The 1918 Pandemic Of Influenza

By the spring of 1918, when American forces joined the conflagration overseas, Europe had already endured four grinding years of trench warfare. When the tide turned in favor of the Allies in the fall of 1918, it appeared that the unimaginable carnage and devastation consuming the world's Great Powers would finally cease.

Then a new scourge appeared. Influenza caused a sudden increase in mortality in the United States (see Figure 2.1) and other countries (Reid et al., 2004). This outbreak was termed a pandemic because of its worldwide scope. It killed at least

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"Per 100,000 population per year.

1 Adapted from Armstrong GL, Conn LA, Pinner RW. Trends in infectious disease mortality in the United States during the 20th century. JAMA 1999:281:61-6.

* American Water Worfcs Association. Water chlorination principles and practices: AWWA manual M20. Denver, Colorado; American Water Works Association, 1973.

FIGURE 2.1 Crude death rate for infectious diseases—United States, 1900-1996. (Graph from CDC, 1999.)

21.5 million individuals, a number that dwarfs the combat casualties of World War I.

A U.S. military facility was an early victim of this outbreak and played an important role in the spread of disease. In Camp Funston (now Fort Riley,) Kansas, on March 11,1918,

100 soldiers reported sick to the infirmary before noon (Barry, 2004). Figure 2.2 is an undated picture of the emergency hospital in Camp Funston.

Although ravaged by this outbreak, Camp Funston continued to train troops who then embarked to domestic and

FIGURE 2.2 Emergency hospital during influenza epidemic, Camp Funston, Kansas. Forces Institute of Pathology, Washington, DC.)

FIGURE 2.2 Emergency hospital during influenza epidemic, Camp Funston, Kansas. Forces Institute of Pathology, Washington, DC.)

>. (Photo from the National Museum of Health and Medicine, Armed overseas assignments, carrying with them a virus more deadly than their arms. Virus spread to the civilian populations of Europe and North America (Public Broadcasting Service, n.d.). The disease became known as "Le Grippe'' or "Spanish flu'' because Spain was not at war, and its domestic press reported on the outbreak.

Figure 2.3 shows the annualized weekly death rates in London, Paris, New York, and Berlin for October and November of 1918. All four cities experienced high mortality rates nearly simultaneously. There was another wave of mortality in early 1919 before this largest of all known epidemics finally burned out on its own, presumably having induced immunity in sufficient numbers of those who had survived.

Where did the outbreak in Camp Funston begin? After seven years of study, Barry (2004) concluded that it began in Haskell County, Kansas, located 300 miles to the west, where an outbreak of severe influenza was underway. Military recruits from Haskell County were inducted into the military at Camp Funston.

What made the 1918 influenza outbreak so deadly? To understand, it is necessary to know a little about influenza. Influenza is actually a family of viruses with three different types (A, B, and C) and many strains. Scientists create names for influenza strains in the A type based on two proteins

(called antigens because they induce immunity in victims) that appear on the surface of the influenza virus and can be measured. Each antigen can take different forms, which are referred to as subtypes: Hemagglutinin (H) antigen with subtypes 1 to 15 and neuraminidase antigen (N) with subtypes 1 to 9. The 1918 virus was named H1N1 because it had on its surface subtype 1 of the hemagglutinin antigen and subtype 1 of the neuraminidase antigen.

All influenza A strains infect birds (and, for this reason, influenza A is also known as avian influenza), but only some of these strains are able to infect humans and other mammals and subsequently be passed directly from person to person (or animal to animal). There are two ways that a strain of influenza A can develop the ability to spread from person to person: (1) mutation in one or more genes, and (2) reassortment of genes. Reassortment is simply the exchange of genes between or among two or more different viruses to give birth to a hybrid virus. A prerequisite for reassortment is that the same cell in a bird or mammal must be simultaneously infected with two or more strains of influenza A. If a "parent'' strain was capable of being transmitted from person to person, the descendant strain may inherit that ability. Reassortment is a common occurrence in influenza, and it is the key reason that influenza remains a major world health concern to this day.

FIGURE 2.3 Influenza pandemic mortality in American and Europe during 1918 and 1919. (From the National Museum of Health and Medicine, Armed Forces Institute of Pathology, Washington, DC.)

To elucidate whether the 1918 strain was a product of reas-sortment or mutation, over the past decade, researchers have searched from the frozen tundra of Alaska to the archives of the Smithsonian Institution to find preserved tissues of birds and humans who died in 1917 and 1918. By using modern techniques of molecular biology, they isolated snippets of genetic material from influenza A viruses isolated from these specimens and compared them with each other. They found that the virus taken from individuals known to have died from the pandemic strain was not a direct descendant from the viruses that they found in birds from that period.The best theory is that the 1918 strain was the result of a mutation, a reassortment of an influenza A virus or viruses circulating in mammals such as horses or swine, or both (Reid and Taubenberger, 2003). Haskell County, Kansas, where animals outnumbered humans by a large factor, was just the type of location where influenza A strains from different mammalian species could converge to develop into the deadliest strain of influenza yet known to humankind (Barry, 2004).

Pandemics of influenza A occurred in 1957 and 1968. The virus strains causing these outbreaks were reassortments of genetic material between human and avian influenza virus strains circulating at the time (Reid and Taubenberger, 2003). An H2N2 strain caused the 1957 pandemic. An H3N2 strain caused the 1968 pandemic and is still circulating today (with gradual mutations over the years). Recently, the 1957 H2N2 strain was mistakenly included in a set of test strains sent to thousands of laboratories worldwide that participate in influenza monitoring for purposes of calibration. This error was potentially catastrophic because human beings born since the late 1960s do not have immunity to this strain (CDC, 2005).

The threat of future pandemics of influenza A is ever present because of the propensity of influenza to reassort or mutate into new forms for which humans do not have immunity. The influenza virus (as well as its control and treatment methods, such as vaccination, quarantine strategies, and antiviral treatments) remains an important area of research and development. Our knowledge is accelerating so rapidly that no textbook can remain current for long. Most of what is known about the 1918 influenza virus has been discovered in the past 5 years. Interested readers should consult the resources listed at the end of the chapter.

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