The Mother of All Pandemics Is 100 Years Old (and Going Strong)!

This year marks the 100th anniversary of the deadliest event in human history. In 1918-1919, pandemic influenza appeared nearly simultaneously around the globe and caused extraordinary mortality (an estimated 50-100 million deaths) associated with unexpected clinical and epidemiological features. The descendants of the 1918 virus remain today; as endemic influenza viruses, they cause significant mortality each year. Although the ability to predict influenza pandemics remains no better than it was a century ago, numerous scientific advances provide an important head start in limiting severe disease and death from both current and future influenza viruses: identification and substantial characterization of the natural history and pathogenesis of the 1918 causative virus itself, as well as hundreds of its viral descendants; development of moderately effective vaccines; improved diagnosis and treatment of influenza-associated pneumonia; and effective prevention and control measures. Remaining challenges include development of vaccines eliciting significantly broader protection (against antigenically different influenza viruses) that can prevent or significantly downregulate viral replication; more complete characterization of natural history and pathogenesis emphasizing the protective role of mucosal immunity; and biomarkers of impending influenza-associated pneumonia.