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Tuberculosis: Tuberculin Skin Testing

Seibert developed a nonsensitizing product obtained by ammonium sulfate precipitation of old tuberculin, purified protein derivative (PPD). Later, Seibert and Glenn reported the preparation of a large lot of PPD from the single strain of M. tuberculosis. This material became the international standard for PPD, referred to as PPD-S.

There are two available test use for the application of a tuberculin test, the percutaneous multiple puncture and the intracutaneous Mantoux Methods.

Percutaneous multiple puncture:

Tine Test: The test applicator is a plastic handle attached to a stainless steel metal disc. Projecting from the disc are four 2mm long prongs, or tines. East prong has been dipped into OT containing gum arabic and lactose as stabilizers and glycerin to prevent the OT firm from faking off. This method is usually referred to as the tine test.

Heaf test and MONO-VACC test: uses a spring loaded gun with a sterile cartridge that delivers liquid tuberculin solution into the skin with six points.

Advantage: ease of administration, stability and a very short administration time. may be used by less trained personnel.

Disadvantage: the amount of antigen which in inoculated cannot be precisely controlled, it is not considered to be as useful as other methods as a diagnostic test.

Reliability: the measured is 48-72 hours after inoculation. If papules occur, the diameter of the le=largest single papule is recorded. any reaction to a multiple puncture test should by confirmed with the Mantoux test. In 1977, FDA recommended that multiple puncture tests provide no false negative results in individuals shown to have a reactive Mantoux test.

Intracutaneous Mantoux test

Five TU has been defined as the delayed hypersensitivity activity contained in 0.1 ug of PPD-S delivered in 0.10 ml. Commercial PPD-S is standardized as the dosage of the product that is biologically equivalent to that in 5 TU PPD-S.

Physical modifications of tuberculin: it can be adsorb on to glass and plastic, which may decrease the administered dose. To minimize this, PPD should not be transferred between containers and administration should be done as soon as possible once aspirated into a syringe. To further assist in minimizing adsorption, the non-ionic detergent Tween-80 is added at 5 parts per million. Vials should be refrigerated, not froze, and kept away from light.

Administration: Should be done by a trained individual to ensure adequate inoculation. The test should be preformed by the intradermal injection of 0.1 ml of PPD into the volar or dorsal surfaces of the forearm.

Reading the Mantoux test: the test should evaluated 48-72 hours after injection, though indurations beyond this point in significant. Measurements are based on indurations , not erythematic. The diameter of the indurations is assessed transversely to the long axis of the arm. The degree of indurations may be determined by inspection using side lighted palpation or the ballpoint pen technique.

Interpretation of the Mantoux test: It is known that subclinical infections with NTM(non-TB Mycobacteria, including BCG vaccination) will cause some reactivity but usually of a smaller diameter than one related to TB. A significant amount of overlap in the size of the reaction to tuberculin between M. tuberculosis and NTMs does exist. because of this overlap, any single cutoff for positivity will produce errors in classification. A small cutoff (eg. 5mm) will include most other the reactions due to M. tuberculosis but also a large number of cross sensitization reactions will be classified as positive. therefore, trades increasing specificity for lower sensitivity.

Currently available skin tests for tuberculosis.

The definition of significant reactivity of the tuberculin test should depending on how important it is to detect the maximum number of true positive results. In individuals in whom a high risk of the development of active TB exists, the cutoff should be low. in individuals without a high risk of TB and the potential of harm from Isoniazid, the cutoff should be correspondingly higher.

Viral infection sand immunizations: Some viral infections can transiently suppress the tuberculin reaction. The relation of measles infection and inhibition of this reaction was the first to be recognized.

Corticosteroids:

It has been shown to have immunosuppressive effects, exogenous corticosteroids should modify the response to tuberculin.