also succeeded in preventing even a single death from influenza through effective quarantines. In Australia, nearly 12,000 perished.[48]

End of the pandemic

After the lethal second wave struck in the fall of 1918, the disease died down abruptly. New cases almost dropped to nothing after the peak in the second wave.[49] In Philadelphia for example, 4,597 people died in the week ending October 16, but by November 11 influenza had almost disappeared from the city. One explanation for the rapid decline of the lethality of the disease is that doctors simply got better at preventing and treating the pneumonia which developed after the victims had contracted the virus, although John Barry states in his book that researchers have found no evidence to support this. Another theory holds that the 1918 virus mutated extremely rapidly to a less lethal strain. This is a common occurrence with influenza viruses: there is a general tendency for pathogenic viruses to become less lethal as time goes by, providing more living hosts. According to this theory, this happened very quickly for the 1918 virus.[49]

Cultural impact

American Red Cross nurses tend to flu patients in temporary wards set up inside Oakland Municipal Auditorium, 1918

In the United States, Great Britain and other countries, despite the relatively high morbidity and mortality rates that resulted from the epidemic in 1918–1919, the Spanish flu began to fade from public awareness over the decades until the arrival of news about bird flu and other pandemics in the 1990s and 2000s.[50] This has led some historians to label the Spanish flu a “forgotten pandemic.”[51] One of the only major works of American literature written after 1918 that deals directly with the Spanish flu is Katherine Anne Porter’s Pale Horse, Pale Rider. In 1935 John O'Hara wrote a long short story, "The Doctor's Son," about the experience of his fictional alter ego during the flu epidemic in a Pennsylvania coal mining town. In 1937 American novelist William Keepers Maxwell, Jr. wrote They Came Like Swallows, a fictional reconstruction of the events surrounding his mother's death from the flu. Mary McCarthy, the American novelist and essayist, wrote about her parents' deaths in Memories of a Catholic Girlhood. In 1992 Bodie and Brock Thoene's "Shiloh Legacy" series leads off with an account of the Spanish Flu in New York and Arkansas in their fictional novel In My Father's House. In 1997 David Morrell's short story If I Die Before I Wake - dealing with a small American town during the second wave - was published in the anthology REVELATIONS, which was framed by Clive Barker. In 2006 Thomas Mullen wrote a novel called The Last Town on Earth about the impact of the Spanish flu on a fictional mill town in Washington.

Several theories have been offered as to why the Spanish flu may have been "forgotten" by historians and the public over so many years. These include the rapid pace of the pandemic (it killed most of its victims in the United States, for example, within a period of less than nine months), previous familiarity with pandemic disease in the late 19th and early 20th centuries, and the distraction of the First World War.[52]

Another explanation involves the age group affected by the disease. The majority of fatalities, in both World War I and in the Spanish Flu epidemic, were young adults. The deaths caused by the flu may have been overlooked due to the large numbers of deaths of young men in the war or as a result of injuries. When people read the obituaries of the era, they saw the war or post-war deaths and the deaths from the influenza side by side. Particularly in Europe, where the war's toll was extremely high, the flu may not have had a great, separate, psychological impact, or may have seemed a mere "extension" of the war's tragedies.[53] The duration of the pandemic and the war could also play a role: the disease would usually only affect a certain area for a month before leaving, while the war, which most expected to end quickly, had lasted for four years by the time the pandemic struck. This left little time for the disease to have a significant impact on the economy. During this time period pandemic outbreaks were not uncommon: typhoid, yellow fever, diphtheria, and cholera all occurred near the same time period. These outbreaks probably lessened the significance of the influenza pandemic for the public.[54]

Spanish flu research

Centers for Disease Control and Prevention’s Dr. Terrence Tumpey examining a reconstructed version of the 1918 flu.

