CDC: 1918 Influenza, a Puzzle with Missing Pieces

Volume 18, Number 2—February 2012
Commentary
David M. MorensComments to Author and Jeffery K. Taubenberger
Author affiliations: National Institutes of Health, Bethesda, Maryland, USA

Suggested citation for this article

Shanks and Brundage offer thought-provoking hypotheses about influenza pathogenesis during the catastrophic 1918–1919 pandemic (1). Although we neither agree nor disagree with their views, its central hypothesis of T-cell–mediated immunopathogenesis begs examination of past events in light of modern immunologic and virologic understanding. We also emphasize that effects of the pandemic virus should not be measured only by illness and death in 1918–1919, but should also take into account disease caused by its descendent seasonal and pandemic influenza viruses up to the present (2). Thus, for human influenza history to be better understood, it must be continually reevaluated.

Figure
Thumbnail of Combined influenza plus pneumonia (P&I) age-specific incidence, mortality, and case-fatality rates, per 1,000 persons/age group, US Public Health Service house-to-house surveys, 8 states, 1918, and US Public Health Service surveys during 1928–1929. A) P&I incidence for 1918; B) mortality rate for 1918 (ill and well persons combined); C) P&I case-fatality rates for 1918 (solid line) compared with a more typical curve of age-specific influenza case-fatality rates (dotted l

Figure. Combined influenza plus pneumonia (P&I) age-specific incidence, mortality, and case-fatality rates, per 1,000 persons/age group, US Public Health Service house-to-house surveys, 8 states, 1918, and US Public Health Service surveys during...

Specifically, Shanks and Brundage hypothesize that high mortality rates in 1918 resulted from immunopathogenic effects of cell-mediated immune responses elicited by previously circulating influenza viruses. They also suggest that clues to immunopathogenic mechanisms are found in the unique, well-documented, W-shaped age-specific mortality curve of the 1918 pandemic (3) (Figure) in which the typical (U-shaped) curve of pandemic influenza, featuring mortality rate peaks in young and old persons, was augmented by an unprecedented third mortality rate peak in persons 20–40 years of age.

A complicating fact about 1918–1919 mortality patterns and pathogenesis hypotheses is that for ≈98% of infected persons, influenza was clinically unremarkable in its traditional signs and symptoms (fever, cough, myalgia) and severity (4). Clinical and epidemiologic differences were confined to 2 aspects: higher frequency of its long-appreciated post-illness complication—bacterial pneumonia (5)—and an unusual peak in fatal or nonfatal pneumonia cases in persons 20–40 years of age. In 1918, a higher percentage of persons of all ages, and especially those 20–40 years old, experienced influenza that led to cases of secondary bacterial pneumonia, which were caused by highly prevalent pneumopathogenic bacteria (especially pneumococci, streptococci, and staphylococci). These bacteria had been continuously causing primary pneumonia and pneumonia after influenza and other respiratory illnesses, and had long been exacting a substantial death toll.

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