TUBERCULINS

Koch’s original preparation of tuberculin was a relatively crude extraction from heat-killed cultures of M. tuberculosis.(4) His material contained a large number of carbohydrate and protein antigens as well as antigens from the beef broth used as a culture medium. Old tuberculin (O.T.) is still produced using methods similar to Koch’s original description, although antigens from the beef broth are no longer present. For many years tuberculins were manufactured without much attempt at standardization. Green described this situation:

It would surely simplify life for manufacture’s if O.T. were plainly described as “any witches” brew derived by evaporation of any unspecified fluid medium in which any unspecified strain of mammalian M. tuberculosis had been grown, provided its potency matched that of another witches’ brew kept in Copenhagen and called international standard, or any allegedly equivalent sub-standard thereof, when tested on an unspecified number of guinea-pigs without worrying too much about statistical analysis of results.(5)

In the 1930s Florence Seibert prepared trichloroacetic acid and ammonium sulfate precipitates of OT and called the material purified protein derivative (PPD).(6) PPD contains a number of antigenic components, most of which are low- and medium-weight proteins. PPD has less carbohydrate antigens than OT and results in fewer nonspecific immediate hypersensitivity reactions. In 1941, Seibert and Glenn(7) prepared a large batch of PPD (PPD-S) that has served as the standard reference material in the United States. The supply of PPD-S is currently becoming exhausted, and a replacement standard is being developed. Other improvements in tuberculin testing include the addition of Tween, a detergent that prevents adsorption of tuberculin to glass and plastic syringes(8,9) and a U.S. Food and Drug Administration requirement that all PPD lots in the United States demonstrate equal potency to PPD-S by bioassay.(10) Despite this demonstration of equal potency, there have been a number of reports suggesting an increase in false-positive reactions in skin testing programs that switched from Tubersol (Connaught, Swiftwater, PA) to Aplisol (Parke-Davis, Morris Plains, NJ).

“Tuberculins” and “PPDs” have been prepared from other mycobacterial species and have provided useful epidemiologic information,(11) but have not been demonstrated to have efficacy as diagnostic tests.

IMMUNE RESPONSE TO TUBERCULIN

Following infection with M. tuberculosis there is a sensitization and proliferation of T lymphocytes specific for antigens contained in tuberculin. In the Mantoux method of tuberculin testing, these T lymphocytes



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