When PPD is More Useful Than QuantiFERON Gold
The PPD (tuberculin skin test) is rarely more useful than QuantiFERON Gold in clinical practice, but it may be preferred when serial testing is needed in high-risk populations where documentation of conversion is important, such as healthcare worker surveillance programs, because PPD allows for clear identification of new infections through documented conversion from negative to positive. 1
Key Clinical Scenarios Favoring PPD
Serial Testing and Conversion Documentation
- PPD is advantageous in serial testing programs (e.g., healthcare workers, prison staff) because it can demonstrate clear conversion from negative to positive, indicating new infection. 1
- QuantiFERON Gold results can remain positive indefinitely after treatment of latent TB, making it difficult to distinguish new infection from prior treated infection in serial testing scenarios. 1, 2
- The CDC guidelines note that caution should be exercised when using QuantiFERON Gold for serial testing because the test may remain positive after treatment. 1
Resource-Limited Settings Without Laboratory Infrastructure
- PPD requires no laboratory infrastructure and can be administered in any clinical setting with basic supplies. 1
- QuantiFERON Gold requires fresh blood specimens with viable white blood cells, trained laboratory personnel, and testing within hours of collection. 1
- PPD may be the only practical option in settings without access to specialized laboratory facilities. 1
Situations Where Two-Step Testing is Beneficial
- PPD allows for two-step testing to detect boosting phenomenon in individuals with remote infection, which is particularly useful in baseline testing of healthcare workers. 1
- QuantiFERON Gold does not trigger an anamnestic (boosting) response because it does not expose persons to antigen. 1
Important Caveats About PPD Limitations
False Positives Are Common
- PPD has significantly lower specificity than QuantiFERON Gold, particularly in BCG-vaccinated populations (49% vs 96% specificity in one study). 1
- Cross-reactivity with BCG vaccine and nontuberculous mycobacteria causes false-positive PPD results. 1
- In BCG-vaccinated medical students, 85.2% were PPD positive but only 10.4% were QuantiFERON positive, demonstrating the high false-positive rate. 3
Practical Disadvantages
- PPD requires a return visit 48-72 hours after placement for reading, leading to incomplete testing when patients don't return. 1
- Reader bias and errors in placement and interpretation are common with PPD. 1
When QuantiFERON Gold is Superior (For Context)
BCG-Vaccinated Populations
- QuantiFERON Gold is not affected by prior BCG vaccination, making it far more specific in these populations. 1
- Agreement between tests improves when higher PPD cutoffs (≥10mm) are used, but QuantiFERON Gold remains more accurate. 4
Single-Point Testing
- For one-time screening (immigrants, pre-biologic therapy screening), QuantiFERON Gold is preferred due to higher specificity and no need for return visit. 1
- CDC guidelines state that QuantiFERON Gold may be used in all circumstances where TST is currently used. 1
Common Pitfalls to Avoid
- Do not use QuantiFERON Gold to monitor treatment response - the test remains positive in 84-87% of patients after completing preventive therapy. 2, 5
- Do not assume PPD is more sensitive - both tests have similar sensitivity for detecting infection in culture-confirmed TB cases (78-81% for PPD vs 81-89% for QuantiFERON Gold). 1
- Do not rely on PPD alone in BCG-vaccinated individuals - the false-positive rate is unacceptably high (up to 86.7% positive in exposed BCG-vaccinated individuals). 6