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Vaccination: Cornerstone of Influenza Control

References

Label Authors Title Source Year
1

References in context

  • Flu vaccine development began just a few years after the first isolation of the influenza virus in 1933.1,2 Pioneering studies demonstrated that influenza A/PR/8/34 (H1N1) virus would infect humans upon subcutaneous administration, inducing virus-neutralizing antibodies.2,3 Soon after these initial observations, studies using formalin-inactivated whole-virus preparations were conducted, the first inactivated influenza vaccines being introduced in the 1940s.2 Most current influenza vaccines are also inactivated formulations, consisting of either split virus or subunit preparations, the latter containing just the isolated viral haemagglutinin (HA) and neuraminidase (NA).2,4,5 These vaccines are generally produced from virus grown on embryonated chicken eggs.
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W Smith, CH Andrews, PP Laidlaw. A virus obtained from influenza patients. Crossref. Lancet ii (1933) (66 - 68) 1933
2

References in context

  • Flu vaccine development began just a few years after the first isolation of the influenza virus in 1933.1,2 Pioneering studies demonstrated that influenza A/PR/8/34 (H1N1) virus would infect humans upon subcutaneous administration, inducing virus-neutralizing antibodies.2,3 Soon after these initial observations, studies using formalin-inactivated whole-virus preparations were conducted, the first inactivated influenza vaccines being introduced in the 1940s.2 Most current influenza vaccines are also inactivated formulations, consisting of either split virus or subunit preparations, the latter containing just the isolated viral haemagglutinin (HA) and neuraminidase (NA).2,4,5 These vaccines are generally produced from virus grown on embryonated chicken eggs.
    Go to context

  • Flu vaccine development began just a few years after the first isolation of the influenza virus in 1933.1,2 Pioneering studies demonstrated that influenza A/PR/8/34 (H1N1) virus would infect humans upon subcutaneous administration, inducing virus-neutralizing antibodies.2,3 Soon after these initial observations, studies using formalin-inactivated whole-virus preparations were conducted, the first inactivated influenza vaccines being introduced in the 1940s.2 Most current influenza vaccines are also inactivated formulations, consisting of either split virus or subunit preparations, the latter containing just the isolated viral haemagglutinin (HA) and neuraminidase (NA).2,4,5 These vaccines are generally produced from virus grown on embryonated chicken eggs.
    Go to context

  • Flu vaccine development began just a few years after the first isolation of the influenza virus in 1933.1,2 Pioneering studies demonstrated that influenza A/PR/8/34 (H1N1) virus would infect humans upon subcutaneous administration, inducing virus-neutralizing antibodies.2,3 Soon after these initial observations, studies using formalin-inactivated whole-virus preparations were conducted, the first inactivated influenza vaccines being introduced in the 1940s.2 Most current influenza vaccines are also inactivated formulations, consisting of either split virus or subunit preparations, the latter containing just the isolated viral haemagglutinin (HA) and neuraminidase (NA).2,4,5 These vaccines are generally produced from virus grown on embryonated chicken eggs.
    Go to context

  • Flu vaccine development began just a few years after the first isolation of the influenza virus in 1933.1,2 Pioneering studies demonstrated that influenza A/PR/8/34 (H1N1) virus would infect humans upon subcutaneous administration, inducing virus-neutralizing antibodies.2,3 Soon after these initial observations, studies using formalin-inactivated whole-virus preparations were conducted, the first inactivated influenza vaccines being introduced in the 1940s.2 Most current influenza vaccines are also inactivated formulations, consisting of either split virus or subunit preparations, the latter containing just the isolated viral haemagglutinin (HA) and neuraminidase (NA).2,4,5 These vaccines are generally produced from virus grown on embryonated chicken eggs.
    Go to context

  • However, despite the introduction of improved techniques for virus purification, local reactogenicity and systemic side effects remain a problem associated with the use of these vaccines, particularly in small children.17 This has led to the development of vaccine formulations consisting of disrupted virus particles, which turned out to be almost equally immunogenic in primed individuals, yet causing significantly fewer side effects.2 These split-virus vaccines, first licensed in the USA in 1968, are among the most widely used formulations to date.
    Go to context

  • However, despite the introduction of improved techniques for virus purification, local reactogenicity and systemic side effects remain a problem associated with the use of these vaccines, particularly in small children.17 This has led to the development of vaccine formulations consisting of disrupted virus particles, which turned out to be almost equally immunogenic in primed individuals, yet causing significantly fewer side effects.2 These split-virus vaccines, first licensed in the USA in 1968, are among the most widely used formulations to date.
    Go to context

JM Wood, MS Williams. History of inactivated influenza vaccines. KG Nicholson, RG Webster, AJ Hay (Eds.) Textbook of Influenza (Blackwell Science, 1998) (317 - 323) 1998
3

References in context

  • Flu vaccine development began just a few years after the first isolation of the influenza virus in 1933.1,2 Pioneering studies demonstrated that influenza A/PR/8/34 (H1N1) virus would infect humans upon subcutaneous administration, inducing virus-neutralizing antibodies.2,3 Soon after these initial observations, studies using formalin-inactivated whole-virus preparations were conducted, the first inactivated influenza vaccines being introduced in the 1940s.2 Most current influenza vaccines are also inactivated formulations, consisting of either split virus or subunit preparations, the latter containing just the isolated viral haemagglutinin (HA) and neuraminidase (NA).2,4,5 These vaccines are generally produced from virus grown on embryonated chicken eggs.
    Go to context

T Francis, TP Magill. The incidence of neutralizing antibodies for human influenza virus in the serum of human individuals of different ages. Crossref. J Exp Med 63 (1936) (655 - 668) 1936
4

References in context

  • Flu vaccine development began just a few years after the first isolation of the influenza virus in 1933.1,2 Pioneering studies demonstrated that influenza A/PR/8/34 (H1N1) virus would infect humans upon subcutaneous administration, inducing virus-neutralizing antibodies.2,3 Soon after these initial observations, studies using formalin-inactivated whole-virus preparations were conducted, the first inactivated influenza vaccines being introduced in the 1940s.2 Most current influenza vaccines are also inactivated formulations, consisting of either split virus or subunit preparations, the latter containing just the isolated viral haemagglutinin (HA) and neuraminidase (NA).2,4,5 These vaccines are generally produced from virus grown on embryonated chicken eggs.
    Go to context

  • Initial inactivated influenza vaccine formulations invariably consisted of whole inactivated virus formulations.2,4 Whole inactivated virus vaccines are generally quite immunogenic.
    Go to context

  • Initial inactivated influenza vaccine formulations invariably consisted of whole inactivated virus formulations.2,4 Whole inactivated virus vaccines are generally quite immunogenic.
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  • Removal of the detergent from the supernatant by adsorption onto a hydrophobic resin, such as Amberlite, results in the formation of rosettes of HA and NA, with only small amounts of contaminating core proteins, such as NP or M1, and viral membrane lipid.4 Influenza subunit vaccines were first licensed in UK in 1980 and are now used in many countries worldwide.
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  • Removal of the detergent from the supernatant by adsorption onto a hydrophobic resin, such as Amberlite, results in the formation of rosettes of HA and NA, with only small amounts of contaminating core proteins, such as NP or M1, and viral membrane lipid.4 Influenza subunit vaccines were first licensed in UK in 1980 and are now used in many countries worldwide.
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IGS Furminger. Vaccine production. KG Nicholson, RG Webster, AJ Hay (Eds.) Textbook of Influenza (Blackwell Science, 1998) (324 - 332) 1998
5

References in context

  • Single radial immunodiffusion (SRD) test of influenza vaccine potency.5 Serial dilutions of detergent-treated vaccine, and a reference antigen (Ref), are added to wells in an agarose gel containing a sheep antiserum against the relevant HA.
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  • Flu vaccine development began just a few years after the first isolation of the influenza virus in 1933.1,2 Pioneering studies demonstrated that influenza A/PR/8/34 (H1N1) virus would infect humans upon subcutaneous administration, inducing virus-neutralizing antibodies.2,3 Soon after these initial observations, studies using formalin-inactivated whole-virus preparations were conducted, the first inactivated influenza vaccines being introduced in the 1940s.2 Most current influenza vaccines are also inactivated formulations, consisting of either split virus or subunit preparations, the latter containing just the isolated viral haemagglutinin (HA) and neuraminidase (NA).2,4,5 These vaccines are generally produced from virus grown on embryonated chicken eggs.
    Go to context

  • Thus far, the hallmark for influenza vaccine efficacy has been the induction of an adequate level of virus-neutralizing antibodies in the serum.5–7 These antibodies are primarily directed against the envelope glycoproteins of the virus, HA and NA, HA being the major target for virus-neutralizing antibodies (see Chapter 4).
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  • That this system of surveillance and recommendation works quite well is demonstrated by the good match achieved in, for example, the influenza seasons from 1987 to 1997.5 Within this period, 23 vaccine strains recommended by the WHO matched with the subsequently circulating total of 30 virus strains (Table 15).
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  • This dose scheme has been formally standardized.5,23,24 The trivalent inactivated influenza vaccine is administered by intramuscular or deep subcutaneous injection.
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  • Not only has the composition of influenza vaccines been standardized in many countries, in the EU, criteria for vaccine immunogenicity have also been implemented.5,22,23 As indicated above, current inactivated influenza vaccines aim at induction of an efficient systemic antibody response against the viral surface antigens.
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  • Antibody titres are generally determined on the basis of haemagglutination–inhibition (HI) activity5,6 or, occasionally, by single radial haemolysis (SRH).5 In the HI assay, serum samples of vaccinated individuals are tested for their ability to inhibit agglutination of erythrocytes, induced by influenza virus through interaction of the viral HA with sialic acid on the red cell surface.
    Go to context

  • Antibody titres are generally determined on the basis of haemagglutination–inhibition (HI) activity5,6 or, occasionally, by single radial haemolysis (SRH).5 In the HI assay, serum samples of vaccinated individuals are tested for their ability to inhibit agglutination of erythrocytes, induced by influenza virus through interaction of the viral HA with sialic acid on the red cell surface.
    Go to context

  • Antibody titres are generally determined on the basis of haemagglutination–inhibition (HI) activity5,6 or, occasionally, by single radial haemolysis (SRH).5 In the HI assay, serum samples of vaccinated individuals are tested for their ability to inhibit agglutination of erythrocytes, induced by influenza virus through interaction of the viral HA with sialic acid on the red cell surface.
    Go to context

