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Influenza Epidemics and Pandemics

Influenza pandemic preparedness

Since the 1997 H5N1 outbreak in Hong Kong there has been a growing recognition that global and national plans should be made and implemented to minimize the potential implications of the next pandemic. In 1999, the WHO issued its first pandemic preparedness plan, 40 x World Health Organization. Influenza pandemic preparedness plan. The role of WHO and guidelines for national or regional planning. (www.who.int/csr/resources/publications/influenza/WHO_CDS_CSR_EDC_99_1/en/) (1999) which was updated in 2005. 41 x World Health Organization. Global influenza preparedness plan. The role of WHO and recommendations for national measures before and during pandemics. (www.who.int/csr/resources/publications/influenza/WHO_CDS_CSR_GIP_2005_5/en/index.html) (2005) In 2002, the WHO adopted the Global Agenda on Influenza Surveillance and Control as a strategic approach to increase the level of global pandemic preparedness. 42, x K Stöhr. The global agenda on influenza surveillance and control. Vaccine 21 (2003) (1774) 1748 43 x World Health Organization. Global agenda on influenza – adopted version. Part I. Wkly Epidemiol Rec 77 (2002) (179 - 182) Part II Wkly Epidemiol Rec 77 (2002) (191 - 196) ( www.who.int/docstore/wer/pdf/2000/wer7535.pdf ) ( www.who.int/docstore/wer/pdf/2002/wer7728.pdf ) This global agenda sets out a series of activities around four primary objectives: (i) strengthening surveillance; (ii) improving knowledge of disease burden; (iii) increasing vaccine usage; and (iv) accelerating pandemic preparedness.

Surveillance and phasing of the pandemic

A critical requirement for pandemic control is the ability to detect viruses of pandemic potential at an initial stage of their emergence. Therefore, surveillance programmes for early detection of virus activity and infection in animal reservoirs and human populations are in place and are currently being expanded. It is anticipated that the activities under the Global Agenda will facilitate a rapid detection of unusual influenza activity. Hopefully, early detection along with a swift institution of appropriate measures may allow us to avert a pandemic before it starts, or at least lessen its impact.

Another important aspect of pandemic preparedness relates to an unambiguous phasing of a pandemic when it occurs. Clearly, a number of conditions must be satisfied in order for an outbreak of influenza to be classified as a “pandemic”. 14 x RG Webster, WG Laver. Pandemic variation of influenza viruses. ED Kilbourne (Ed.) The Influenza Viruses and Influenza (Academic Press, 1975) (269 - 314) These include: (i) the emergence of a new influenza A virus subtype in the human population, unrelated to the virus subtypes that circulated immediately before the outbreak; (ii) a total lack of immunity to the new virus among the population; (iii) capacity of the virus to spread by person-to-person transmission; and (iv) rapid dissemination of the infection beyond its site of origin. Based on these definitions, the WHO has developed an algorithm to identify specific phases in the period preceding a pandemic and during the actual pandemic, which require different levels of alertness and actions. 41 x World Health Organization. Global influenza preparedness plan. The role of WHO and recommendations for national measures before and during pandemics. (www.who.int/csr/resources/publications/influenza/WHO_CDS_CSR_GIP_2005_5/en/index.html) (2005) These phases are indicated in Table 4 .

Table 4 Definition of successive pre-pandemic and pandemic phases. Source: WHO global influenza pandemic preparedness plan. The role of WHO and recommendations for national measures before and during pandemics. 41 x World Health Organization. Global influenza preparedness plan. The role of WHO and recommendations for national measures before and during pandemics. (www.who.int/csr/resources/publications/influenza/WHO_CDS_CSR_GIP_2005_5/en/index.html) (2005)

Specific pandemic phases defined in WHO global influenza preparedness plan
Interpandemic period
  • Phase 1: No new influenza virus subtypes have been detected in humans. An influenza virus subtype that has caused human infection may be present in animals. If present in animals, risk of human infection or disease is considered to be low.
  • Phase 2: No new influenza virus subtypes have been detected in humans. However, a circulating animal influenza virus subtype poses a substantial risk of human disease.
Pandemic alert period
  • Phase 3: Human infection(s) with a new subtype, but no human-to-human spread, or at most rare instances of spread to a close contact.
  • Phase 4: Small cluster(s) with limited human-to-human transmission but spread is highly localized, suggesting that the virus is not well adapted to humans.
  • Phase 5: Larger cluster(s) but human-to-human spread still localized, suggesting that the virus is becoming increasingly better adapted to humans, but may not yet be fully transmissible (substantial pandemic risk).
Pandemic period
  • Phase 6: Pandemic: increased and sustained transmission in general population.

