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

Chapter: Appendix 10: Histoplasma capsulatum

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Suggested Citation:"Appendix 10: Histoplasma capsulatum." 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 10
Histoplasma capsulatum

Histoplasmosis is a common pulmonary mycosis of humans and animals. It is caused by Histoplasma capsulatum, a dimorphic soil fungus that is isolated from soil with high nitrogen concentrations. It has a definite association with the droppings of bat and avian habitats.

Histoplasmosis occurs at highest incidence in central and eastern areas of the United States, in particular the Ohio River Valley and portions of the Mississippi Valley.

DISEASE BURDEN

Epidemiology

For the purposes of the calculations in this report, the committee estimated that there are 500,000 new infections with Histoplasma capsulatum each year in the United States. The incidence rate varies with age; the highest incidence is seen in people between 15 and 34 years of age. H. capsulatum infections are clustered geographically. The committee estimated that half of the infections occur in people born in the region and half occur in migrants into the area. The infections was associated with an average mortality rate of 0.05 per 100,000 (138 deaths per year). See Table A10–1.

See Appendix 28 for more information.

Suggested Citation:"Appendix 10: Histoplasma capsulatum." 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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Table A10–1 Incidence and Mortality Rates for Histoplasma Infection

Age Groups

Population

Incidence Rates (per 100,000)

% Distribution of Cases

<1

3,963,000

79.28

0.0063

1–4

16,219,000

79.28

0.0257

5–14

38,056,000

105.11

0.0800

15–24

36,263,000

348.84

0.2530

25–34

41,670,000

325.17

0.2710

35–44

42,149,000

161.33

0.1360

45–54

30,224,000

163.78

0.0990

55–64

21,241,000

174.19

0.0740

65–74

18,964,000

102.83

0.0390

75–84

11,088,000

54.47

0.0121

85+

3,598,000

54.47

0.0039

Total

263,435,000

189.80

1.000

 

500,000 cases

 

Age Groups

Population

Mortality Rates (per 100,000)

% Distribution of Deaths

<1

3,963,000

0.04

0.0114

1–4

16,219,000

0.01

0.0093

5–14

38,056,000

0.01

0.0290

15–24

36,263,000

0.03

0.0918

25–34

41,670,000

0.03

0.0983

35–44

42,149,000

0.08

0.2467

45–54

30,224,000

0.08

0.1796

55–64

21,241,000

0.09

0.1342

65–74

18,964,000

0.10

0.1415

75–84

11,088,000

0.05

0.0438

85+

3,598,000

0.05

0.0142

Total

263,435,000

0.05

1.0000

 

138 deaths

 

Disease Scenarios

For the purposes of the calculation in this report, the committee assumed that most infections are asymptomatic. Half of symptomatic infections were presumed to be associated with a mild flu-like illness. Other manifestations include pneumonitis, disseminated disease, and chronic pulmonary disease. Outpatient treatment of pneumonitis was associated with both inpatient and outpatient treatment. Disseminated histoplasma was associated with an acute and severe phase of illness followed by a more moderate but lengthy recovery. Health utility indexes associated with histoplasma disease range from .9 for a mild flu-like illness to .39 for the acute illness associated with disseminated disease. Table A10–2 shows the HUI and duration associated with the disease scenarios used in the calculations for the report.

Suggested Citation:"Appendix 10: Histoplasma capsulatum." Institute of Medicine. 2000. Vaccines for the 21st Century: A Tool for Decisionmaking. Washington, DC: The National Academies Press. doi: 10.17226/5501.
×

COST INCURRED BY DISEASE

Table A10–3 summarizes the health care costs incurred by histoplasma infections. For the purposes of the calculations in this report, it was assumed that all patients with flu-like illness associated with histoplasma infection require outpatient care of a physician and that half receive medications or diagnostics. All patients with pneumonitis were assumed to incur costs associated with specialist visits and diagnostics. Inpatient hospital costs are included for a small fraction of these patients. It was assumed that half of the patients with disseminated disease would require hospitalization. All patients with disseminated disease would require outpatient treatment lasting several months and including 8 visits to a specialist and expensive medication and diagnostic costs. Approximately 40% of patients with chronic pulmonary disease would require hospitalization and all of the patients would require outpatient treatment similar to that estimated for disseminated disease but for 3 times the duration and cost.

VACCINE DEVELOPMENT

The committee assumed that it will take 15 years until licensure of a histoplasma 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 all infants in endemic regions (approximately 900,000 annually) and migrants into the area (approximately 1,300,000 annually at an average age of 28.9 per migrant vaccinee). It was assumed that 90% of the infants born in the region and 10% of migrants 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. 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.

