Tuberculosis Diagnosis and Evaluation

These tests tell us if the immune system has “seen” the TB bacteria, but they cannot distinguish between latent infection and active disease.

The Tuberculin Skin Test (TST) / Mantoux

This is the traditional screening method, in use for over a century.

• Technique: A standardized dose of PPD (Purified Protein Derivative) is injected intradermally (between skin layers) on the forearm.
• Reading: The test must be read by a trained professional within 48-72 hours. The measurement is based on the induration (palpable hardness), not the redness (erythema).
• Interpretation Criteria: The threshold for a tuberculosis mantoux test positive result varies by risk:
  • >5 mm: Positive for HIV+ persons, recent contacts of active cases, or those with fibrotic chest X-rays.
  • >10 mm: Positive for recent immigrants from high-prevalence countries, IV drug users, residents of high-risk settings, children <4 years, and those with medical risk factors (diabetes, kidney failure).
  • >15 mm: Positive for persons with no known risk factors.
• The Booster Phenomenon: In older adults, the first test may be negative due to waned immunity. A second test, 1-3 weeks later, may elicit a positive reaction (a boost), indicating an old infection rather than a new conversion. This is the basis for “two-step testing.”

Interferon-Gamma Release Assays (IGRAs)

Modern blood tests like QuantiFERON-TB Gold Plus and T-SPOT.TB.

• Mechanism: They measure the release of interferon-gamma by T-cells in response to specific M. tuberculosis antigens (ESAT-6, CFP-10).
• Advantages:
  • Specificity: These antigens are not found in the BCG vaccine strain, so IGRAs do not produce false positives in vaccinated individuals—a huge advantage in many countries.
  • Logistics: Single patient visit; no need to return for reading.
  • Objectivity: No reader bias compared to measuring skin induration.
• Role: They are the preferred test for BCG-vaccinated individuals and those who may not return for TST reading.