What blood test is used to confirm a diagnosis of tuberculosis?

Blood Tests for Tuberculosis Diagnosis

No blood test can confirm the diagnosis of active tuberculosis disease—blood tests like interferon-gamma release assays (IGRAs) detect TB infection but cannot distinguish between latent TB infection (LTBI) and active TB disease. 1

Understanding What Blood Tests Actually Measure

IGRAs measure immune response to TB infection, not active disease itself. The two FDA-approved blood tests are:

• QuantiFERON-TB Gold In-Tube (QFT-GIT): Measures interferon-gamma concentration in plasma after whole blood incubation with TB antigens (ESAT-6, CFP-10, TB7.7) 1
• T-SPOT.TB: Enumerates interferon-gamma-secreting T cells using ELISPOT methodology with ESAT-6 and CFP-10 antigens 1

Critical Limitation: Cannot Confirm Active TB

A positive IGRA or tuberculin skin test (TST) indicates TB infection but requires additional evaluation to exclude active TB disease. 1 This distinction is crucial because:

• Active TB requires multi-drug treatment for 6-9 months
• LTBI requires single or dual-drug preventive therapy for 3-9 months
• The clinical implications and public health management differ dramatically

Confirming Active TB Requires These Tests Instead

To confirm active TB disease, you must obtain: 1, 2

• At least three AFB sputum smears collected 8-24 hours apart, with at least one early morning specimen 2
• Mycobacterial culture (gold standard)—liquid cultures have 88-90% sensitivity and average 10-14 days for results 2
• Nucleic acid amplification test (NAAT) on at least one respiratory specimen, with results available within 48 hours 1, 2
• Chest radiography to assess for upper-lobe infiltration, cavitation, or nodular infiltrates 2

When IGRAs Are Actually Useful

IGRAs are indicated for diagnosing TB infection (not confirming active disease) in these scenarios: 1

• Screening contacts of active TB cases
• Pre-treatment evaluation for immunosuppressive therapy
• Healthcare worker surveillance
• Immigration screening

The T-SPOT.TB demonstrates higher sensitivity (82.3%) compared to QFT-GIT (67.3%) for detecting TB infection, though specificities are similar (82.6% vs 80.4%). 3 However, neither test is sufficiently sensitive to rule out active TB in clinical practice. 3

Practical Algorithm for TB Diagnosis

When evaluating suspected active TB: 1, 2

1. Collect respiratory specimens immediately—three sputum samples for AFB smear, culture, and NAAT
2. Order chest imaging—radiograph or CT to identify characteristic findings
3. Do not rely on IGRA results to confirm or exclude active TB disease
4. If IGRA is positive, this supports TB infection but mandates full evaluation for active disease including symptoms assessment, imaging, and microbiological testing 1

Common Pitfalls to Avoid

Never use a positive IGRA alone to diagnose active TB—this is a fundamental error that delays appropriate multi-drug therapy. 1 The test cannot differentiate infection states.

Never use a negative IGRA to exclude active TB in high-risk patients—sensitivity ranges from 67-82%, meaning 18-33% of infected individuals test negative. 3 In immunocompromised patients (HIV-positive, transplant recipients), sensitivity is even lower. 1

Indeterminate IGRA results occur in 0-35% of cases, particularly in young children and immunocompromised patients. 1 When QFT-GIT yields indeterminate results, T-SPOT.TB resolves 84.8% of cases when performed within 30 days. 4

Special Populations

In HIV-positive patients, both IGRAs show reduced sensitivity but higher specificity compared to HIV-negative individuals. 3 This paradoxically makes negative results less reliable in the population at highest risk for TB progression.

In children under 5 years, IGRA indeterminate rates are substantially higher, and phlebotomy failure is common. 1 The TST remains preferred for this age group despite BCG cross-reactivity. 1