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Aplisol (Tuberculin) - Description and Clinical Pharmacology

 
 



DESCRIPTION

Aplisol (tuberculin PPD, diluted) is a sterile aqueous solution of a purified protein fraction for intradermal administration as an aid in the diagnosis of tuberculosis. The solution is stabilized with polysorbate (Tween) 80, buffered with potassium and sodium phosphates and contains approximately 0.35% phenol as a preservative. This product is ready for immediate use without further dilution.

The purified protein fraction is isolated from culture media filtrates of a human strain of Mycobacterium tuberculosis by the method of F.B. Seibert. 1,2 Tuberculin PPD, diluted, is prepared from Tuberculin PPD Powder Master Lot 154616 which is clinically bioequivalent in potency to the standard PPD-S* (5 TU** per 0.1mL) of the U.S. Public Health Service, National Centers for Disease Control. This product is made from a single master lot (No. 154616) to eliminate lot to lot variation inherent in manufacturing.

The potency of each lot of tuberculin PPD, diluted is determined in sensitized guinea pigs.

CLINICAL PHARMACOLOGY

In the United States, the prevalence of Mycobacterium tuberculosis infection and active disease varies for different segments of the population; however, the risk for M. tuberculosis infection in the overall population is low. Tuberculosis (TB) case rates declined steadily for decades in the United States. However, in 1985 the TB case rate stabilized and subsequently increased through 1992, accompanied by a 14% increase in the TB mortality rate in 1988. This has been attributed to several complex social and medical factors, including the human immunodeficiency virus (HIV) epidemic, the occurrence of TB in foreign-born persons from countries that have a high prevalence of TB, the emergence of drug-resistant strains of TB, and the transmission of M. tuberculosis in congregate settings. (e.g., health-care facilities, correctional facilities, drug-treatment centers, and homeless shelters). Because the overall risk of acquiring M. tuberculosis is low for the total U.S. population, the primary strategy for preventing and controlling TB in the United States is to minimize the risk of transmission by the early identification and treatment of patients who have active infectious TB, finding and screening persons who have been in contact with active infectious TB patients and screening high-risk populations.

Tuberculin PPD is recommended by the American Lung Association as an aid in the detection of infection with Mycobacterium tuberculosis. 3, 4 After a person becomes infected with mycobacteria, T lymphocytes proliferate and become sensitized. These sensitized T cells enter the bloodstream and circulate for months or years. This sensitization process occurs principally in the regional lymph nodes and may take 2-10 weeks to develop following infection. Once acquired, tuberculin sensitivity tends to persist, although it often wanes with time and advancing age. The injection of tuberculin into the skin stimulates the lymphocytes and activates the series of events leading to a delayed-type hypersensitivity (DTH) response. This response is called "delayed" because the reaction becomes evident hours after injection. Dermal reactivity involves vasodilation, edema, and the infiltration of lymphocytes, basophils, monocytes, and neutrophils into the site of antigen injection. Antigen-specific T lymphocytes proliferate and release lymphokines, which mediate the accumulation of other cells at the site. The area of induration reflects DTH activity. 5 In most tuberculin-sensitive individuals, the delayed hypersensitivity reaction is evident 5-6 hours after administration of a tuberculin skin test and is maximal 48-72 hours. In geriatric patients or in patients receiving a tuberculin skin test for the first time, the reaction may develop more slowly and may not be maximal until after 72 hours. 6 Because their immune systems are immature, many neonates and infants < 6 weeks of age, who are infected with M. tuberculosis, do not react at all to tuberculin tests. 5

Immediate erythematous or other hypersensitivity reactions to tuberculin or the constituents of the diluent may occur at the injection site.

A possible decrease in responsiveness to skin testing may occur in the presence of tuberculous infections including viral infections, live virus vaccination, overwhelming tuberculosis, other bacterial infections, drugs and malignancy.

Tuberculin skin-test results are also less reliable as CD4 counts decline in HIV infected individuals. 3

The 5TU dose of Tuberculin PPD intradermally (Mantoux) is recommended as the standard tuberculin test, and Tuberculin PPD is recommended by the American Lung Association as an aid in the detection of infection with Mycobacterium tuberculosis. Reactions to the Mantoux test are interpreted on the basis of a quantitative measurement of the response to a specific dose (5 TU PPD-S or equivalent) of Tuberculin PPD. 7

To determine that Tuberculin PPD Master Lot 154616 is clinically bioequivalent in potency to standard 5TU PPD-S*, 3 dose-response studies were conducted in the following populations (1) persons with a history of bacteriologically confirmed TB; (2) healthy volunteers in a geographical region of low endemicity of atypical mycobacterial infection; and (3) healthy volunteers in a geographical location of high endemicity of atypical mycobacterial infection.

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