The propensity of influenza viruses to undergo rapid and unpredictable antigenic change has given influenza a prominent place among emerging and reemerging diseases.(29, 50, 81) Historical accounts suggest that influenza viruses, which cause a highly contagious, febrile, acute respiratory illness in humans, have been around for centuries.(48) Epidemics of various severity have occurred almost annually. Pandemics of influenza, which generally have had a more widespread and dramatic impact than annual epidemics, have occurred unpredictably at irregular intervals. The three most dramatic events caused by influenza viruses during this century were the pandemics of "Spanish" influenza beginning in 1918, the 1957 "Asian" influenza, and most recently, the 1968 "Hong Kong" influenza. In each pandemic, novel influenza viruses swept rapidly and pervasively around the globe and caused disease in all age groups.(78) Each pandemic was associated with high rates of morbidity, considerable social disruption, and substantial economic losses. In addition, the Spanish influenza pandemic was associated with a relatively high case-fatality rate in young and previously healthy adults. This unique pattern of mortality had profound medical, social, and political consequences.(13) Although not considered a true pandemic by many,(38) the reemergence in 1977 of influenza A (H1N1) viruses ("Russian" influenza) is also notable because these viruses swept rapidly around the globe and caused considerable morbidity among individuals under 20 years of age.(78) Two features of influenza virus replication and evolution account for the epidemiologic success of these viruses. First, there is relatively rapid and unpredictable antigenic change (antigenic drift) in the surface proteins, hemagglutinin (HA), and neuraminidase (NA). Antigenic drift occurs as part of the continuing evolution of influenza viruses after they emerge in pandemic form and become established in humans. As antibody levels to the pandemic strain rise within the human population, the circulating influenza viruses must change antigenically to survive. Antigenic drift renders an individual susceptible to new strains because the antigenically drifted influenza viruses are able to escape neutralization by antibody to previously circulating strains. Annual epidemics occur during the interpandemic period because sufficient numbers of individuals in the population become susceptible to the antigenically variant strain. Second, there is the emergence of novel influenza A viruses in humans (antigenic shift). Antigenic shift occurs when certain animal influenza viruses, which normally infect only avian or swine reservoirs and are unrelated to the influenza viruses currently circulating in humans, are transmitted to humans. Evidence suggests that emergence of novel pandemic strains may occur either after genetic reassortment between human and animal influenza viruses or, alternatively, via direct transmission of an animal strain to humans.(80, 81) Thus, antigenic shift is defined as the appearance in the human population of a new influenza virus containing a novel HA or novel HA and NA that are immunologically distinct from those of the influenza viruses that have been circulating in man in recent decades. A pandemic takes place when human-to-human transmission of these novel viruses occurs and leads to disease in a large and immunologically susceptible human population.