JM Wood. Standardization of inactivated influenza vaccines. KG Nicholson, RG Webster, AJ Hay (Eds.) Textbook of Influenza (Blackwell Science, 1998) (333 - 345) 1998
6

References in context

  • Thus far, the hallmark for influenza vaccine efficacy has been the induction of an adequate level of virus-neutralizing antibodies in the serum.5–7 These antibodies are primarily directed against the envelope glycoproteins of the virus, HA and NA, HA being the major target for virus-neutralizing antibodies (see Chapter 4).
    Go to context

  • Active immunization against any infectious disease, including influenza, aims at induction of antimicrobial immunity by inoculating the person with an attenuated or inactivated form of the pathogen involved.
    Go to context

  • Antibody titres are generally determined on the basis of haemagglutination–inhibition (HI) activity5,6 or, occasionally, by single radial haemolysis (SRH).5 In the HI assay, serum samples of vaccinated individuals are tested for their ability to inhibit agglutination of erythrocytes, induced by influenza virus through interaction of the viral HA with sialic acid on the red cell surface.
    Go to context

D Hobson, RL Curry, AS Beare, A Ward-Gardner. The role of serum haemagglutination-inhibiting antibody in protection against challenge virus infection with A2 and B viruses. Crossref. J Hyg (Lond) 70 (1972) (767 - 777) 1972
7

References in context

  • Thus far, the hallmark for influenza vaccine efficacy has been the induction of an adequate level of virus-neutralizing antibodies in the serum.5–7 These antibodies are primarily directed against the envelope glycoproteins of the virus, HA and NA, HA being the major target for virus-neutralizing antibodies (see Chapter 4).
    Go to context

  • Active immunization against any infectious disease, including influenza, aims at induction of antimicrobial immunity by inoculating the person with an attenuated or inactivated form of the pathogen involved.
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PR Small, RA Waldman, JC Bruono, GE Gifford. Influenza infection in ferrets: Role of serum antibody in protection and recovery. Infect Immun 13 (1976) (417 - 424) 1976
8

References in context


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  • These strains are included in the vaccines on recommendation of the WHO.8,9 This recommendation is based on an extensive review of epidemiological data and antigenic and genetic analyses of virus isolates by the four WHO Collaborating Centres.
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Y Ghendon. Influenza surveillance. Bull World Health Org 61 (1991) (509 - 515) 1991
9

References in context


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  • The safety record of inactivated influenza vaccines is excellent.9,14 Hundreds of millions of vaccine doses are distributed worldwide each year, adverse effects being extremely rare.
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  • These strains are included in the vaccines on recommendation of the WHO.8,9 This recommendation is based on an extensive review of epidemiological data and antigenic and genetic analyses of virus isolates by the four WHO Collaborating Centres.
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  • For a long time, doubts and misconceptions about the risk–benefit ratio of influenza vaccination have hampered the implementation of recommended policies for influenza vaccination.
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  • Inactivated influenza vaccines have an excellent safety record.9,14 Currently, about 300 million vaccine doses are being administered annually around the globe,10 and the overall rate of adverse reactions is extremely low.
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World Health Organization. Influenza vaccines. Wkly Epidemiol Rec 75 (2000) (281 - 288) 2000
10

References in context


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  • Vaccination results in reductions of influenza-related respiratory illness and numbers of physician visits among all age groups, and in lower hospitalization rates and deaths among the elderly and patients at risk for serious complications of influenza.12,13 Vaccination coverage among target groups has increased considerably in recent years10 as the awareness of the impact of influenza is growing and influenza has become an important issue on the public-health agenda in many countries.15,16 However, the use of available influenza vaccines is still far from optimal.
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  • However, in recent years, influenza vaccination has become a prominent issue on the public-health agenda in an increasing number of countries.10 Many developed as well as developing countries have now adopted formal recommendations on influenza vaccination for specific target groups.
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  • The elderly represent the primary target group.10,11 This recommendation follows the increased susceptibility of the elderly for infectious diseases in general, which may be explained, at least partly, by a gradual decline in immune competence with age, particularly at the level of T cell function (see Chapter 4).
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  • The elderly represent the primary target group.10,11 This recommendation follows the increased susceptibility of the elderly for infectious diseases in general, which may be explained, at least partly, by a gradual decline in immune competence with age, particularly at the level of T cell function (see Chapter 4).
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  • The elderly represent the primary target group.10,11 This recommendation follows the increased susceptibility of the elderly for infectious diseases in general, which may be explained, at least partly, by a gradual decline in immune competence with age, particularly at the level of T cell function (see Chapter 4).
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  • The most dramatic changes in this respect have occurred in Korea, Latin America, Japan and some central and eastern European countries.10 Figure 27 presents a survey of influenza vaccine distribution in 56 developed and rapidly developing countries in 1997 and 2003.
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  • In 1994, these figures were 80% and 20%, respectively.10 This trend indicates that many countries, including developing countries, are moving towards implementation of measures for influenza prevention and control on an annual basis.
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  • Inactivated influenza vaccines have an excellent safety record.9,14 Currently, about 300 million vaccine doses are being administered annually around the globe,10 and the overall rate of adverse reactions is extremely low.
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  • To improve the vaccination coverage rates in target groups, in accordance with WHO recommendations,10,11,36 it is important that existing national vaccination policies are effectively implemented.
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The Macroepidemiology of Influenza Vaccination (MIV) Study Group. The macroepidemiology of influenza vaccination in 56 countries, 1997–2003. Vaccine 23 (2005) (5133 - 5143) 2005
11

References in context


  • Go to context

  • The elderly represent the primary target group.10,11 This recommendation follows the increased susceptibility of the elderly for infectious diseases in general, which may be explained, at least partly, by a gradual decline in immune competence with age, particularly at the level of T cell function (see Chapter 4).
    Go to context


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  • To improve the vaccination coverage rates in target groups, in accordance with WHO recommendations,10,11,36 it is important that existing national vaccination policies are effectively implemented.
    Go to context

World Health Organization. Influenza vaccines. Wkly Epidemiol Rec 77 (2002) (230 - 239) 2002
12

References in context


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  • Vaccination results in reductions of influenza-related respiratory illness and numbers of physician visits among all age groups, and in lower hospitalization rates and deaths among the elderly and patients at risk for serious complications of influenza.12,13 Vaccination coverage among target groups has increased considerably in recent years10 as the awareness of the impact of influenza is growing and influenza has become an important issue on the public-health agenda in many countries.15,16 However, the use of available influenza vaccines is still far from optimal.
    Go to context

  • The recommendation is also based on the proven clinical efficacy and effectiveness of flu vaccination of the elderly.12 In most countries, flu vaccination is recommended for all individuals above 60 or 65 years of age.
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  • The recommendation is also based on the proven clinical efficacy and effectiveness of flu vaccination of the elderly.12 In most countries, flu vaccination is recommended for all individuals above 60 or 65 years of age.
    Go to context

  • The recommendation is also based on the proven clinical efficacy and effectiveness of flu vaccination of the elderly.12 In most countries, flu vaccination is recommended for all individuals above 60 or 65 years of age.
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  • However, despite the increased vaccine use, recent surveys in Europe show that the coverage rates in target populations are still far from the WHO-recommended 75% in 2010.29,36 The current coverage rates range from 18% (Poland) to 67% (Spain) for the elderly and from 3% to 40% for various risk groups in younger populations.28,29,37 In the USA, only 35% of adults between the ages of 18 and 64 years who are at risk for serious complications due to influenza were being vaccinated in 2003.38 The implication of these findings is that many elderly and at-risk patients are not receiving the best possible protective treatment to prevent influenza or minimize the consequences of an influenza infection.
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  • As a result, many clinical studies have now produced consistent data showing the clear-cut benefits of influenza vaccination.12,13,33,35,40 Since the elderly comprise by far the largest target population for flu vaccination, the majority of studies evaluating the benefits of vaccination have been conducted among people in this age group; these will be discussed in more detail below.
    Go to context

  • In evaluating the outcome of influenza vaccination, a distinction is often made between vaccine efficacy per se and the clinical effectiveness of vaccination.12,13 Vaccine efficacy is defined as the reduction in the rate of laboratory-confirmed influenza among vaccinated compared to non-vaccinated individuals.
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  • It is defined as the reduction of clinically relevant, but not necessarily influenza-specific, disease in a “real-life” situation, including all influenza-like illness (ILI), hospitalizations due to pneumonia from all causes or death from all causes.12,13,40 As this parameter includes – by definition – disease that is not caused by the influenza virus, clinical effectiveness of vaccination is generally estimated to be lower than the actual vaccine efficacy, as illustrated by the hypothetical example presented in Figure 28.13 Therefore, clinical effectiveness should not be confused for vaccine efficacy, as this may result in a substantial underestimation of the actual performance of the vaccine.
    Go to context

  • Numerous studies have convincingly demonstrated the clinical benefits of influenza vaccination in the elderly.12,13,40,48,49 For example, in a large study in the USA, spanning two influenza seasons (1998–2000) and involving 300,000 community-dwelling elderly people (≥65 years), influenza vaccination was performed in 55.5–59.7% of the population.
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  • Economic evaluations, conducted in many different countries, have indicated that vaccination of senior citizens against influenza is always cost-effective and frequently cost-saving.12,13 For example, in a 6-year study carried out in Minnesota, USA, influenza vaccination of nursing-home residents was associated with an average net saving of $73 per person as a result of reductions in direct medical costs.12 Vaccination appears to be cost-effective or even cost-saving for both healthy senior citizens and high-risk elderly with underlying chronic medical conditions.
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  • Economic evaluations, conducted in many different countries, have indicated that vaccination of senior citizens against influenza is always cost-effective and frequently cost-saving.12,13 For example, in a 6-year study carried out in Minnesota, USA, influenza vaccination of nursing-home residents was associated with an average net saving of $73 per person as a result of reductions in direct medical costs.12 Vaccination appears to be cost-effective or even cost-saving for both healthy senior citizens and high-risk elderly with underlying chronic medical conditions.
    Go to context


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  • This is why there is an increasing awareness of the potential benefits of vaccination of working adults.12,13 Several prospective clinical studies have demonstrated the efficacy of inactivated influenza vaccines among healthy younger adults.
    Go to context

