What is the diagnostic approach for tuberculosis?

Diagnostic Approach for Tuberculosis

The definitive diagnostic approach for tuberculosis (TB) requires tuberculin skin testing (TST) or interferon-gamma release assay (IGRA) for latent TB infection, followed by chest radiography and bacteriological confirmation through sputum examination with microscopy, rapid molecular tests, and culture for active TB disease. 1

Initial Screening for TB Infection

Tuberculin Skin Test (TST/Mantoux Test)

• Administration technique:

  • Inject 0.1 mL of purified protein derivative (PPD) (5 tuberculin units) intradermally on the volar or dorsal surface of the forearm 1
  • Proper injection creates a 6-10 mm wheal (pale elevation of skin) 1, 2
  • If injection is improperly administered, repeat immediately at a site several centimeters away 1

• Reading the test:

  • Read between 48-72 hours after injection (maximum induration) 1
  • Measure induration (hardened area), not erythema (redness) 1, 2
  • Measure diameter transversely to the long axis of the forearm in millimeters 1
  • Record absence of induration as "0 mm," not "negative" 1

• Interpretation of results:

  • ≥5 mm induration is positive in: HIV-infected persons, recent contacts of TB cases, persons with fibrotic changes on chest X-ray, and immunosuppressed patients 1
  • ≥10 mm induration is positive in: recent immigrants from high-prevalence countries, injection drug users, residents of congregate settings, healthcare workers with TB exposure, and persons with certain medical conditions (diabetes, chronic renal failure, etc.) 1
  • ≥15 mm induration is positive in: persons with no known risk factors 1

Interferon-Gamma Release Assay (IGRA)

• Recommended over TST for individuals ≥5 years old who are likely to be infected with M. tuberculosis 1
• Advantages: requires only one patient visit, results available within 24 hours, not affected by BCG vaccination 1
• Cannot distinguish between active and latent TB infection 1

Diagnostic Workup for Active TB

Clinical Assessment

• Evaluate for symptoms: persistent cough (≥3 weeks), bloody sputum, night sweats, weight loss, fever 1
• Higher index of suspicion needed in high-prevalence areas or high-risk populations 1

Chest Radiography

• Obtain for patients with positive TST/IGRA or symptoms suggestive of TB 1
• Radiographic findings suggestive of active TB: upper-lobe infiltration (especially with cavitation), patchy or nodular infiltrates in apical or posterior upper lobes 1
• HIV-infected patients may present with atypical radiographic findings 1

Bacteriological Confirmation

• Sputum collection:

  • Collect at least three sputum specimens on different days 1
  • For children or patients unable to produce sputum: consider sputum induction, bronchoscopy, gastric washings 1

• Laboratory methods:

  • Acid-fast bacilli (AFB) smear microscopy: rapid but less sensitive (detects ~60% of culture-positive cases) 1
  • WHO-recommended rapid molecular tests (e.g., GeneXpert MTB/RIF): faster detection and drug resistance identification 1
  • Culture: gold standard for definitive diagnosis, allows drug susceptibility testing 1
  • Drug susceptibility testing: essential to guide appropriate treatment 1

• For extrapulmonary TB:

  • Obtain appropriate specimens from suspected sites of involvement 1
  • Use combination of microscopy, culture, molecular tests, and histopathology 1

Special Considerations

Pediatric TB Diagnosis

• More challenging due to paucibacillary nature and difficulty obtaining specimens 1
• In children with negative bacteriological results, diagnosis may be based on:
  • Abnormal chest imaging consistent with TB
  • History of exposure to infectious case
  • Evidence of TB infection (positive TST/IGRA)
  • Clinical findings suggestive of TB 1

Immunocompromised Patients

• Higher false-negative rate (up to 25%) for TST in acutely ill or immunosuppressed patients 1
• TST cannot be used to rule out active TB in these populations 1
• HIV-infected patients may have atypical presentations and radiographic findings 1

Common Pitfalls and Caveats

1. False-negative TST results can occur due to:

   • Poor nutrition and general health
   • Overwhelming acute illness
   • Immunosuppression (HIV, medications, malignancy)
   • Recent live-attenuated virus vaccination 1

2. False-positive TST results can occur due to:

   • Infection with non-tuberculous mycobacteria
   • Previous BCG vaccination (though not a contraindication to testing) 2

3. Multiple-puncture tests are not as reliable as the Mantoux method and should not be used as a diagnostic test 1

4. Two-step testing may be necessary for periodic screening programs to avoid misinterpreting boosted reactions as new infections 1

5. Neither TST nor IGRA can distinguish between active TB and latent TB infection - additional evaluation is always required 1

By following this systematic diagnostic approach, clinicians can effectively identify both latent TB infection and active TB disease, enabling appropriate treatment and preventing further transmission.