References in context

  • Based on these definitions, the WHO has developed an algorithm to identify specific phases in the period preceding a pandemic and during the actual pandemic, which require different levels of alertness and actions.41 These phases are indicated in Table 4.
    Go to context

Improvement of knowledge about burden of disease

In many countries, influenza is not a prominent item on the national health agenda due to other health priorities. As a consequence, in these countries, there is no or an insufficient infrastructure for influenza virus and disease surveillance, and a lack of knowledge about the burden of disease. Without a proper infrastructure for epidemic influenza control, the opportunities for effective pandemic containment will be much more limited than in the presence of such infrastructure. Therefore, the WHO currently intensifies and expands its viral surveillance programme to these countries and promotes studies to establish the burden of disease. It is anticipated that the outcome of such studies might be a natural incentive to improve the infrastructure for the control of epidemic influenza and increase the level of pandemic preparedness in the countries concerned. During recent international meetings on global pandemic preparedness, strategies have been developed to effectively implement an action plan to achieve the necessary increased level of epidemic and pandemic influenza control. 44, x World Health Organization. Meeting on avian influenza and human pandemic influenza. Geneva. (www.who.int/mediacentre/events/2005/avian_influenza/en/index.html) (7–9 November 2005) 45 x International pledging conference on avian and human pandemic influenza (Co-sponsored by the Government of the People's Republic of China, the European Commission & the World Bank, Beijing, 17–18 January 2006) (www.who.int/dg/lee/speeches/2006/flumeeting_beijing/en/index.html)

Stimulation of vaccine uptake and development of pandemic vaccines

According to the WHO, one important way to achieve a considerably improved level of pandemic preparedness is to encourage the annual uptake of influenza vaccines. 42, x K Stöhr. The global agenda on influenza surveillance and control. Vaccine 21 (2003) (1774) 1748 46 x World Health Organization. Guidelines on the Use of Vaccines and Antivirals during Influenza Pandemics. Geneva, 2004. Document WHO/CDS/CSR/RMD/2004.8. (www.who.int/csr/resources/publications/influenza/en/11_29_01_A.pdf) Following the logic of “demand drives supply” for seasonal influenza vaccines, an increased annual use of influenza vaccines, according to existing recommendations, will be followed by investments from the vaccine industry to increase their vaccine production capacity. Clearly, an increased global vaccine production capacity will lead to a much improved worldwide vaccine availability in the case of a pandemic. At the same time increased annual vaccine use will reduce the yearly burden of influenza (see also Chapters 6 and 8).

There is also an urgent need for development of more effective vaccine formulations, such that the dose of antigen per vaccination may be reduced and a more equitable global distribution of scarce pandemic vaccine may be achieved (see also Chapter 9). Recent studies with candidate H5N1 vaccines have demonstrated the need for adjuvants to be included in pandemic vaccine formulations. Non-adjuvanted H5N1 vaccines need a very high dosing to elicit adequately protective antibody titres in unprimed individuals. This would dramatically reduce the volume of effective vaccine doses which can be produced and distributed given the current global vaccine production capabilities. At a technical meeting organised by the WHO in 2005, all major influenza vaccine manufacturers have indicated that they are developing adjuvanted pandemic vaccine candidates. 47 x World Health Organization. Meeting on development and evaluation of influenza pandemic vaccines. Geneva. (www.who.int/vaccine_research/diseases/influenza/mtg_021205/en/) (2–3 November 2005) In addition, early registration of pandemic influenza vaccine formulations will considerably expedite the availability of vaccine during a pandemic. 48 x European Medicines Agency (EMEA). Guideline on submission of marketing authorisation application for pandemic influenza vaccines through the centralised procedure. April 2004. Document EMEA/CPMP/VEG/4986/03. ( www.emea.eu.int/pdfs/human/vwp/498603en.pdf ) ( www.emea.eu.int/pdfs/human/vwp/471703en.pdf )

Improvement of pandemic preparedness

Pandemic preparedness should be achieved at global, regional and national levels. 41 x World Health Organization. Global influenza preparedness plan. The role of WHO and recommendations for national measures before and during pandemics. (www.who.int/csr/resources/publications/influenza/WHO_CDS_CSR_GIP_2005_5/en/index.html) (2005) The WHO and other global bodies such as the FAO (UN Food and Agriculture Organization) and OIE (World Organization for Animal Health) are responsible for the infrastructure at a global level, whereas national health authorities are primarily responsible for the infrastructural measures within individual countries. The WHO has provided recommendations for appropriate measures in the regions and the countries to increase pandemic preparedness. Apart from the general infrastructural measures to cope with national emergency situations, the level of pandemic preparedness in countries will depend very much on their ability to have timely access to antiviral agents and pandemic vaccines.