  • As demonstrated by a number of studies, conducted in different countries, vaccination significantly reduces illness, absenteeism and influenza-related costs for healthy adults in the work place.12,13 Indeed, vaccination reduces upper respiratory tract and influenza-like illnesses from all causes by approximately 30%, related physician visits by >40% and work loss by >35% (Table 20).60,61 Accordingly, cost–benefit analyses, based on clinical trials or on modelling, have shown that vaccination of healthy working adults is cost-effective and in many cases cost-saving, provided that indirect costs associated with work absenteeism (see Chapter 6) are explicitly taken into account.62 For example, trials conducted in the USA have shown that – with an average cost for vaccine production and administration of $20 – the net saving would be $23 per person vaccinated.63 In another study comparing 131 vaccinated employees from six textile plants in North Carolina, USA, with 131 age- and gender-matched non-vaccinated controls from different plants, the “cost per saved lost work day” was $22.36, resulting in an overall saving of $2.58 per dollar invested in the vaccination programme.64 Other, model-based, studies also indicate that vaccinating working adults would be cost-saving.12 While recent international guidelines for pharmacoeconomic analyses do explicitly recommend the inclusion of production gains and losses,62 also when such indirect costs are not taken into account, vaccination of adults below the age of 65 turns out to be highly cost-effective.
    Go to context

  • As demonstrated by a number of studies, conducted in different countries, vaccination significantly reduces illness, absenteeism and influenza-related costs for healthy adults in the work place.12,13 Indeed, vaccination reduces upper respiratory tract and influenza-like illnesses from all causes by approximately 30%, related physician visits by >40% and work loss by >35% (Table 20).60,61 Accordingly, cost–benefit analyses, based on clinical trials or on modelling, have shown that vaccination of healthy working adults is cost-effective and in many cases cost-saving, provided that indirect costs associated with work absenteeism (see Chapter 6) are explicitly taken into account.62 For example, trials conducted in the USA have shown that – with an average cost for vaccine production and administration of $20 – the net saving would be $23 per person vaccinated.63 In another study comparing 131 vaccinated employees from six textile plants in North Carolina, USA, with 131 age- and gender-matched non-vaccinated controls from different plants, the “cost per saved lost work day” was $22.36, resulting in an overall saving of $2.58 per dollar invested in the vaccination programme.64 Other, model-based, studies also indicate that vaccinating working adults would be cost-saving.12 While recent international guidelines for pharmacoeconomic analyses do explicitly recommend the inclusion of production gains and losses,62 also when such indirect costs are not taken into account, vaccination of adults below the age of 65 turns out to be highly cost-effective.
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  • Finally, vaccination of children appears to be highly cost-effective and in many cases cost-saving.
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KL Nichol. The efficacy, effectiveness and cost-effectiveness of inactivated influenza virus vaccines. Crossref. Vaccine 21 (2003) (1769 - 1775) 2003
13

References in context


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  • Vaccination results in reductions of influenza-related respiratory illness and numbers of physician visits among all age groups, and in lower hospitalization rates and deaths among the elderly and patients at risk for serious complications of influenza.12,13 Vaccination coverage among target groups has increased considerably in recent years10 as the awareness of the impact of influenza is growing and influenza has become an important issue on the public-health agenda in many countries.15,16 However, the use of available influenza vaccines is still far from optimal.
    Go to context

  • Table 17 presents the recommendations for influenza vaccination adopted in most countries.
    Go to context

  • As a result, many clinical studies have now produced consistent data showing the clear-cut benefits of influenza vaccination.12,13,33,35,40 Since the elderly comprise by far the largest target population for flu vaccination, the majority of studies evaluating the benefits of vaccination have been conducted among people in this age group; these will be discussed in more detail below.
    Go to context

  • In evaluating the outcome of influenza vaccination, a distinction is often made between vaccine efficacy per se and the clinical effectiveness of vaccination.12,13 Vaccine efficacy is defined as the reduction in the rate of laboratory-confirmed influenza among vaccinated compared to non-vaccinated individuals.
    Go to context

  • It is defined as the reduction of clinically relevant, but not necessarily influenza-specific, disease in a “real-life” situation, including all influenza-like illness (ILI), hospitalizations due to pneumonia from all causes or death from all causes.12,13,40 As this parameter includes – by definition – disease that is not caused by the influenza virus, clinical effectiveness of vaccination is generally estimated to be lower than the actual vaccine efficacy, as illustrated by the hypothetical example presented in Figure 28.13 Therefore, clinical effectiveness should not be confused for vaccine efficacy, as this may result in a substantial underestimation of the actual performance of the vaccine.
    Go to context

  • It is defined as the reduction of clinically relevant, but not necessarily influenza-specific, disease in a “real-life” situation, including all influenza-like illness (ILI), hospitalizations due to pneumonia from all causes or death from all causes.12,13,40 As this parameter includes – by definition – disease that is not caused by the influenza virus, clinical effectiveness of vaccination is generally estimated to be lower than the actual vaccine efficacy, as illustrated by the hypothetical example presented in Figure 28.13 Therefore, clinical effectiveness should not be confused for vaccine efficacy, as this may result in a substantial underestimation of the actual performance of the vaccine.
    Go to context

  • Numerous studies have convincingly demonstrated the clinical benefits of influenza vaccination in the elderly.12,13,40,48,49 For example, in a large study in the USA, spanning two influenza seasons (1998–2000) and involving 300,000 community-dwelling elderly people (≥65 years), influenza vaccination was performed in 55.5–59.7% of the population.
    Go to context

  • Economic evaluations, conducted in many different countries, have indicated that vaccination of senior citizens against influenza is always cost-effective and frequently cost-saving.12,13 For example, in a 6-year study carried out in Minnesota, USA, influenza vaccination of nursing-home residents was associated with an average net saving of $73 per person as a result of reductions in direct medical costs.12 Vaccination appears to be cost-effective or even cost-saving for both healthy senior citizens and high-risk elderly with underlying chronic medical conditions.
    Go to context


  • Go to context

  • This is why there is an increasing awareness of the potential benefits of vaccination of working adults.12,13 Several prospective clinical studies have demonstrated the efficacy of inactivated influenza vaccines among healthy younger adults.
    Go to context

  • As demonstrated by a number of studies, conducted in different countries, vaccination significantly reduces illness, absenteeism and influenza-related costs for healthy adults in the work place.12,13 Indeed, vaccination reduces upper respiratory tract and influenza-like illnesses from all causes by approximately 30%, related physician visits by >40% and work loss by >35% (Table 20).60,61 Accordingly, cost–benefit analyses, based on clinical trials or on modelling, have shown that vaccination of healthy working adults is cost-effective and in many cases cost-saving, provided that indirect costs associated with work absenteeism (see Chapter 6) are explicitly taken into account.62 For example, trials conducted in the USA have shown that – with an average cost for vaccine production and administration of $20 – the net saving would be $23 per person vaccinated.63 In another study comparing 131 vaccinated employees from six textile plants in North Carolina, USA, with 131 age- and gender-matched non-vaccinated controls from different plants, the “cost per saved lost work day” was $22.36, resulting in an overall saving of $2.58 per dollar invested in the vaccination programme.64 Other, model-based, studies also indicate that vaccinating working adults would be cost-saving.12 While recent international guidelines for pharmacoeconomic analyses do explicitly recommend the inclusion of production gains and losses,62 also when such indirect costs are not taken into account, vaccination of adults below the age of 65 turns out to be highly cost-effective.
    Go to context

KL Nichol. Efficacy/clinical effectiveness of inactivated influenza virus vaccines in adults. KG Nicholson, RG Webster, AJ Hay (Eds.) Textbook of Influenza (Blackwell Science, 1998) (358 - 372) 1998
14

References in context

  • The safety record of inactivated influenza vaccines is excellent.9,14 Hundreds of millions of vaccine doses are distributed worldwide each year, adverse effects being extremely rare.
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  • The most frequently occurring side effects are local reactions at the site of injection, which usually do not last more than 1–2 days.14 Generally, the reactions are mild and of a transient nature.
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  • The most frequently occurring side effects are local reactions at the site of injection, which usually do not last more than 1–2 days.14 Generally, the reactions are mild and of a transient nature.
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MJ Wiselka. Vaccine safety. KG Nicholson, RG Webster, AJ Hay (Eds.) Textbook of Influenza (Blackwell Science, 1998) (346 - 357) 1998
15

References in context

  • Vaccination results in reductions of influenza-related respiratory illness and numbers of physician visits among all age groups, and in lower hospitalization rates and deaths among the elderly and patients at risk for serious complications of influenza.12,13 Vaccination coverage among target groups has increased considerably in recent years10 as the awareness of the impact of influenza is growing and influenza has become an important issue on the public-health agenda in many countries.15,16 However, the use of available influenza vaccines is still far from optimal.
    Go to context

K Stöhr. The global agenda on influenza surveillance and control. Vaccine 21 (2003) (1744 - 1748) 2003
16

References in context

  • Vaccination results in reductions of influenza-related respiratory illness and numbers of physician visits among all age groups, and in lower hospitalization rates and deaths among the elderly and patients at risk for serious complications of influenza.12,13 Vaccination coverage among target groups has increased considerably in recent years10 as the awareness of the impact of influenza is growing and influenza has become an important issue on the public-health agenda in many countries.15,16 However, the use of available influenza vaccines is still far from optimal.
    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/emc/diseases/flu/global_agenda_report/Contentpandemic.htm) 2002
17

References in context

  • However, despite the introduction of improved techniques for virus purification, local reactogenicity and systemic side effects remain a problem associated with the use of these vaccines, particularly in small children.17 This has led to the development of vaccine formulations consisting of disrupted virus particles, which turned out to be almost equally immunogenic in primed individuals, yet causing significantly fewer side effects.2 These split-virus vaccines, first licensed in the USA in 1968, are among the most widely used formulations to date.
    Go to context

FL Ruben. Prevention and control of influenza. Role of vaccine. Crossref. Am J Med 82 (Suppl 6a) (1987) (31 - 34) 1987
18

References in context

  • Initial inactivated influenza vaccine formulations invariably consisted of whole inactivated virus formulations.2,4 Whole inactivated virus vaccines are generally quite immunogenic.
    Go to context

KG Nicholson, DAJ Tyrrell, P Harrison, et al.. Clinical studies of monovalent inactivated whole virus and subunit A/USSR/77 (H1N1) vaccine: serological responses and clinical reactions. Crossref. J Biol Stand 7 (1979) (123 - 136) 1979
19

