All pandemics are different. The minimum requirement seems to be a major change or shift in the HA antigen (1968). In 1957, changes in both HA and NA antigens were associated with higher rates of illness and death.

The memorable and probably unique severity of the 1918 pandemic may have depended, at least in part, on wartime conditions and secondary bacterial infections in the absence of antimicrobial drugs. Also, mechanical respirators and supplemental oxygen were not available.

Although evidence is strong that recombinational capture of animal influenza HA or NA antigens may be essential for pandemic origins, extreme antigenic drift, such as that which occurred in 1947, can lead to global dissemination and disease by the multiply mutated virus.