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Vaccines for the 21st Century: A Tool for Decisionmaking (2000)

Chapter: Appendix 12: Influenza A and B

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Suggested Citation:"Appendix 12: Influenza A and B." Institute of Medicine. 2000. Vaccines for the 21st Century: A Tool for Decisionmaking. Washington, DC: The National Academies Press. doi: 10.17226/5501.
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APPENDIX 12
Influenza A and B

The variability of the influenza virus can explain why reinfection is so common. The two major structural proteins, nucleoprotein (NP) and matrix protein (M), produce antigenic differences which classify the influenza virus as type A, B, or C. Influenza A and B are pleomorphic-enveloped viruses with a genome of 8 different (-)RNA nucleocapsid segments. The reassortment of these segments along with mutations enhance genetic diversity upon infection with two different strains (Murray, Kibosh, et. al., 620). Both types are covered with the glycoprotein spikes, hemagglutinin (HA) and neuraminidase (NA). Influenza A is further subtyped into groups based on the characteristics of the NA and HA (Murray et. al., 918).

The HA is responsible for viral attachment to sialic acid on epithelial cell surfaces, fusion of the envelope to the cell membrane, and agglutination of erythrocytes. Mutagenic changes in HA can induce an antigenic shift which is seen only with influenza A (Murray, Kibosh et. al., 620). This antigenic shift is a result of genome reassortment between different virus strains, including animal strains. The NA cleaves the sialic acid, removing it from the virus and infected cells to prevent clumping and to allow the release of the virus from infected cells (Murray, 919). Minor mutagenic alterations (usually brought about by accumulated point mutations) in HA and/or NA prompts an antigenic drift of both influenza A and B. These two types of antigenic variations (antigenic shift and drift) allow the influenza virus to evade preexisting immunity and evolve into pandemics and epidemics.

The highly contagious influenza virus accounts for many epidemics and pandemics of respiratory illnesses. Some of the milder symptoms of this illness include fever, pharyngitis, rhinitis, cough, myalgia, and malaise. In children, otitis media may develop with influenza. Influenza A has been associated prima-

Suggested Citation:"Appendix 12: Influenza A and B." Institute of Medicine. 2000. Vaccines for the 21st Century: A Tool for Decisionmaking. Washington, DC: The National Academies Press. doi: 10.17226/5501.
×

rily with increased mortality in the elderly population. Therefore, influenza encompasses a variety of clinical responses ranging from asymptomatic or mild respiratory infection to primary viral pneumonia or secondary bacterial pneumonia with fatal outcome.

Recently, epidemics have alternated between those caused primarily by type A and those caused by type B. Both are transmitted by sneezing, coughing, speaking, and also by direct contact through small-particle aerosols. Transmission usually occurs during the initial stages when infected individuals shed substantial amounts of the virus through respiratory secretions. The episodes of winter influenza are partly explained by the ability of small droplets to remain infectious in the cold and in low humidity.

DISEASE BURDEN

Epidemiology

For the purposes of the calculations in this report, the committee estimated that there are approximately 54,000,000 cases of influenza A and B each year in the United States. Incidence rates in children under 14 years of age are over twice that in adults 35 years of age and older. There were approximately 42,250 deaths each year due to influenza, with very high mortality in people 65 years of age and older. See Table A12–1.

Disease Scenarios

For the purposes of the calculation in this report, the committee assumed that 98% of influenza infections are associated with a moderate to severe respiratory illness not requiring hospitalization. It was assumed that most of these infections require only 3 days of bed rest and 2 weeks of mild recovery. Approximately 10% of infections are associated with a more serious sinusitis in conjunction with the 2-week recovery. It was assumed that approximately 5% of influenza infections are associated with a 3-month period of fatigue in addition to the scenario described above. It was assumed that 2% of influenza infections result in hospitalization for pneumonia. It was further assumed that a small number (.1%) of influenza infections exacerbate underlying cardiac or pulmonary conditions. This exacerbation of chronic disease was assumed to be associated with an extra disease burden of 8.5 days of an HUI of .53. See Table A12–2.

