An influenza pandemic is a global outbreak of influenza and occurs when a new influenza virus emerges, spreads and causes disease worldwide. Influenza A viruses continuously undergo antigenic evolution. There are two main mechanisms by which they do so: antigenic drift causes regular influenza epidemics, while antigenic shift is the cause of occasional global outbreaks of influenza (pandemics). Antigenic shift implies that an influenza A virus with a new HA subtype is introduced into the human population. This may occur by (i) direct transmission of an avian virus from birds to humans, (ii) genetic reassortment between an avian and a human virus, or (iii) reintroduction of an old strain into the population.
(i)Rarely, a highly pathogenic avian influenza virus is transmitted directly from birds to humans. During the 1997 bird flu outbreak in Hong Kong, 18 people were infected with the H5N1 virus, 6 of whom died. To date, H5N1 has not efficiently transmitted from birds to humans and therefore has not yet been able to cause a pandemic. However, the death rates clearly show the deadliness of the virus.
(ii)Genetic reassortment may occur when a host cell is simultaneously infected with two influenza A viruses. During the reassembly of new virus particles, the RNA segments from the two strains can get mixed together, leading to the emergence of a third viral strain with a unique combination of genes. Pigs provide an ideal mixing vessel for influenza A viruses, as they can be infected by both human and avian influenza viruses. Other species, including humans, may also serve as a mixing vessel.
(iii)A virus may remain hidden and re-emerge as a pandemic virus when the immunity in the population has waned. The virus that caused the Russian flu in 1977 turned out to be identical in all of its genes to the H1N1 virus that caused a major epidemic in 1950.