References in context

  • Subunit vaccines contain the HA and NA surface glycoproteins purified from other viral components.4 Because of their high purity, subunit vaccines have a favourable profile in terms of local and systemic side effects, compared to whole-virus and split vaccines.19 Yet, subunit vaccines are equally immunogenic in primed individuals.
    Go to context

WEP Beyer, AM Palache, ADME Osterhaus. Comparison of serology and reactogenicity between influenza subunit vaccines and whole or split vaccines. A review and meta-analysis of the literature. Crossref. Clin Drug Invest 15 (1998) (1 - 12) 1998
20

References in context

  • Recently, a mathematical modeling approach for mapping of the antigenic distance between virus strains has been included in the strain selection process.20 In order to allow vaccine manufacturers sufficient time for production, in February of each year the WHO issues its recommendation about which viral strains should be included in the next winter's vaccine for the northern hemisphere.
    Go to context

DJ Smith, AS Lapedes, JC de Jong, et al.. Mapping the antigenic and genetic evolution of influenza virus. Crossref. Science 305 (2004) (371 - 376) 2004
21

References in context

  • Several studies have shown that a vaccine dose of ≥10 µg HA per strain induces an adequate immune response in primed individuals.21,22 Current trivalent inactivated influenza vaccines contain 15 µg of HA per strain as assessed by the SRD assay.
    Go to context

AM Palache, WEP Beyer, G Lüchters, et al.. Influenza vaccines: the effect of vaccine dose on antibody response in primed populations during the ongoing interpandemic period. A review of the literature. Crossref. Vaccine 11 (1993) (892 - 908) 1993
22

References in context

  • Several studies have shown that a vaccine dose of ≥10 µg HA per strain induces an adequate immune response in primed individuals.21,22 Current trivalent inactivated influenza vaccines contain 15 µg of HA per strain as assessed by the SRD assay.
    Go to context

  • Not only has the composition of influenza vaccines been standardized in many countries, in the EU, criteria for vaccine immunogenicity have also been implemented.5,22,23 As indicated above, current inactivated influenza vaccines aim at induction of an efficient systemic antibody response against the viral surface antigens.
    Go to context

J Treanor, W Keitel, R Belshe, et al.. Evaluation of a single dose of half strength inactivated influenza vaccine in healthy adults. Crossref. Vaccine 20 (2002) (1099 - 1105) 2002
23

References in context

  • Criteria of the European Medicines Agency (EMEA) of the EU for the evaluation of influenza vaccine efficacy.
    Go to context

  • This dose scheme has been formally standardized.5,23,24 The trivalent inactivated influenza vaccine is administered by intramuscular or deep subcutaneous injection.
    Go to context

  • Not only has the composition of influenza vaccines been standardized in many countries, in the EU, criteria for vaccine immunogenicity have also been implemented.5,22,23 As indicated above, current inactivated influenza vaccines aim at induction of an efficient systemic antibody response against the viral surface antigens.
    Go to context

  • The European Medicines Agency (EMEA) has formally standardized the EU requirements for annual evaluation of influenza vaccine efficacy (Table 16).23,24 These requirements include specified numbers of seroconversions and/or numbers of individuals achieving a certain antibody titre upon vaccination within a study population of a specified age range.
    Go to context

  • Immediately after the first batches of trivalent vaccine have been released for use, two serological clinical studies (in people aged 18–60 and >60 years) are performed to satisfy the licensing criteria of the European regulatory authorities,23,24 as discussed above.
    Go to context

European Medicines Agency (EMEA). Note for guidance on harmonization of requirements for influenza vaccines. CPMP/BWP/214/96. (www.emea.eu.int/pdfs/human/bwp/021496en.pdf) (1997) 1997
24

References in context

  • This dose scheme has been formally standardized.5,23,24 The trivalent inactivated influenza vaccine is administered by intramuscular or deep subcutaneous injection.
    Go to context

  • The European Medicines Agency (EMEA) has formally standardized the EU requirements for annual evaluation of influenza vaccine efficacy (Table 16).23,24 These requirements include specified numbers of seroconversions and/or numbers of individuals achieving a certain antibody titre upon vaccination within a study population of a specified age range.
    Go to context

  • Immediately after the first batches of trivalent vaccine have been released for use, two serological clinical studies (in people aged 18–60 and >60 years) are performed to satisfy the licensing criteria of the European regulatory authorities,23,24 as discussed above.
    Go to context

JM Wood, RA Levandowski. The influenza vaccine licensing process. Crossref. Vaccine 21 (2003) (1786 - 1788) 2003
25

References in context

  • The European Medicines Agency (EMEA) has formally standardized the EU requirements for annual evaluation of influenza vaccine efficacy (Table 16).23,24 These requirements include specified numbers of seroconversions and/or numbers of individuals achieving a certain antibody titre upon vaccination within a study population of a specified age range.
    Go to context

Voordouw B. Influenza Vaccination in Community Dwelling Elderly Persons. PhD thesis, Erasmus University, Rotterdam, 2005. ISBN 90-8559-103-1.
26

References in context

  • As almost all current influenza vaccines are prepared from egg-grown virus (Figure 26), the annual vaccine production cycle begins with the estimation and ordering of the required numbers of embryonated chicken eggs well before actual vaccine production starts.26 Then, after the WHO has issued its recommendation, seed viruses are generated and characterized for approval by the WHO Collaborating Centres.
    Go to context

C Gerdil. The annual production cycle for influenza vaccine. Crossref. Vaccine 21 (2003) (1776 - 1779) 2003
27

References in context

  • This is particularly relevant because of the relatively low vaccine coverage rates in patients at risk who are younger than 65 years of age.27–29 Currently, more countries are considering lowering the age limit for vaccination recommendation.
    Go to context

MW Kroneman, GA van Essen, MA Tacken, et al.. Does a population survey provide reliable influenza vaccine uptake rates among high-risk groups? A case-study of The Netherlands. Crossref. Vaccine 22 (2004) (2163 - 2170) 2004
28

References in context

  • This is particularly relevant because of the relatively low vaccine coverage rates in patients at risk who are younger than 65 years of age.27–29 Currently, more countries are considering lowering the age limit for vaccination recommendation.
    Go to context

  • However, despite the increased vaccine use, recent surveys in Europe show that the coverage rates in target populations are still far from the WHO-recommended 75% in 2010.29,36 The current coverage rates range from 18% (Poland) to 67% (Spain) for the elderly and from 3% to 40% for various risk groups in younger populations.28,29,37 In the USA, only 35% of adults between the ages of 18 and 64 years who are at risk for serious complications due to influenza were being vaccinated in 2003.38 The implication of these findings is that many elderly and at-risk patients are not receiving the best possible protective treatment to prevent influenza or minimize the consequences of an influenza infection.
    Go to context

M Kroneman, GA van Essen, W John Paget. Influenza vaccination coverage and reasons to refrain among high-risk persons in four European countries. Crossref. Vaccine 24 (2006) (622 - 628) 2006
29

References in context

  • This is particularly relevant because of the relatively low vaccine coverage rates in patients at risk who are younger than 65 years of age.27–29 Currently, more countries are considering lowering the age limit for vaccination recommendation.
    Go to context

  • However, despite the increased vaccine use, recent surveys in Europe show that the coverage rates in target populations are still far from the WHO-recommended 75% in 2010.29,36 The current coverage rates range from 18% (Poland) to 67% (Spain) for the elderly and from 3% to 40% for various risk groups in younger populations.28,29,37 In the USA, only 35% of adults between the ages of 18 and 64 years who are at risk for serious complications due to influenza were being vaccinated in 2003.38 The implication of these findings is that many elderly and at-risk patients are not receiving the best possible protective treatment to prevent influenza or minimize the consequences of an influenza infection.
    Go to context

  • However, despite the increased vaccine use, recent surveys in Europe show that the coverage rates in target populations are still far from the WHO-recommended 75% in 2010.29,36 The current coverage rates range from 18% (Poland) to 67% (Spain) for the elderly and from 3% to 40% for various risk groups in younger populations.28,29,37 In the USA, only 35% of adults between the ages of 18 and 64 years who are at risk for serious complications due to influenza were being vaccinated in 2003.38 The implication of these findings is that many elderly and at-risk patients are not receiving the best possible protective treatment to prevent influenza or minimize the consequences of an influenza infection.
    Go to context

  • Therefore, primary-care physicians and other health-care workers play a major role in implementing influenza vaccination programmes,29 as discussed in more detail in the last paragraph of this chapter.
    Go to context

  • National health authorities of eight different European countries have recently discussed possible ways to reach the WHO vaccine coverage rate objectives for 2010.29 Health-care professionals play the single most important role in making this happen.
    Go to context

TD Szucs, D Muller. Influenza vaccination coverage rates in five European countries – a population-based cross-sectional analysis of two consecutive influenza seasons. Crossref. Vaccine 23 (2005) (5055 - 5063) 2005
30

References in context

  • Table 17 presents the recommendations for influenza vaccination adopted in most countries.
    Go to context

  • As demonstrated by a number of studies, conducted in different countries, vaccination significantly reduces illness, absenteeism and influenza-related costs for healthy adults in the work place.12,13 Indeed, vaccination reduces upper respiratory tract and influenza-like illnesses from all causes by approximately 30%, related physician visits by >40% and work loss by >35% (Table 20).60,61 Accordingly, cost–benefit analyses, based on clinical trials or on modelling, have shown that vaccination of healthy working adults is cost-effective and in many cases cost-saving, provided that indirect costs associated with work absenteeism (see Chapter 6) are explicitly taken into account.62 For example, trials conducted in the USA have shown that – with an average cost for vaccine production and administration of $20 – the net saving would be $23 per person vaccinated.63 In another study comparing 131 vaccinated employees from six textile plants in North Carolina, USA, with 131 age- and gender-matched non-vaccinated controls from different plants, the “cost per saved lost work day” was $22.36, resulting in an overall saving of $2.58 per dollar invested in the vaccination programme.64 Other, model-based, studies also indicate that vaccinating working adults would be cost-saving.12 While recent international guidelines for pharmacoeconomic analyses do explicitly recommend the inclusion of production gains and losses,62 also when such indirect costs are not taken into account, vaccination of adults below the age of 65 turns out to be highly cost-effective.
    Go to context

J Chancellor. Lowering the age threshold for routine influenza vaccination to 50 years: cost-effectiveness analysis for European countries. Vaccine (2006) in press. 2006
31

