Soldiers from Fort Riley, Kansas ill with Spanish influenza at a hospital ward at Camp Funston in 1918, where the worldwide pandemic is hypothesized by some to have begun.

Influenza (Flu)
Types
Avian (A/H5N1 subtype) Canine Equine Swine (A/H1N1 subtype)
Vaccines
2009 pandemic (Pandemrix) ACAM-FLU-A Fluzone Influvac Live attenuated (FluMist) Optaflu
Treatment
Amantadine Arbidol Laninamivir Oseltamivir Peramivir Rimantadine Vitamin D Zanamivir
Pandemics
2009 Swine 1968–1969 Hong Kong 1918
Outbreaks
2008 West Bengal 2007 Bernard Matthews H5N1 2007 Australian equine 2006 H5N1 India 1976 swine flu
See also
Flu season Influenza evolution Influenza research Influenza-like illness
v t e

The 1918 flu pandemic (the "Spanish flu") was an influenza pandemic, and the first of the two pandemics involving H1N1 influenza virus (the second was the 2009 flu pandemic, an outbreak of swine flu). It was an unusually severe and deadly pandemic that spread across the world. Historical and epidemiological data are inadequate to identify the geographic origin.^[1] Most victims were healthy young adults, in contrast to most influenza outbreaks, which predominantly affect juvenile, elderly, or weakened patients. The flu pandemic was implicated in the outbreak of encephalitis lethargica in the 1920s.^[2]

The pandemic lasted from January 1918 to December 1920,^[3] spreading even to the Arctic and remote Pacific islands. Between 50 and 130 million died, making it one of the deadliest natural disasters in human history.^{[4][1][5][6][7]} Even using the lower estimate of 50 million people, 3% of the world's population (which was 1.86 billion at the time^[8]) died of the disease. Some 500 million, or 27%, were infected.^[1]

Tissue samples from frozen victims were used to reproduce the virus for study. This research concluded, among other things, that the virus kills through a cytokine storm (overreaction of the body's immune system), which perhaps explains its unusually severe nature and the concentrated age profile of its victims. The strong immune system reactions of young adults ravaged the body, whereas the weaker immune systems of children and middle-aged adults resulted in fewer deaths.^[9]

Origins of name[link]

The first cases of influenza were registered in the continental U.S. and the rest of Europe before getting to Spain. The 1918 pandemic received its nickname "Spanish flu" because of the early perceptions of the disease's severity in Spain.^[10] Spain was a neutral country in World War I and had no censorship of news regarding the disease and its consequences. Germany, the United States, Britain and France all had media blackouts on news that might lower morale,^[11] and did not want to disclose information about disease and the number of deaths to their enemies.^[12]

History[link]

World War I did not cause the flu, but the close troop quarters and massive troop movements hastened the pandemic and probably both increased transmission and augmented mutation; it may also have increased the lethality of the virus^{[citation needed]}. Some speculate the soldiers' immune systems were weakened by malnourishment, as well as the stresses of combat and chemical attacks, increasing their susceptibility.^[13] Andrew Price-Smith has made the controversial argument that the virus helped tip the balance of power in the later days of the war towards the Allied cause. 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.^[14]

A large factor in the worldwide occurrence of this flu was increased travel. Modern transportation systems made it easier for soldiers, sailors, and civilian travelers to spread the disease.^[15]

In the United States, the disease was first observed at Haskell County, Kansas, in January 1918, prompting local doctor Loring Miner to warn the U.S. Public Health Service's academic journal. On 4 March 1918, company cook Albert Gitchell reported sick at Fort Riley, Kansas. By noon on 11 March 1918, over 100 soldiers were in the hospital.^[16] Within days, 522 men at the camp had reported sick.^[17] By 11 March 1918 the virus had reached Queens, New York.^[18]

In August 1918, a more virulent strain appeared simultaneously in Brest, France, in Freetown, Sierra Leone, and in the U.S. in 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.^[19]

• 

  Number of deaths in New York City Berlin, Paris, and London (Museum of Health & Medicine, Washington), c. 1918–1919

• 

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

• 

  Albertan farmers wore masks to protect themselves from the flu.

