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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-
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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
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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
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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
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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.
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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.
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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.
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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
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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.
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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.
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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.
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Representative terms from entire chapter:
target population