References in context

  • Table 17 presents the recommendations for influenza vaccination adopted in most countries.
    Go to context

  • Initial trials, conducted among military recruits several decades ago,57 showed that the vaccine was 70–90% efficacious in preventing laboratory-confirmed influenza, provided there was a good antigenic match between vaccine and circulating virus.58 A review of more recent clinical studies shows that the efficacy of inactivated influenza vaccines varied from 65% for all influenza seasons to 72% for those seasons where there was a good match between vaccine and circulating virus.31 Additional studies have reported vaccine efficacies in terms of prevention of confirmed influenza in the range of 80–90% in cases where there was a good match.59,60 Clearly, current inactivated influenza vaccines attain very high efficacy values among healthy younger adults (Table 20).
    Go to context

  • As demonstrated by a number of studies, conducted in different countries, vaccination significantly reduces illness, absenteeism and influenza-related costs for healthy adults in the work place.12,13 Indeed, vaccination reduces upper respiratory tract and influenza-like illnesses from all causes by approximately 30%, related physician visits by >40% and work loss by >35% (Table 20).60,61 Accordingly, cost–benefit analyses, based on clinical trials or on modelling, have shown that vaccination of healthy working adults is cost-effective and in many cases cost-saving, provided that indirect costs associated with work absenteeism (see Chapter 6) are explicitly taken into account.62 For example, trials conducted in the USA have shown that – with an average cost for vaccine production and administration of $20 – the net saving would be $23 per person vaccinated.63 In another study comparing 131 vaccinated employees from six textile plants in North Carolina, USA, with 131 age- and gender-matched non-vaccinated controls from different plants, the “cost per saved lost work day” was $22.36, resulting in an overall saving of $2.58 per dollar invested in the vaccination programme.64 Other, model-based, studies also indicate that vaccinating working adults would be cost-saving.12 While recent international guidelines for pharmacoeconomic analyses do explicitly recommend the inclusion of production gains and losses,62 also when such indirect costs are not taken into account, vaccination of adults below the age of 65 turns out to be highly cost-effective.
    Go to context

DA Turner, AJ Wailoo, NJ Cooper, et al.. The cost-effectiveness of influenza vaccination of healthy adults 50–64 years of age. Crossref. Vaccine 24 (2006) (1035 - 1043) 2006
32

References in context

  • Table 17 presents the recommendations for influenza vaccination adopted in most countries.
    Go to context

Centers for Disease Control and Prevention. Influenza vaccination in pregnancy: practices among obstetrician-gynecologists – United States, 2003–04 influenza season. MMWR 54 (2005) (1050 - 1052) (www.cdc.gov/mmwr/preview/mmwrhtml/mm5441a4.htm) 2005
33

References in context

  • Table 17 presents the recommendations for influenza vaccination adopted in most countries.
    Go to context

  • As a result, many clinical studies have now produced consistent data showing the clear-cut benefits of influenza vaccination.12,13,33,35,40 Since the elderly comprise by far the largest target population for flu vaccination, the majority of studies evaluating the benefits of vaccination have been conducted among people in this age group; these will be discussed in more detail below.
    Go to context


  • Go to context

  • However, there is increasing epidemiological evidence of the burden of disease in children33 and of vaccination effectiveness.33,35,66 In addition to the direct benefits for the vaccinated children, a vaccination programme for children may also have the potential for reducing the impact of influenza epidemics, because children play an important role in the spread of influenza infections in communities.66,67 In addition, influenza among children is a significant cause of parental work loss.
    Go to context

  • However, there is increasing epidemiological evidence of the burden of disease in children33 and of vaccination effectiveness.33,35,66 In addition to the direct benefits for the vaccinated children, a vaccination programme for children may also have the potential for reducing the impact of influenza epidemics, because children play an important role in the spread of influenza infections in communities.66,67 In addition, influenza among children is a significant cause of parental work loss.
    Go to context

  • However, there is increasing epidemiological evidence of the burden of disease in children33 and of vaccination effectiveness.33,35,66 In addition to the direct benefits for the vaccinated children, a vaccination programme for children may also have the potential for reducing the impact of influenza epidemics, because children play an important role in the spread of influenza infections in communities.66,67 In addition, influenza among children is a significant cause of parental work loss.
    Go to context

T Heikkinen, R Booy, M Campins, et al.. Should healthy children be vaccinated against influenza? A consensus report of the Summits of Independent European Vaccination Experts. Eur J Pediatr 21 (2005) (1 - 6) 2005
34

References in context

  • Table 17 presents the recommendations for influenza vaccination adopted in most countries.
    Go to context

  • Because of the non-specific criteria of influenza-like illness (ILI), the outcome of clinical effectiveness studies depends on the used case definition in the particular study.
    Go to context

T Heikkinen, O Ruuskanen. Influenza vaccines in healthy children (letter to the editor). Crossref. Lancet 365 (2005) (2086 - 2087) 2005
35

References in context

  • Table 17 presents the recommendations for influenza vaccination adopted in most countries.
    Go to context

  • As a result, many clinical studies have now produced consistent data showing the clear-cut benefits of influenza vaccination.12,13,33,35,40 Since the elderly comprise by far the largest target population for flu vaccination, the majority of studies evaluating the benefits of vaccination have been conducted among people in this age group; these will be discussed in more detail below.
    Go to context

  • However, there is increasing epidemiological evidence of the burden of disease in children33 and of vaccination effectiveness.33,35,66 In addition to the direct benefits for the vaccinated children, a vaccination programme for children may also have the potential for reducing the impact of influenza epidemics, because children play an important role in the spread of influenza infections in communities.66,67 In addition, influenza among children is a significant cause of parental work loss.
    Go to context

  • A similar observation has been made in a recent study in Russia.35 School children in some regions in the Moscow area were systematically vaccinated with a classical inactivated subunit vaccine, whereas in control areas no such vaccination strategy was installed.
    Go to context

  • A similar observation has been made in a recent study in Russia.35 School children in some regions in the Moscow area were systematically vaccinated with a classical inactivated subunit vaccine, whereas in control areas no such vaccination strategy was installed.
    Go to context

YZ Ghendon, AN Kaira, GA Elshina. The effect of mass influenza immunization in children on the morbidity of the unvaccinated elderly. Epidemiol Infect 134 (2006) (71 - 78) 2006
36

References in context

  • However, despite the increased vaccine use, recent surveys in Europe show that the coverage rates in target populations are still far from the WHO-recommended 75% in 2010.29,36 The current coverage rates range from 18% (Poland) to 67% (Spain) for the elderly and from 3% to 40% for various risk groups in younger populations.28,29,37 In the USA, only 35% of adults between the ages of 18 and 64 years who are at risk for serious complications due to influenza were being vaccinated in 2003.38 The implication of these findings is that many elderly and at-risk patients are not receiving the best possible protective treatment to prevent influenza or minimize the consequences of an influenza infection.
    Go to context

  • However, despite the increased vaccine use, recent surveys in Europe show that the coverage rates in target populations are still far from the WHO-recommended 75% in 2010.29,36 The current coverage rates range from 18% (Poland) to 67% (Spain) for the elderly and from 3% to 40% for various risk groups in younger populations.28,29,37 In the USA, only 35% of adults between the ages of 18 and 64 years who are at risk for serious complications due to influenza were being vaccinated in 2003.38 The implication of these findings is that many elderly and at-risk patients are not receiving the best possible protective treatment to prevent influenza or minimize the consequences of an influenza infection.
    Go to context


  • Go to context

  • As indicated in Chapter 3 and further described in Chapter 9, there is a societal urgency to achieve the WHO objectives,36 because this will not only ameliorate the annual burden of influenza but also contribute to a better level of pandemic preparedness.
    Go to context

  • As indicated in Chapter 3 and further described in Chapter 9, there is a societal urgency to achieve the WHO objectives,36 because this will not only ameliorate the annual burden of influenza but also contribute to a better level of pandemic preparedness.
    Go to context

Resolution WHA56.19. Prevention and control of influenza pandemics and annual epidemics (Fifty-Sixth World Health Assembly, Geneva, 19–28 May 2003) (www.who.int/gb/ebwha/pdf_files/WHA56/ea56r19.pdf) 1928 May 2003
37

References in context

  • However, despite the increased vaccine use, recent surveys in Europe show that the coverage rates in target populations are still far from the WHO-recommended 75% in 2010.29,36 The current coverage rates range from 18% (Poland) to 67% (Spain) for the elderly and from 3% to 40% for various risk groups in younger populations.28,29,37 In the USA, only 35% of adults between the ages of 18 and 64 years who are at risk for serious complications due to influenza were being vaccinated in 2003.38 The implication of these findings is that many elderly and at-risk patients are not receiving the best possible protective treatment to prevent influenza or minimize the consequences of an influenza infection.
    Go to context

  • The value of immunization against influenza is sometimes being questioned, as outbreaks of flu continue despite increased influenza vaccination coverage.39 Therefore, there has been a strong demand for sound scientific data on the effects of influenza vaccination.
    Go to context

SA Smith, GA Poland. The use of influenza and pneumococcal vaccines in people with diabetes (technical review). Crossref. Diabetes Care 23 (2000) (95 - 108) 2000
38

References in context

  • However, despite the increased vaccine use, recent surveys in Europe show that the coverage rates in target populations are still far from the WHO-recommended 75% in 2010.29,36 The current coverage rates range from 18% (Poland) to 67% (Spain) for the elderly and from 3% to 40% for various risk groups in younger populations.28,29,37 In the USA, only 35% of adults between the ages of 18 and 64 years who are at risk for serious complications due to influenza were being vaccinated in 2003.38 The implication of these findings is that many elderly and at-risk patients are not receiving the best possible protective treatment to prevent influenza or minimize the consequences of an influenza infection.
    Go to context

Centers for Disease Control and Prevention. Influenza vaccination levels among person aged ≥65 years and among persons aged 18–64 years with high-risk conditions – United States, 2003. MMWR 54 (2005) (1045 - 1049) (www.cdc.gov/mmwr/preview/mmwrhtml/mm5441a3.htm) 2005
39

References in context

  • The value of immunization against influenza is sometimes being questioned, as outbreaks of flu continue despite increased influenza vaccination coverage.39 Therefore, there has been a strong demand for sound scientific data on the effects of influenza vaccination.
    Go to context

