Influenza Pandemic of 1918
Influenza Pandemic of 1918
Disease History, Characteristics, and Transmission
Introduction
Influenza (“flu” for short) is an infection of the lungs and bronchial tubes by an influenza virus. Common symptoms of flu include cough, muscle aches, vomiting, loss of appetite, and fever. Flu can also cause death, usually from respiratory failure and in people with weakened immune systems. The 1918 influenza pandemic, a global wave of flu infection in 1918– 1919, was one of the most deadly infectious-disease events in human history. A figure of 20–50 million deaths has traditionally been attributed to the pandemic, but in 2002, the Bulletin of the History of Medicine estimated that the toll was more likely between 50 and 100 million. The pandemic killed about 675,000 people in the United States, some 18 million in India (about 5% of the population at that time), and similar percentages elsewhere. The virus eventually evolved into less harmful forms. The lethal 1918 influenza virus was re-created by U.S. government scientists in 2005 for medical research purposes. There have been a number of flu outbreaks since 1918, but none have been anywhere near as deadly as that which occurred in 1918.
Disease History, Characteristics, and Transmission
Disease History
The exact origin of the virus strain that caused the 1918 flu pandemic is still a mystery. Although the flu was called the Spanish Flu at the time, it may have originated not in Spain but, like most new flu varieties, in Asia. Another hypothesis, based upon epidemiological evidence, places the origin in the United States.
Normally, in the United States, about 5% to 20% of the population gets a symptomatic flu infection each year. One hundred thousand to 200,000 people are hospitalized with flu complications annually, and up to 36,000 people, mostly elderly, die. Similar figures apply to most countries of the world in proportion to population. In the 1918 pandemic, however, 25–40% of the world population contracted flu and 2.5–5% of those persons died. In the United States, about 2.5% of persons with the flu died, resulting in about 675,000 deaths—about 10 times as many Americans as died in World War I (1914–1918). Two hundred thousand people died in the United States in October 1918 alone. Previous influenza outbreaks had death rates of about 0.1% in the United States, only one twenty-fifth as high as the 2.5% rate of 1918–1919.
The 1918 flu appeared 28 years after the pandemic of 1890, sweeping the world suddenly in September 1918. The flu was called Spanish Flu in the United States because it was especially deadly in Spain early in its history, killing as many as 8 million people. The 1918 flu was unique in that it was deadlier for young people than for the elderly: 99% of its victims were under age 65. Victims sometimes died within a few hours of infection. It should be noted that the great majority of those infected did not die. It struck rich, poor, and middleclass alike, with similar death rates for all groups.
By late November 1918, the death rate from the flu was tapering off in the United States. By early 1919, the pandemic was over, both in the United States and most of the rest of the world.
Disease Characteristics
Influenza is an infection of the lungs and other parts of the respiratory tract (breathing organs) that is caused by a virus. Viruses are tiny clusters of molecules that are smaller than a cell. Each individual virus, called a virion or virus particle, consists of a sheath or covering called a capsid, which is made of proteins (proteins are a type of complex molecule basic to life). The capsid carries a core of RNA (sometimes DNA). A virus cannot live on its own, but reproduces by attaching to a true cell such as a bacterium or human body cell and injecting its RNA or DNA into that cell. The cell is tricked into using the viral RNA or DNA to manufacture new virus particles, which can then infect other cells.
WORDS TO KNOW
CAPSID: The protein shell surrounding a virus particle.
CREPITANT: A crackling sound that accompanies breathing, a common symptom of pneumonia, or other diseases of the lungs.
PANDEMIC: Pandemic, which means all the people, describes an epidemic that occurs in more than one country or population simultaneously.
RALES: French term for a rattling sound in the throat or chest.
REASSORTMENT: A condition resulting when two or more different types of viruses exchange genetic material to form a new, genetically different virus.
A global influenza pandemic occurs when a form of flu virus evolves that can be easily transmitted between human beings. There were three global flu pandemics in the twentieth century (1918–1919, 1957–1958, and 1967–1968). There had been none in the twenty-first century as of early 2007.
