What blood test is used for tuberculosis?

Blood Tests for Tuberculosis

The blood tests for tuberculosis are interferon-gamma release assays (IGRAs), specifically QuantiFERON-TB Gold (and its newer versions) and T-SPOT.TB, which measure immune responses to TB-specific antigens in a blood sample. 1, 2

Available IGRA Tests

The two FDA-approved blood tests are:

• QuantiFERON-TB Gold In-Tube (QFT-GIT): Requires a minimum of 3 mL of whole blood drawn directly into specialized heparinized tubes pre-coated with TB antigens (ESAT-6, CFP-10, and TB7.7 peptides), with results available within 24 hours 1, 2

• T-SPOT.TB: Requires a minimum of 2 mL of blood that must be processed within 8 hours (or 32 hours with T-cell Xtend additive) to isolate peripheral blood mononuclear cells, which are then tested using an ELISPOT technique 1

• QuantiFERON-TB Gold Plus (QFT-Plus): The newest generation approved in Europe and pending U.S. approval, containing enhanced CD8 T-cell stimulating peptides from CFP-10 (without TB7.7) 1

How These Tests Work

Both IGRAs detect TB infection by measuring interferon-γ released from sensitized T-cells after exposure to antigens specific to Mycobacterium tuberculosis 2. The key antigens (ESAT-6 and CFP-10) are present in all M. tuberculosis strains but absent from BCG vaccine strains and most nontuberculous mycobacteria, making these tests highly specific 1, 2

Critical Collection Requirements

Blood must be collected in heparinized tubes and incubated with antigens within 12 hours to preserve white blood cell viability—this is non-negotiable for accurate results. 3

• For QFT tests: Direct collection into specialized tubes allows immediate antigen exposure 3
• For T-SPOT: Blood can be in heparin or CPT Ficoll tubes but requires processing within the specified timeframe 1
• Other anticoagulants (EDTA, citrate) are inappropriate as they impair lymphocyte function 3

Interpretation Criteria

QuantiFERON-TB Gold is positive when:

• The difference between TB antigen response and nil control is ≥0.35 IU/mL of interferon-γ, AND
• The antigen response is 25% greater than the nil control 1

Indeterminate results occur when:

• Mitogen control shows inadequate response (≤0.5 IU/mL), indicating non-viable cells, OR
• Nil control has very high background (>8 IU/mL) 1

Clinical Advantages Over Tuberculin Skin Test

IGRAs are recommended by the CDC in all situations where TST is indicated because they offer: 1, 2

• Superior specificity, especially in BCG-vaccinated populations (no cross-reactivity with vaccine strains) 2
• No return visit required (single blood draw vs. 48-72 hour TST reading) 2
• No reader bias or placement errors 2
• No boosting phenomenon with repeat testing 2
• Results within 24 hours 2

Important Limitations and Caveats

These tests cannot distinguish latent TB infection from active TB disease—clinical evaluation with chest X-ray and symptom assessment is mandatory before interpreting results. 1

• Sensitivity is reduced in immunocompromised patients (HIV, immunosuppressive therapy, extremes of age) due to impaired T-cell responses 2, 4

• Negative results do not exclude TB infection in high-risk individuals (recent contacts, immunosuppressed patients, those with symptoms)—clinical judgment must guide further evaluation 1

• Values near the cutoff (around 0.35 IU/mL) have higher variability and may produce discordant results on repeat testing (8-11% variance rate) 1, 5

• Pre-analytical errors are common pitfalls: delayed processing, improper tube agitation, temperature extremes during transport can all compromise accuracy 2, 5

When to Use Which Test

The CDC recommends IGRAs over TST for: 1

• Contact investigations for recent TB exposure
• Screening recent immigrants from high-incidence countries
• Serial testing of healthcare workers and occupational groups
• BCG-vaccinated individuals (to avoid false positives)

Both QFT and T-SPOT show excellent agreement (93.9%, kappa = 0.85) with similar sensitivity (97-99%) and specificity (98%) 6, 7. The choice between them often depends on laboratory infrastructure—QFT requires less hands-on processing while T-SPOT may perform slightly better in immunocompromised patients 4

Dual Testing Strategy

Consider using both TST and IGRA when: 1

• Initial test is negative but high clinical suspicion persists (use second test to increase detection sensitivity)
• Initial test is positive in low-risk individuals (require both positive to increase specificity and reduce false positives)
• Initial IGRA is indeterminate or has unusual values (repeat with new blood sample)