The WHO has made recommendations for stockpiling antivirals and H5N1 vaccines for immediate use at the onset of a potential pandemic outbreak. 41, x World Health Organization. Global influenza preparedness plan. The role of WHO and recommendations for national measures before and during pandemics. (www.who.int/csr/resources/publications/influenza/WHO_CDS_CSR_GIP_2005_5/en/index.html) (2005) 46 x World Health Organization. Guidelines on the Use of Vaccines and Antivirals during Influenza Pandemics. Geneva, 2004. Document WHO/CDS/CSR/RMD/2004.8. (www.who.int/csr/resources/publications/influenza/en/11_29_01_A.pdf) It has also advised national health authorities to make pre-pandemic purchase agreements with vaccine manufacturers for pandemic vaccines. 46 x World Health Organization. Guidelines on the Use of Vaccines and Antivirals during Influenza Pandemics. Geneva, 2004. Document WHO/CDS/CSR/RMD/2004.8. (www.who.int/csr/resources/publications/influenza/en/11_29_01_A.pdf) It will take at least 4–6 months after the WHO has announced the pandemic before the first pandemic vaccine doses will become available for distribution. Countries with pre-pandemic purchase agreements will be the first beneficiaries of the scarce volumes of pandemic vaccine. Although there is a general moral feeling that there should be an equitable distribution of scarce antivirals and pandemic vaccines, unfortunately, there is currently no proper mechanism in place in the world to achieve such a fair distribution.

One way to achieve a more equitable distribution of pandemic vaccine is to expand the global vaccine production capacity. Indeed, industry, sometimes with the help of national governments, is expanding its production capacity, while several countries are currently considering to build influenza vaccine production facilities on their soil. Although expansion of global vaccine production capacity is needed and must be stimulated, it should also be noted that once these facilities are operational, the risk of global interpandemic overproduction capacity may become realistic. Therefore, strategies to address the concerns about pandemic vaccine shortages should also take into account the need for a sustainable interpandemic influenza vaccine market.

As an integral part of pandemic preparedness planning, a “pandemic simulation” project “Common Ground” was carried out in the European Union in November 2005. 49 x Health Protection Agency. Health Protection Agency coordinates EU pandemic influenza exercise. (www.medicalnewstoday.com/medicalnews.php?newsid=32376) The objective was to test the level of preparedness of each of the member states and identify gaps in their respective national pandemic preparedness plans. During this exercise, all stakeholders, including not only representatives of national health authorities and national influenza centres, but also the WHO, the European Medicines Agency (EMEA) and the European Centre for Disease Control (ECDC), as well as the vaccine and antiviral industry, had to deal with three different stages of a simulated pandemic. This highly educational exercise, which is being formally and fully evaluated, revealed the need to improve communication lines between the different stakeholders. Similar pandemic simulations are planned elsewhere in the near future.

 
x

Table 4 Definition of successive pre-pandemic and pandemic phases. Source: WHO global influenza pandemic preparedness plan. The role of WHO and recommendations for national measures before and during pandemics. 41 x World Health Organization. Global influenza preparedness plan. The role of WHO and recommendations for national measures before and during pandemics. (www.who.int/csr/resources/publications/influenza/WHO_CDS_CSR_GIP_2005_5/en/index.html) (2005)

Specific pandemic phases defined in WHO global influenza preparedness plan
Interpandemic period
  • Phase 1: No new influenza virus subtypes have been detected in humans. An influenza virus subtype that has caused human infection may be present in animals. If present in animals, risk of human infection or disease is considered to be low.
  • Phase 2: No new influenza virus subtypes have been detected in humans. However, a circulating animal influenza virus subtype poses a substantial risk of human disease.
Pandemic alert period
  • Phase 3: Human infection(s) with a new subtype, but no human-to-human spread, or at most rare instances of spread to a close contact.
  • Phase 4: Small cluster(s) with limited human-to-human transmission but spread is highly localized, suggesting that the virus is not well adapted to humans.
  • Phase 5: Larger cluster(s) but human-to-human spread still localized, suggesting that the virus is becoming increasingly better adapted to humans, but may not yet be fully transmissible (substantial pandemic risk).
Pandemic period
  • Phase 6: Pandemic: increased and sustained transmission in general population.

