What is the Purified Protein Derivative (PPD) test, its placement and interpretation, the type of hypersensitivity reaction it elicits, and the disease processes that can cause false positives and false negatives, as well as the Quantiferon (Interferon-Gamma Release Assay) test and its performance?

From the Guidelines

The PPD test is a screening tool for tuberculosis infection that involves intradermal injection of tuberculin, with interpretation depending on risk factors, and elicits a Type IV hypersensitivity reaction, while QuantiFERON-TB Gold is a blood test that measures interferon-gamma release from T cells exposed to TB-specific antigens, offering improved specificity over PPD. The PPD test, also known as the Mantoux tuberculin skin test, involves intradermal injection of tuberculin (0.1 mL) into the forearm, creating a small wheal, and after 48-72 hours, the site is examined for induration, which is measured in millimeters across the forearm 1. The interpretation of the PPD test results depends on risk factors, with ≥5mm being positive in HIV-positive individuals or recent TB contacts, ≥10mm for those from high-prevalence areas or with certain medical conditions, and ≥15mm for low-risk individuals.

Key Points About PPD Test

• The PPD test elicits a Type IV (delayed-type) hypersensitivity reaction, mediated by T cells responding to mycobacterial antigens 1.
• False positives can occur with BCG vaccination, nontuberculous mycobacterial infections, and in some autoimmune conditions.
• False negatives may result from immunosuppression (HIV, medications, malnutrition), recent TB infection (within 8-10 weeks), overwhelming TB disease, very young or elderly patients, or improper test administration.

QuantiFERON-TB Gold Test

• QuantiFERON-TB Gold is an alternative blood test that measures interferon-gamma release from T cells when exposed to TB-specific antigens, such as early secretory antigenic target-6 (ESAT-6) and culture filtrate protein 10 (CFP-10) 1.
• It requires drawing blood samples, incubating them with TB antigens, and measuring interferon-gamma production.
• Unlike PPD, QuantiFERON is not affected by BCG vaccination, requires only one visit, and results are available within 24 hours, making it increasingly preferred for TB screening.

Disease Processes Affecting Test Results

• Certain disease processes can cause false positives or false negatives in both PPD and QuantiFERON tests, including immunosuppression, recent TB infection, and overwhelming TB disease 1.
• Risk factors for progression of infection to active tuberculosis include HIV infection, recent TB contact, and certain medical conditions, such as silicosis, diabetes mellitus, and chronic renal failure 1.

From the Research

PPD Test and Hypersensitivity Reaction

• The PPD (Purified Protein Derivative) test, also known as the tuberculin skin test (TST), is used to diagnose latent tuberculosis infection (LTBI) 2.
• The test involves injecting a small amount of PPD into the skin, and after 48-72 hours, the skin is checked for induration (swelling) 2.
• The TST elicits a type IV hypersensitivity reaction, also known as a delayed-type hypersensitivity reaction, which involves the activation of T cells and the release of cytokines 2.

Interpretation and Disease Processes

• The interpretation of the TST result depends on the size of the induration, with larger indurations indicating a positive result 2.
• False positives can occur due to cross-reactivity with other mycobacteria, such as those used in the BCG vaccine, or due to other disease processes such as sarcoidosis 3.
• False negatives can occur due to immunosuppression, such as in individuals with HIV/AIDS, or due to other disease processes such as viral infections 3.

Quantiferon Test

• The QuantiFERON test is an interferon-gamma release assay (IGRA) that measures the release of interferon-gamma from T cells in response to tuberculosis antigens 4, 3.
• The test is performed by collecting a blood sample and incubating it with tuberculosis antigens, then measuring the amount of interferon-gamma released 4.
• The QuantiFERON test is more specific than the TST and can distinguish between latent tuberculosis infection and cross-reactivity with other mycobacteria 4, 3.

Performance and Limitations

• The QuantiFERON test has been shown to be positive in individuals with latent tuberculosis infection, as well as in those with active tuberculosis disease 4.
• However, the test may not be useful for monitoring the effect of preventive therapy, as the results may not change after treatment 4, 5.
• The dynamic changes of interferon-gamma levels during latent tuberculosis infection treatment have been studied, and it has been found that the levels may not decrease significantly after treatment 5.