COST INCURRED BY DISEASE

Table A12–3 summarizes the health care costs incurred by influenza A and B infections. For the purposes of the calculations in this report, it was assumed

Suggested Citation:"Appendix 12: Influenza A and B." Institute of Medicine. 2000. Vaccines for the 21st Century: A Tool for Decisionmaking. Washington, DC: The National Academies Press. doi: 10.17226/5501.
×

Table A12–1 Incidence and Mortality of Influenza A and B Disease

INCIDENCE RATES

5-Year Age Groups

Total Population

Incidence Rates (per 100,000) (5-yr age groups)

Cases

Age Groups

Population

Incidence Rates (per 100,000)

% Distribution of Cases

0–4

20,182,000

33,700

6,801,334

<1

3,963,000

33,700

0.0246

5–9

19,117,000

39,300

7,512,981

1–4

16,219,000

33,700

0.1006

10–14

18,939,000

30,200

5,719,578

5–14

38,056,000

34,771

0.2435

15–19

17,790,000

30,200

5,372,580

15–24

36,263,000

24,851

0.1658

20–24

18,473,000

19,700

3,639,181

25–34

41,670,000

15,500

0.1189

25–29

19,294,000

15,500

2,990,570

35–44

42,149,000

14,800

0.1148

30–34

22,376,000

15,500

3,468,280

45–54

30,224,000

14,800

0.0823

35–39

22,215,000

14,800

3,287,820

55–64

21,241,000

14,800

0.0579

40–44

19,934,000

14,800

2,950,232

65–74

18,964,000

14,800

0.0517

45–49

16,873,000

14,800

2,497,204

75–84

11,088,000

14,800

0.0302

50–54

13,351,000

14,800

1,975,948

• 85

3,598,000

14,800

0.0098

55–59

11,050,000

14,800

1,635,400

Total

263,435,000

20,627

1.0000

60–64

10,191,000

14,800

1,508,268

 

65–69

10,099,000

14,800

1,494,652

70–74

8,865,000

14,800

1,312,020

75–79

6,669,000

14,800

987,012

80–84

4,419,000

14,800

654,012

• 85

3,598,000

14,800

532,504

Total

263,435,000

 

54,339,576

Suggested Citation:"Appendix 12: Influenza A and B." Institute of Medicine. 2000. Vaccines for the 21st Century: A Tool for Decisionmaking. Washington, DC: The National Academies Press. doi: 10.17226/5501.
×

MORTALITY RATES

5-Year Age Groups

Total Population

Incidence Rates (per 100,000) (5-yr age groups)

Cases

Age Groups

Population

Incidence Rates (per 100,000)

% Distribution of Cases

0–4

20,182,000

2.7

545

<1

3,963,000

2.7

0.0025

5–9

19,117,000

0.9

172

1–4

16,219,000

2.7

0.0104

10–14

18,939,000

0.9

170

5–14

38,056,000

0.9

0.0081

15–19

17,790,000

0.9

160

15–24

36,263,000

1.0

0.0086

20–24

18,473,000

1.1

203

25–34

41,670,000

1.1

0.0108

25–29

19,294,000

1.1

212

35–44

42,149,000

1.1

0.0110

30–34

22,376,000

1.1

246

45–54

30,224,000

10.2

0.0730

35–39

22,215,000

1.1

244

55–64

21,241,000

10.2

0.0513

40–44

19,934,000

1.1

219

65–74

18,964,000

103.5

0.4646

45–49

16,873,000

10.2

1,721

75–84

11,088,000

103.5

0.2716

50–54

13,351,000

10.2

1,362

• 85

3,598,000

103.5

0.0881

55–59

11,050,000

10.2

1,127

Total

263,435,000

16.0

1.0000

60–64

10,191,000

10.2

1,039

 

65–69

10,099,000

103.5

10,452

70–74

8,865,000

103.5

9,175

75–79

6,669,000

103.5

6,902

80–84

4,419,000

103.5

4,574

• 85

3,598,000

103.5

3,724

Total

263,435,000

 

42,250

Suggested Citation:"Appendix 12: Influenza A and B." Institute of Medicine. 2000. Vaccines for the 21st Century: A Tool for Decisionmaking. Washington, DC: The National Academies Press. doi: 10.17226/5501.
×

Table A12–2 Disease Scenarios for Influenza A and B Infection

 

No. of Cases

% of Cases

Committee HUI Values

Duration (years)

Moderate to severe respiratory illness

45,264,867

83.30%

 

bed rest

 

