What are the cutoff and borderline values for Latent Tuberculosis Infection (LTBI) diagnosis using Quantiferon (Interferon-Gamma Release Assay)?

Cutoff and Borderline Values for LTBI on Quantiferon Testing

For diagnosing Latent Tuberculosis Infection (LTBI) using QuantiFERON-TB Gold, a positive result is defined as a TB response ≥0.35 IU/mL (TB antigen minus nil value) AND ≥25% of the nil value, with different cutoffs applied based on patient risk factors. 1

Interpretation Criteria for QuantiFERON-TB Gold

Basic Interpretation Parameters

• Nil value: Measures background level of interferon-gamma (IFN-γ) in patient's blood without stimulation

  • Normal: ≤8.0 IU/mL
  • Elevated (>8.0 IU/mL): Results in indeterminate test 1

• TB response calculation: (IFN-γ in TB antigen tube) - (IFN-γ in nil tube) 1

• Mitogen response: Control to confirm immune function and specimen validity

Cutoff Values for Positive Results

1. Current QuantiFERON-TB Gold In-Tube/Plus cutoff values:

   • Positive: TB response ≥0.35 IU/mL AND ≥25% of nil value
   • Negative: TB response <0.35 IU/mL OR <25% of nil value (with valid mitogen)
   • Indeterminate: Invalid nil (>8.0 IU/mL) OR inadequate mitogen response 1

2. Risk-stratified cutoffs (older QFT version):

   • For persons at increased risk for LTBI: percentage tuberculin response >15%
   • For persons at low risk for LTBI: percentage tuberculin response >30% 2

Borderline Considerations

While the current QuantiFERON-TB Gold assay doesn't officially define a "borderline" range, results near the cutoff value (0.35 IU/mL) should be interpreted with caution, especially in:

• Immunocompromised patients
• Recent TB contacts
• Patients with clinical suspicion of TB 1

Clinical Application of Cutoff Values

High-Risk Populations

For individuals at increased risk for LTBI (recent immigrants from high TB-prevalence countries, injection drug users, prison residents/employees, healthcare workers with TB exposure):

• Lower threshold for considering positive results
• Consider treatment for LTBI with positive result 2, 1

Low-Risk Populations

For individuals at low risk for LTBI:

• Higher threshold for considering positive results
• Confirmation with additional testing may be warranted for positive results 2

Special Considerations

• Immunocompromised patients: Higher risk of false-negative results; maintain high clinical suspicion despite negative results 1

• Indeterminate results: Options include:

  • Repeat testing with new blood specimen
  • Perform tuberculin skin test (TST)
  • Proceed with comprehensive TB evaluation if clinical suspicion is high 1

Test Performance Characteristics

• Cannot differentiate between latent TB infection and active TB disease
• Sensitivity approximately 80% for detecting M. tuberculosis infection in untreated culture-confirmed TB
• More specific than TST, especially in BCG-vaccinated individuals 1
• Remains positive in most patients (84-87%) after completion of preventive therapy 3

Pitfalls and Caveats

• Blood must be incubated with test antigens within 12 hours of collection
• False-negative results more common in immunosuppressed patients
• Performance in children under 17 years not well documented 1
• Serial testing may show conversions (12.1%) and reversions (4.5%), particularly in patients on immunosuppressive therapy 4
• Not recommended for monitoring treatment response as most patients remain positive after therapy 3

By understanding these cutoff values and their clinical implications, clinicians can more accurately diagnose and manage LTBI, ultimately reducing progression to active TB disease and improving patient outcomes.