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Influenza Epidemics and Pandemics

Influenza viruses continuously undergo antigenic evolution. 1 x PF Wright, RG Webster. Orthomyxoviruses. DM Knipe, PM Howley, DE Griffin (Eds.) et al. Fields Virology 4th edn. (Lippincott Williams & Wilkins, 2001) (1533 - 1579) It is this quality that allows them to evade the pre-existing immunity of the host, which implies that immune responses mounted against earlier forms of the virus are less effective or completely ineffective against newer variants. Since the viral surface glycoprotein HA is the antigen against which virus-neutralizing antibodies are directed (see Chapter 4), it is primarily the antigenic variation of HA that is responsible for the immune escape of influenza viruses. Other viral antigens undergo significantly less variation, but – under immunological pressure – may also contribute to the evasion of the immune defence of the host. 2 x PG Thomas, R Keating, DJ Hulse-Post, PC Doherty. Cell-mediated protection in influenza infection. Emerg Infect Dis 12 (2006) (48 - 54) The antigenic evolution of influenza viruses forms the primary basis for the occurrence of annual influenza epidemics and occasional pandemics. Also, it necessitates regular updates of the composition of the influenza vaccine (see Chapter 8).

There are two main mechanisms by which influenza A viruses change their antigenic properties. These are commonly referred to as “antigenic drift” and “antigenic shift”. 1 x PF Wright, RG Webster. Orthomyxoviruses. DM Knipe, PM Howley, DE Griffin (Eds.) et al. Fields Virology 4th edn. (Lippincott Williams & Wilkins, 2001) (1533 - 1579) Antigenic drift occurs through continuous mutation of the RNA genome of the virus. As a result, amino acid changes in the viral proteins arise, including substitutions in the antigenic epitopes of HA. Virus variants with such substitutions have a selective advantage over the original virus, since they are no longer or less efficiently countered by the immunity of the host.

Occasionally, an entirely new influenza A virus subtype of avian origin emerges in the human population. This is called antigenic shift. Since there is no immunity whatsoever to the new virus subtype in the population, this shift forms the scenario for a pandemic outbreak of influenza. Antigenic shift may be the result of direct transmission of an avian virus to humans. Alternatively, a human influenza virus may acquire a subset of genes from an avian virus, pigs or humans serving as a “mixing vessel”. This process of genetic “reassortment” (see Chapter 2) might result in the formation of a new virus with most of the properties of a normal human influenza virus, yet having a new HA on its surface to which the population is immunologically naive. 1 x PF Wright, RG Webster. Orthomyxoviruses. DM Knipe, PM Howley, DE Griffin (Eds.) et al. Fields Virology 4th edn. (Lippincott Williams & Wilkins, 2001) (1533 - 1579)

Three major influenza pandemics struck the world in the 20th century. By far the most devastating pandemic was the Spanish flu outbreak, which hit at the end of the First World War. 3, x JK Taubenberger, DM Morens. 1918 influenza: the mother of all pandemics. Emerg Inf Dis 12 (2006) (15 - 22) 4 x ED Kilbourne. Influenza pandemics of the 20th century. Emerg Inf Dis 12 (2006) (9 - 14) It spread across the globe in three consecutive waves in 1918–19, killing at least 50 million people. 5 x NP Johnson, J Mueller. Updating the accounts: global mortality of the 1918–1920 “Spanish” influenza pandemic. Bull Hist Med 76 (2002) (105 - 115) The subsequent pandemics in 1957 and 1968 were milder, 4 x ED Kilbourne. Influenza pandemics of the 20th century. Emerg Inf Dis 12 (2006) (9 - 14) but nonetheless also caused a total of approximately 2 million deaths. There is no doubt that there will be other pandemics in the future. 6, x RJ Webby, RG Webster. Are we ready for pandemic influenza?. Science 302 (2003) (1519 - 1522) 7 x KG Nicholson, JM Wood, M Zambon. Influenza. Lancet 362 (2003) (1733 - 1745) Having its reservoir among migratory waterfowl, the influenza virus is non-eradicable and will continue to affect humans. The recent outbreaks of highly pathogenic avian influenza, and the occasional transmissions to humans with a fatality rate of over 50%, should serve as a warning that the emergence of a new pandemic is just a matter of time. Accordingly, the WHO is urging individual countries to be aware of the need to start formal influenza pandemic preparedness planning as soon as possible.

