Spanish flu

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The 1918 flu pandemic was a category 5 influenza pandemic between 1918 and 1920 caused by an unusually severe and deadly Influenza A virus strain of subtype H1N1. By far the most destructive pandemic in history, it killed some 50 million to 100 million people worldwide in just 18 months, ^[1][2] dwarfing the bloodshed due to World War I (1914-1918). Many of its victims were healthy young adults, in contrast to most influenza outbreaks which predominantly affect juvenile, elderly, or otherwise weakened patients. The disease was first observed at Fort Riley, Kansas, U.S.. The Allies of World War I came to call it the Spanish Flu, primarily because the pandemic received greater press attention in Spain than in the rest of the world, as Spain was not involved in the war and had not imposed wartime censorship.

Scientists have used tissue samples from frozen victims to reproduce the virus for study.^[3] Given the strain's extreme virulence and the possibility of accidental escape (or deliberate release) from quarantine, 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, which explains its unusually severe nature and the unusual age profile of its victims.

Contents 1 History 1.1 Patterns of fatality 1.2 Devastated communities 1.3 Unaffected Locales 2 Spanish flu research 2.1 Blood plasma as an effective treatment 3 Sources and notes 4 Further reading 5 External links

[edit] History

The global mortality rate from the 1918/1919 pandemic is not known, but is estimated at 2.5 – 5% of the human population, with 20% of the world population suffering from the disease to some extent. Influenza may have killed as many as 25 million in its first 25 weeks; in contrast, AIDS killed 25 million in its first 25 years. Some estimates put the total killed at over twice that number, possibly even 100 million.

An estimated 17 million died in India, about 5% of India's population at the time. In the Indian Army, almost 22% of troops who caught the disease died of it. In the U.S., about 28% of the population suffered, and 500,000 to 675,000 died. In Britain 200,000 died; in France more than 400,000. Entire villages perished in Alaska and southern Africa. In Australia an estimated 10,000 people died and in the Fiji Islands, 14% of the population died during only two weeks, and in Western Samoa 22%.

While World War I did not cause the flu, the close quarters and mass movement of troops quickened its spread. Researchers speculate that the soldiers' immune systems were weakened by the stresses of combat and chemical attacks, increasing their susceptibility to the disease.

A large factor in the spread of the disease was the increased amount of travel. The modernization of transportation made it easier for sailors to spread the disease more quickly and to a wider range of communities.

[edit] Patterns of fatality

The influenza strain was unusual in that this pandemic killed many young adults and otherwise healthy victims - typical influenzas kill mostly infants (aged 0-2 years), the old, and the immune-compromised. Another oddity was that this influenza outbreak struck hardest in summer and fall (in the Northern Hemisphere). Typically, influenza is worse in the winter months.

People without symptoms could be struck suddenly and within hours be too feeble to walk; many died the next day. Symptoms included a blue tint to the face and coughing up blood caused by severe obstruction of the lungs. In some cases, the virus caused an uncontrollable hemorrhaging that filled the lungs, and patients drowned in their body fluids.

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

[edit] Devastated communities

While in most places less than one-third of the population was infected and a fraction of that died, in a number of towns in several countries entire populations were wiped out.

Even in areas where mortality was low, those incapacitated by the illness were often so numerous as to bring much of everyday life to a stop. Some communities closed all stores or required customers not to enter the store but place their orders outside the store for filling. There were many reports of places with no health care workers to tend the sick because of their own ill health and no able bodied grave diggers to bury the dead. Mass graves were dug by steam shovel and bodies buried without coffins in many places.

[edit] Unaffected Locales

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. The only sizeable inhabited place with no documented outbreak of the flu in 1918–1919 was the island of Marajó at the mouth of the Amazon River in Brazil. In the Pacific, American Samoa^[4] and the French colony of New Caledonia ^[5] also succeeded in preventing even a single death from influenza through effective quarantines.