There are three basic types of flu virus, termed influenza A, B, and C. Influenza A viruses are the most common. They are also called avian viruses because “avian” means having to do with birds and these viruses are hosted by birds as well as by humans and some other mammals. The 1918 flu virus was an influenza A virus.
Each influenza A capsid consists of eleven different proteins. Two of these proteins tend to vary widely among flu strains. These are hemagglutinin (HA) and neuraminidase (NA). Strains of influenza A virus are named for which kinds of HA and NA protein they contain. For example, there are H1N1 flu viruses, H3N2 flu viruses, and dozens of others. The strain that caused the 1918 flu was an H1N1 virus. Not all H1N1 viruses are identical, as there are other proteins in the virus that can differ, and the H1 (HA number 1) protein itself can take on slightly different forms.
These differences are a matter of life and death. In the body, the immune system fights viral infections by destroying virus particles and the cells that have been infected by them. It decides what cells or particles to destroy by detecting molecules that belong to the virus. These molecules are called antigens. The HA protein of an influenza A virus is an especially important antigen. When the body's immune system knows to attack a particular form of HA, it can effectively fight the virus bearing that form of HA. If a form of HA is unknown to the immune system, however, the virus is free to spread through the body while the immune system is learning how to identify it. If a person survives that variety of flu, they are permanently immune to it afterward because their immune system remembers it.
From about 1919–2005, the 1918 H1N1 flu strain was considered extinct. However, samples of the virus's RNA were recovered in the 1990s from an Inuit Eskimo woman who had died of the flu in 1918 in Alaska and whose body had been frozen in permafrost since that time, as well as from preserved laboratory samples of lung tissue of four U.S. soldiers who died of flu in 1918. The full RNA sequence of the virus, which was reconstructed by scientists studying these samples and published in the journal Science in 2005, showed that the 1918 virus was probably transmitted directly from birds—which are a large natural reservoir of influenza A viruses—to human beings, unlike later pandemic influenzas, which are thought to have originated via reassortment. Reassortment can occur when two different (but related) viruses infect a single cell. Their RNA fragments, mixing inside the cell, can be reassembled into a new virus, a reassortant that contains RNA from both. The pandemic flu strains of 1957 and 1968 were probably reassortant viruses that mixed human flu viruses with avian flu viruses, but the 1918 flu was apparently a purely avian flu virus.
Re-creation of the 1918 flu virus has yielded some understanding of why this particular influenza A virus was so deadly. First, the virus replicates rapidly in the body's tissues. How it does so is not entirely understood, but it was known as of early 2007 that the particular form of HA protein possessed by the 1918 virus was necessary to this rapid spreading. The HA protein is used by a flu virus to stick to host cells, and the form of HA protein possessed by the 1918 virus may be more efficient at doing this job. Also, the 1918 virus spreads more widely in the body than most flu viruses. Most flu viruses use a molecule called trypsin to activate HA molecules and attach to cells. The trypsin must usually come from the cell being attacked. Lung cells are rich in trypsin, which is why flu viruses thrive in lung tissue. In contrast, the NA protein of the 1918 virus can activate the virus's own HA attachment molecule without help from cellular trypsin. The 1918 virus, therefore, was equipped to rapidly attack a wider variety of cells.
A second factor in the deadliness of the 1918 virus is that it triggers an excessive immune response from the body. Excess amounts of the chemicals called interferons, cytokines, and chemokines are produced by the tissues attacked by the virus, and these substances themselves damage the tissues—an event called by immunologists a “cytokine storm.” Cells of the immune system also attack the tissues in response to these chemicals. In effect, the 1918 virus not only attacks the body but also tricks the body into attacking itself. This explains why the 1918 virus was most fatal to young adults—the population that has, on average, the strongest immune system.
Disease Transmission
Flu virus is spread mostly through contact with droplets emitted during coughing and sneezing. It is also spread through direct skin contact. The contagious period, during which a person infected with the disease can spread virus particles to an uninfected person, is about one day before symptoms appear to five days after symptoms appear. Typically, about half of all flu infections are asymptomatic (the person does not feel sick). Whether this was true of the 1918 flu is not known, because the viral nature of the disease was not understood until 1933, so asymptomatic cases could not be discovered.