References

Label Authors Title Source Year
1

References in context


  • Go to context

  • Influenza viruses continuously undergo antigenic evolution.1 It is this quality that allows them to evade the pre-existing immunity of the host, which implies that immune responses mounted against earlier forms of the virus are less effective or completely ineffective against newer variants.
    Go to context

  • These are commonly referred to as “antigenic drift” and “antigenic shift”.1 Antigenic drift occurs through continuous mutation of the RNA genome of the virus.
    Go to context

  • Occasionally, an entirely new influenza A virus subtype of avian origin emerges in the human population.
    Go to context

  • Antigenic drift is a gradual process.
    Go to context

  • As illustrated in Figure 13, the 1957 Asian H2N2 virus subtype obtained its HA, NA, and PB1 genes from an avian virus and the other fives genes from the circulating H1N1 human strain,1,4,7,14–17 the human H1N1 virus in turn being a distant descendent of the 1918 Spanish flu virus.3 Likewise, the 1968 Hong Kong H3N2 virus acquired its HA and PB1 genes from an avian virus, but retained the NA and remaining five other genes from the then circulating H2N2 human virus.
    Go to context

PF Wright, RG Webster. Orthomyxoviruses. DM Knipe, PM Howley, DE Griffin (Eds.) et al. Fields Virology 4th edn. (Lippincott Williams & Wilkins, 2001) (1533 - 1579) 2001
2

References in context

  • Other viral antigens undergo significantly less variation, but – under immunological pressure – may also contribute to the evasion of the immune defence of the host.2 The antigenic evolution of influenza viruses forms the primary basis for the occurrence of annual influenza epidemics and occasional pandemics.
    Go to context

PG Thomas, R Keating, DJ Hulse-Post, PC Doherty. Cell-mediated protection in influenza infection. Emerg Infect Dis 12 (2006) (48 - 54) 2006
3

References in context

  • By far the most devastating pandemic was the Spanish flu outbreak, which hit at the end of the First World War.3,4 It spread across the globe in three consecutive waves in 1918–19, killing at least 50 million people.5 The subsequent pandemics in 1957 and 1968 were milder,4 but nonetheless also caused a total of approximately 2 million deaths.
    Go to context

  • Rarely, a highly pathogenic avian influenza (HPAI; see also Chapter 2) virus is transmitted directly from birds to humans.3,11,15–18 It was not until the 1997 H5N1 bird flu outbreak in Hong Kong that it was appreciated that such direct transmission could occur.
    Go to context

  • Indeed, there is some circumstantial evidence that the 1918 virus entered the human population several years before the pandemic.3,22 There is a close genetic relationship between the 1918 virus and the porcine A/Swine/Iowa/30 (H1N1) virus.
    Go to context

  • Indeed, there is some circumstantial evidence that the 1918 virus entered the human population several years before the pandemic.3,22 There is a close genetic relationship between the 1918 virus and the porcine A/Swine/Iowa/30 (H1N1) virus.
    Go to context

  • Indeed, there is some circumstantial evidence that the 1918 virus entered the human population several years before the pandemic.3,22 There is a close genetic relationship between the 1918 virus and the porcine A/Swine/Iowa/30 (H1N1) virus.
    Go to context

  • Indeed, there is some circumstantial evidence that the 1918 virus entered the human population several years before the pandemic.3,22 There is a close genetic relationship between the 1918 virus and the porcine A/Swine/Iowa/30 (H1N1) virus.
    Go to context

  • As illustrated in Figure 13, the 1957 Asian H2N2 virus subtype obtained its HA, NA, and PB1 genes from an avian virus and the other fives genes from the circulating H1N1 human strain,1,4,7,14–17 the human H1N1 virus in turn being a distant descendent of the 1918 Spanish flu virus.3 Likewise, the 1968 Hong Kong H3N2 virus acquired its HA and PB1 genes from an avian virus, but retained the NA and remaining five other genes from the then circulating H2N2 human virus.
    Go to context

JK Taubenberger, DM Morens. 1918 influenza: the mother of all pandemics. Emerg Inf Dis 12 (2006) (15 - 22) 2006
4

References in context

  • By far the most devastating pandemic was the Spanish flu outbreak, which hit at the end of the First World War.3,4 It spread across the globe in three consecutive waves in 1918–19, killing at least 50 million people.5 The subsequent pandemics in 1957 and 1968 were milder,4 but nonetheless also caused a total of approximately 2 million deaths.
    Go to context

  • By far the most devastating pandemic was the Spanish flu outbreak, which hit at the end of the First World War.3,4 It spread across the globe in three consecutive waves in 1918–19, killing at least 50 million people.5 The subsequent pandemics in 1957 and 1968 were milder,4 but nonetheless also caused a total of approximately 2 million deaths.
    Go to context

