Predominant role of bacterial pneumonia as a cause of death in pandemic influenza: implications for pandemic influenza preparedness

Abstract

Background: Despite the availability of published data on 4 pandemics that have occurred over the past 120 years, there is little modern information on the causes of death associated with influenza pandemics.

Methods: We examined relevant information from the most recent influenza pandemic that occurred during the era prior to the use of antibiotics, the 1918-1919 "Spanish flu" pandemic. We examined lung tissue sections obtained during 58 autopsies and reviewed pathologic and bacteriologic data from 109 published autopsy series that described 8398 individual autopsy investigations.

Results: The postmortem samples we examined from people who died of influenza during 1918-1919 uniformly exhibited severe changes indicative of bacterial pneumonia. Bacteriologic and histopathologic results from published autopsy series clearly and consistently implicated secondary bacterial pneumonia caused by common upper respiratory-tract bacteria in most influenza fatalities.

Conclusions: The majority of deaths in the 1918-1919 influenza pandemic likely resulted directly from secondary bacterial pneumonia caused by common upper respiratory-tract bacteria. Less substantial data from the subsequent 1957 and 1968 pandemics are consistent with these findings. If severe pandemic influenza is largely a problem of viral-bacterial copathogenesis, pandemic planning needs to go beyond addressing the viral cause alone (e.g., influenza vaccines and antiviral drugs). Prevention, diagnosis, prophylaxis, and treatment of secondary bacterial pneumonia, as well as stockpiling of antibiotics and bacterial vaccines, should also be high priorities for pandemic planning.

Figure 1

Examples of hematoxylin and eosin–stained postmortem lung sections from 4 victims of the 1918–1919 influenza pandemic (see text). A, Typical picture of severe, widespread bacterial bronchopneumonia with transmural infiltration of neutrophils in a bronchiole and with neutrophils filling the airspaces of surrounding alveoli (original magnification, 40×). B, Massive infiltration of neutrophils in the airspaces of alveoli associated with bacterial bronchopneumonia as in A (original magnification, 200×). C, Bronchopneumonia with intra-alveolar edema and hemorrhage. Numerous bacteria are visible both in the edema fluid and in the cytoplasm of macrophages (original magnification, 400×). D, Bronchopneumonia with evidence of pulmonary repair. The alveolar epithelium is hyperplastic; interstitial fibrosis is seen between alveoli (original magnification, 200×).