Although only 2 to 3 percent of those who fell ill died, the unusually high fatality rate among previously healthy young adults meant the loss of a disproportionate number of society's most productive members. This first wave spread rapidly, encircling the globe in less than five months.

The disease resurfaced in a more virulent form in the United States in August of 1918, causing large numbers of deaths in many U.S. cities as it spread from the East Coast to California. Health authorities reacted by requiring citizens to wear masks in public places and by taking other steps that were presumed to prevent the spread of disease. Many of these efforts were not put in place, however, until the worst of the epidemic had passed.

A third wave, in the spring of 1919, completed what is usually described as the Great Pandemic, although substantial influenza mortality in 1920 might have been the result of the same outbreak (Kilbourne, 1987). The 1918 influenza pandemic affected such a large number of people over such a wide geographic area that it has been the focus of a number of studies (Hoehling, 1961; Crosby, 1976; Osborn, 1977; Neustadt and Fineberg, 1978; Kilbourne, 1987).

Although the 1918 pandemic ranks as one of the single most devastating outbreaks of infectious disease in human history, the technology of the time did not permit the virus to be isolated. Thus, no sample of the causative influenza strain is available for study, which means that the virus's remarkable virulence and transmissibility have not been investigated using the tools of modern molecular virology. Serological evidence suggests, however, that a virus antigenically similar to the 1918 influenza virus persists to this day in swine.

Since the 1918 pandemic, there have been two major global outbreaks of influenza A in the twentieth century—in 1957 and 1968. Significant but less serious pandemics occurred in 1947 and 1977. A potentially serious outbreak appeared imminent in 1976 but, for reasons that are still not clear, never materialized. Some see this 1976 episode as evidence of a failure to judge correctly the threat posed by a human pathogen. Others say that the experience simply points out how difficult it is to predict accurately the course of what could have been a devastating epidemic.

It is impossible to know when the next influenza pandemic will strike. Dangerous new pandemic influenza viruses are most likely to be the result of genetic reassortment of two different, existing influenza viruses. Fortunately, "successful" reassortments are rare. Even so, the danger of such recombinations is always present, and many scientists believe it is simply a matter of time before one occurs again. The lethal 1983 epidemic of avian influenza in chickens (caused by a point mutation in the H5N2 subtype) is a stark reminder that small changes in the viral genome can produce pathogens of exceptional virulence and transmissibility (Kawaoka and Webster, 1988).



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