Annual human influenza epidemics occur because the influenza viruses change their antigenic structure ('antigenic drift') to produce new strains that can cause infection in persons who have been previously infected or vaccinated with different strains. The influenza viruses are also capable of major changes to their antigenic structure ('antigenic shift') to produce new strains that can potentially infect any person. Pandemics, or world-wide epidemics, occur when antigenic shift causes the sudden and unpredictable emergence of a new human influenza virus to which most of the population is susceptible.

Three influenza pandemics occurred during the 20th century, the “Spanish” (1918), “Asian” (1957) and “Hong Kong” (1968) pandemics. The Spanish pandemic resulted in 20-40 million or more deaths (mostly in young adults) worldwide, while the Asian and Hong Kong pandemics resulted in 1-4 million deaths (mostly in older adults) worldwide. By comparison, “inter-pandemic” influenza results in 0.5-2 million deaths (mostly in older adults) worldwide each year.