The 1918 flu may have been more easily transmitted than later strains of flu because of the extreme number of virus particles probably produced in lung tissue of people that contracted it. Experiments in 2005 showed that 50 times more virus particles were released from human lung tissue growing in laboratory culture than were released when the tissue was infected by a modern H1N1 flu strain called the Texas virus. Mouse lungs infected with the 1918 virus contained 39,000 times more virus particles after 4 days than mouse lungs infected with the modern virus. However, a 2004 study published in Nature concluded from historical information that the transmissibility of the 1918 flu was “not large relative to many other infectious diseases.”
Transportation systems such as ships and planes contribute to the global spread of viruses. The worldwide travel activity of troops during World War I (1914– 1918) probably helped the 1918 flu pandemic to occur by spreading the virus quickly between countries and continents. Today, commercial jet travel is the usual means of global flu transport.
A LEGACY OF DEATH
The influenza pandemic of 1918 killed more people—mostly otherwise healthy young adults—than any other disease of similar duration in world history. Exact numbers of those struck by influenza are unknown. In 1919, a U.S. Public Health Service survey of eleven cities and towns discovered that about 280 out of 1,000 persons had influenza during the pandemic, yielding an estimated national infection rate of over 25 million afflicted Americans in 1918–1919.
Scope and Distribution
H1N1 flu virus varieties are widespread today in humans and pigs. However, a number of genetic differences distinguish the present-day strains of H1N1 from the deadly 1918 strain. Today, the precise strain of H1N1 that caused the 1918 flu pandemic exists only in a few laboratories.
Treatment and Prevention
In 1918 the viral natural of influenza was not understood. No antiviral drugs had yet been discovered, and even antibiotics were not available. Antibiotics are drugs that kill bacteria; they are not useful directly against viral infections because they do not destroy virus particles, but they can help patients survive bacterial infections that may occur when the body is weakened by the primary, viral infection.
Influenza vaccines are now considered the best way to prevent flu. Each year, a new dominant type of influenza reliably appears in Asia. Medical researchers identify the strain and produce a vaccine that is distributed in parts of the world that have not yet experienced the new virus strain. A vaccine is a preparation that contains antigens—chemicals that alert the body's immune system to fight back against a specific invader. After being trained on specific antigens by a vaccine, the body can attack a disease agent carrying those antigens as soon as it appears. In the case of a flu vaccine, the HA protein, which is harmless by itself, is often used as the antigen. Virus particles that have been damaged so that they cannot cause an infection are also used in vaccines.
International surveillance of new influenza viruses is coordinated by the World Health Organization (WHO) Influenza Surveillance Network, set up in 1952. Scores of medical institutions in 83 countries collect flu specimens and send them to four centers (one each in Australia, Japan, the United Kingdom, and the United States) for analysis. WHO scientists study these samples each year to design vaccines for the northern and southern hemispheres, then send these vaccine designs to manufacturers for mass production. The Influenza Surveillance network works well for the industrialized countries of the world, but according to the U.S. National Academy of Science, the network is not as effective in Africa and Asia. This leaves more people vulnerable to flu pandemic in those places.
Today, vaccines are not the only tool for fighting a flu pandemic. Several antiviral drugs are available that would probably be effective against the 1918 virus or a similar virus. These drugs are designed to interfere with the functioning of one or more of the proteins a virus uses to reproduce. For instance, relenza and tamiflu are flu-specific drugs called neuraminidase inhibitors. That is, they are designed to interfere with the action of the NA (neuraminidase) proteins that help viruses spread through the body. The drugs must be given very soon after infection in order to stop its spread; they do not kill the virus, but slow its progress while the body's immune system actually kills the virus particles.
These drugs are relatively expensive to produce and not available today in stockpiles large enough to treat the populations of whole countries. Therefore, despite the existence of effective antiviral drugs, the World Health Organization warns that a 1918-type flu pandemic could still be a global disaster.