Suggested Citation:"Appendix 10: Histoplasma capsulatum." Institute of Medicine. 2000. Vaccines for the 21st Century: A Tool for Decisionmaking. Washington, DC: The National Academies Press. doi: 10.17226/5501.
×

Table A10–2 Disease Scenarios for Histoplasma Infection

 

No. of Cases

% of Cases

Committee HUI Values

Duration (years)

Total Deaths

138

 

Total Cases (new symptomatic and asymptomatic infections)

500,000

 

Asymptomatic

 

90%

1.00

 

Flu-like illness

 

5.0%

0.90

0.0384 (14 days)

Pneumonitis: outpatient only

 

3.5%

0.78

0.0384 (14 days)

Pneumonitis: w/ inpatient

 

0.9%

 

inpatient care

 

0.67

0.0274 (10 days)

outpatient care

 

0.78

0.0384 (14 days)

Disseminated histoplasmosis

 

0.5%

 

disseminated intravascular coagulation, splenomegaly, hepatomegaly, fever

 

0.39

0.0192 (7 days)

recovery

 

0.90

0.2500 (3 months)

Chronic pulmonary

 

0.1%

 

symptomatic, untreated

 

0.90

0.1667 (2 months)

outpatient treatment

 

0.90

0.7500 (9 months)

RESULTS

If a vaccine program for H. capsulatum 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 1,200. 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 35.

If a vaccine program for H. capsulatum 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 $29.7 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 $860,000.

If a vaccine program for H. capsulatum 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 $390 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 $12.7 million.

Suggested Citation:"Appendix 10: Histoplasma capsulatum." Institute of Medicine. 2000. Vaccines for the 21st Century: A Tool for Decisionmaking. Washington, DC: The National Academies Press. doi: 10.17226/5501.
×

Table A10–3 Health Care Costs Associated with Histoplasma Disease

 

% with Care

Cost per Unit

Units per Case

Form of treatment

Flu-like illness

 

(single state)

100%

$50

2.0

physician a

 

50%

$150

1.0

medication b, diagnostic b

Pneumonitis: outpatient only

 

(single state)

100%

$350

1.0

outpatient treatment 2 physician b, medication b, diagnostic b

Pneumonitis: w/ inpatient

 

inpatient care

100%

$5,000

1.0

hospitalization

outpatient care

100%

$350

1.0

outpatient treatment (same as above)

Disseminated histoplasmosis

 

disseminated intravascular coagulation, splenomegaly, hepatomegaly, fever

50%

$5,000

1.0

hospitalization

outpatient only

50%

$1,250

1.0

outpatient—3 months (8 physician b, 3 medicaion c)

recovery

50%

$1,250

1.0

outpatient—3 months

Chronic pulmonary

 

symptomatic (untreated, initial treatment)

40%

$5,000

1.0

hospitalization

outpatient treatment

100%

$1,250

3.0

outpatient (same as for disseminated disease)

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 H. capsulatum 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 $300,000. 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 $600,000.

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

Suggested Citation:"Appendix 10: Histoplasma capsulatum." Institute of Medicine. 2000. Vaccines for the 21st Century: A Tool for Decisionmaking. Washington, DC: The National Academies Press. doi: 10.17226/5501.
×

READING LIST

Bullock WE. Histoplasma Capsulatum. In: Principles and Practice of Infectious Diseases. GL Mandell, JE Bennett, Dolin R eds. New York, NY: Churchill Livingstone, 1995, pp. 2340–2353.

Byerly E, Deardorff K. National and State Population Estimates: 1990 to 1994, U.S. Bureau of the Census, Current Population Reports, pp. 25–1127, U.S. Government Printing Office, Washington, DC, 1995.


Hansen KA. Geographical Mobility: March 1993 to March 1994, U.S. Bureau of the Census, Current Population Reports, pp. 20–485, U.S. Government Printing Office, Washington, DC, 1995.


Leissa B, Widerman BL. Histoplasmosis. In: Textbook of Pediatric Infectious Diseases. RD Feigin and JD Cherry eds. Philadelphia, PA: WB Saunder Company, 1992, pp. 1952–1964.


Ventura SJ, Martin JA, Mathews TJ, et al. Advance Report of Final Natality Statistics, 1994. Monthly Vital Statistics Report 1996; 44.

Suggested Citation:"Appendix 10: Histoplasma capsulatum." Institute of Medicine. 2000. Vaccines for the 21st Century: A Tool for Decisionmaking. Washington, DC: The National Academies Press. doi: 10.17226/5501.
×
Page 207
Suggested Citation:"Appendix 10: Histoplasma capsulatum." Institute of Medicine. 2000. Vaccines for the 21st Century: A Tool for Decisionmaking. Washington, DC: The National Academies Press. doi: 10.17226/5501.
×
Page 208
Suggested Citation:"Appendix 10: Histoplasma capsulatum." Institute of Medicine. 2000. Vaccines for the 21st Century: A Tool for Decisionmaking. Washington, DC: The National Academies Press. doi: 10.17226/5501.
×
Page 209
Suggested Citation:"Appendix 10: Histoplasma capsulatum." Institute of Medicine. 2000. Vaccines for the 21st Century: A Tool for Decisionmaking. Washington, DC: The National Academies Press. doi: 10.17226/5501.
×
Page 210
Suggested Citation:"Appendix 10: Histoplasma capsulatum." Institute of Medicine. 2000. Vaccines for the 21st Century: A Tool for Decisionmaking. Washington, DC: The National Academies Press. doi: 10.17226/5501.
×
Page 211
Suggested Citation:"Appendix 10: Histoplasma capsulatum." Institute of Medicine. 2000. Vaccines for the 21st Century: A Tool for Decisionmaking. Washington, DC: The National Academies Press. doi: 10.17226/5501.
×
Page 212
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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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