Historical thoughts on influenza viral ecosystems, or behold a pale horse, dead dogs, failing fowl, and sick swine

OBJECTIVES To understand human influenza in a historical context of viral circulation in avian species, mammals, and in the environment. DESIGN Historical review. SETTING Global events in a variety of circumstances over more than 3,000 years time. SAMPLE Comprehensive review of the historical literature including all major publications on pandemic and panzootic influenza. MAIN OUTCOME MEASURES Influenza pandemics, panzootics, major epidemics and epizootics, and instances of interspecies transmission of influenza A. RESULTS Extensive documentation of human and animal influenza over many centuries suggests that influenza A viruses have adapted to a variety of species and environmental milieu and are capable of switching between many different hosts under widely varying circumstances. CONCLUSIONS The genetic elements of influenza A viruses circulate globally in an extensive ecosystem comprised of many avian and mammalian species and a spectrum of environments. Unstable gene constellations found in avian species become stable viruses only upon switching to secondary hosts, but may then adapt and circulate independently. It may be desirable to think of influenza A viruses as existing and evolving in a large ecosystem involving multiple hosts and environments. Implications for understanding human influenza are discussed.