What are the Infectious Diseases Society of America (IDSA) guidelines regarding the use of QuantiFERON-TB (Interferon Gamma Release Assay) Gold In-Tube test versus T-SPOT.TB test for diagnosing latent tuberculosis (TB) infection?

IDSA Guidelines on QuantiFERON-TB Gold In-Tube vs T-SPOT.TB Testing

The IDSA/ATS/CDC guidelines do not differentiate between QuantiFERON-TB Gold In-Tube and T-SPOT.TB tests—both are considered equivalent interferon-gamma release assays (IGRAs) that can be used interchangeably for diagnosing latent tuberculosis infection. 1

Key Guideline Recommendations

Both IGRAs Are FDA-Approved and Equally Acceptable

• The CDC explicitly states that both QuantiFERON-TB Gold In-Tube (QFT-GIT) and T-SPOT.TB are FDA-approved IGRAs that may be used as aids in diagnosing M. tuberculosis infection, including both latent infection and active tuberculosis disease 1
• No preference is given to one IGRA over the other in official guidelines—they are treated as a single class of diagnostic tests 1

When to Use IGRAs (Either Test)

The IDSA/ATS/CDC guidelines recommend performing an IGRA rather than tuberculin skin test (TST) in specific populations:

Strong Recommendation (for individuals ≥5 years old): 1

• Likely to be infected with M. tuberculosis
• Low or intermediate risk of disease progression
• Testing for LTBI is warranted AND either:
  • History of BCG vaccination, OR
  • Unlikely to return for TST reading

Conditional Recommendation: 1

• All other individuals ≥5 years old who are likely infected with M. tuberculosis and have low or intermediate risk of disease progression
• TST remains an acceptable alternative in both scenarios

Technical Differences Between the Two Tests

While guidelines treat them equivalently, the tests differ mechanistically:

QuantiFERON-TB Gold In-Tube (QFT-GIT)

• Uses enzyme-linked immunosorbent assay (ELISA) methodology 1
• Measures the amount of interferon-γ in supernatant of whole blood cell suspension 1
• Results available within 8-30 hours 1
• Requires blood processing within 12 hours of collection 1

T-SPOT.TB

• Uses enzyme-linked immunospot (ELISpot) methodology 1
• Counts the number of individual cells producing interferon-γ 1
• May obtain higher number of positive results than QFT-GIT in some studies 2
• May have slightly lower specificity compared to QFT-GIT 2

Practical Considerations for Test Selection

When Either Test Is Appropriate

Both tests share key advantages over TST: 1, 3

• Not affected by prior BCG vaccination
• Require only one patient visit (no return needed)
• No reader bias or placement errors
• No cross-reactivity with most nontuberculous mycobacteria (except M. kansasii, M. marinum, M. szulgai) 1

Clinical Scenarios Where Test Choice May Matter

Immunocompromised patients: 4

• Research suggests T-SPOT.TB may be slightly more sensitive in immunosuppressed populations
• However, both IGRAs can have reduced sensitivity with severe immunosuppression 2
• Consider dual testing (IGRA plus TST) to increase sensitivity in high-risk immunocompromised patients 1

Steroid therapy: 4

• High-dose corticosteroids (>10-20 mg prednisone daily) can suppress both TST and IGRA responses 3
• Some evidence suggests QFT-GIT may be more affected by steroid use than T-SPOT.TB 4

Dual Testing Strategy

For patients at highest risk of progression to active TB: 1

• Guidelines suggest considering dual testing with both IGRA and TST
• A positive result from either test is considered positive
• This approach increases sensitivity at the cost of reduced specificity 1

For patients unlikely to be infected: 1

• Consider confirmatory testing when initial test is positive
• Helps identify false-positive results in low-risk populations

Common Pitfalls to Avoid

Do not assume one IGRA is superior to the other based on guidelines—the IDSA/ATS/CDC explicitly treat them as equivalent options 1

Do not use IGRAs alone to exclude active tuberculosis—all patients with positive IGRA results must be evaluated clinically and radiographically to rule out active disease before treating for LTBI 1

Do not repeat IGRAs frequently in low-risk populations—both tests show variability and higher false conversion rates than TST in serial testing 5, 6

Ensure proper specimen handling—blood must be processed within 12 hours for QFT-GIT, and both tests require strict adherence to manufacturer protocols to minimize preanalytical variability 5

Test Selection Algorithm

1. Determine if IGRA testing is indicated (vs TST or no testing) based on patient risk factors and likelihood of follow-up 1

2. If IGRA is chosen, select based on local availability and laboratory capabilities 1

   • Both tests are equivalent per guidelines
   • Choose based on laboratory experience, cost, and turnaround time

3. Consider T-SPOT.TB specifically if:

   • Patient is severely immunocompromised and you want potentially higher sensitivity 4, 2
   • Patient is on high-dose corticosteroids 4

4. Consider QFT-GIT specifically if:

   • Laboratory has more experience with ELISA-based methodology
   • Slightly higher specificity is prioritized over sensitivity 2

5. Consider dual testing (IGRA + TST) if: 1

   • Patient has high risk of progression to active TB
   • Patient is severely immunocompromised
   • Consequences of missing LTBI exceed risks of treatment toxicity