Impacts and Issues
As described above, the 1918 flu virus is no longer extinct. In 2005, scientists at the Centers for Disease Control and Prevention (a U.S. government group) in Atlanta, Georgia, reconstructed live virus from RNA fragments recovered from tissue dating to the original pandemic. This caused some controversy. Most scientists agreed that prevention of a future flu pandemic could be aided by studying live 1918 virus. However, some also argued that resurrecting the 1918 virus itself created an unacceptable risk; if the virus were to escape from the laboratories that were using it to infect mice, monkeys, and tissue cultures, it could cause another global pandemic all by itself. Others argued that publishing the RNA information for the virus might enable sophisticated terrorists to re-create the virus as a weapon. An emergency meeting of the U.S. National Science Advisory Board for Biosecurity was called before publication of the virus data in 2005, and the board decided that the benefits of the work outweighed the risks. While it may be unlikely that the 1918 flu will escape from captivity and cause a global pandemic, WHO and other expert groups warn that a new virus might evolve naturally with properties similar to those of the 1918 flu.
By 2007, an H5N1 virus causing a variety of avian flu had been circulating in Asia for several years and was causing increasing international concern as it moved into Africa, Russia, and Europe. The present form of the virus, which was highly dangerous to humans, could only be contracted directly from birds, or by intimate association of family members or health care providers with a person sick with Avian Flu. Human to human transmission by routine contact had not been documented as of April 2007, making that form of H5N1 an unlikely candidate for a human pandemic. However, if the properties of this virus are modified by re-assortment or mutation (always an ongoing process) so that it can spread quickly among humans, it is possible to cause a global pandemic with millions of casualties. As of 2004, WHO estimated that such a pandemic would cause at least two to seven million deaths worldwide and perhaps over 50 million—comparable to the 1918 pandemic. Such large numbers of deaths are possible because the modern antiviral drugs that are effective against influenza would not be available in large enough supply, and a targeted vaccine, if one could be developed before the pandemic fulminated (reached its peak), could not be manufactured in sufficient quantities quickly enough to vaccinate enough of the population to prevent the pandemic.
RECONSTRUCTING PAST PANDEMICS, PREPARING FOR THE FUTURE?
In 2005, scientists announced that they had sequenced the genetic structure of the virus responsible for the 1918 influenza pandemic. By analyzing tissue samples recovered from a 1918 flu victim found frozen in the Alaskan tundra, along with preserved lung tissue samples from affected World War I soldiers, scientists were able to determine that the virus is a variety of avian (bird) influenza, known as the H1N1 strain. In 2005, the World Health Organization warned that the H5N1 avian influenza strain (commonly known as the “bird flu”), which recently emerged in Asia, may lead to the next global influenza pandemic. Evidence suggests that the H5N1 flu is genetically similar to the virus that caused the 1918 pandemic.
IN CONTEXT: TRENDS AND STATISTICS
Deaths from the 1918 flu in the United States reduced the statistical average life span of an American by 10 years. In the age range of 15 to 34 years, the death rate in 1918 due to pneumonia and influenza was 20 times higher than the normal rate. The large number of deaths in many of the young generation had an economic effect for decades to come. South America, Asia, and the South Pacific were also devastated by the infection.
In the United States the influenza outbreak greatly affected daily life. Gatherings of people, such as at funerals, parades, or even sales at commercial establishments were either banned or were of very short duration.
Primary Source Connection
The influenza pandemic of 1918 killed more people than any other epidemic in recorded history, including the bubonic plague pandemic of the fourteenth century known as the Black Death. The flu moved too quickly for public health authorities to adequately respond. In both military and civilian life, hospital resources were strained by the sheer number of persons sick with influenza. Physicians and nurses were overwhelmed and in short supply. Quarantine measures were enacted, but did little to stem the spread of the disease. Mortuaries were overcrowded. One Army physician, known only as “Roy,” documented his observations of the epidemic at the base hospital at Camp Devens, Massachusetts, in the letter below. The letter was found years later and now resides in the archives at the University of Michigan.
