IOM Vaccine Candidates- 2000

Syphilis is a prominent example of an infection in the immunocompetent host that poses both a substantial disease burden and a substantial expenditure of public health resources in the United States, and against which the development of a vaccine seems unlikely in the near future. The late 1980s saw a dramatic resurgence of syphilis, especially among women (with a parallel increase in congenitally acquired infections) and among ethnic minority groups in urban areas. At least 20,000 cases of primary or secondary syphilis are reported each year, but it is estimated that only one in three or four cases is reported. Because this is a sexually transmitted infection, both the infected individual and the exposed sexual partner require counseling, diagnostic testing, treatment, and follow-up testing.

The causative agent, T. pallidum, has a complex morphology and composition. An outer membrane surrounds the endoflagella, cytoplasmic membrane, and the protoplasmic cylinder. It also is believed that T. pallidum has a glycosaminoglycan surface layer that is antiphagocytic. The organism also has more than 15 major protein constituents, some of which are covalently linked to fatty acids. The outer membrane consists of a lipid bilayer, presumably with few proteins. However, the precise cellular locations of these antigens and the identities of nonprotein constituents remain controversial.

Humoral immunity in syphilis has been studied for nearly a century. Human infection uniformly invokes immunoglobulin G (IgG) and IgM antibodies to a wide variety of T. pallidumproteins, but that infection progresses to secondary and eventually tertiary manifestations unless specific therapy is administered. Passive administration of serum from rabbits recovering from experimental infection attenuates but does not prevent infection. This finding and other evidence suggest that humoral immunity is not sufficient for the prevention of infection, and recent data indicate that cellular immune mechanisms are considerably more important. Thus, most experts conclude that despite the impressive disease burden attributable to syphilis, there is insufficient knowledge concerning mechanisms of protective immunity to T. pallidum to propose that a vaccine be developed in the near future.

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COST INCURRED BY DISEASE

Health care costs are incurred through diagnostic evaluation, physician visits, and antibiotics. Table A1–3 summarizes the health care costs incurred by borrelia infections. For the purposes of the calculations, it was assumed that all people with acute manifestations incur two physician visits and a prescription antibiotic, and that half receive diagnostic tests. It was assumed that each recurrence is associated with two physician visits and a prescription medication, and that the recurrences occur for 10 years.

VACCINE DEVELOPMENT

The committee assumed that the development of a Borrelia burgdorferi vaccine is feasible and that licensure is imminent (a Borrelia vaccine for use in persons 15 years of age and older was licensed prior to the completion of this report). The estimates for this report are that it will take 3 years until licensure is completed and that $120 million needs to be invested. Table 4–1 summarizes vaccine development assumptions for all vaccines considered in this report.

VACCINE PROGRAM CONSIDERATIONS

Target Population

The committee’s analysis assumes that immunization with this vaccine will occur only in those geographic regions discussed under the epidemiology section. Immunization will occur during infancy or within 1 year of migration to the area. It is estimated that 90% of infants will receive the immunization. The committee estimates that only 10% of migrants into an area will receive the immunization.

Vaccine Schedule, Efficacy, and Costs

The committee estimated that this vaccine would cost $100 per dose. Vaccine administration would cost an additional $10. The committee has accepted default assumptions for this vaccine that estimate it will require a series of 3 doses and that efficacy will be 75%. Table 4–1 summarizes vaccine program assumptions for all vaccines considered in this report.

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Table A1–2 Borrelia burgdorferi

Table A1–3 Health Care Costs—Borrelia burgdorferi

RESULTS

If a vaccine program for B. burgdorferi 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 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 39.

If a vaccine program for B. burgdorferi 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 $2 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 $410,000.

If a vaccine program for B. burgdorferi 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 $690 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 $280 million.

Using committee assumptions of time and costs until licensure, the fixed cost of vaccine development has been amortized and is $3.6 million for a B. burgdorferi 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 $3.5 million. 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 $7.3 million.

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

READING LIST

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.

CDC. Summary of Notifiable Diseases, United States 1994. Morbidity and Mortality Weekly Report 1994; 43:1–80.

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.

Stechenberg BW. Borrelia: Lyme Disease. In: Textbook of Pediatric Infectious Diseases. RD Feigin and JD Cherry eds. Philadelphia, PA: WB Saunder Company, 1992, pp. 1062–1067.

Steere AC. Borrelia burgdorferi (Lyme Disease, Lyme Borreliosis). In: Principles and Practice of Infectious Diseases. GL Mandell, JE Bennett, Dolin R eds. New York: Churchill Livingstone, 1995, pp. 2143–2155.

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

Wormser GP. Prospects for a Vaccine to Prevent Lyme Disease in Humans. Clinical Infectious Diseases 1995; 21:1267–1274.

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