How do you diagnose active tuberculosis?

How to Test if Tuberculosis is Now Active

Begin with chest radiography as the initial imaging test, followed immediately by collection of at least three sputum specimens (8-24 hours apart, with at least one early morning sample) for AFB smear microscopy and mycobacterial culture—the definitive diagnostic test for active TB. 1, 2

Initial Clinical Assessment

Evaluate for hallmark symptoms that suggest active disease rather than latent infection:

• Respiratory symptoms: Prolonged cough (>2-3 weeks), hemoptysis 1, 3, 4
• Constitutional symptoms: Unexplained weight loss, night sweats, fever, fatigue 1, 2
• Risk factors: Recent TB contact, residence in TB-endemic country, immunocompromised status (HIV with low CD4 count, anti-TNF medications, chronic corticosteroids), or exposure in high-risk settings (prisons, homeless shelters, healthcare facilities) 1, 5

Imaging Strategy

Chest Radiography (First-Line)

Order frontal chest X-ray immediately as it has high sensitivity for detecting active TB manifestations. 1, 6

Look for these specific findings that warrant respiratory isolation and sputum collection:

• Upper lobe fibro-cavitary disease involving apical posterior segments of upper lobes or superior segments of lower lobes 1, 6
• Lobar pneumonia with hilar and/or mediastinal adenopathy 1, 6
• Cavitary air space disease 1
• Pleural effusion 1

CT Scanning (When Indicated)

Proceed directly to CT in these specific situations:

• Chest X-ray findings are equivocal or non-diagnostic 1, 2, 6
• Patient is severely immunocompromised (HIV with CD4 <200, on anti-TNF therapy) even if chest X-ray appears normal 1, 2, 5
• AFB smear-negative but high clinical suspicion persists 2

Critical pitfall: Immunocompromised patients, particularly those with AIDS and very low CD4 counts, frequently have deceptively normal chest radiographs—do not rely on negative chest X-ray to exclude active TB in this population. 1, 2, 5

Microbiological Confirmation (Definitive Diagnosis)

Sputum Collection Protocol

Collect at least three sputum specimens 8-24 hours apart, with at least one early morning specimen. 2

• Supervise collection to ensure adequate sputum production 2
• If patient cannot produce sputum spontaneously, induce expectoration using hypertonic saline aerosol 2
• Consider bronchoscopy with bronchoalveolar lavage if sputum is non-diagnostic 2

Laboratory Testing Sequence

1. AFB smear microscopy (rapid, indicates infectiousness level):

   • Provides results within hours 2
   • Only 63% of culture-positive TB cases have positive smears 2
   • Critical pitfall: Never rely on negative AFB smears to exclude TB if clinical and radiographic suspicion is high—37% of culture-positive cases are smear-negative 2

2. Mycobacterial culture (gold standard):

   • Definitive diagnosis and allows drug susceptibility testing 2, 7, 8
   • Results typically available within 28 days using liquid culture methods 2
   • Culture is mandatory even with positive smear 2, 7

3. Nucleic acid amplification (NAA) testing:

   • Facilitates rapid detection but should not replace culture 2
   • Use as adjunct in moderate to high TB suspicion, especially when smear-negative 7, 3

Distinguishing Active from Latent TB

Active TB requires evidence of current disease through:

• Clinical symptoms of active disease (cough, fever, weight loss, night sweats) 1, 4
• Radiographic evidence of current active disease (infiltrates, cavitation, not just old scarring) 1
• Microbiological confirmation (positive culture or NAA test from sputum/tissue) 1, 8

Latent TB infection shows:

• Positive tuberculin skin test (≥5mm induration in immunocompromised, those with TB contact, or radiographic evidence of old TB; ≥10mm in other high-risk groups; ≥15mm in low-risk individuals) 1, 5
• Positive interferon-gamma release assay (IGRA), preferred in BCG-vaccinated individuals 1, 5
• No clinical symptoms of active disease 1
• No radiographic evidence of current active disease 1
• Negative bacteriologic studies 1

Critical distinction: Positive TST/IGRA only indicates TB infection (latent or active), not active disease—positive results require imaging and microbiological workup to distinguish active from latent TB. 5

Immediate Actions Upon Suspicion

Initiate respiratory isolation immediately upon radiographic suspicion of active TB, before microbiological confirmation. 2

• Maintain isolation until three negative AFB smears obtained or alternative diagnosis established 3
• When chest radiography confirms clinical suspicion of active TB, this is sufficient to warrant respiratory isolation pending sputum cultures 1

Special Considerations for Immunocompromised Patients

In HIV-infected patients with low CD4 counts (<200):

• Proceed directly to CT even with normal or equivocal chest X-ray 1, 2, 5
• Expect atypical presentations with diffuse infiltrates rather than classic upper lobe cavitary disease 5, 6
• Negative TST/IGRA does not exclude active TB due to anergy 1, 5
• Consider extrapulmonary TB involvement more frequently 5

Culture-Negative Active TB

If clinical and radiographic features suggest active TB but cultures remain negative:

• Carefully reevaluate after 2 months of empiric therapy 1
• If clinical or radiographic improvement noted and no other etiology identified, continue treatment for active TB 1
• HIV-infected patients with culture-negative pulmonary TB should be treated for minimum of 6 months 1