IN CONTEXT: EPIDEMIC NUMBERS
In 2005, the world's population totalled about 6.5 billion people—more than three times greater than the 1918 population. An influenza pandemic with mortality rates similar to those seen in the 1918 epidemic could kill an estimated 150 million people.
Camp Devens Letter
Camp Devens, Mass.
Surgical Ward No 16
29 September 1918
(Base Hospital)
My dear Burt,
It is more than likely that you would be interested in the news of this place, for there is a possibility that you will be assigned here for duty, so having a minute between rounds I will try to tell you a little about the situation here as I have seen it in the last week.
As you know I have not seen much Pneumonia in the last few years in Detroit, so when I came here I was somewhat behind in the niceties of the Army way of intricate diagnosis. Also to make it good, I have had for the last week an exacerbation of my old “ear rot” as Artie Ogle calls it, and could not use a Stethoscope at all, but had to get by on my ability to “spot” 'em thru my general knowledge of pneumonias. I did well enough, and finally found an old Phonendoscope that I pieced together, and from then on was all right. You know the Army regulations require very close locations etc.
Camp Devens is near Boston, and has about 50,000 men, or did have before this epidemic broke loose. It also has the Base Hospital for the Div. of the N. East. This epidemic started about four weeks ago, and has developed so rapidly that the camp is demoralized and all ordinary work is held up till it has passed. All assemblages of soldiers taboo.
These men start with what appears to be an ordinary attack of La Grippe or Influenza, and when brought to the Hosp. they very rapidly develop the most viscous type of Pneumonia that has ever been seen. Two hours after admission they have the mahogany spots over the cheek bones, and a few hours later you can begin to see the cyanosis extending from their ears and spreading all over the face, until it is hard to distinguish the coloured men from the white. It is only a matter of a few hours then until death comes, and it is simply a struggle for air until they suffocate. It is horrible. One can stand it to see one, two, or twenty men die, but to see these poor devils dropping like flies sort of gets on your nerves. We have been averaging about 100 deaths per day, and still keeping it up. There is no doubt in my mind that there is a new mixed infection here, but what I don't know.
My total time is taken up hunting rales, rales dry or moist, sibilant or crepitant or any other of the hundred things that one may find in the chest, they all mean but one thing here—Pneumonia—and that means in about all cases death.
The normal number of resident Drs. here is about 25 and that has been increased to over 250, all of whom (of course excepting me) have temporary orders—“Return to your proper Station on completion of work.” Mine says “Permanent Duty,” but I have been in the Army just long enough to learn that it doesn't always mean what it says. So I don't know what will happen to me at the end of this.
We have lost an outrageous number of nurses and Drs., and the little town of Ayer is a sight. It takes Special trains to carry away the dead. For several days there were no coffins and the bodies piled up something fierce, we used to go down to the morgue (which is just back of my ward) and look at the boys laid out in long rows. It beats any sight they ever had in France after a battle. An extra long barracks has been vacated for the use of the morgue, and it would make any man sit up and take notice to walk down the long lines of dead soldiers all dressed and laid out in double rows. We have no relief here, you get up in the morning at 5.30 and work steady till about 9.30 P.M., sleep, then go at it again. Some of the men of course have been here all the time, and they are TIRED.
If this letter seems somewhat disconnected, overlook it, for I have been called away from it a dozen times the last time just now by the Officer of the Day, who came in to tell me that they have not as yet found at any of the autopsies any case beyond the Red. Hepatitis stage. It kills them before they get that far.
I don't wish you any hard luck, Old Man, but I do wish you were here for a while at least. It's more comfortable when one has a friend about. The men here are all good fellows, but I get so damned sick of pneumonia that when I go to eat I want to find some fellow who will not “Talk Shop” but there ain't none nohow. We eat it, live it, sleep it, and dream it, to say nothing of breathing it 16 hours a day. I would be very grateful indeed if you would drop me a line or two once in a while, and I will promise you that if you ever get into a fix like this, I will do the same for you.
