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Influenza Epidemics and Pandemics

Will there be a new pandemic?

There is no doubt that there will be influenza pandemics in the future. 7, x KG Nicholson, JM Wood, M Zambon. Influenza. Lancet 362 (2003) (1733 - 1745) 11, x RG Webster, M Peiris, H Chen, et al.. H5N1 outbreaks and enzootic influenza. Emerg Inf Dis 12 (2006) (3 - 8) 22 x RG Webster. 1918 Spanish influenza: the secrets remain elusive. Proc Natl Acad Sci 96 (1999) (1164 - 1166) It is not so much a matter of whether they will occur but rather when they will occur. All the ingredients for the formation of new influenza viruses with pandemic potential are there, particularly in Asia. As indicated above, the 1957 H2N2 and 1968 H3N2 viruses originated in China. It is thought that the ecological conditions in China, as well as many other Asian countries, are such that new viruses with pandemic potential may arise comparatively easily. These include the year-round circulation of influenza viruses, along with the dense populations of people, pigs and domestic poultry, often living in close proximity – conditions that facilitate genetic reassortment or direct transfer of avian viruses to humans. However, new viruses with pandemic potential could also arise elsewhere. In fact, human–avian reassortant viruses have been found in Italy and the Netherlands. Also, the 2003 H7N7 fowl plague outbreak in the Netherlands, with a fatal human infection (see below), and the ongoing outbreaks of H5N1 not only in Asia but also in Europe, Africa and the Middle East, underline the risk of reassortment or adaptation to humans, and indicates that new viruses with pandemic potential need not necessarily arise in Asia. Also, previous pandemic human virus subtypes (e.g. the H2N2 virus) may re-emerge when the immunity in the population against such viruses has gradually disappeared. It is likely that this has happened frequently in the past.

It is not possible to predict when the next pandemic will strike. Since 1889, pandemics have occurred at intervals ranging from 10 to 40 years. A cyclic theory has been proposed suggesting that pandemics may appear in a specific recurring pattern. 28 x K Nakajima, U Desselberger, P Palese. Recent human influenza A (H1N1) viruses are closely related genetically to strains isolated in 1950. Nature 274 (1978) (334 - 339) The interval between the 1889 (H2) and 1900 pandemics (H3) matches that between the 1957 (H2) and 1968 (H3) pandemics. However, the approximate 20-year interval between the 1900 and 1918 pandemics would have predicted a global outbreak around 1988, 20 years after the 1968 pandemic, but this did not occur.

“Near misses” of the recent past
“H5N1” (1997–2006)

It is widely assumed that the mass slaughter of 1.5 million chickens in December 1997 in the Hong Kong H5N1 outbreak may well have averted a new human pandemic. Since this incident, the H5N1 virus has re-emerged several times. There is evidence that the precursor viruses of the H5N1 bird flu virus, including the goose H5N1 virus, remained in circulation. 32 x Y Guan, KF Shortridge, S Krauss, et al.. H9N2 influenza viruses possessing H5N1-like internal genomes continue to circulate in poultry in southeastern China. J Virol 74 (2000) (9372 - 9380) Since 1998, culling has also included geese to prevent the goose H5N1 precursor virus from taking a firm hold in poultry in Hong Kong.

In May 2001, and in February and April 2002, the H5N1 virus subtype was once again detected in Hong Kong's poultry markets, 7, x KG Nicholson, JM Wood, M Zambon. Influenza. Lancet 362 (2003) (1733 - 1745) 33 x Y Guan, JSM Peiris, AS Lipatov, et al.. Emergence of multiple genotypes of H5N1 avian influenza viruses in Hong Kong SAR. Proc Natl Acad Sci USA 99 (2002) (8950 - 8955) the specific virus strain differing significantly from the 1997 H5N1 bird flu virus. It had apparently crossed from geese to ducks, undergone reassortment and then crossed to other poultry, but at the time it caused no human infections. However, in February 2003, a 9-year-old boy was hospitalized with an influenza A H5N1 illness, which also affected other members of his family. He survived but his father and 8-year-old sister died. Then, in the spring of 2004, there was a major outbreak of highly pathogenic H5N1 avian influenza first detected in southern Vietnam and then spreading quickly to neighbouring countries, and quite recently also to Europe and Africa.34, 35, and 36 x A Apisarnthanarak, R Kitphati, K Thongphubeth, et al.. Atypical avian influenza (H5N1). Emerg Infect Dis 10 (2004) (1321 - 1324) x MD de Jong, VC Bach, TQ Phan, et al.. Fatal avian influenza A (H5N1) in a child presenting with diarrhea followed by coma. New Engl J Med 352 (2005) (686 - 691) x TH Tran, TL Nguyen, TD Nguyen, et al.. Avian influenza A (H5N1) in 10 patients in Vietnam. New Engl J Med 350 (2004) (1179 - 1188) To date (March 1, 2006) there have been 179 confirmed cases of human H5N1 infections, with 94 fatalities, including four deaths in Turkey in January 2006. 37 x World Health Organization. Cumulative number of confirmed human cases of avian influenza A/(H5N1) reported to WHO. (www.who.int/csr/disease/avian_influenza/country/en/index.html) This high case-fatality rate underscores the extremely high pathogenicity of the H5N1 virus involved.