References in context

  • Based on these definitions, the WHO has developed an algorithm to identify specific phases in the period preceding a pandemic and during the actual pandemic, which require different levels of alertness and actions.41 These phases are indicated in Table 4.
    Go to context

References

Label Authors Title Source Year
14

References in context

  • Occasionally, a new influenza virus subtype is introduced into the human population, in a process referred to as antigenic shift.14 As indicated above, there are several ways by which such new human virus subtypes may arise (Figure 12), and it is likely that each has played a role in the influenza pandemics of the 20th 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

  • Clearly, a number of conditions must be satisfied in order for an outbreak of influenza to be classified as a “pandemic”.14 These include: (i) the emergence of a new influenza A virus subtype in the human population, unrelated to the virus subtypes that circulated immediately before the outbreak; (ii) a total lack of immunity to the new virus among the population; (iii) capacity of the virus to spread by person-to-person transmission; and (iv) rapid dissemination of the infection beyond its site of origin.
    Go to context

RG Webster, WG Laver. Pandemic variation of influenza viruses. ED Kilbourne (Ed.) The Influenza Viruses and Influenza (Academic Press, 1975) (269 - 314) 1975
40

References in context

  • In 1999, the WHO issued its first pandemic preparedness plan,40 which was updated in 2005.41 In 2002, the WHO adopted the Global Agenda on Influenza Surveillance and Control as a strategic approach to increase the level of global pandemic preparedness.42,43 This global agenda sets out a series of activities around four primary objectives: (i) strengthening surveillance; (ii) improving knowledge of disease burden; (iii) increasing vaccine usage; and (iv) accelerating pandemic preparedness.
    Go to context

World Health Organization. Influenza pandemic preparedness plan. The role of WHO and guidelines for national or regional planning. (www.who.int/csr/resources/publications/influenza/WHO_CDS_CSR_EDC_99_1/en/) (1999) 1999
41

References in context

  • Definition of successive pre-pandemic and pandemic phases.
    Go to context

  • In 1999, the WHO issued its first pandemic preparedness plan,40 which was updated in 2005.41 In 2002, the WHO adopted the Global Agenda on Influenza Surveillance and Control as a strategic approach to increase the level of global pandemic preparedness.42,43 This global agenda sets out a series of activities around four primary objectives: (i) strengthening surveillance; (ii) improving knowledge of disease burden; (iii) increasing vaccine usage; and (iv) accelerating pandemic preparedness.
    Go to context

  • Based on these definitions, the WHO has developed an algorithm to identify specific phases in the period preceding a pandemic and during the actual pandemic, which require different levels of alertness and actions.41 These phases are indicated in Table 4.
    Go to context

  • Pandemic preparedness should be achieved at global, regional and national levels.41 The WHO and other global bodies such as the FAO (UN Food and Agriculture Organization) and OIE (World Organization for Animal Health) are responsible for the infrastructure at a global level, whereas national health authorities are primarily responsible for the infrastructural measures within individual countries.
    Go to context

  • The WHO has made recommendations for stockpiling antivirals and H5N1 vaccines for immediate use at the onset of a potential pandemic outbreak.41,46 It has also advised national health authorities to make pre-pandemic purchase agreements with vaccine manufacturers for pandemic vaccines.46 It will take at least 4–6 months after the WHO has announced the pandemic before the first pandemic vaccine doses will become available for distribution.
    Go to context

World Health Organization. Global influenza preparedness plan. The role of WHO and recommendations for national measures before and during pandemics. (www.who.int/csr/resources/publications/influenza/WHO_CDS_CSR_GIP_2005_5/en/index.html) (2005) 2005
42

References in context

  • In 1999, the WHO issued its first pandemic preparedness plan,40 which was updated in 2005.41 In 2002, the WHO adopted the Global Agenda on Influenza Surveillance and Control as a strategic approach to increase the level of global pandemic preparedness.42,43 This global agenda sets out a series of activities around four primary objectives: (i) strengthening surveillance; (ii) improving knowledge of disease burden; (iii) increasing vaccine usage; and (iv) accelerating pandemic preparedness.
    Go to context

  • According to the WHO, one important way to achieve a considerably improved level of pandemic preparedness is to encourage the annual uptake of influenza vaccines.42,46 Following the logic of “demand drives supply” for seasonal influenza vaccines, an increased annual use of influenza vaccines, according to existing recommendations, will be followed by investments from the vaccine industry to increase their vaccine production capacity.
    Go to context