0.75

0.0082 (3 days)

discomfort following bed rest

 

0.90

0.0384 (14 days)

Respiratory illness with sinusitis

5,325,278

9.80%

 

bed rest

 

0.75

0.0082 (3 days)

sinusitis

 

0.75

0.0192 (7 days)

discomfort following bed rest

 

0.90

0.0192 (7 days)

Respiratory illness w/post-influenza fatigue

2,662,639

4.90%

 

bed rest

 

0.75

0.0082 (3 days)

discomfort following bed rest

 

0.90

0.0384 (14 days)

post-influenza fatigue

 

0.87

0.2466 (90 days)

Pneumonia

978,112

1.80%

 

acute care hospitalization

 

0.65

0.0274 (10 days)

recuperation

 

0.90

0.0384 (14 days)

Pneumonia—ICU

108,679

0.20%

 

ICU hospitalization

 

0.52

0.0274 (10 days)

recuperation

 

0.90

0.0384 (14 days)

Exacerbation of underlying asthma/heart disease

54,340

0.10%

0.53

0.0233 (8.5 days)

that everyone requiring bed rest for acute influenza infection incurs costs for an over-the-counter symptomatic treatment. The cost calculations include one visit to a physician and a prescription medication for 20% of the patients during the acute phase. Recovery phases were assumed to include costs for over-the-counter medications and physician visits for some of the patients with sinusitis and post-influenza fatigue. Hospitalization costs, diagnostics, inpatient and with outpatient physician visits, and medications were included costs for patients with pneumonia. There were no costs calculated for the exacerbation of underlying chronic disease states by influenza infection with pneumonia.

Suggested Citation:"Appendix 12: Influenza A and B." Institute of Medicine. 2000. Vaccines for the 21st Century: A Tool for Decisionmaking. Washington, DC: The National Academies Press. doi: 10.17226/5501.
×

Table A12–3 Health Care Costs Associated with Influenza A and B Disease

 

% with Care

Cost per Unit

Units per Case

Form of Treatment

Moderate to severe respiratory illness

 

bed rest

50%

$50

1.0

physician a

 

20%

$50

1.0

medication b

100%

$10

1.0

medication a

discomfort following bed rest

50%

$10

1.0

medication a

Respiratory illness with sinusitis

 

bed rest

50%

$50

1.0

physician a

 

20%

$50

1.0

medication b

100%

$10

1.0

medication a

sinusitis

50%

$50

1.0

medication b

 

100%

$10

1.0

medication a

discomfort following bed rest

50%

$50

1.0

physician a

Respiratory illness with post-influenza fatigue

 

bed rest

50%

$50

1.0

physician a

 

50%

$50

1.0

medication b

100%

$10

1.0

medication a

discomfort following bed rest

50%

$10

1.0

medication a

post-influenza fatigue

50%

$50

1.0

physician a

Pneumonia

 

acute care and ICU together

100%

$50

1.0

physician a

percentage of cases adjusted

100%

$4,000

1.0

hospitalization

 

100%

$100

1.0

physician b

100%

$100

1.0

diagnostic b

recuperation

100%

$50

1.0

physician a

 

100%

$50

1.0

medication b

100%

$10

1.0

medication a

VACCINE DEVELOPMENT

The committee assumed that it will take 7 years until licensure of a influenza vaccine and that $360 million needs to be invested. The committee assumed that the licensed vaccine would most likely be a DNA vaccine requiring immunization every 5 years. Table 4–1 summarizes vaccine development assumptions for all vaccines considered in this report.

Suggested Citation:"Appendix 12: Influenza A and B." Institute of Medicine. 2000. Vaccines for the 21st Century: A Tool for Decisionmaking. Washington, DC: The National Academies Press. doi: 10.17226/5501.
×

VACCINE PROGRAM CONSIDERATIONS

Target Population

For the purposes of the calculations in this report, it is assumed that the target population for this vaccine is one-fifth of the entire population every year. It was assumed that 30% of the target population would utilize the vaccine.

Vaccine Schedule, Efficacy, and Costs

For the purposes of the calculations in this report, it was estimated that this vaccine would cost $50 per dose and that administration costs would be $10 per dose. It was assumed that 1 dose would be required every 5 years. It is assumed that the current influenza immunization program would no longer be needed. Default assumption of 75% effectiveness were accepted. Table 4–1 summarizes vaccine program assumptions for all vaccines considered in this report.