“SPANISH FLU” OR “LA GRIPPE:” AN EFFICIENT KILLER
The 1918 influenza outbreak was called the “Spanish Flu” or “La Grippe.” The moniker came from the some 8 million influenza deaths that occurred in Spain in one month at the height of the outbreak. Ironically, more recent research has demonstrated that the strain of influenza that ravaged Spain was different from that which spread influenza around the world.
Recent research has demonstrated that the particular strain of virus was one that even an efficiently functioning immune system was not well equipped to cope with. A mutation produced a surface protein on the virus that was not immediately recognized by the immune system; this contributed to the ability of the virus to cause an infection.
Each man here gets a ward with about 150 beds (mine has 168) and has an Asst. Chief to boss him, and you can imagine what the paper work alone is—fierce—and the Govt. demands all paper work be kept up in good shape. I have only four day nurses and five night nurses (female), a ward-master, and four orderlies. So you can see that we are busy. I write this in piecemeal fashion. It may be a long time before I can get another letter to you, but will try.
This letter will give you an idea of the monthly report which has to be in Monday. I have mine most ready now. My Boss was in just now and gave me a lot more work to do so I will have to close this.
Goodbye old Pal, “God be with you till we meet again”
Keep the Bouells open.
(Sgd) Roy.
Roy
“CAMP DEVENS LETTER.” BRITISH MEDICAL JOURNAL (DECEMBER 22–29, 1979).
See AlsoAvian Influenza; H5N1 Virus; Influenza; Influenza Pandemic of 1957; Influenza, Tracking Seasonal Influences and Virus Mutation; Pandemic Preparedness; Viral Disease.
BIBLIOGRAPHY
Books
Corsby, Alfred W. America's Forgotten Pandemic. New York: Cambridge University Press, 2003.
Duncan, K. Hunting the 1918 Flu: One Scientist's Search for a Killer Virus. Toronto: University of Toronto Press, 2003.
Kolata, Gina. Flu: The Story of the Great Influenza Pandemic of 1918 & the Search for the Virus That Caused It. Upland, PA: Diane Pub. Co., 2001.
Periodicals
Holmes, Edward C. “1918 and All That.” Nature. 303 (2004): 1787–1788.
Johnson, Niall P.A.S. “Updating the Accounts: Global Mortality of the 1918–1920 ‘Spanish’ Influenza Pandemic.” Bulletin of the History of Medicine.76 (2002): 105–115.
Kaiser, Jocelyn. “Resurrected Influenza Virus Yields Secrets of Deadly 1918 Pandemic.” Science. 310 (2005): 28029.
Koelle, Katia, et al. “Epochal Evolution Shapes the Phylodynamics of Interpandemic Influenza A (H3N2) in Humans.” Science. 314(2006): 1898–1903.
Laver, Graeme, and Elspeth Garman. “The Origin and Control of Pandemic Influenza.” Science. 293 (2001): 1776–1777.
Loo, Yueh-Ming, and Michael Gale Jr. “Fatal Immunity and the 1918 Virus.” Nature. 445 (2007): 18–19.
Mills, Christina E., James M. Robins, and March Lipsitch. “Transmissibility of 1918 Pandemic Influenza.” Science. 432 (2004): 904–906.
Smith, Kerri. “Concern as Revived 1918 Flu Virus Kills Monkeys” Nature. 445 (2007): 237.
Tumpey, Terrence M., et al. “Characterization of the Reconstructed 1918 Spanish Influenza Pandemic Virus.” Science. 310 (2005): 77–80.
Web Sites
National Vaccine Program Office, United States Department of Health and Human Services. “Pandemics and Pandemic Scares in the 20th Century.” <http://www.hhs.gov/nvpo/pandemics/flu3.htm#10> (accessed January 23, 2007).
The White House (U.S. Government). “National Strategy for Pandemic Influenza.” November 1, 2005 <http://www.whitehouse.gov/homeland/pandemic-influenza.html> (accessed January 23, 2007).
U.S. Department of Health and Human Services. “PandemicFlu.org/AsianFlu.org.” August 24, 2006 <http://www.pandemicflu.gov> (accessed January 25, 2007).
Larry Gilman