DS Fedson, K Nichol. Should we question the benefits of influenza vaccination for elderly people? Infectious Disease News, Guest Editorial. (www.infectiousdiseasenews.com/200508/guested1.asp) (August 2005) August 2005
40

References in context

  • As a result, many clinical studies have now produced consistent data showing the clear-cut benefits of influenza vaccination.12,13,33,35,40 Since the elderly comprise by far the largest target population for flu vaccination, the majority of studies evaluating the benefits of vaccination have been conducted among people in this age group; these will be discussed in more detail below.
    Go to context

  • It is defined as the reduction of clinically relevant, but not necessarily influenza-specific, disease in a “real-life” situation, including all influenza-like illness (ILI), hospitalizations due to pneumonia from all causes or death from all causes.12,13,40 As this parameter includes – by definition – disease that is not caused by the influenza virus, clinical effectiveness of vaccination is generally estimated to be lower than the actual vaccine efficacy, as illustrated by the hypothetical example presented in Figure 28.13 Therefore, clinical effectiveness should not be confused for vaccine efficacy, as this may result in a substantial underestimation of the actual performance of the vaccine.
    Go to context

  • Numerous studies have convincingly demonstrated the clinical benefits of influenza vaccination in the elderly.12,13,40,48,49 For example, in a large study in the USA, spanning two influenza seasons (1998–2000) and involving 300,000 community-dwelling elderly people (≥65 years), influenza vaccination was performed in 55.5–59.7% of the population.
    Go to context


  • Go to context

AC Voordouw, MC Sturkenboom, JP Dieleman, et al.. Annual revaccination against influenza and mortality risk in community-dwelling elderly persons. Crossref. J Am Med Assoc 292 (2004) (2089 - 2095) 2004
41

References in context

  • The value of immunization against influenza is sometimes being questioned, as outbreaks of flu continue despite increased influenza vaccination coverage.39 Therefore, there has been a strong demand for sound scientific data on the effects of influenza vaccination.
    Go to context

  • In most countries, healthy toddlers and children are not included in the target groups for annual influenza immunization.
    Go to context

  • The efficacy of influenza vaccination among children has been evaluated in a number of randomized, controlled trials, involving the use of either trivalent inactivated or experimental live-attenuated vaccines.68–70 From these studies, it appears that vaccination is highly efficacious in terms of preventing laboratory-confirmed influenza for children in their teens (∼90%), whereas a lower efficacy is seen with younger children (Table 20).
    Go to context

SA Harper, K Fukuda, TM Uyeki, et al.. Advisory Committee on Immunization Practices (ACIP), Centers for Disease Control and Prevention (CDC). Prevention and control of influenza. Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 54 (RR-8) (2005) (1 - 40) 2005
42

References in context

  • The value of immunization against influenza is sometimes being questioned, as outbreaks of flu continue despite increased influenza vaccination coverage.39 Therefore, there has been a strong demand for sound scientific data on the effects of influenza vaccination.
    Go to context

  • The vaccination was associated with significant reductions in pneumonia (29–32%), cardiac disease (19%) and cerebrovascular disease (16–23%).42 Other studies have indicated that influenza vaccination of patients who have had a myocardial infarction results in a significant reduction in 1-year mortality rates (66% reduction) or risk of further ischaemic events.
    Go to context

KL Nichol, J Nordin, J Mullooly, et al.. Influenza vaccination and reduction in hospitalizations for cardiac disease and stroke among the elderly. Crossref. New Engl J Med 348 (2003) (1322 - 1332) 2003
43

References in context

  • Indeed, applying different case definitions to one data set from a single clinical study resulted in very different study outcomes.43 A recent literature review revealed that all published clinical effectiveness studies applied different case definitions for ILI44 and that by simply changing the sensitivity and specificity of case definitions and observation periods, differences of as much as 30% in study outcome for vaccination effectiveness may be found.
    Go to context

KL Nichol, P Mendelman. Influence of clinical case definitions with differing levels of sensitivity and specificity on estimates of the relative and absolute health benefits of influenza vaccination among healthy working adults and implications for economic analyses. Crossref. Virus Res 103 (2004) (3 - 8) 2004
44

References in context

  • Indeed, applying different case definitions to one data set from a single clinical study resulted in very different study outcomes.43 A recent literature review revealed that all published clinical effectiveness studies applied different case definitions for ILI44 and that by simply changing the sensitivity and specificity of case definitions and observation periods, differences of as much as 30% in study outcome for vaccination effectiveness may be found.
    Go to context

  • Indeed, applying different case definitions to one data set from a single clinical study resulted in very different study outcomes.43 A recent literature review revealed that all published clinical effectiveness studies applied different case definitions for ILI44 and that by simply changing the sensitivity and specificity of case definitions and observation periods, differences of as much as 30% in study outcome for vaccination effectiveness may be found.
    Go to context

WEP Beyer. Heterogeneity of case-definitions used in vaccine effectiveness studies and its impact on meta-analysis. Vaccine (2006) in press. 2006
45

References in context

  • In recent systematic reviews (Cochrane) on influenza vaccination effectiveness in healthy adults45 and children,46 literature data were pooled for the review process, but the differences in case definitions of individual studies were not taken into account.
    Go to context

V Demicheli, D Rivetti, JJ Deeks, et al.. Vaccines for preventing influenza in healthy adults. Cochrane Database Syst Rev 3 (2004) CD001269 Review. 2004
46

References in context

  • In recent systematic reviews (Cochrane) on influenza vaccination effectiveness in healthy adults45 and children,46 literature data were pooled for the review process, but the differences in case definitions of individual studies were not taken into account.
    Go to context

T Jefferson, S Smith, V Demicheli, et al.. Assessment of the efficacy and effectiveness of influenza vaccines in healthy children: systematic review. Lancet 365 (2005) (773 - 780) 2005
47

References in context

  • Because of the non-specific criteria of influenza-like illness (ILI), the outcome of clinical effectiveness studies depends on the used case definition in the particular study.
    Go to context

K Nichol, J Nordin, J Mullooly. Influence of clinical outcome and outcome period definitions on estimates of absolute clinical and economic benefits of influenza vaccination in community dwelling elderly persons. Crossref. Vaccine 24 (2006) (1562 - 1568) 2006
48

References in context

  • For example, in a large, randomized, double-blind, placebo-controlled trial among 1838 subjects of 60 years of age or older in the Netherlands, vaccine efficacy was found to be 58%.48 This trial was conducted in the 1991–92 winter season and involved the use of a multivalent inactivated influenza vaccine, matching well with the circulating virus.
    Go to context

  • Numerous studies have convincingly demonstrated the clinical benefits of influenza vaccination in the elderly.12,13,40,48,49 For example, in a large study in the USA, spanning two influenza seasons (1998–2000) and involving 300,000 community-dwelling elderly people (≥65 years), influenza vaccination was performed in 55.5–59.7% of the population.
    Go to context


  • Go to context

TME Govaert, CTMCN Thijs, N Masurel, et al.. The efficacy of influenza vaccination in elderly individuals. A randomized double-blind placebo-controlled trial. J Am Med Assoc 272 (1994) (1661 - 1665) 1994
49

References in context

  • Numerous studies have convincingly demonstrated the clinical benefits of influenza vaccination in the elderly.12,13,40,48,49 For example, in a large study in the USA, spanning two influenza seasons (1998–2000) and involving 300,000 community-dwelling elderly people (≥65 years), influenza vaccination was performed in 55.5–59.7% of the population.
    Go to context


  • Go to context

KL Nichol. Influenza vaccination in the elderly. Impact on hospitalization and mortality. Crossref. Drugs Aging 22 (2005) (495 - 515) 2005
50

References in context

  • A meta-analysis, including a large number of individual studies among senior citizens living in the community, concluded that vaccination significantly reduces hospitalization and death rates among the elderly (Table 18).50 Another meta-analysis has shown that influenza vaccination is also highly effective among residents of nursing homes (Table 18).51 These findings necessitate a proactive immunization practice by health-care providers in order to allow more elderly people to benefit from existing safe and efficacious influenza vaccines.
    Go to context


  • Go to context

T Vu, S Farish, M Jenkins, H Kelly. A meta-analysis of effectiveness of influenza vaccine in persons aged 65 years and over living in the community. Crossref. Vaccine 20 (2002) (1831 - 1836) 2002
51

References in context

  • A meta-analysis, including a large number of individual studies among senior citizens living in the community, concluded that vaccination significantly reduces hospitalization and death rates among the elderly (Table 18).50 Another meta-analysis has shown that influenza vaccination is also highly effective among residents of nursing homes (Table 18).51 These findings necessitate a proactive immunization practice by health-care providers in order to allow more elderly people to benefit from existing safe and efficacious influenza vaccines.
    Go to context


  • Go to context

PA Gross, AW Hermogenes, HS Sachs, J Lau, RA Levandowski. The efficacy of influenza vaccine in elderly persons: a meta-analysis and review of the literature. Ann Intern Med 123 (1995) (518 - 527) 1995
52

References in context

  • In a study conducted in the Netherlands in the 1995–96 and 1997–98 seasons, influenza vaccination was found to be cost-saving for high-risk elderly and cost-effective for all elderly and elderly at low risk, the cost-effectiveness ratios being &z.euro;1820 per life-year gained for all elderly and &z.euro;6900 per life-year gained for those at low risk.52 Similar studies have been conducted in other countries with similar outcomes.
    Go to context

MJ Postma, JM Bos, M Van Gennip, et al.. Economic evaluation of influenza vaccination. Assessment for The Netherlands. Crossref. Pharmacoeconomics 16 (Suppl 1) (1999) (33 - 40) 1999
53

References in context

  • Inactivated influenza vaccines have an excellent safety record.9,14 Currently, about 300 million vaccine doses are being administered annually around the globe,10 and the overall rate of adverse reactions is extremely low.
    Go to context

JM Watson, JF Cordier, KG Nicholson. Does influenza immunisation cause exacerbations of chronic airflow obstruction or asthma?. Crossref. Thorax 52 (1997) (190 - 194) 1997
54

References in context

  • Inactivated influenza vaccines have an excellent safety record.9,14 Currently, about 300 million vaccine doses are being administered annually around the globe,10 and the overall rate of adverse reactions is extremely low.
    Go to context

CL Park, AL Frank, M Sullivan, et al.. Influenza vaccination of children during acute asthma exacerbation and concurrent prednisone therapy. Pediatrics 98 (1996) (196 - 200) 1996
55