• 

  Policemen wearing masks provided by the American Red Cross in Seattle, 1918

• 

  A street car conductor in Seattle in 1918 refusing to allow passengers aboard who are not wearing masks

• 

  Red Cross workers remove a flu victim in St. Louis, Missouri (1918)

• 

  Influenza ward at Walter Reed Hospital during the Spanish flu pandemic of 1918–1919

• 

  Burying flu victims, North River, Labrador (1918)

• 

  1919 Tokyo, Japan

• 

  Japanese poster in 1919

• 

  Demonstration at the Red Cross Emergency Ambulance Station in Washington, D.C., during the influenza pandemic of 1918

• 

  Cavalry memorial on the hill Lueg, memory of the Bernese cavalrymen victims of the 1918 flu pandemic; Emmental, Bern, Switzerland

Theories about source[link]

Some theorized the flu originated in the Far East.^[20] Dr. C. Hannoun, leading expert of the 1918 flu for the Institut Pasteur, asserted 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.^[21] Hannoun considered several other theories of origin, such as Spain, Kansas, and Brest, as being possible, but not likely.

Historian Alfred W. Crosby speculated the flu originated in Kansas.^[22]

Political scientist Andrew Price-Smith published data from the Austrian archives suggesting the influenza had earlier origins, beginning in Austria in the spring of 1917.^[23]

Popular writer John Barry echoed Crosby in describing Haskell County, Kansas as the likely point of origin.^[24]

Investigative work by a British team led by virologist John Oxford^[25] of St Bartholomew's Hospital and the Royal London Hospital, suggested a major 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.^[26]

Mortality[link]

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)^[27]

Three pandemic waves: weekly combined influenza and pneumonia mortality, United Kingdom, 1918–1919^[28]

The global mortality rate from the 1918/1919 pandemic is not known, but an estimated 10% to 20% of those who were infected died. With about a third of the world population infected, this case-fatality ratio means 3% to 6% of the entire global population died.^[29] Influenza may have killed as many as 25 million people in its first 25 weeks. Older estimates say it killed 40–50 million people,^[4] while current estimates say 50—100 million people worldwide were killed.^[30] This pandemic has been described as "the greatest medical holocaust in history" and may have killed more people than the Black Death.^[31] It is said that this flu killed more people in 24 weeks than AIDS has killed in 24 years, more in a year than the Black Death killed in a century.^[32]

As many as 17 million died in India, about 5% of the population.^[33] In Japan, 23 million people were affected, and 390,000 died.^[34] In the U.S., about 28% of the population suffered, and 500,000 to 675,000 died.^[35] In Britain, as many as 250,000 died; in France, more than 400,000.^[36] In Canada 50,000 died.^[37] Entire villages perished in Alaska.^[38] In West Africa, an influenza epidemic killed at least 100,000 people in Ghana.^[39] In the Dutch East Indies (now Indonesia), 1.5 million were assumed to have died from 30 million inhabitants.^[40] In Tahiti, 14% of the population died during only two months. Similarly, in Samoa in November 1918, 20% of the population of 38,000 died within two months.^[41]

Tafari Makonnen (the future Haile Selassie, Emperor of Ethiopia) was one of the first Ethiopians who contracted influenza but survived,^[42] although many of his subjects did not; estimates for the fatalities in the capital city, Addis Ababa, range from 5,000 to 10,000, or higher,^[43] while in British Somaliland one official estimated that 7% of the native population died.^[44]

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] 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."^[30] 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.^[27]

The unusually severe disease killed up to 20% of those infected, as opposed to the usual flu epidemic mortality rate of 0.1%.^[27][30] According to historian John M. Barry, the most vulnerable of all, "those most likely, of the most likely", to die, were pregnant women. He reported that in thirteen studies of hospitalized women in the pandemic, the death rate ranged from 23% to 71%. Of the pregnant women who survived childbirth, over one-quarter (26%) lost the child.^[45]

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.^[46] This is unusual, since influenza is normally most deadly to the very young (under age two) and the very old (over age 70), and may have been due to partial protection caused by exposure to the previous Russian flu pandemic of 1889.^[47] Modern analysis has shown the virus to be particularly deadly because it triggers a cytokine storm, which ravages the stronger immune system of young adults.^{[citation needed]}

Patterns of fatality[link]

Typical influenzas kill weak individuals, such as infants (aged 0–2 years), the elderly, and the immunocompromised. In the 1918 pandemic, though, older adults may have had some immunity from the earlier Russian flu pandemic of 1889.^[47] Another oddity was that the outbreak was widespread in the summer and autumn (in the Northern Hemisphere); influenza is usually worse in winter.^[48]

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.^[49]

Deadly second wave[link]

The second wave of the 1918 pandemic was much deadlier than the first. The first wave had resembled typical flu epidemics; those most at risk were the sick and elderly, while younger, healthier people recovered easily. But in August, when the second wave began in France, Sierra Leone and the United States,^[50] the virus had mutated to a much deadlier form. This has been attributed to the circumstances of the First World War.^[51] In civilian life, evolutionary pressures favour a mild strain: those who get very sick stay home, and those mildly ill continue with their lives, 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. The second wave began and the flu quickly spread around the world again.^[52] It was the same flu, in that most of those who recovered from first-wave infections were immune, but it was now far more deadly, and the most vulnerable people were those who were like the soldiers in the trenches—young, otherwise healthy adults.^[53] Consequently, during modern pandemics, health officials pay attention when the virus reaches places with social upheaval, looking for deadlier strains of the virus.^[52]

