The 1918 influenza pandemic: lessons for 2009 and the future

Abstract

The 1918 to 1919 H1N1 influenza pandemic is among the most deadly events in recorded human history, having killed an estimated 50 to 100 million persons. Recent H5N1 avian influenza epizootics associated with sporadic human fatalities have heightened concern that a new influenza pandemic, one at least as lethal as that of 1918, could be developing. In early 2009, a novel pandemic H1N1 influenza virus appeared, but it has not exhibited unusually high pathogenicity. Nevertheless, because this virus spreads globally, some scientists predict that mutations will increase its lethality. Therefore, to accurately predict, plan, and respond to current and future influenza pandemics, we must first better-understand the events and experiences of 1918. Although the entire genome of the 1918 influenza virus has been sequenced, many questions about the pandemic it caused remain unanswered. In this review, we discuss the origin of the 1918 pandemic influenza virus, the pandemic's unusual epidemiologic features and the causes and demographic patterns of fatality, and how this information should impact our response to the current 2009 H1N1 pandemic and future pandemics. After 92 yrs of research, fundamental questions about influenza pandemics remain unanswered. Thus, we must remain vigilant and use the knowledge we have gained from 1918 and other influenza pandemics to direct targeted research and pandemic influenza preparedness planning, emphasizing prevention, containment, and treatment.

Figure 1

A, Three pandemic waves were observed in many locales in 1918 to 1919, as in these data from Breslau, Silesia (now Wroclaw, Poland), documenting monthly influenza mortality from June 1918 through December 1922. The figure is reproduced from data of Lubinski (21), on which we have superimposed indications of the three 1918 to 1919 “waves” (W1, W2, and W3) and the first three annual winter postpandemic recurrences of 1919 to 1920 (R1), 1920 to 1921 (R2), and 1921 to 1922 (R3). B, Age-specific influenza mortality, Breslau, October 1918 to April 1922. The dark blue line combines influenza mortality in W2 and W3 of 1918 to 1919. The light blue line reflects influenza mortality in the first winter recurrence of January to April 1920 (R1). The orange line reflects influenza mortality in the R3 winter recurrence of December 1921 to April 1922. The young adult mortality peak, documented worldwide, is evident in the W2 + W3 and R1 curves of 1919 to 1921 but has completely disappeared by 1922.

Figure 2

Histologic appearance of lung sections from two fatal cases of 1918 influenza, showing distinct clinical–pathologic forms. A, Some deaths, probably a minority, were associated with a severe and rapidly progressing clinical form thought to be similar to acute respiratory distress syndrome (8), which had not been characterized at that time. These patients had rapid progression and fluid-filled alveoli, although they also frequently had concomitant bacterial bronchopneumonia in other sections of the lungs. B, The majority of deaths in 1918 to 1919 appear to have been associated with severe bacterial bronchopneumonia from which Streptococcus pneumoniae, Streptococcus pyogenes, or, less commonly, Staphylococcus aureus could be cultured. The extent to which secondary bacterial pneumonia may have followed primary viral pneumonia is unclear, but most cases with histologic evidence of bacterial pneumonia also showed focal areas consistent with primary viral changes, as in (A). Hematoxylin & eosin stain; original magnifications 200×.

Figure 3

U-shaped and W-shaped combined influenza and pneumonia mortality, by age at death, per 100,000 persons in each age group, US, 1911 to 1918. Influenza/pneumonia-specific death rates are plotted for the years before the pandemic, ie, 1911 to 1917 (blue line), and for the pandemic year 1918 (red line) (7, 66, 67).

Figure 4

Influenza pandemic occurrence, 1500 to 2009. Information was compiled from historical references (, , –, –104) and scientific publications from 1889 to the present (not cited). Interpandemic intervals are noted on the top of the figure. Pandemics are associated with abrupt and widespread epidemicity in multiple locales in two or more geographic regions, rapid progression through large open populations, high clinical illness rates affecting a broad age range, and no other pandemic activity within 5 yrs (to adjust for the possibility of slow and interrupted pandemic spread before the mid 19th century). Especially before 1697, pandemics may be difficult to verify and track because of slower spread (86) as a result of slower and less frequent human travel. Some cited sources suggest different interpretations than those presented here (see text) (, , –, –101). *The 1977 re-emergence and global spread of an “extinct” descendant of the 1918 pandemic virus is included here as a pandemic emergence, although it might also be considered to reflect continuing spread of the original pandemic virus.