Influenza pandemics can occur when a novel strain of virus causes an epidemic that spreads over a wide geographic area and affects an exceptionally high proportion of the population. Intervals between previous pandemics have varied from 11 to 42 years with no recognisable pattern. The last pandemic was in 1968/69. Prior to that pandemics occurred in 1957/58 and 1918/19. The impact of the next pandemic could have a devastating effect on the health and well being of the American public. Widespread illness in the community will also increase the likelihood of sudden and potentially significant shortages of personnel who provide other essential community services.
Influenza pandemics have occurred throughout recorded history and have been documented since the 16th century. There have been substantial differences between them, including between the three pandemics of the last century. There is therefore considerable uncertainty about both the timing of a future pandemic and its precise impact - the severity of illness caused by the new virus strain, the rapidity of its spread and the groups of the population which will be most susceptible are all unknown factors. Nonetheless, for planning purposes, reports of previous pandemics give an interesting insight into the likely range of impact.
Cause of Pandemics
Influenza pandemics occur when there is a notable genetic change (termed genetic shift) in the circulating strain of influenza. Because of this genetic shift, a large portion of the human population is entirely vulnerable to infection from the new pandemic strain.
Three virus types, influenza A, B and C, can cause respiratory illness and are easily transmitted in crowded and enclosed spaces. Regional and widespread epidemics are most often attributed to influenza A and B viruses, while type C is associated with mild illness, sporadic cases, or minor outbreaks. Influenza A causes the most severe disease in humans, and is the most likely to trigger a pandemic.
Influenza A and B possess two surface glycoprotein's: the hemagglutinin (H) and neuraminidase (N). The H subtypes are epidemiologically most important, as they govern the ability of the virus to bind to and enter cells, where multiplication of the virus then occurs. The N subtypes govern the release of newly formed virus from the cells. Influenza A viruses are further subdivided into subtypes dependent on differences in these surface glycoprotein's. Although only two influenza A subtypes currently co-circulate globally in humans (H1N1 and H3N2), at least 16 distinct antigenic subtypes of HAs (H1 to H16) and nine NAs (N1 to N9) have been identified in wild aquatic birds.
A minor change in these antigens (antigenic drift) may result in epidemics, since incomplete protection remains from past exposure to similar viruses. A major change (antigenic shift) may result in a worldwide pandemic if the virus, for which humans have no protection, is efficiently transmitted from human to human. Antigenic shift occurs only with influenza A viruses. Influenza A viruses were the cause of the three Pandemics in the 20th Century.
Difficulty in controlling illness from one flu season to the next is due to changes in virus types A and B. Both undergo constant, but relatively subtle mutations (antigenic drift), accounting for the different influenza epidemiology, strains, and vaccines seen from year to year. As they lack a proof-reading mechanism, the small errors that occur when the virus copies itself are left undetected and uncorrected. As a result, influenza A viruses undergo constant stepwise changes in their genetic make-up. This strategy, known as antigenic drift, works well as a short-term survival tactic for the virus: the speed with which slight variations develop keeps populations susceptible to infection.
Pandemics occur when an entirely new subtype of influenza A virus emerges (antigenic shift) through recombination of human and animal antigens (swine or avian). Not all antigenic shifts cause a pandemic, but if a novel subtype is virulent and easily transmitted, a pandemic is probable. Apart from being highly unstable and prone to small mutational errors, influenza viruses have a segmented genome, consisting of eight genes, that allows easy swapping of genetic material - like the shuffling of cards - coinfecting a host with two different viruses. If this new "hybrid" virus contains the right mix of genes, causing severe disease and allowing easy and sustainable human-to-human transmission, it will ignite a pandemic. This works well as a long-term survival tactic: immunologically, a new virus subtype starts from scratch and is guaranteed a very large population of susceptible hosts.
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