One theory is that the virus strain originated at Fort Riley, Kansas, by two genetic mechanisms– genetic drift and antigenic shift– in viruses in poultry and swine which the fort bred for food; the soldiers were then sent from Fort Riley to different places around the world, where they spread the disease. However, evidence from a recent reconstruction of the virus suggests that it jumped directly from birds to humans, without traveling through swine.[55][56] This suggestion is however controversial,[57] and other research suggests that the strain originated in a mammalian species.[58]

An effort to recreate the 1918 flu strain (a subtype of avian strain H1N1) was a collaboration among the Armed Forces Institute of Pathology, Southeast Poultry Research Laboratory and Mount Sinai School of Medicine in New York; the effort resulted in the announcement (on October 5, 2005) that the group had successfully determined the virus's genetic sequence, using historic tissue samples recovered by pathologist Johan Hultin from a female flu victim buried in the Alaskan permafrost and samples preserved from American soldiers.[59]

On January 18, 2007, Kobasa et al. reported that monkeys (Macaca fascicularis) infected with the recreated strain exhibited classic symptoms of the 1918 pandemic and died from a cytokine storm[60]– an overreaction of the immune system. This may explain why the 1918 flu had its surprising effect on younger, healthier people, as a person with a stronger immune system would potentially have a stronger overreaction.[61]

On September 16, 2008, the body of Yorkshireman Sir Mark Sykes was exhumed to study the RNA of the Spanish flu virus in efforts to understand the genetic structure of modern H5N1 bird flu. Sykes had been buried in 1919 in a lead coffin which scientists hope will have helped preserve the virus.[62]

In December, 2008 research by Yoshihiro Kawaoka of University of Wisconsin linked the presence of three specific genes (termed PA, PB1, and PB2) and a nucleoprotein derived from 1918 flu samples to the ability of the flu virus to invade the lungs and cause pneumonia. The combination triggered similar symptoms in animal testing.[63]

Victims

Influenza ward at Walter Reed Hospital during the Spanish flu pandemic of 1918-1919.
Albertan farmers wearing masks to protect themselves from the flu.