K Stöhr. The global agenda on influenza surveillance and control. Vaccine 21 (2003) (1774) 1748 2003
43

References in context

  • In 1999, the WHO issued its first pandemic preparedness plan,40 which was updated in 2005.41 In 2002, the WHO adopted the Global Agenda on Influenza Surveillance and Control as a strategic approach to increase the level of global pandemic preparedness.42,43 This global agenda sets out a series of activities around four primary objectives: (i) strengthening surveillance; (ii) improving knowledge of disease burden; (iii) increasing vaccine usage; and (iv) accelerating pandemic preparedness.
    Go to context

World Health Organization. Global agenda on influenza – adopted version. Part I. Wkly Epidemiol Rec 77 (2002) (179 - 182) Part II Wkly Epidemiol Rec 77 (2002) (191 - 196) ( www.who.int/docstore/wer/pdf/2000/wer7535.pdf ) ( www.who.int/docstore/wer/pdf/2002/wer7728.pdf ) 2002
44

References in context

  • In many countries, influenza is not a prominent item on the national health agenda due to other health priorities.
    Go to context

World Health Organization. Meeting on avian influenza and human pandemic influenza. Geneva. (www.who.int/mediacentre/events/2005/avian_influenza/en/index.html) (7–9 November 2005) 79 November 2005
45

References in context

  • In many countries, influenza is not a prominent item on the national health agenda due to other health priorities.
    Go to context

International pledging conference on avian and human pandemic influenza (Co-sponsored by the Government of the People's Republic of China, the European Commission & the World Bank, Beijing, 17–18 January 2006) (www.who.int/dg/lee/speeches/2006/flumeeting_beijing/en/index.html) 1718 January 2006
46

References in context

  • According to the WHO, one important way to achieve a considerably improved level of pandemic preparedness is to encourage the annual uptake of influenza vaccines.42,46 Following the logic of “demand drives supply” for seasonal influenza vaccines, an increased annual use of influenza vaccines, according to existing recommendations, will be followed by investments from the vaccine industry to increase their vaccine production capacity.
    Go to context

  • The WHO has made recommendations for stockpiling antivirals and H5N1 vaccines for immediate use at the onset of a potential pandemic outbreak.41,46 It has also advised national health authorities to make pre-pandemic purchase agreements with vaccine manufacturers for pandemic vaccines.46 It will take at least 4–6 months after the WHO has announced the pandemic before the first pandemic vaccine doses will become available for distribution.
    Go to context

  • The WHO has made recommendations for stockpiling antivirals and H5N1 vaccines for immediate use at the onset of a potential pandemic outbreak.41,46 It has also advised national health authorities to make pre-pandemic purchase agreements with vaccine manufacturers for pandemic vaccines.46 It will take at least 4–6 months after the WHO has announced the pandemic before the first pandemic vaccine doses will become available for distribution.
    Go to context

World Health Organization. Guidelines on the Use of Vaccines and Antivirals during Influenza Pandemics. Geneva, 2004. Document WHO/CDS/CSR/RMD/2004.8. (www.who.int/csr/resources/publications/influenza/en/11_29_01_A.pdf)
47

References in context

  • There is also an urgent need for development of more effective vaccine formulations, such that the dose of antigen per vaccination may be reduced and a more equitable global distribution of scarce pandemic vaccine may be achieved (see also Chapter 9).
    Go to context

World Health Organization. Meeting on development and evaluation of influenza pandemic vaccines. Geneva. (www.who.int/vaccine_research/diseases/influenza/mtg_021205/en/) (2–3 November 2005) 23 November 2005
48

References in context

  • There is also an urgent need for development of more effective vaccine formulations, such that the dose of antigen per vaccination may be reduced and a more equitable global distribution of scarce pandemic vaccine may be achieved (see also Chapter 9).
    Go to context

European Medicines Agency (EMEA). Guideline on submission of marketing authorisation application for pandemic influenza vaccines through the centralised procedure. April 2004. Document EMEA/CPMP/VEG/4986/03. ( www.emea.eu.int/pdfs/human/vwp/498603en.pdf ) ( www.emea.eu.int/pdfs/human/vwp/471703en.pdf )
49

References in context

  • As an integral part of pandemic preparedness planning, a “pandemic simulation” project “Common Ground” was carried out in the European Union in November 2005.49 The objective was to test the level of preparedness of each of the member states and identify gaps in their respective national pandemic preparedness plans.
    Go to context

Health Protection Agency. Health Protection Agency coordinates EU pandemic influenza exercise. (www.medicalnewstoday.com/medicalnews.php?newsid=32376)

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