What tests are used to diagnose tuberculosis (TB)?

Diagnostic Tests for Tuberculosis (TB)

The most comprehensive approach to diagnosing tuberculosis includes acid-fast bacilli (AFB) smear microscopy, liquid and solid mycobacterial cultures, and nucleic acid amplification tests (NAATs) such as GeneXpert MTB/RIF on respiratory specimens from patients with suspected pulmonary TB. 1

Initial Diagnostic Tests for Suspected Active TB

Microbiological Testing

• AFB Smear Microscopy

  • Strongly recommended for all patients with suspected pulmonary TB 1
  • Collect at least 3 specimens (optimal volume 5-10 mL) 1
  • Use concentrated respiratory specimens and fluorescence microscopy 1
  • Note: False-negative results are common; a negative AFB smear does not exclude TB 1

• Mycobacterial Culture (Gold Standard)

  • Both liquid and solid cultures should be performed on all specimens 1
  • Liquid cultures provide faster results but may have contamination issues 1
  • Solid cultures have lower sensitivity but may detect isolates missed by liquid culture 1
  • All isolates should be identified according to clinical laboratory standards 1

• Nucleic Acid Amplification Tests (NAATs)

  • Recommended on initial respiratory specimen from patients with suspected TB 1, 2
  • Options include:
    • GeneXpert MTB/RIF (sensitivity 95%, specificity 98% for detecting rifampin resistance) 2
    • Hologic Amplified MTB Direct (MTD) test 1
  • Interpretation:
    • In AFB smear-positive patients: negative NAAT makes TB unlikely
    • In AFB smear-negative patients: positive NAAT is presumptive evidence of TB, but negative NAAT cannot exclude TB 1

Imaging Studies

• Chest X-ray: Shows suggestive signs of TB 3
• Advanced imaging (CT, MRI, PET-CT): More useful for extrapulmonary TB 1, 3

Testing for Latent TB Infection (LTBI)

Available Tests

• Tuberculin Skin Test (TST)

  • Intracutaneous (Mantoux) administration of 0.1 mL PPD (5 TU) 1
  • Must be read by trained personnel between 48-72 hours after injection 1
  • Measure induration (not erythema) in millimeters 1
  • Interpretation varies based on risk factors 1

• Interferon-Gamma Release Assays (IGRAs)

  • TB Gold (IGRA): Measures immune response to M. tuberculosis antigens 2
  • Better specificity than TST in BCG-vaccinated individuals 2, 4, 5
  • Options include:
    • QuantiFERON-TB Gold In-Tube (QFT-GIT)
    • T-SPOT.TB

Comparative Performance

• IGRAs have higher specificity and less cross-reactivity with BCG vaccination 2, 4
• T-SPOT.TB shows higher sensitivity (90%) compared to TST (64%) 5
• QFT-GIT appears more sensitive than TST (75% vs 64%) with similar specificity 5
• Both tests have limitations in immunocompromised patients 2, 6

Special Considerations

Pediatric TB Diagnosis

• For children with suspected intrathoracic TB:
  • Seek bacteriological confirmation through appropriate samples (induced sputum, gastric washings) 1
  • If bacteriological results are negative, diagnosis may be based on:
    • Abnormal chest imaging
    • History of TB exposure
    • Positive TST/IGRA
    • Clinical findings suggestive of TB 1

Drug Resistance Testing

• Rapid molecular drug susceptibility testing for rifampin (with/without isoniazid) is recommended for:
  • AFB smear-positive patients
  • Patients with positive NAAT results
  • High-risk patients (previously treated, from high TB-burden countries, HIV-infected) 1, 2

Common Pitfalls and Limitations

• AFB smear microscopy: False-negative and false-positive results are common 1
• NAATs: May detect non-viable MTB DNA in patients with previous TB history 2
• IGRAs:
  • Reduced sensitivity in immunocompromised patients 2, 6
  • Higher cost than TST 2
  • Higher false conversion rates in serial testing 2
• TST: Cross-reactivity with BCG vaccination and non-tuberculous mycobacteria 4

Algorithm for TB Diagnosis

1. For suspected active pulmonary TB:

   • Collect 3 sputum specimens for AFB smear microscopy
   • Perform NAAT on initial specimen
   • Culture all specimens (both liquid and solid media)
   • Obtain chest imaging
   • Perform drug susceptibility testing if positive

2. For suspected latent TB:

   • Preferred: IGRA testing (especially if BCG-vaccinated)
   • Alternative: TST (if IGRA unavailable)
   • Consider dual testing approach in high-risk individuals 2

Remember that no single test can definitively rule out TB infection, especially in immunocompromised patients. A comprehensive diagnostic approach using multiple testing modalities provides the highest diagnostic accuracy.