[edit] Spanish flu research

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 local consumption. But evidence from a recent reconstruction of the virus suggests that it jumped directly from birds to humans, without traveling through swine.^[6]

In February 1998, a team led by Jeffery Taubenberger of the US Armed Forces Institute of Pathology (AFIP) recovered samples of the 1918 influenza from the frozen corpse of a Native Alaskan woman buried for nearly eight decades in permafrost near Brevig Mission, Alaska. Brevig Mission lost approximately 85% of its population to the Spanish flu in November 1918. One of the four recovered samples contained viable genetic material of the virus. This sample provided scientists a first-hand opportunity to study the virus, which was inactivated with guanidinium thiocyanate before transport. This sample and others found in AFIP archives allowed researchers to completely analyze the critical gene structures of the 1918 virus. "We have now identified three cases: the Brevig Mission case and two archival cases that represent the only known sources of genetic material of the 1918 influenza virus", said Taubenberger, chief of AFIP's molecular pathology division and principal investigator on the project.^[7]

The February 6, 2004 edition of Science magazine reported that two research teams, one led by Sir John Skehel, director of the National Institute for Medical Research in London, another by Professor Ian Wilson of The Scripps Research Institute in San Diego, had managed to synthesize the hemagglutinin protein responsible for the 1918 outbreak of Spanish Flu. They did this by piecing together DNA from a lung sample from an Inuit woman buried in the Alaskan tundra and a number of preserved samples from American soldiers of the First World War. The teams had analyzed the structure of the gene and discovered how subtle alterations to the shape of a protein molecule had allowed it to move from birds to humans with such devastating effects.

On October 5, 2005, researchers announced that the genetic sequence of the 1918 flu strain, a subtype of avian strain H1N1, had been reconstructed using historic tissue samples. ^[8]

Influenza viruses have a relatively high mutation rate that is characteristic of RNA viruses. The H5N1 virus has mutated into a variety of types with differing pathogenic profiles; some pathogenic to one species but not others, some pathogenic to multiple species. ^[9] The ability of various influenza strains to show species-selectivity is largely due to variation in the hemagglutinin genes. Genetic mutations in the hemagglutinin gene that cause single amino acid substitutions can significantly alter the ability of viral hemagglutinin proteins to bind to receptors on the surface of host cells. Such mutations in avian H5N1 viruses can change virus strains from being inefficient at infecting human cells to being as efficient in causing human infections as more common human influenza virus types. ^[10] This doesn't mean one amino acid substitution can cause a pandemic but it does mean one amino acid substitution can cause an avian flu virus that is not pathogenic in humans to become pathogenic in humans.

In July 2004, researchers led by H. Deng of the Harbin Veterinary Research Institute, Harbin, China and Professor Robert Webster of the St Jude Children's Research Hospital, Memphis, Tennessee, reported results of experiments in which mice had been exposed to 21 isolates of confirmed H5N1 strains obtained from ducks in China between 1999 and 2002. They found "a clear temporal pattern of progressively increasing pathogenicity". ^[11] Results reported by Dr. Webster in July 2005 reveal further progression toward pathogenicity in mice and longer virus shedding by ducks.

Recent research of Taubenberger et al has suggested that the 1918 virus, like H5N1, could have arisen directly from an avian influenza virus. ^[12] However, researchers at University of Virginia and Australian National University have suggested that there may be an alternative interpretation of the data used in the Taubenberger et al. paper.^[13][14] Taubenberger et al responded to these letters and defended their original interpretation. ^[15]

Other research by Tumpey and colleagues who reconstructed the H1N1 virus of 1918 came to the conclusion that it is was most notably the polymerase genes and the HA and NA genes that caused the extreme virulence of this virus. ^[16] The sequences of the polymerase proteins (PA, PB1, and PB2) of the 1918 virus and subsequent human viruses differ by only 10 amino acids from the avian influenza viruses. Viruses with seven of the ten amino acids in the human influenza locations have already been identified in currently circulating H5N1. This has led some researchers to suggest that other mutations may surface and make the H5N1 virus capable of human-to-human transmission. Another important factor is the change of the HA protein to a binding preference for alpha 2,6 sialic acid (the major form in the human respiratory tract). In avian virus the HA protein preferentially binds to alpha 2,3 sialic acid, which is the major form in the avian enteric tract. It has been shown that only a single amino acid change can result in the change of this binding preference. Altogether, only a handful of mutations may need to take place in order for H5N1 avian flu to become a pandemic virus like the one of 1918. However it is important to note that likelihood of mutation does not indicate the likelihood for the evolution of such a strain; since some of the necessary mutations may be constrained by stabilizing selection.