Notable fatalities

Notable survivors

See also

References

Notes
  1. ^ 1918 Influenza Pandemic | CDC EID.
  2. ^ Vilensky JA, Foley P, Gilman S (2007). "Children and encephalitis lethargica: a historical review". Pediatr. Neurol. 37 (2): 79–84. doi:10.1016/j.pediatrneurol.2007.04.012. PMID 17675021. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  3. ^ Institut Pasteur. La Grippe Espagnole de 1918 (Powerpoint presentation in French).
  4. ^ a b c Patterson, KD (1991). "The geography and mortality of the 1918 influenza pandemic". Bull Hist Med. 65 (1): 4–21. PMID 2021692. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  5. ^ a b Centers for Disease Control and Prevention. Jeffery K. Taubenberger and David M. Morens. 1918 Influenza: the Mother of All Pandemics, January, 2006. Retrieved on May 9, 2009.
  6. ^ Tindall 2007
  7. ^ The 1918 Influenza Pandemic. Accessed 2009-05-01. Archived 2009-05-04.
  8. ^ Johnson NP, Mueller J (2002). "Updating the accounts: global mortality of the 1918–1920 "Spanish" influenza pandemic". Bull Hist Med. 76 (1): 105–15. doi:10.1353/bhm.2002.0022. PMID 11875246.
  9. ^ a b c Taubenberger, J (2006). "1918 Influenza: the mother of all pandemics". Emerg Infect Dis. 12 (1): 15–22. PMID 16494711. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help) Cite error: The named reference "Taubenberger" was defined multiple times with different content (see the help page).
  10. ^ 1918 Influenza: the Mother of All Pandemics
  11. ^ Taubenberger, J., Morens, M. (2006). "1918 Influenza Pandemic". www.cdc.gov. Retrieved 2009-05-14. {{cite web}}: Text "CDC EID" ignored (help)CS1 maint: multiple names: authors list (link)
  12. ^ a b c Knobler 2005, pp. 60–61.
  13. ^ Potter, CW (2006). "A History of Influenza". J Appl Microbiol. 91 (4): 572–579. doi:10.1046/j.1365-2672.2001.01492.x. PMID 11576290. {{cite journal}}: Unknown parameter |month= ignored (help)
  14. ^ Flu experts warn of need for pandemic plans. British Medical Journal.
  15. ^ "Spanish Influenza in Japanese Armed Forces, 1918–1920". Centers for Disease Control and Prevention (CDC).
  16. ^ Pandemics and Pandemic Threats since 1900, U.S. Department of Health & Human Services.
  17. ^ The 'bird flu' that killed 40 million. BBC News. October 19, 2005.
  18. ^ "A deadly virus rages throughout Canada at the end of the First World War". CBC History.
  19. ^ "The Great Pandemic of 1918: State by State". Archived from the original on 2009-05-06. Retrieved 2009-05-04. {{cite web}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)
  20. ^ a b Harold Marcus, Haile Sellassie I: The formative years, 1892–1936 (Trenton: Red Sea Press, 1996), pp. 36f; Pankhurst 1990, p. 48f.
  21. ^ Pankhurst 1990, p. 63.
  22. ^ Pankhurst 1990, p. 51f.
  23. ^ Simonsen, L (1998). "Pandemic versus epidemic influenza mortality: a pattern of changing age distribution". J Infect Dis. 178 (1): 53–60. PMID 9652423. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  24. ^ a b O Hansen, 1923, Undersøkelser om influenzaens opptræden specielt i Bergen 1918–1922 Skrifter utgit ved Klaus Hanssens Fond. Bergen: Medicinsk avdeling, Haukeland Sykehus, 1923: 3.
  25. ^ Duncan 2003, p. 7
  26. ^ Ewald 1994, p. 110.
  27. ^ Andrew Price-Smith, Contagion and Chaos, MIT Press, 2009.
  28. ^ 1918 killer flu secrets revealed. BBC News. February 5, 2004.
  29. ^ Pr. C. HANNOUN :
    La Grippe, Ed Techniques EMC (Encyclopédie Médico-Chirurgicale), Maladies infectieuses, 8-069-A-10, 1993.
    Documents de la Conférence de l'Institut Pasteur : La Grippe Espagnole de 1918.
  30. ^ Crosby 2003
  31. ^ Andrew Price-Smith, Contagion and Chaos, Cambridge, MA: MIT Press, 2009.
  32. ^ Barry, John. The site of origin of the 1918 influenza pandemic and its public health implications, Journal of Translational Medicine, 2:3. Accessed 2009-05-01. Archived 2009-05-04.
  33. ^ Avian Bird Flu. 1918 Flu (Spanish flu epidemic).
  34. ^ Channel 4 - News - Spanish flu facts.
  35. ^ "EU Research Profile on Dr. John Oxford". Archived from the original on 2009-05-11. Retrieved 2009-05-09. {{cite web}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)
  36. ^ Connor, Steve, "Flu epidemic traced to Great War transit camp", The Guardian (UK), Saturday, 8 January 2000. Accessed 2009-05-09. Archived 2009-05-11.
  37. ^ Key Facts about Swine Influenza [1] accessed 22:45 GMT-6 30/04/2009. Archived 2009-05-04.
  38. ^ a b c d e f g h i j k l m Collier 1974
  39. ^ UK Parliament - http://www.parliament.the-stationery-office.com/pa/ld200506/ldselect/ldsctech/88/88.pdf. Accessed 2009-05-06. Archived 2009-05-08.
  40. ^ Gladwell, Malcolm. "The Dead Zone". The New Yorker (September 29, 1997): 55.
  41. ^ a b Gladwell, Malcolm. "The Dead Zone". The New Yorker (September 29, 1997): 63.