This effect was most dramatically illustrated in Copenhagen, which escaped with combined mortality rate of just 0.29% (0.02% in first wave and 0.27% in second wave) because of exposure to the less lethal first wave.^[54]

Devastated communities[link]

Chart of deaths in major cities

Even in areas where mortality was low, so many were incapacitated that much of everyday life was hampered. Some communities closed all stores or required customers to leave orders outside. There were reports that the health-care workers could not tend the sick nor the gravediggers bury the dead because they too were ill. Mass graves were dug by steam shovel and bodies buried without coffins in many places.^[55] 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%, 9,000 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 when Governor John Martin Poyer imposed a blockade.^[56] In New Zealand itself, 8,573 deaths were attributed to the 1918 pandemic influenza, resulting in a total population fatality rate of 0.74%.^[57]

Less-affected areas[link]

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^[58] and the French colony of New Caledonia^[59] also succeeded in preventing even a single death from influenza through effective quarantines. In Australia, nearly 12,000 perished.^[60]

By the end of pandemic, only one major region on the entire planet had not reported an outbreak: an isolated island called Marajo, located in Brazil's Amazon River Delta.^[61]

Aspirin poisoning[link]

In a 2009 paper published in the journal Clinical Infectious Diseases, Karen Starko proposed that aspirin poisoning had contributed substantially to the fatalities. She based this on the reported symptoms in those dying from the flu, and the timing of the big "death spike" in October 1918, right after the Surgeon General^{[clarification needed]}, the US Army, and the Journal of the American Medical Association all recommended very large (by today's standards) dosages of aspirin.^[62] Further, Starko suggests that the wave of aspirin poisonings was due to a "perfect storm" of events: Bayer's patent on aspirin ran out, so that many companies rushed in to make a profit and greatly increased the supply; this coincided with the flu pandemic; and the symptoms of aspirin poisoning (such as Reye's syndrome) were not known at the time.^[62]

This hypothesis, insofar as it sought to provide an explanation to the universally high mortality rate, was questioned in a letter to the journal published in April 2010. In it, Andrew Noymer and Daisy Carreon of the University of California, Irvine, and Niall Johnson, of the Australian Commission on Safety and Quality in Health Care, questioned this universal applicability given the high mortality rate in countries such as India, where there was little or no access to aspirin at the time.^[63] On this basis, they concluded that "the salicylate [aspirin poisoning] hypothesis [was] difficult to sustain as the primary explanation for the unusual virulence of the 1918–1919 influenza pandemic".^[63] In responding, Starko pointed to anecdotal evidence of aspirin over-prescription in India and argued that even if aspirin over-prescription had not contributed to the high Indian mortality rate, it could still have been a major factor for other high rates in areas where other exacerbating factors present in India played less of a role.^[64]

End of the pandemic[link]

After the lethal second wave struck in the autumn of 1918, new cases dropped abruptly – almost to nothing after the peak in the second wave.^[9] In Philadelphia, for example, 4,597 people died in the week ending 16 October, but by 11 November, 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 that developed after the victims had contracted the virus, although John Barry stated 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 tendency for pathogenic viruses to become less lethal with time, providing more living hosts.^[9]

Cultural and economic impact[link]

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

In the United States, the United Kingdom 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.^[65] This has led some historians to label the Spanish flu a "forgotten pandemic".^[22]

Various theories of why the Spanish flu was "forgotten" include the rapid pace of the pandemic, which killed most of its victims in the United States, for example, within a period of less than nine months, resulting in limited media coverage. The general population was familiar with patterns of pandemic disease in the late 19th and early 20th centuries: typhoid, yellow fever, diphtheria, and cholera all occurred near the same time. These outbreaks probably lessened the significance of the influenza pandemic for the public.^[66] In some areas, the flu was not reported on, the only mention being that of ads for medicines claiming to cure it.^[67]

In addition, the outbreak coincided with the deaths and media focus on the First World War.^[68] Another explanation involves the age group affected by the disease. The majority of fatalities, from both the war and the epidemic, were among 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, they saw the war or postwar 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.^[69] The duration of the pandemic and the war could have also played 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.