RESULTS

If a vaccine program for influenza were implemented today and the vaccine was 100% efficacious and utilized by 100% of the target population, the annualized present value of the QALYs gained would be 800,000. Using committee assumptions of less-than-ideal efficacy and utilization and including time and monetary costs until a vaccine program is implemented, the annualized present value of the QALYs gained would be 125,000.

If a vaccine program for influenza were implemented today and the vaccine was 100% efficacious and utilized by 100% of the target population, the annualized present value of the health care costs saved would be $6.4 billion. Using committee assumptions of less-than-ideal efficacy and utilization and including time and monetary costs until a vaccine program is implemented, the annualized present value of the health care costs saved would be $1 billion.

If a vaccine program for influenza were implemented today and the vaccine was 100% efficacious and utilized by 100% of the target population, the annualized present value of the program cost would be $3.2 billion. Using committee assumptions of less-than-ideal efficacy and utilization and including time and monetary costs until a vaccine program is implemented, the annualized present value of the program cost would be $430 million.

Using committee assumptions of time and costs until licensure, the fixed cost of vaccine development has been amortized and is $10.8 million for an influenza vaccine.

Suggested Citation:"Appendix 12: Influenza A and B." Institute of Medicine. 2000. Vaccines for the 21st Century: A Tool for Decisionmaking. Washington, DC: The National Academies Press. doi: 10.17226/5501.
×

If a vaccine program were implemented today and the vaccine were 100% efficacious and utilized by 100% of the target population, the annualized present value of the cost per QALY gained is -$4,000. A negative value represents a saving in costs in addition to a saving in QALYs. Using committee assumptions of less-than-ideal utilization and including time and monetary costs until a vaccine program is implemented, the annualized present value of the cost per QALY gained is -$4,500.

See Chapters 4 and 5 for details on the methods and assumptions used by the committee for the results reported.

READING LIST

Barker WH. Excess Pneumonia and Influenza Associated Hospitalization during Influenza Epidemics in the United States, 1970–78. American Journal of Public Health 1986; 76:761–765.

Betts RF. Influenza Virus. In: Principles and Practice of Infectious Diseases. GL Mandell, JE Bennett, Dolin R eds. New York, NY: Churchill Livingstone, 1995, pp. 1546–1567.


CDC. Influenza Surveillance—United States, 1992–3 and 1993–4. Morbidity and Mortality Weekly Report 1997; 46:1–12.

CDC. Prevention and Control of Influenza. Morbidity and Mortality Weekly Report 1996; 45:9–24.

CDC. Prevention and Control of Influenza. Morbidity and Mortality Weekly Report 1997; 46:1–25.


Glezen WP. Influenza in an urban area. Canadian Journal of Infectious Diseases 1993; 4:272–4.

Glezen WP, Cherry JD. Influenza Viruses. In: Textbook of Pediatric Infectious Diseases. RD Feigin and JD Cherry eds. Philadelphia, PA: WB Saunder Company, 1992, pp. 1688–1704.

Glezen WP, Couch RB. Influenza Viruses. In: Virus Infections of Humans. Evans AS, ed. 3rd ed. New York, NY: Plenum Medical Book Company, 1989.

Gruber WC, Belshe RB, King JC. Evaluation of Live Attenuated Influenza Vaccines in Children 6–18 Months of Age: Safety, Immunogenicity, and Efficacy. The Journal of Infectious Diseases 1996; 173:1313–1319.


Marwick C. Facing Inevitable Future Flu Seasons, Experts Set 1996 Vaccine and Plan for Unpredictable Pandemic. JAMA 1995; 273:1079–1080.

McBean AM, Babish JD, Warren JL. The Impact and Cost of Influenza in the Elderly. Archives of Internal Medicine 1993; 153:2105–2111.

Mullooly JP, Bennett MD, Hornbrook MC, et al. Influenza Vaccination Programs for Elderly Persons: Cost-effectiveness in a Health Maintenance Organization. Annals of Internal Medicine 1994; 121:947–952.


Nichol KL, Lind A, Margolis KL, et al. The Effectiveness of Vaccination Against Influenza in Healthy, Working Adults. The New England Journal of Medicine 1995; 333:889–893.

