Phylogenetic evidence for a mild H1 pandemic in the early 1900s

In contrast to 2009, the 1918 influenza pandemic was a defining infectious disease event for a generation (1). Even during a period when epidemic polio and smallpox were common, the sharp spikes in mortality attributable to influenza that occurred between mid-1918 and 1920 stood out in every population for which reliable data are available (2). However, it was not only the number of deaths that made the 1918 pandemic unique, but also the distribution of ages of those that died: Far more young adults died relative to both children and older adults compared with other pandemics and intrapandemic seasons. In PNAS, an article by Worobey et al. (3) presents a new theory—backed up by robust phylogenetic evidence—of a previously overlooked mild H1 influenza pandemic in the very early 1900s. The authors also draw upon historical seroepidemiolgy results and the concept of antigenic imprinting to suggest that prior circulation of a previously unreported H1N8 strain for 10 y can explain both the number and age distribution of severe infections during the 1918 pandemic. With a large set of viral samples covering a substantial period, phylogenetic models allow us to test many different hypotheses relevant to public health. By combining known dates of isolation and time-dependent mutational models of evolution, the coalescent model (4) allows the joint estimation of dated evolutionary trees and the underlying parameters of the mutational model for all genes for which sequence data are available. Within these gene-specific phylogenies are estimates of the times of most recent common …