On 18 January 2007, Kobasa et al reported that infected monkeys (Macaca fascicularis) exhibited classic symptoms of the 1918 pandemic and died from a cytokine storm.^[17]

[edit] Blood plasma as an effective treatment

In the event of another pandemic, US military researchers have proposed reusing a treatment from the deadly pandemic of 1918 in order to blunt the effects of the flu. Some military doctors injected severely afflicted patients with blood or blood plasma from people who had recovered from the flu. Data collected during that time indicates that the blood-injection treatment reduced mortality rates by as much as 50 percent. Navy researchers have launched a test to see if the 1918 treatment will work against deadly Asian bird flu. Results thus far have been inconclusive. Human H5N1 plasma may be an effective, timely, and widely available treatment for the next flu pandemic. A new international study using modern data collection methods, would be a difficult, slow process. But many flu experts, citing the months-long wait for a vaccine for the next pandemic, are of the opinion that the 1918 method is something to consider.^[18]

In the world wide Spanish flu pandemic of 1918, "[p]hysicians tried everything they knew, everything they had ever heard of, from the ancient art of bleeding patients, to administering oxygen, to developing new vaccines and sera (chiefly against what we now call Hemophilus influenzae—a name derived from the fact that it was originally considered the etiological agent—and several types of pneumococci). Only one therapeutic measure, transfusing blood from recovered patients to new victims, showed any hint of success."^[19]

[edit] Sources and notes

[edit] Further reading

Flu

Flu Flu season Flu vaccine Flu treatment Avian flu H5N1 flu Flu research Genome sequencing

• Niall Johnson (2006) Britain and the 1918-19 Influenza Pandemic: A Dark Epilogue. Routledge, London and New York. ISBN 0-415-36560-0

• Terrence M. Tumpey, Adolfo García-Sastre, Andrea Mikulasova, Jeffery K. Taubenberger, David E. Swayne, Peter Palese, and Christopher F. Basler (2002) "Existing antivirals are effective against influenza viruses with genes from the 1918 pandemic virus". Proceedings of the National Academy of Sciences 99, 13849–13854.

• Alfred W. Crosby (1990). America's Forgotten Pandemic: The Influenza of 1918. Cambridge University Press. ISBN 0-521-38695-0.

• John M. Barry (2004). The Great Influenza: The Epic Story of the Greatest Plague in History. Viking Penguin. ISBN 0-670-89473-7.

• Andrew Noymer and 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.

• Geoffrey W. Rice and Edwina Palmer (1993). "Pandemic Influenza in Japan, 1918–19: Mortality Patterns and Official Responses". Journal of Japanese Studies, 19(2):389–420.

• Geoffrey W. Rice, Black November: the 1918 Influenza Pandemic in New Zealand , Canterbury University Press, 2005 ISBN 1-877257-35-4

• Jean Little, Dear Canada: If I Die Before I Wake: The Flu Epidemic Diary of Fiona Macgregor, Toronto, Ontario, 1918, Scholastic Canada, 2007

[edit] External links

• Video from Expert Panel Discussion on Avian Flu
• Nature "Web Focus" on 1918 flu, including new research
• Influenza Pandemic on stanford.edu
• Article: The Deadliest Fall
• Influenza 1918 in the United States on pbs.org
• Secrets of the Dead: Killer Flu (PBS)
• Flu by Eileen A. Lynch. The devastating effect of the Spanish flu in the city of Philadelphia, PA, USA
• Dialog: An Interview with Dr. Jeffery Taubenberger on Reconstructing the Spanish Flu
• The Deadly Virus - The Influenza Epidemic of 1918, by the National Archives and Records Administration (see actual pictures and records of the time).
• The 1918 Influenza Pandemic in New Zealand - includes recorded recollections of people who lived through it
• Experts Unlock Clues to Spread of 1918 Flu Virus - The New York Times
• PBS - recovery of flu samples from Alaskan flu victims
• An Avian Connection as a Catalyst to the 1918-1919 Influenza Pandemic
• Alaska Science Forum - Permafrost Preserves Clues to Deadly 1918 Flu
• Pathology of Influenza in France, 1920 Report
• "Deadly secret of 1918 flu virus unmasked", Cosmos magazine, September 2006
• Yesterday's News blog, 1918 newspaper account on impact of flu on Minneapolis
• "Lethal secrets of 1918 flu virus" BBC News, January 2007
• "Study uncovers a lethal secret of 1918 influenza virus" University of Wisconsin - Madison, January 17, 2007