References in context

  • There have been reports about a possible association between GBS and influenza vaccination, particularly during the swine flu vaccination campaign in the USA in 1976–77.55 More recent studies suggest that GBS may occur at a very low rate of about one additional case per million vaccinees.56 However, it is unclear whether this marginal increase, against a background incidence of GBS of 10–20 per million, is truly associated with influenza vaccination.
    Go to context

TJ Safranek, DN Lawrence, LT Kurland, et al.. Reassessment of the association between Guillain-Barré syndrome and receipt of swine influenza vaccine in 1976–1977: results of a two-state study. Am J Epidemiol 133 (1991) (940 - 951) 1991
56

References in context

  • There have been reports about a possible association between GBS and influenza vaccination, particularly during the swine flu vaccination campaign in the USA in 1976–77.55 More recent studies suggest that GBS may occur at a very low rate of about one additional case per million vaccinees.56 However, it is unclear whether this marginal increase, against a background incidence of GBS of 10–20 per million, is truly associated with influenza vaccination.
    Go to context

T Lasky, GJ Terracciano, L Magder, et al.. The Guillain-Barré syndrome and the 1992–1993 and 1993–1994 influenza vaccines. Crossref. New Engl J Med 339 (1998) (1797 - 1802) 1998
57

References in context

  • Initial trials, conducted among military recruits several decades ago,57 showed that the vaccine was 70–90% efficacious in preventing laboratory-confirmed influenza, provided there was a good antigenic match between vaccine and circulating virus.58 A review of more recent clinical studies shows that the efficacy of inactivated influenza vaccines varied from 65% for all influenza seasons to 72% for those seasons where there was a good match between vaccine and circulating virus.31 Additional studies have reported vaccine efficacies in terms of prevention of confirmed influenza in the range of 80–90% in cases where there was a good match.59,60 Clearly, current inactivated influenza vaccines attain very high efficacy values among healthy younger adults (Table 20).
    Go to context

G Meiklejohn, CH Kempe, WG Thalman, et al.. Effectiveness of polyvalent influenza A vaccine during an influenza A-prime epidemic. Am J Hyg 59 (3) (1954) (241 - 248) 1954
58

References in context

  • Initial trials, conducted among military recruits several decades ago,57 showed that the vaccine was 70–90% efficacious in preventing laboratory-confirmed influenza, provided there was a good antigenic match between vaccine and circulating virus.58 A review of more recent clinical studies shows that the efficacy of inactivated influenza vaccines varied from 65% for all influenza seasons to 72% for those seasons where there was a good match between vaccine and circulating virus.31 Additional studies have reported vaccine efficacies in terms of prevention of confirmed influenza in the range of 80–90% in cases where there was a good match.59,60 Clearly, current inactivated influenza vaccines attain very high efficacy values among healthy younger adults (Table 20).
    Go to context

V Demicheli, T Jefferson, D Rivetti, et al.. Prevention and early treatment of influenza in healthy adults. Crossref. Vaccine 18 (2000) (957 - 1030) 2000
59

References in context

  • Initial trials, conducted among military recruits several decades ago,57 showed that the vaccine was 70–90% efficacious in preventing laboratory-confirmed influenza, provided there was a good antigenic match between vaccine and circulating virus.58 A review of more recent clinical studies shows that the efficacy of inactivated influenza vaccines varied from 65% for all influenza seasons to 72% for those seasons where there was a good match between vaccine and circulating virus.31 Additional studies have reported vaccine efficacies in terms of prevention of confirmed influenza in the range of 80–90% in cases where there was a good match.59,60 Clearly, current inactivated influenza vaccines attain very high efficacy values among healthy younger adults (Table 20).
    Go to context

JA Wilde, JA McMillan, J Serwint, et al.. Effectiveness of influenza vaccine in health care professionals: a randomized trial. Crossref. J Am Med Assoc 281 (1999) (908 - 913) 1999
60

References in context

  • Initial trials, conducted among military recruits several decades ago,57 showed that the vaccine was 70–90% efficacious in preventing laboratory-confirmed influenza, provided there was a good antigenic match between vaccine and circulating virus.58 A review of more recent clinical studies shows that the efficacy of inactivated influenza vaccines varied from 65% for all influenza seasons to 72% for those seasons where there was a good match between vaccine and circulating virus.31 Additional studies have reported vaccine efficacies in terms of prevention of confirmed influenza in the range of 80–90% in cases where there was a good match.59,60 Clearly, current inactivated influenza vaccines attain very high efficacy values among healthy younger adults (Table 20).
    Go to context

  • As demonstrated by a number of studies, conducted in different countries, vaccination significantly reduces illness, absenteeism and influenza-related costs for healthy adults in the work place.12,13 Indeed, vaccination reduces upper respiratory tract and influenza-like illnesses from all causes by approximately 30%, related physician visits by >40% and work loss by >35% (Table 20).60,61 Accordingly, cost–benefit analyses, based on clinical trials or on modelling, have shown that vaccination of healthy working adults is cost-effective and in many cases cost-saving, provided that indirect costs associated with work absenteeism (see Chapter 6) are explicitly taken into account.62 For example, trials conducted in the USA have shown that – with an average cost for vaccine production and administration of $20 – the net saving would be $23 per person vaccinated.63 In another study comparing 131 vaccinated employees from six textile plants in North Carolina, USA, with 131 age- and gender-matched non-vaccinated controls from different plants, the “cost per saved lost work day” was $22.36, resulting in an overall saving of $2.58 per dollar invested in the vaccination programme.64 Other, model-based, studies also indicate that vaccinating working adults would be cost-saving.12 While recent international guidelines for pharmacoeconomic analyses do explicitly recommend the inclusion of production gains and losses,62 also when such indirect costs are not taken into account, vaccination of adults below the age of 65 turns out to be highly cost-effective.
    Go to context

CB Bridges, WW Thompson, MI Meltzer, et al.. Effectiveness and cost-benefit of influenza vaccination of healthy working adults: a randomized controlled trial. Crossref. J Am Med Assoc 284 (2000) (1655 - 1663) 2000
61

References in context

  • As demonstrated by a number of studies, conducted in different countries, vaccination significantly reduces illness, absenteeism and influenza-related costs for healthy adults in the work place.12,13 Indeed, vaccination reduces upper respiratory tract and influenza-like illnesses from all causes by approximately 30%, related physician visits by >40% and work loss by >35% (Table 20).60,61 Accordingly, cost–benefit analyses, based on clinical trials or on modelling, have shown that vaccination of healthy working adults is cost-effective and in many cases cost-saving, provided that indirect costs associated with work absenteeism (see Chapter 6) are explicitly taken into account.62 For example, trials conducted in the USA have shown that – with an average cost for vaccine production and administration of $20 – the net saving would be $23 per person vaccinated.63 In another study comparing 131 vaccinated employees from six textile plants in North Carolina, USA, with 131 age- and gender-matched non-vaccinated controls from different plants, the “cost per saved lost work day” was $22.36, resulting in an overall saving of $2.58 per dollar invested in the vaccination programme.64 Other, model-based, studies also indicate that vaccinating working adults would be cost-saving.12 While recent international guidelines for pharmacoeconomic analyses do explicitly recommend the inclusion of production gains and losses,62 also when such indirect costs are not taken into account, vaccination of adults below the age of 65 turns out to be highly cost-effective.
    Go to context

KL Nichol, A Lind, KL Margolis, et al.. The effectiveness of vaccination against influenza in healthy, working adults. Crossref. New Engl J Med 333 (1995) (889 - 893) 1995
62

References in context

  • As demonstrated by a number of studies, conducted in different countries, vaccination significantly reduces illness, absenteeism and influenza-related costs for healthy adults in the work place.12,13 Indeed, vaccination reduces upper respiratory tract and influenza-like illnesses from all causes by approximately 30%, related physician visits by >40% and work loss by >35% (Table 20).60,61 Accordingly, cost–benefit analyses, based on clinical trials or on modelling, have shown that vaccination of healthy working adults is cost-effective and in many cases cost-saving, provided that indirect costs associated with work absenteeism (see Chapter 6) are explicitly taken into account.62 For example, trials conducted in the USA have shown that – with an average cost for vaccine production and administration of $20 – the net saving would be $23 per person vaccinated.63 In another study comparing 131 vaccinated employees from six textile plants in North Carolina, USA, with 131 age- and gender-matched non-vaccinated controls from different plants, the “cost per saved lost work day” was $22.36, resulting in an overall saving of $2.58 per dollar invested in the vaccination programme.64 Other, model-based, studies also indicate that vaccinating working adults would be cost-saving.12 While recent international guidelines for pharmacoeconomic analyses do explicitly recommend the inclusion of production gains and losses,62 also when such indirect costs are not taken into account, vaccination of adults below the age of 65 turns out to be highly cost-effective.
    Go to context

  • As demonstrated by a number of studies, conducted in different countries, vaccination significantly reduces illness, absenteeism and influenza-related costs for healthy adults in the work place.12,13 Indeed, vaccination reduces upper respiratory tract and influenza-like illnesses from all causes by approximately 30%, related physician visits by >40% and work loss by >35% (Table 20).60,61 Accordingly, cost–benefit analyses, based on clinical trials or on modelling, have shown that vaccination of healthy working adults is cost-effective and in many cases cost-saving, provided that indirect costs associated with work absenteeism (see Chapter 6) are explicitly taken into account.62 For example, trials conducted in the USA have shown that – with an average cost for vaccine production and administration of $20 – the net saving would be $23 per person vaccinated.63 In another study comparing 131 vaccinated employees from six textile plants in North Carolina, USA, with 131 age- and gender-matched non-vaccinated controls from different plants, the “cost per saved lost work day” was $22.36, resulting in an overall saving of $2.58 per dollar invested in the vaccination programme.64 Other, model-based, studies also indicate that vaccinating working adults would be cost-saving.12 While recent international guidelines for pharmacoeconomic analyses do explicitly recommend the inclusion of production gains and losses,62 also when such indirect costs are not taken into account, vaccination of adults below the age of 65 turns out to be highly cost-effective.
    Go to context

MJ Postma, P Jansema, ML van Genugten, et al.. Pharmaco-economics of vaccinating healthy working adults against influenza; reviewing the available evidence. Crossref. Drugs 62 (2002) (1013 - 1024) 2002
63