  42. ^ Gladwell, Malcolm. "The Dead Zone". The New Yorker (September 29, 1997): 56.
  43. ^ Fortune article "Viruses of Mass Destruction" written 1st November 2004 [2] accessed 01:12 GMT+1 30/04/2009
  44. ^ DENOON, Donald, “New Economic Orders: Land, Labour and Dependency”, in DENOON, Donald (éd.), The Cambridge History of the Pacific Islanders, Cambridge University Press, 2004, ISBN 0-521-00354-7, p. 247.
  45. ^ MELEISEA, Malama, Lagaga: A Short History of Western Samoa, University of the South Pacific, 1987, ISBN 982-02-0029-6, p. 130.
  46. ^ "Influenza of 1918 (Spanish Flu) and the US Navy". www.history.navy.mil. Retrieved 2009-05-14.
  47. ^ World Health Organization Writing Group (2006). "Nonpharmaceutical interventions for pandemic influenza, international measures". Centers for Disease Control and Prevention (CDC) Emerging Infectious Diseases (EID) Journal. 12 (1): 189.
  48. ^ Anne Grant, History House, Portland. Influenza Pandemic 1919. Portland Victoria.
  49. ^ a b Barry 2004
  50. ^ Honigsbaum
  51. ^ Crosby 2003
  52. ^ Crosby 2003, pp. 320–322.
  53. ^ Simonsen, L; Clarke M, Schonberger L, Arden N, Cox N, Fukuda K (Jul 1998). "Pandemic versus epidemic influenza mortality: a pattern of changing age distribution."
  54. ^ Morrisey, Carla R. "The Influenza Epidemic of 1918." Navy Medicine 77, no. 3 (May-June 1986): 11–17.
  55. ^ Sometimes a virus contains both avian adapted genes and human adapted genes. Both the H2N2 and H3N2 pandemic strains contained avian flu virus RNA segments. "While the pandemic human influenza viruses of 1957 (H2N2) and 1968 (H3N2) clearly arose through reassortment between human and avian viruses, the influenza virus causing the 'Spanish flu' in 1918 appears to be entirely derived from an avian source (Belshe 2005)." (from Chapter Two: Avian Influenza by Timm C. Harder and Ortrud Werner, an excellent free on-line Book called Influenza Report 2006 which is a medical textbook that provides a comprehensive overview of epidemic and pandemic influenza.)
  56. ^ Taubenberger JK, Reid AH, Lourens RM, Wang R, Jin G, Fanning TG (2005). "Characterization of the 1918 influenza virus polymerase genes". Nature. 437 (7060): 889–93. doi:10.1038/nature04230. PMID 16208372. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  57. ^ Antonovics J, Hood ME, Baker CH (2006). "Molecular virology: was the 1918 flu avian in origin?". Nature. 440 (7088): E9, discussion E9–10. doi:10.1038/nature04824. PMID 16641950. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  58. ^ Vana G, Westover KM (2008). "Origin of the 1918 Spanish influenza virus: a comparative genomic analysis". Molecular Phylogenetics and Evolution. 47 (3): 1100–10. doi:10.1016/j.ympev.2008.02.003. PMID 18353690. {{cite journal}}: Unknown parameter |month= ignored (help)
  59. ^ Center for Disease Control: Researchers Reconstruct 1918 Pandemic Influenza Virus; Effort Designed to Advance Preparedness Retrieved on 2008-08-14.
  60. ^ Kobasa, Darwyn (2007). "Aberrant innate immune response in lethal infection of macaques with the 1918 influenza virus". Nature. 445: 319–323. doi:10.1038/nature05495. {{cite journal}}: Cite has empty unknown parameter: |month= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)
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Bibliography
  • Barry, John M. (2004). The Great Influenza: The Epic Story of the Greatest Plague in History. Viking Penguin. ISBN 0-670-89473-7.
  • Collier, Richard (1974). The Plague of the Spanish Lady - The Influenza Pandemic of 1918–19. USA: Atheneum. ISBN 978-0689105920.
  • Crosby, Alfred W. (1976). Epidemic and Peace, 1918. Westport, Ct: Greenwood Press. ISBN 0-8371-8376-6.
  • Crosby, Alfred W. (2003). America's Forgotten Pandemic: The Influenza of 1918 (2 ed.). Cambridge: Cambridge University Press. ISBN 0689105924.
  • Duncan, Kirsty (2003), Hunting the 1918 flu: one scientist's search for a killer virus (illustrated ed.), University of Toronto Press, ISBN 9780802087485
  • Ewald, Paul. Evolution of infectious disease, New York, Oxford University Press, 1994.
  • Hakim, Joy (1995). War, Peace, and all that Jazz. New York: Oxford University Press.
  • Honigsbaum, Mark. Living with Enza: The Forgotten Story of Britain and the Great Flu Pandemic of 1918, ISBN 978-0230217744.
  • 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. {{cite book}}: External link in |chapterurl= (help); Unknown parameter |chapterurl= ignored (|chapter-url= suggested) (help)CS1 maint: multiple names: editors list (link)
  • Pankhurst, Richard. An Introduction to the Medical History of Ethiopia. Trenton: Red Sea Press, 1990
  • Tindall, George Brown & Shi, David Emory. America: A Narrative History, 7th ed. copyright 2007 by W.W Norton & Company, Inc.