“H9N2” (1999)

In southern China, nine cases of human infection with an H9N2 avian virus were reported in 1998. In March 1999, there were two further cases in Hong Kong. 38 x M Peiris, KY Yuen, CW Leung, et al.. Human infection with influenza H9N2. Lancet 354 (1999) (916 - 917) In no case was there serological evidence for H9N2 infection among family members or health-care workers in close contact with the infected individuals, indicating that there was no human-to-human transmission. The virus was similar to one of the putative precursor viruses of the 1997 outbreak in Hong Kong. It appears that the H9N2 viruses are also circulating in pigs, together with human and porcine H1N1 and H3N2 viruses, providing conditions required for the generation of a reassortant virus with pandemic potential in humans.

“H7N7” (2003)

In the Netherlands in 2003, an outbreak of H7N7 fowl plague affected mainly poultry workers and veterinarians, causing conjunctivitis in most cases and influenza-like illness in about 10%. 39 x RA Fouchier, PM Schneeberger, FW Rozendaal, et al.. Avian influenza A virus (H7N7) associated with human conjunctivitis and a fatal case of acute respiratory distress syndrome. Proc Natl Acad Sci USA 101 (2004) (1356 - 1361) There was one death – a 57-year-old veterinarian who visited one of the infected farms and later died of acute respiratory distress syndrome. Mass culling of affected poultry was instigated and agricultural workers in contact with affected poultry were treated prophylactically with antiviral drugs. Also, these poultry workers were vaccinated for the human influenza strains circulating at the time to minimize dual infections as an opportunity for genetic reassortment.

References

Label Authors Title Source Year
7

References in context


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  • 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.
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  • 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.
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  • 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.
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  • 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
11

References in context

  • Currently available information suggests that the natural reservoir of influenza A viruses is among aquatic birds.11–13 All 16 HA and nine NA subtypes have been identified in birds (see Chapter 2).
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  • 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.
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  • 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.
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  • Remarkably, the H5N1 virus isolated from victims of the recent outbreaks in Asia have acquired a number of mutations in the polymerase complex that are also present in the 1918 virus.25 These mutations are likely important for efficient replication of the virus in humans.
    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

RG Webster, M Peiris, H Chen, et al.. H5N1 outbreaks and enzootic influenza. Emerg Inf Dis 12 (2006) (3 - 8) 2006
22

References in 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

  • 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.
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  • 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

  • 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

RG Webster. 1918 Spanish influenza: the secrets remain elusive. Proc Natl Acad Sci 96 (1999) (1164 - 1166) 1999
28

References in 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.
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  • As mentioned above, the virus was subsequently found to be virtually identical to one that had caused a human epidemic in 1950.28 Consequently, most people over 23 years old possessed antibody to it.
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  • A cyclic theory has been proposed suggesting that pandemics may appear in a specific recurring pattern.28 The interval between the 1889 (H2) and 1900 pandemics (H3) matches that between the 1957 (H2) and 1968 (H3) pandemics.
    Go to context

K Nakajima, U Desselberger, P Palese. Recent human influenza A (H1N1) viruses are closely related genetically to strains isolated in 1950. Nature 274 (1978) (334 - 339) 1978
32

References in context

  • There is evidence that the precursor viruses of the H5N1 bird flu virus, including the goose H5N1 virus, remained in circulation.32 Since 1998, culling has also included geese to prevent the goose H5N1 precursor virus from taking a firm hold in poultry in Hong Kong.
    Go to context