One final issue that the 1918 Spanish flu outbreak had on the world was the effects on the global economy. As could be expected, statistics show many businesses in the entertainment and service industries suffered losses in revenue, but the health care industry reported profit gains.^[70]

Spanish flu research[link]

Centers for Disease Control and Prevention as Dr. Terrence Tumpey examines a reconstructed version of the 1918 flu

An electron micrograph showing recreated 1918 influenza virions

The origin of the Spanish flu pandemic, and the relationship between the near-simultaneous outbreaks in humans and swine, have been controversial. One hypothesis is that the virus strain originated at Fort Riley, Kansas, in viruses in poultry and swine which the fort bred for food; the soldiers were then sent from Fort Riley around the world, where they spread the disease.^{[citation needed]} Similarities between a reconstruction of the virus and avian viruses, combined with the human pandemic preceding the first reports of influenza in swine, led researchers to conclude the influenza virus jumped directly from birds to humans, and swine caught the disease from humans.^[71][72] Others have disagreed,^[73] and more recent research has suggested the strain may have originated in a nonhuman, mammalian species.^[74] An estimated date for its appearance in mammalian hosts has been put at the period 1882–1913.^[75] This ancestor virus diverged about 1913–1915 into two clades (or biological groups), which gave rise to the classical swine and human H1N1 influenza lineages. The last common ancestor of human strains dates to between February 1917 and April 1918. Because pigs are more readily infected with avian influenza viruses than are humans, they were suggested as the original recipients of the virus, passing the virus to humans sometime between 1913 and 1918.

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 City; the effort resulted in the announcement (on 5 October 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.^[76]

On 18 January 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^[77]—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.^[78]

On 16 September 2008, the body of British politician and diplomat Sir Mark Sykes was exhumed to study the RNA of the 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 hoped to have helped preserve the virus.^[79] However, the coffin was found to be split because of the weight of soil over it, and the cadaver was badly decomposed. Nonetheless, samples of lung and brain tissue were taken through the split, with the coffin remaining in situ in the grave during this process.^[80]

In December 2008, research by Yoshihiro Kawaoka of the 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.^[81]

In June 2010, a team at the Mount Sinai School of Medicine reported the 2009 flu pandemic vaccine provided some cross-protection against the 1918 flu pandemic strain.^[82]

One of the few things known for certain about the influenza in 1918 and for some years after was that it was, out of the laboratory, exclusively a disease of human beings.^[83]

References[link]

Notes

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 978-0-689-10592-0. 
• 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 0-689-10592-4. http://books.google.com/?id=KYtAkAIHw24C. 
• Duncan, Kirsty (2003). Hunting the 1918 flu: one scientist's search for a killer virus (illustrated ed.). University of Toronto Press. ISBN 978-0-8020-8748-5. http://books.google.com/?id=HPDI_30wRsEC. 
• 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. ISBN 0-19-512767-6. 
• Garrett TA (2007), Economic Effects of the 1918 Influenza Pandemic: Implications for a Modern-day Pandemic, Retrieved from http://www.stlouisfed.org/community_development/assets/pdf/pandemic_flu_report.pdf on 11/4/2010
• Honigsbaum, Mark. Living with Enza: The Forgotten Story of Britain and the Great Flu Pandemic of 1918, ISBN 978-0-230-21774-4.
• 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. http://books.nap.edu/openbook.php?record_id=11150&page=57. 
• 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[link]

• Barry, John M. (2004). The Great Influenza: The Epic Story of the Deadliest Plague in History. Viking Press. ISBN 978-0-670-89473-4. 
• 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; Juergen Mueller (2002). "Updating the accounts: global mortality of the 1918–1920 'Spanish' influenza pandemic". Bulletin of the History of Medicine 76 (1): 105–15. DOI:10.1353/bhm.2002.0022. PMID 11875246. 
• 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 978-0-439-98837-7. 
• Noymer, Andrew; Michel Garenne (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. PMC 2740912. PMID 19530360. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2740912. 
• 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. 
• 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. 
• Pettit, Dorothy; Janice Bailie (2008). A Cruel Wind: Pandemic Flu in America, 1918–1920. Murfreesboro, TN: Timberlane Books. ISBN 9780971542822(Pap.). 
• Phillips, Howard; David Killingray (eds) (2003). The Spanish Flu Pandemic of 1918: New Perspectives. London and New York: Routledge. 
• Rice, Geoffrey W.; Edwina Palmer (1993). "Pandemic Influenza in Japan, 1918–1919: Mortality Patterns and Official Responses". Journal of Japanese Studies 19 (2): 389–420. DOI:10.2307/132645. JSTOR 132645. 
• 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. PMC 129786. PMID 12368467. http://www.pnas.org/cgi/content/full/99/21/13849.