APPENDIX 16
Mycobacterium tuberculosis
In the majority of infected individuals, the primary lesions of mycobacterium tuberculosis (TB) heal completely and leave no clinical evidence of prior infection except hypersensitivity to tuberculin. In some however, the primary infection progresses directly and evolves into a pneumonic process as the organisms spread through the bronchi or when a tuberculous node ruptures into a bronchus. Contiguous spread can cause infection in the pleural and pericardial spaces. At this stage, pleurisy, which is usually abrupt and resembles bacterial pneumonia with fever, chest pain, and shortness of breath are present.
Secondary tuberculosis is usually caused by organisms seeded in the apices of the lungs during the primary infection. These foci may evolve soon after seeding or after a long period of dormancy. Small patches of pneumonia develop around the foci. As the disease progresses, there is an insidious onset and development of nonspecific symptoms such as fatigue, fever, anorexia, night sweats, and general wasting. Cough and sputum denote more advanced disease.
Miliary tuberculosis occurs when the tubercle bacilli gain access to the lymphatics and bloodstream and seed distant organs. Miliary lesions may develop in almost any organ of the body, but of the most favored sites are bones and joints, the genitourinary tract, meninges, lymph nodes, and peritoneum. Miliary tuberculosis in its primary infection stage, when associated with meningitis, is responsible for deaths in young children.
See Appendix 28 for more information.
DISEASE BURDEN
Epidemiology
For the purposes of the calculations in this report, the committee estimated that there are approximately 23,000 new cases of mycobacterium tuberculosis (TB) in the United States each year. It was assumed that incidence of TB infection increases with age. It is assumed that half the cases occur in people belonging to a high-risk group and half occur in people in multi-drug resistant areas. It was estimated that there are approximately 1,500 deaths associated with TB annually. See Table A16–1.
Disease Scenarios
For the purposes of the calculation in this report, the committee assumed that most cases of TB infection result in pulmonary disease. Extrapulmonary disease is seen in the remaining 12% of infected people. The health utility index (HUI) was assumed to range from 1.0 for treatment of asymptomatic people (described below) to .89 for the 9-month treatment phase for pulmonary TB and .72 for 20 days of severe extrapulmonary TB (including hospitalization). See Table A16–2.
COST INCURRED BY DISEASE
Table 16–3 summarizes the health care costs incurred by TB infections. For the purposes of the calculations in this report, it was assumed that costs are incurred for both active and asymptomatic (suspected and latent) cases of TB. It is assumed that for every case of confirmed, active TB disease, treatment for 3 to 5 asymptomatic (suspected or latent) cases of TB is required until TB infection is confirmed. Asymptomatic, latent infections require additional treatment. These treatments are assumed to include two visits to a general physician, three visits to a nurse, diagnostic evaluation, and medications. Although the model assumes that all suspected cases of TB undergo the care described above, it is assumed that adherence to a 6-month treatment regime for latent infections is not complete (e.g., that 40% of patients take medications for only 3 months).
Health care costs incurred for pulmonary and extrapulmonary TB are assumed to involve hospitalization followed by 9 months of outpatient treatment. This follow-up involves monthly costs for a physician visit, diagnostic evaluation, and medication.
Table A16–1 Incidence and Mortality Rates of TB Infections
Age Groups |
Population |
Incidence Rates (per 100,000) |
% Distribution of Cases |
Cases |
<1 |
3,963,000 |
2.66 |
0.0046 |
106 |
1–4 |
16,219,000 |
2.66 |
0.0189 |
432 |
5–14 |
38,056,000 |
2.66 |
0.0445 |
1,014 |
15–24 |
36,263,000 |
4.69 |
0.0746 |
1,700 |
25–34 |
41,670,000 |
9.82 |
0.1794 |
4,090 |
35–44 |
42,149,000 |
9.82 |
0.1815 |
4,137 |
45–54 |
30,224,000 |
11.63 |
0.1542 |
3,515 |
55–64 |
21,241,000 |
11.63 |
0.1084 |
2,470 |
65–74 |
18,964,000 |
15.85 |
0.1318 |
3,005 |
75–84 |
11,088,000 |
15.85 |
0.0771 |
1,757 |
85+ |
3,598,000 |
15.85 |
0.0250 |
570 |
Total |
263,435,000 |
8.65 |
1.0000 |
22,795 |
Age Groups |
Population |
Mortality Rates (per 100,000) |
% Distribution of Cases |
Cases |
<1 |
3,963,000 |
0.00 |
0.0000 |
0 |
1–4 |
16,219,000 |
0.02 |
0.0020 |
3 |
5–14 |
38,056,000 |
0.00 |
0.0007 |
1 |
15–24 |
36,263,000 |
0.04 |
0.0102 |
15 |
25–34 |
41,670,000 |
0.18 |
0.0495 |
73 |
35–44 |
42,149,000 |
0.33 |
0.0928 |
137 |
45–54 |
30,224,000 |
0.50 |
0.1030 |
152 |
55–64 |
21,241,000 |
0.96 |
0.1382 |
204 |
65–74 |
18,964,000 |
1.65 |
0.2121 |
313 |
75–84 |
11,088,000 |
3.22 |
0.2419 |
357 |
85+ |
3,598,000 |
6.14 |
0.1497 |
221 |
Total |
263,435,000 |
0.56 |
1.0000 |
1,476 |
VACCINE DEVELOPMENT
The committee assumed that it will take 15 years until licensure of a TB vaccine and that $360 million needs to be invested. Table 4–1 summarizes vaccine development assumptions for all vaccines considered in this report.