  • Despite their annual seasonal character, influenza epidemics are unpredictable.4,7 When precisely they will start and how long they will last are questions that are difficult to answer in advance. Figure 11 illustrates the variation in the onset and duration of influenza epidemics recorded in the Netherlands in the last three decades of the previous century.
    Go to context

  • While the bird flu outbreak in 1997 was the first documented example of a purely avian virus causing respiratory disease and deaths among humans,18–20 it has since become apparent that the 1918 Spanish flu virus was also an avian virus.3,22–25 Even though the precise origin of the 1918 virus remains enigmatic,3,11,22 based on characterization of genetic material isolated from victims of the 1918 pandemic, it is clear now that the virus was not a human–avian reassortant, but rather an avian-like virus that was introduced in its entirety into the human population and subsequently adapted to the new host.
    Go to context

  • As illustrated in Figure 13, the 1957 Asian H2N2 virus subtype obtained its HA, NA, and PB1 genes from an avian virus and the other fives genes from the circulating H1N1 human strain,1,4,7,14–17 the human H1N1 virus in turn being a distant descendent of the 1918 Spanish flu virus.3 Likewise, the 1968 Hong Kong H3N2 virus acquired its HA and PB1 genes from an avian virus, but retained the NA and remaining five other genes from the then circulating H2N2 human virus.
    Go to context

  • A third way by which an antigenic shift may occur and a pandemic arise is reintroduction of an “old” strain into the human population.
    Go to context

  • Figure 14 gives an overview of the influenza pandemics that occurred in the past century.4,29,30 The most terrible outbreak was the Spanish flu in 1918, with an estimated 50 million deaths,5 justifying its description as “the last great plague of mankind”.
    Go to context

ED Kilbourne. Influenza pandemics of the 20th century. Emerg Inf Dis 12 (2006) (9 - 14) 2006
5

References in context

  • By far the most devastating pandemic was the Spanish flu outbreak, which hit at the end of the First World War.3,4 It spread across the globe in three consecutive waves in 1918–19, killing at least 50 million people.5 The subsequent pandemics in 1957 and 1968 were milder,4 but nonetheless also caused a total of approximately 2 million deaths.
    Go to context

  • Figure 14 gives an overview of the influenza pandemics that occurred in the past century.4,29,30 The most terrible outbreak was the Spanish flu in 1918, with an estimated 50 million deaths,5 justifying its description as “the last great plague of mankind”.
    Go to context

  • In just 10 months, approximately 50 million people worldwide were killed,5 more than the total number of victims of the 1914–18 war.
    Go to context

NP Johnson, J Mueller. Updating the accounts: global mortality of the 1918–1920 “Spanish” influenza pandemic. Bull Hist Med 76 (2002) (105 - 115) 2002
6

References in context

  • There is no doubt that there will be other pandemics in the future.6,7 Having its reservoir among migratory waterfowl, the influenza virus is non-eradicable and will continue to affect humans.
    Go to context

RJ Webby, RG Webster. Are we ready for pandemic influenza?. Science 302 (2003) (1519 - 1522) 2003
7

References in context


  • Go to context

  • There is no doubt that there will be other pandemics in the future.6,7 Having its reservoir among migratory waterfowl, the influenza virus is non-eradicable and will continue to affect humans.
    Go to context

  • Despite their annual seasonal character, influenza epidemics are unpredictable.4,7 When precisely they will start and how long they will last are questions that are difficult to answer in advance. Figure 11 illustrates the variation in the onset and duration of influenza epidemics recorded in the Netherlands in the last three decades of the previous century.
    Go to context

  • As illustrated in Figure 13, the 1957 Asian H2N2 virus subtype obtained its HA, NA, and PB1 genes from an avian virus and the other fives genes from the circulating H1N1 human strain,1,4,7,14–17 the human H1N1 virus in turn being a distant descendent of the 1918 Spanish flu virus.3 Likewise, the 1968 Hong Kong H3N2 virus acquired its HA and PB1 genes from an avian virus, but retained the NA and remaining five other genes from the then circulating H2N2 human virus.
    Go to context

  • There is no doubt that there will be influenza pandemics in the future.7,11,22 It is not so much a matter of whether they will occur but rather when they will occur.
    Go to context

  • In May 2001, and in February and April 2002, the H5N1 virus subtype was once again detected in Hong Kong's poultry markets,7,33 the specific virus strain differing significantly from the 1997 H5N1 bird flu virus.
    Go to context

KG Nicholson, JM Wood, M Zambon. Influenza. Lancet 362 (2003) (1733 - 1745) 2003

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