Suggested Citation:"Appendix 12: Influenza A and B." Institute of Medicine. 2000. Vaccines for the 21st Century: A Tool for Decisionmaking. Washington, DC: The National Academies Press. doi: 10.17226/5501.
×

Nichol KL, Margolis KL, Wuorenma J, et al. The Efficacy and Cost Effectiveness of Vaccination Against Influenza Among Elderly Persons Living in the Community. The New England Journal of Medicine 1994; 331:778–784.


Patriarca PA, Strikas RA. Influenza Vaccine for Healthy Adults? The New England Journal of Medicine 1995; 333:933–934.


Sullivan KM, Monto AS, Longini IM. Estimates of the U.S. Health Impact of Influenza. American Journal of Public Health 1993; 83:1712–1716.

Suggested Citation:"Appendix 12: Influenza A and B." Institute of Medicine. 2000. Vaccines for the 21st Century: A Tool for Decisionmaking. Washington, DC: The National Academies Press. doi: 10.17226/5501.
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Suggested Citation:"Appendix 12: Influenza A and B." Institute of Medicine. 2000. Vaccines for the 21st Century: A Tool for Decisionmaking. Washington, DC: The National Academies Press. doi: 10.17226/5501.
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Suggested Citation:"Appendix 12: Influenza A and B." Institute of Medicine. 2000. Vaccines for the 21st Century: A Tool for Decisionmaking. Washington, DC: The National Academies Press. doi: 10.17226/5501.
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Suggested Citation:"Appendix 12: Influenza A and B." Institute of Medicine. 2000. Vaccines for the 21st Century: A Tool for Decisionmaking. Washington, DC: The National Academies Press. doi: 10.17226/5501.
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Suggested Citation:"Appendix 12: Influenza A and B." Institute of Medicine. 2000. Vaccines for the 21st Century: A Tool for Decisionmaking. Washington, DC: The National Academies Press. doi: 10.17226/5501.
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Suggested Citation:"Appendix 12: Influenza A and B." Institute of Medicine. 2000. Vaccines for the 21st Century: A Tool for Decisionmaking. Washington, DC: The National Academies Press. doi: 10.17226/5501.
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Suggested Citation:"Appendix 12: Influenza A and B." Institute of Medicine. 2000. Vaccines for the 21st Century: A Tool for Decisionmaking. Washington, DC: The National Academies Press. doi: 10.17226/5501.
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Suggested Citation:"Appendix 12: Influenza A and B." Institute of Medicine. 2000. Vaccines for the 21st Century: A Tool for Decisionmaking. Washington, DC: The National Academies Press. doi: 10.17226/5501.
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Suggested Citation:"Appendix 12: Influenza A and B." Institute of Medicine. 2000. Vaccines for the 21st Century: A Tool for Decisionmaking. Washington, DC: The National Academies Press. doi: 10.17226/5501.
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Suggested Citation:"Appendix 12: Influenza A and B." Institute of Medicine. 2000. Vaccines for the 21st Century: A Tool for Decisionmaking. Washington, DC: The National Academies Press. doi: 10.17226/5501.
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Suggested Citation:"Appendix 12: Influenza A and B." Institute of Medicine. 2000. Vaccines for the 21st Century: A Tool for Decisionmaking. Washington, DC: The National Academies Press. doi: 10.17226/5501.
×
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Vaccines have made it possible to eradicate the scourge of smallpox, promise the same for polio, and have profoundly reduced the threat posed by other diseases such as whooping cough, measles, and meningitis.

What is next? There are many pathogens, autoimmune diseases, and cancers that may be promising targets for vaccine research and development.

This volume provides an analytic framework and quantitative model for evaluating disease conditions that can be applied by those setting priorities for vaccine development over the coming decades. The committee describes an approach for comparing potential new vaccines based on their impact on morbidity and mortality and on the costs of both health care and vaccine development. The book examines:

  • Lessons to be learned from the polio experience.
  • Scientific advances that set the stage for new vaccines.
  • Factors that affect how vaccines are used in the population.
  • Value judgments and ethical questions raised by comparison of health needs and benefits.

The committee provides a way to compare different forms of illness and set vaccine priorities without assigning a monetary value to lives. Their recommendations will be important to anyone involved in science policy and public health planning: policymakers, regulators, health care providers, vaccine manufacturers, and researchers.

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