What is the probability that QuantiFERON Gold (Interferon-Gamma Release Assay) is falsely negative?

From the Guidelines

The probability of a false negative result with QuantiFERON-TB Gold (QFT-G) test is approximately 10-30%. This estimate is based on the most recent and highest quality study available, which highlights the limitations of the test in certain populations and scenarios 1. False negatives occur for several reasons, including:

• Immunosuppression (from medications like corticosteroids or conditions like HIV)
• Recent TB infection (within 8 weeks) before an adequate immune response develops
• Extremes of age (very young or elderly)
• Malnutrition
• Technical errors in sample collection, handling, or processing

The test works by measuring interferon-gamma release from T cells in response to TB antigens, so any factor that impairs T cell function can reduce test sensitivity 1. Blood samples must be processed within 16 hours of collection and maintained at specific temperatures to preserve lymphocyte viability. Healthcare providers should consider these limitations when interpreting negative results, especially in high-risk patients or those with strong clinical suspicion of TB, and may need to use alternative diagnostic methods such as tuberculin skin testing, chest imaging, or direct microbiological testing when appropriate 1.

The updated guidelines for using interferon gamma release assays to detect Mycobacterium tuberculosis infection, published in 2010, provide further guidance on the use of QFT-G and other IGRAs, including recommendations for quality control, test selection, and medical management after testing 1. However, the key point remains that a negative QFT-G result does not entirely rule out the possibility of TB infection, and clinical judgment should be used to determine the need for further testing or treatment.

From the Research

Factors Influencing False-Negative Results of QuantiFERON-TB Gold In-Tube

• The probability of false-negative results with QuantiFERON-TB Gold In-Tube (QFT-GIT) is influenced by several factors, including:
  • Immunocompromised conditions, such as immunosuppressant diseases 2
  • Advanced age, with odds ratio (OR) of 1.57 for age ≥ 65 years 3
  • Bilateral disease on chest radiography, with OR of 1.75 3
  • Malignancy, with OR of 2.42 3
  • Lymphocytopenia, with OR of 1.86 for total lymphocyte count < 1.0 × 10^9/L 3
  • High levels of markers of inflammation, such as C-reactive protein (CRP), with increased probability of indeterminate and negative QFT-GIT results 4
  • Low platelet, protein, and albumin levels 2

Prevalence of False-Negative Results

• The prevalence of false-negative QFT-GIT results varies across studies, with reported rates of:
  • 14.1% in a study of 362 non-HIV-infected patients with culture-confirmed tuberculosis 2
  • 14.4% in a multicenter retrospective cohort study of 1,264 culture-confirmed TB patients 3
  • 12.9% in a study of 1301 patients diagnosed with TB 4

Clinical Implications

• The results of QFT-GIT tests should be interpreted with caution in patients with factors associated with false-negative results, such as immunocompromised conditions, advanced age, and high levels of inflammation 2, 3, 4
• Additional tests for TB may be necessary to confirm diagnosis in patients with negative or indeterminate QFT-GIT results 4