Y Guan, KF Shortridge, S Krauss, et al.. H9N2 influenza viruses possessing H5N1-like internal genomes continue to circulate in poultry in southeastern China. J Virol 74 (2000) (9372 - 9380) 2000
33

References in 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

Y Guan, JSM Peiris, AS Lipatov, et al.. Emergence of multiple genotypes of H5N1 avian influenza viruses in Hong Kong SAR. Proc Natl Acad Sci USA 99 (2002) (8950 - 8955) 2002
34

References in context

  • Then, in the spring of 2004, there was a major outbreak of highly pathogenic H5N1 avian influenza first detected in southern Vietnam and then spreading quickly to neighbouring countries, and quite recently also to Europe and Africa.34–36 To date (March 1, 2006) there have been 179 confirmed cases of human H5N1 infections, with 94 fatalities, including four deaths in Turkey in January 2006.37 This high case-fatality rate underscores the extremely high pathogenicity of the H5N1 virus involved.
    Go to context

A Apisarnthanarak, R Kitphati, K Thongphubeth, et al.. Atypical avian influenza (H5N1). Emerg Infect Dis 10 (2004) (1321 - 1324) 2004
35

References in context

  • Then, in the spring of 2004, there was a major outbreak of highly pathogenic H5N1 avian influenza first detected in southern Vietnam and then spreading quickly to neighbouring countries, and quite recently also to Europe and Africa.34–36 To date (March 1, 2006) there have been 179 confirmed cases of human H5N1 infections, with 94 fatalities, including four deaths in Turkey in January 2006.37 This high case-fatality rate underscores the extremely high pathogenicity of the H5N1 virus involved.
    Go to context

MD de Jong, VC Bach, TQ Phan, et al.. Fatal avian influenza A (H5N1) in a child presenting with diarrhea followed by coma. New Engl J Med 352 (2005) (686 - 691) 2005
36

References in context

  • Then, in the spring of 2004, there was a major outbreak of highly pathogenic H5N1 avian influenza first detected in southern Vietnam and then spreading quickly to neighbouring countries, and quite recently also to Europe and Africa.34–36 To date (March 1, 2006) there have been 179 confirmed cases of human H5N1 infections, with 94 fatalities, including four deaths in Turkey in January 2006.37 This high case-fatality rate underscores the extremely high pathogenicity of the H5N1 virus involved.
    Go to context

TH Tran, TL Nguyen, TD Nguyen, et al.. Avian influenza A (H5N1) in 10 patients in Vietnam. New Engl J Med 350 (2004) (1179 - 1188) 2004
37

References in context

  • Then, in the spring of 2004, there was a major outbreak of highly pathogenic H5N1 avian influenza first detected in southern Vietnam and then spreading quickly to neighbouring countries, and quite recently also to Europe and Africa.34–36 To date (March 1, 2006) there have been 179 confirmed cases of human H5N1 infections, with 94 fatalities, including four deaths in Turkey in January 2006.37 This high case-fatality rate underscores the extremely high pathogenicity of the H5N1 virus involved.
    Go to context

World Health Organization. Cumulative number of confirmed human cases of avian influenza A/(H5N1) reported to WHO. (www.who.int/csr/disease/avian_influenza/country/en/index.html)
38

References in context

  • In March 1999, there were two further cases in Hong Kong.38 In no case was there serological evidence for H9N2 infection among family members or health-care workers in close contact with the infected individuals, indicating that there was no human-to-human transmission.
    Go to context

M Peiris, KY Yuen, CW Leung, et al.. Human infection with influenza H9N2. Lancet 354 (1999) (916 - 917) 1999
39

References in context

  • In the Netherlands in 2003, an outbreak of H7N7 fowl plague affected mainly poultry workers and veterinarians, causing conjunctivitis in most cases and influenza-like illness in about 10%.39 There was one death – a 57-year-old veterinarian who visited one of the infected farms and later died of acute respiratory distress syndrome.
    Go to context

RA Fouchier, PM Schneeberger, FW Rozendaal, et al.. Avian influenza A virus (H7N7) associated with human conjunctivitis and a fatal case of acute respiratory distress syndrome. Proc Natl Acad Sci USA 101 (2004) (1356 - 1361) 2004

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