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 500,000 high-risk people. 300,000 of those people are high-risk individuals in multi-drug-resistant areas. It was assumed that 90% of the selective high-risk population would utilize the vaccine and that
Table A16–2 Disease Scenarios for TB Infection
|
No. of Cases |
% of Cases |
Committee HUI Values |
Duration (years) |
Total Deaths (from acute infection) |
1,476 |
|
||
Total Cases (reported) |
22,795 |
|
||
Asymptomatic—suspect suspect cases (treatment begun) |
68,385 |
300.00% |
1.0000 |
0.2500 (3 months) |
Asymptomatic—latent infection preventive treatment for latent infection |
113,975 |
500.00% |
1.0000 |
0.5000 (6 months) |
Pulmonary TB inpatient |
20,060 |
88.00% |
0.8700 |
0.0548 (20 days) |
Pulmonary TB outpatient |
19,057 |
83.60% |
0.8900 |
0.7500 (9 months) |
Extrapulmonary TB inpatient |
2,735 |
12.00% |
0.7200 |
0.0548 (20 days) |
Extrapulmonary TB outpatient |
2,462 |
10.80% |
0.8600 |
0.7500 (9 months) |
60% of the targeted population in multi-drug-resistant areas would receive 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. Default assumptions of a 3-dose series and 75% effectiveness were accepted. Table 4–1 summarizes vaccine program assumptions for all vaccines considered in this report.
RESULTS
If a vaccine program for TB 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 $4,000. 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 1,300.
Table A16–3 Health Care Costs Associated with TB Infection
|
% with Care |
Cost per Unit |
Units per Case |
Form of Treatment |
Asymptomatic—suspect |
|
|||
treated (detected in screening, etc.) |
|
|||
suspect cases: 3 months treatment until culture results available |
100% |
$50 |
2.0 |
physician a |
|
100% |
$25 |
3.0 |
nurse visit |
100% |
$50 |
1.0 |
diagnostic a |
|
100% |
$50 |
3.0 |
medication b |
|
Asymptomatic—latent |
|
|||
treated (detected in screening, etc.) |
75% |
$50 |
3.0 |
physician a |
preventive treatment for latent infection: 6 months |
75% |
$25 |
6.0 |
nurse visit |
estimated 60% complete treatment; rest complete half of treatment |
100% |
$50 |
1.0 |
diagnostic a |
|
60% |
$50 |
6.0 |
medication b: completes course |
40% |
$50 |
3.0 |
medication b: completes half course |
|
Pulmonary TB |
|
|||
inpatient |
100% |
$6,000 |
1.0 |
hospitalization |
|
100% |
$100 |
3.0 |
physician b |
100% |
$50 |
1.0 |
diagnostic a |
|
25% |
$500 |
1.0 |
diagnostic c |
|
Pulmonary TB |
|
|||
outpatient |
100% |
$50 |
9.0 |
physician a |
|
100% |
$50 |
9.0 |
diagnostic a |
100% |
$50 |
9.0 |
medication b |
|
Extrapulmonary TB |
|
|||
inpatient |
100% |
$6,000 |
1.0 |
hospitalization |
|
100% |
$100 |
3.0 |
physician b |
100% |
$50 |
1.0 |
diagnostic b |
|
25% |
$500 |
1.0 |
diagnostic c |
|
Extrapulmonary TB |
|
|||
outpatient |
100% |
$50 |
9.0 |
physician a |
|
100% |
$50 |
9.0 |
diagnostic a |
100% |
$50 |
9.0 |
medication b |
If a vaccine program for TB 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 $100 million. 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 $34.2 million.
If a vaccine program for TB 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 $90 million. 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 $35.9 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 a TB vaccine.
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 −$3,000. 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 $9,500.
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. The Role of BCG Vaccine in the Prevention and Control of Tuberculosis in the United States. Morbidity and Mortality Weekly Report 1996; 45:1–18.
CDC. Tuberculosis Morbidity—United States, 1995. Morbidity and Mortality Weekly Report 1996; 45:365–370.
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