What is PPD (Purified Protein Derivative)?

Purified Protein Derivative (PPD)

PPD (Purified Protein Derivative) is a standardized extract isolated from culture filtrates of tubercle bacilli that produces a delayed-type hypersensitivity reaction when injected intradermally, and is the primary reagent used for tuberculin skin testing to identify infection with Mycobacterium tuberculosis. 1

Composition and Preparation

• PPD is isolated from culture filtrates of Mycobacterium tuberculosis through protein precipitation methods, primarily using either ammonium sulfate (Aplisol) or trichloroacetic acid (Tubersol) 1
• The composition is complex, containing primarily small proteins with molecular masses of approximately 10,000 Da, along with polysaccharides and some lipids 1, 2
• The standard reference material in the United States is PPD-S (lot 49608), produced by Seibert and Glenn in 1939, which serves as the international standard 1
• All commercially produced PPD lots must undergo bioassay to demonstrate equal potency to PPD-S 1

Standardization and Dosage

• The standard dose used for tuberculin skin testing is 5 tuberculin units (TU), defined as the delayed skin test activity contained in 0.1 mg/0.1 ml of PPD-S 1
• Commercial PPD preparations are standardized to elicit reactions of equivalent size (±20%) to 5 TU of PPD-S 1
• Other concentrations (1 TU and 250 TU) exist but have minimal clinical utility and are not commonly available 1
• PPD contains a small amount of detergent (Tween 80) to reduce adsorption to glass and plastic containers 1

Immunologic Basis of the Tuberculin Reaction

• The reaction to intracutaneously injected tuberculin is the classic example of a delayed-type hypersensitivity reaction 1
• T cells previously sensitized by infection with M. tuberculosis are recruited to the skin site where they release lymphokines 1
• These lymphokines induce induration through local vasodilatation, edema, fibrin deposition, and recruitment of other inflammatory cells 1
• The reaction typically begins 5-6 hours after injection, reaches maximum at 48-72 hours, and may persist for up to a week 1

Clinical Applications

• PPD is the primary reagent used in tuberculin skin testing (Mantoux test) to identify latent tuberculosis infection 1
• The test is interpreted by measuring the induration (not just erythema) at the injection site after 48-72 hours 1
• Different cut-off values for positivity are used depending on the patient's risk factors and immune status (e.g., ≥5 mm for HIV-infected individuals) 3
• PPD testing is safe during pregnancy and should not be delayed when indicated 3

Limitations and Considerations

• PPD is not 100% sensitive or specific for M. tuberculosis infection 1
• False-positive reactions can occur due to infection with nontuberculous mycobacteria or prior BCG vaccination 1
• False-negative results may occur in immunocompromised patients, including those with HIV infection 1
• Anergy testing (using control antigens like Candida or mumps) may be considered for HIV-infected individuals to assess for PPD anergy 1
• Newer specific antigens (ESAT-6, CFP-10) are being developed to overcome the limitations of PPD, particularly to distinguish between M. tuberculosis infection and BCG vaccination 4, 5

Proper Handling and Administration

• PPD should never be transferred between containers to avoid reduction in potency through adsorption 1
• The solution should be kept refrigerated (not frozen) and protected from strong light 1
• Skin tests should be administered as soon as possible after the syringe has been filled 1
• The Mantoux method with intradermal injection is the recommended technique for administration 3