What is the blood test for tuberculosis?

Blood Tests for Tuberculosis

The blood tests for tuberculosis are Interferon-Gamma Release Assays (IGRAs), which include QuantiFERON-TB Gold In-Tube (QFT-GIT), QuantiFERON-TB Gold Plus (QFT-Plus), and T-SPOT.TB. 1

How IGRAs Work

• IGRAs detect Mycobacterium tuberculosis infection by measuring interferon-gamma released from sensitized T-cells when blood is exposed to TB-specific antigens (ESAT-6 and CFP-10) that are present in M. tuberculosis but absent from BCG vaccine strains and most nontuberculous mycobacteria. 1

• This mechanism provides superior specificity compared to the tuberculin skin test, particularly in BCG-vaccinated populations. 1

Available IGRA Tests

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

• Requires ≥3 mL of whole blood drawn directly into specialized heparinized tubes pre-coated with ESAT-6, CFP-10, and TB7.7 peptides. 1

• Results are available within 24 hours. 1

• Blood must be incubated with antigens within 12 hours of collection to preserve white blood cell viability. 1

QuantiFERON-TB Gold Plus (QFT-Plus)

• Newer generation test that adds CD8-stimulating CFP-10 peptides (without TB7.7) to improve T-cell detection. 1

• Uses the same collection and processing requirements as QFT-GIT. 1

T-SPOT.TB

• Requires ≥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 for ELISPOT testing. 1

• Uses enzyme-linked immunospot assay to detect increases in the number of cells secreting interferon-gamma after antigen stimulation. 2

Interpretation of Results

Positive Result (QFT)

• (TB antigen – nil) ≥0.35 IU/mL AND the antigen response is ≥25% greater than the nil control. 1

• A positive result indicates M. tuberculosis infection but cannot differentiate latent TB infection from active disease—chest radiograph and symptom assessment are required. 1

Indeterminate Result

• Mitogen control ≤0.5 IU/mL (indicating non-viable cells) OR nil control >8 IU/mL (high background). 1

• Pre-analytical errors (delayed processing, improper tube agitation, temperature extremes during transport) are common causes of indeterminate results. 1

Negative Result

• Does not rule out infection in high-risk groups (recent contacts, immunosuppressed patients, children <5 years, patients starting TNF-α inhibitors). 2

• For persons with recent TB contact, negative results should be confirmed with repeat testing 8-10 weeks after exposure ends. 2

CDC Recommendations for IGRA Use

The CDC recommends IGRAs can be used in all circumstances where the tuberculin skin test is indicated. 2, 1

Specific Indications Include:

• Contact investigations for recent TB exposure. 1

• Screening recent immigrants from high-TB-incidence countries. 1

• Testing BCG-vaccinated individuals to avoid false-positive TSTs. 1

• Serial testing surveillance programs for infection control (e.g., healthcare workers). 2

Advantages Over Tuberculin Skin Test:

• Single-visit testing with no need for 48-72 hour return visit. 1

• Elimination of reader bias and placement errors. 1

• No boosting phenomenon on repeat testing. 1

• Rapid turnaround with results within 24 hours. 1

• Superior specificity, especially in BCG-vaccinated populations. 1

Critical Collection Requirements

• Blood must be collected in heparinized tubes only—EDTA or citrate tubes impair lymphocyte function and are not appropriate. 3

• For QFT assays, direct collection into specialized tubes provides immediate antigen exposure. 3

• Blood must be incubated with test antigens within 12 hours of collection, as delayed processing compromises white blood cell viability and test accuracy. 3

Important Limitations and Caveats

• Reduced sensitivity in immunocompromised patients (HIV-positive, immunosuppressive therapy, extremes of age). 1

• Results close to the 0.35 IU/mL cutoff show 8-11% discordance rate on repeat testing. 1

• A negative IGRA alone should not exclude M. tuberculosis infection in severely immunosuppressed adults, children <5 years, or patients about to undergo TNF-α inhibitor treatment, where consequences of false-negative results are severe. 2

• IGRAs cannot predict which individuals with latent infection will progress to active TB. 4

When to Consider Dual Testing

• Perform a second test (TST or repeat IGRA) when the initial IGRA is negative but clinical suspicion remains high, to increase detection sensitivity. 1

• Require both tests to be positive in low-risk individuals to improve specificity and reduce false-positives. 1

• Repeat testing with a new blood sample if the initial IGRA is indeterminate or yields atypical values. 1