Further reading

  • Beiner, Guy (2006). "Out in the Cold and Back: New-Found Interest in the Great Flu". Cultural and Social History. 3 (4): 496–505.
  • Johnson, Niall (2006). Britain and the 1918–19 Influenza Pandemic: A Dark Epilogue. London and New York: Routledge. ISBN 0-415-36560-0.
  • Johnson, Niall (2003). "Measuring a pandemic: Mortality, demography and geography". Popolazione e Storia: 31–52.
  • Johnson, Niall (2003). "Scottish 'flu – The Scottish mortality experience of the "Spanish flu". Scottish Historical Review. 83 (2): 216–226.
  • Johnson, Niall (2002). "Updating the accounts: global mortality of the 1918–1920 'Spanish' influenza pandemic". Bulletin of the History of Medicine. 76: 105–15. doi:10.1353/bhm.2002.0022. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  • Kolata, Gina (1999). Flu: The Story of the Great Influenza Pandemic of 1918 and the Search for the Virus That Caused It. New York: Farrar, Straus and Giroux. ISBN 0-374-15706-5.
  • Little, Jean (2007). If I Die Before I Wake: The Flu Epidemic Diary of Fiona Macgregor, Toronto, Ontario, 1918. Dear Canada. Markham, Ont.: Scholastic Canada. ISBN 9780439988377.
  • Noymer, Andrew (2000). "The 1918 Influenza Epidemic's Effects on Sex Differentials in Mortality in the United States". Population and Development Review. 26 (3): 565–581. doi:10.1111/j.1728-4457.2000.00565.x. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  • Oxford JS, Sefton A, Jackson R, Innes W, Daniels RS, Johnson NP (2002). "World War I may have allowed the emergence of "Spanish" influenza". The Lancet infectious diseases. 2 (2): 111–4. doi:10.1016/S1473-3099(02)00185-8. PMID 11901642.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  • Oxford JS, Sefton A, Jackson R, Johnson NP, Daniels RS (1999). "Who's that lady?". Nat. Med. 5 (12): 1351–2. doi:10.1038/70913. PMID 10581070.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  • Phillips, Howard (2003). The Spanish Flu Pandemic of 1918: New Perspectives. London and New York: Routledge. {{cite book}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  • Rice, Geoffrey W. (1993). "Pandemic Influenza in Japan, 1918–1919: Mortality Patterns and Official Responses". Journal of Japanese Studies. 19 (2): 389–420. doi:10.2307/132645. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  • Rice, Geoffrey W. (2005). Black November: the 1918 Influenza Pandemic in New Zealand. Canterbury University Press: Canterbury Univ. Press. ISBN 1-877257-35-4.
  • Tumpey TM, García-Sastre A, Mikulasova A; et al. (2002). "Existing antivirals are effective against influenza viruses with genes from the 1918 pandemic virus". Proc. Natl. Acad. Sci. U.S.A. 99 (21): 13849–54. doi:10.1073/pnas.212519699. PMID 12368467. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)