waves of illness. Perhaps the surface proteins of the virus drifted more rapidly than other influenza virus strains, or perhaps the virus had an unusually effective mechanism for evading the human immune system.
The influenza epidemic of 1918 killed an estimated 675,000 Americans, including 43,000 servicemen mobilized for World War I (Crosby, 1989). The impact was so profound as to depress average life expectancy in the United States by more than 10 years (Grove and Hetzel, 1968) (Figure 1-1) and may have played a significant role in ending the World War I conflict (Crosby, 1989; Ludendorff, 1919).
Many individuals who died during the pandemic succumbed to secondary bacterial pneumonia (Jordan, 1927; LeCount, 1919; Wolbach, 1919) because no antibiotics were available in 1918. However, a subset died rapidly after the onset of symptoms often with either massive acute pulmonary hemorrhage or pulmonary edema, often in less than 5 days (LeCount, 1919; Winternitz et al., 1920; Wolbach, 1919). In the hundreds of autopsies performed in 1918, the primary pathologic findings were confined to the respiratory tree and death was due to pneumonia and respiratory failure (Winternitz et al., 1920). These findings are consistent with infection by a well-adapted influenza virus capable of rapid replication throughout the entire respiratory tree (Reid and Taubenberger, 1999; Taubenberger et al.,