References in context

  • As demonstrated by a number of studies, conducted in different countries, vaccination significantly reduces illness, absenteeism and influenza-related costs for healthy adults in the work place.12,13 Indeed, vaccination reduces upper respiratory tract and influenza-like illnesses from all causes by approximately 30%, related physician visits by >40% and work loss by >35% (Table 20).60,61 Accordingly, cost–benefit analyses, based on clinical trials or on modelling, have shown that vaccination of healthy working adults is cost-effective and in many cases cost-saving, provided that indirect costs associated with work absenteeism (see Chapter 6) are explicitly taken into account.62 For example, trials conducted in the USA have shown that – with an average cost for vaccine production and administration of $20 – the net saving would be $23 per person vaccinated.63 In another study comparing 131 vaccinated employees from six textile plants in North Carolina, USA, with 131 age- and gender-matched non-vaccinated controls from different plants, the “cost per saved lost work day” was $22.36, resulting in an overall saving of $2.58 per dollar invested in the vaccination programme.64 Other, model-based, studies also indicate that vaccinating working adults would be cost-saving.12 While recent international guidelines for pharmacoeconomic analyses do explicitly recommend the inclusion of production gains and losses,62 also when such indirect costs are not taken into account, vaccination of adults below the age of 65 turns out to be highly cost-effective.
    Go to context

KL Nichol, KP Mallon, PM Mendelman. Cost benefit of influenza vaccination in healthy, working adults: an economic analysis based on the results of a clinical trial of trivalent live attenuated influenza virus vaccine. Crossref. Vaccine 21 (2003) (2207 - 2217) 2003
64

References in context

  • As demonstrated by a number of studies, conducted in different countries, vaccination significantly reduces illness, absenteeism and influenza-related costs for healthy adults in the work place.12,13 Indeed, vaccination reduces upper respiratory tract and influenza-like illnesses from all causes by approximately 30%, related physician visits by >40% and work loss by >35% (Table 20).60,61 Accordingly, cost–benefit analyses, based on clinical trials or on modelling, have shown that vaccination of healthy working adults is cost-effective and in many cases cost-saving, provided that indirect costs associated with work absenteeism (see Chapter 6) are explicitly taken into account.62 For example, trials conducted in the USA have shown that – with an average cost for vaccine production and administration of $20 – the net saving would be $23 per person vaccinated.63 In another study comparing 131 vaccinated employees from six textile plants in North Carolina, USA, with 131 age- and gender-matched non-vaccinated controls from different plants, the “cost per saved lost work day” was $22.36, resulting in an overall saving of $2.58 per dollar invested in the vaccination programme.64 Other, model-based, studies also indicate that vaccinating working adults would be cost-saving.12 While recent international guidelines for pharmacoeconomic analyses do explicitly recommend the inclusion of production gains and losses,62 also when such indirect costs are not taken into account, vaccination of adults below the age of 65 turns out to be highly cost-effective.
    Go to context

DS Campbell, MH Rumley. Cost-effectiveness of the influenza vaccine in a healthy, working-age population. Crossref. J Occup Environ Med 5 (1997) (408 - 414) 1997
65

References in context

  • As demonstrated by a number of studies, conducted in different countries, vaccination significantly reduces illness, absenteeism and influenza-related costs for healthy adults in the work place.12,13 Indeed, vaccination reduces upper respiratory tract and influenza-like illnesses from all causes by approximately 30%, related physician visits by >40% and work loss by >35% (Table 20).60,61 Accordingly, cost–benefit analyses, based on clinical trials or on modelling, have shown that vaccination of healthy working adults is cost-effective and in many cases cost-saving, provided that indirect costs associated with work absenteeism (see Chapter 6) are explicitly taken into account.62 For example, trials conducted in the USA have shown that – with an average cost for vaccine production and administration of $20 – the net saving would be $23 per person vaccinated.63 In another study comparing 131 vaccinated employees from six textile plants in North Carolina, USA, with 131 age- and gender-matched non-vaccinated controls from different plants, the “cost per saved lost work day” was $22.36, resulting in an overall saving of $2.58 per dollar invested in the vaccination programme.64 Other, model-based, studies also indicate that vaccinating working adults would be cost-saving.12 While recent international guidelines for pharmacoeconomic analyses do explicitly recommend the inclusion of production gains and losses,62 also when such indirect costs are not taken into account, vaccination of adults below the age of 65 turns out to be highly cost-effective.
    Go to context

  • The analysis by the US Office of Technology Assessment, referred to above,65 indicates that vaccination of children below 3 years of age would cost US $1122 per year of healthy life gained, while vaccinating children 3–14 years of age would only cost US $853 per year of healthy life gained.
    Go to context

Office of Technology Assessment. Cost-effectiveness of influenza vaccination (Congress of the United States, Washington, DC, 1981) 1981
66

References in context

  • However, there is increasing epidemiological evidence of the burden of disease in children33 and of vaccination effectiveness.33,35,66 In addition to the direct benefits for the vaccinated children, a vaccination programme for children may also have the potential for reducing the impact of influenza epidemics, because children play an important role in the spread of influenza infections in communities.66,67 In addition, influenza among children is a significant cause of parental work loss.
    Go to context

  • However, there is increasing epidemiological evidence of the burden of disease in children33 and of vaccination effectiveness.33,35,66 In addition to the direct benefits for the vaccinated children, a vaccination programme for children may also have the potential for reducing the impact of influenza epidemics, because children play an important role in the spread of influenza infections in communities.66,67 In addition, influenza among children is a significant cause of parental work loss.
    Go to context

R Jordan, M Connock, E Albon, et al.. Universal vaccination of children against influenza: Are there indirect benefits to the community? A systematic review of the evidence. Crossref. Vaccine 24 (2006) (1047 - 1062) 2006
67

References in context

  • However, there is increasing epidemiological evidence of the burden of disease in children33 and of vaccination effectiveness.33,35,66 In addition to the direct benefits for the vaccinated children, a vaccination programme for children may also have the potential for reducing the impact of influenza epidemics, because children play an important role in the spread of influenza infections in communities.66,67 In addition, influenza among children is a significant cause of parental work loss.
    Go to context

  • In a study conducted in Michigan, USA, during the 1968–69 pandemic outbreak of Hong Kong flu, vaccination of school-age children resulted in three-fold lower rates of influenza-like illness than in a control community.72 Interestingly, a 20-year programme in Japan, involving vaccination of school-age children, has indicated that there may be a correlation between increased vaccination of children and lower excess mortality among the elderly,67 substantiating the notion that vaccination of children reduces secondary influenza transmission.
    Go to context

TA Reichert, N Sugaya, DS Fedson, et al.. The Japanese experience with vaccinating schoolchildren against influenza. Crossref. New Engl J Med 344 (2001) (889 - 896) 2001
68

References in context

  • The efficacy of influenza vaccination among children has been evaluated in a number of randomized, controlled trials, involving the use of either trivalent inactivated or experimental live-attenuated vaccines.68–70 From these studies, it appears that vaccination is highly efficacious in terms of preventing laboratory-confirmed influenza for children in their teens (∼90%), whereas a lower efficacy is seen with younger children (Table 20).
    Go to context

KM Neuzil, WD Dupont, PF Wright, KM Edwards. Efficacy of inactivated and cold-adapted vaccines against influenza A infection, 1985 to 1990: the pediatric experience. Crossref. Pediatr Infect Dis J 20 (2001) (733 - 740) 2001
69

References in context

  • The efficacy of influenza vaccination among children has been evaluated in a number of randomized, controlled trials, involving the use of either trivalent inactivated or experimental live-attenuated vaccines.68–70 From these studies, it appears that vaccination is highly efficacious in terms of preventing laboratory-confirmed influenza for children in their teens (∼90%), whereas a lower efficacy is seen with younger children (Table 20).
    Go to context

  • Other studies generally confirm this picture.69 The comparatively modest immunogenicity of influenza vaccines among small children is probably due to their lack of pre-exposure to either influenza virus or vaccine.
    Go to context

KM Neuzil, KM Edwards. Influenza vaccines in children. Crossref. Semin Pediatr Infect Dis 13 (2002) (174 - 181) 2002
70

References in context

  • The efficacy of influenza vaccination among children has been evaluated in a number of randomized, controlled trials, involving the use of either trivalent inactivated or experimental live-attenuated vaccines.68–70 From these studies, it appears that vaccination is highly efficacious in terms of preventing laboratory-confirmed influenza for children in their teens (∼90%), whereas a lower efficacy is seen with younger children (Table 20).
    Go to context

Y Schonbeck, EA Sanders, AW Hoes, et al.. Rationale and design of the prevention of respiratory infections and management in children (PRIMAKid) study: a randomized controlled trial on the effectiveness and costs of combined influenza and pneumococcal vaccination in pre-school children with recurrent respiratory tract infections. Crossref. Vaccine 23 (2005) (4906 - 4914) 2005
71

References in context

  • A common complication of influenza among young children is acute otitis media (see Chapter 5).
    Go to context

T Heikkinen, O Ruuskanen, M Waris, et al.. Influenza vaccination in the prevention of acute otitis media in children. Crossref. Am J Dis Child 145 (1991) (445 - 448) 1991
72

References in context

  • In a study conducted in Michigan, USA, during the 1968–69 pandemic outbreak of Hong Kong flu, vaccination of school-age children resulted in three-fold lower rates of influenza-like illness than in a control community.72 Interestingly, a 20-year programme in Japan, involving vaccination of school-age children, has indicated that there may be a correlation between increased vaccination of children and lower excess mortality among the elderly,67 substantiating the notion that vaccination of children reduces secondary influenza transmission.
    Go to context

AS Monto, FM Davenport, JA Napier, T Francis. Modification of an outbreak of influenza in Tecumseh, Michigan by vaccination of schoolchildren. Crossref. J Infect Dis 122 (1970) (16 - 25) 1970
73

References in context

  • Finally, vaccination of children appears to be highly cost-effective and in many cases cost-saving.
    Go to context

GM Cohen, MD Nettleman. Economic impact of influenza vaccination in preschool children. Crossref. Pediatrics 106 (2000) (973 - 976) 2000
74

References in context

  • Accumulating epidemiological data of the burden of disease in young children, together with the demonstrated direct and indirect benefits of vaccination programmes for very young and school-aged children, would justify also including this segment of the population in the recommendations for routine immunization.
    Go to context

European Scientific Working Group on Influenza (ESWI). Influenza vaccination for one third of the population of the European Union (EU) 25 Member States by 2010. (www.eswi.org) (2005) 2005

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