In a patient suspected of miliary tuberculosis, how does the CB‑NAAT (GeneXpert MTB/RIF) positivity rate compare to that in classic pulmonary tuberculosis?

CB-NAAT Positivity in Miliary TB vs Pulmonary TB

CB-NAAT (GeneXpert MTB/RIF) has significantly lower sensitivity in miliary tuberculosis compared to classic pulmonary TB, with positivity rates of approximately 50-60% in miliary disease versus 85-96% in AFB smear-positive pulmonary TB. 1, 2

Comparative Diagnostic Yield

Pulmonary TB Performance

• In AFB smear-positive pulmonary TB specimens, CB-NAAT achieves 96-97% sensitivity and 85-95% specificity 2, 3
• In AFB smear-negative pulmonary TB, sensitivity drops to 66-79% with specificity of 80-98% 2
• Overall sensitivity for culture-confirmed pulmonary TB ranges from 80-90% 3

Miliary TB Performance

• Sputum cultures in miliary TB are positive in only 76% of cases, and CB-NAAT performs even worse than culture in disseminated disease 4
• Gastric aspirate cultures show 75% positivity in miliary TB, suggesting respiratory specimens have lower bacillary burden 4
• The disseminated nature of miliary TB means bacilli are spread throughout multiple organs rather than concentrated in respiratory secretions, fundamentally limiting respiratory specimen sensitivity 5

Critical Clinical Implications

Why the Difference Exists

• Miliary TB results from massive lymphohematogenous dissemination with tiny tubercles throughout organs, not concentrated cavitary disease in the lungs 5
• Classic pulmonary TB, especially with cavitation, produces high bacillary loads in sputum that CB-NAAT readily detects 2
• The "miliary pattern" represents diffuse seeding rather than focal consolidation, yielding lower organism density in any single respiratory specimen 5

Diagnostic Strategy for Miliary TB

• A negative CB-NAAT result absolutely cannot exclude miliary TB—false-negative rates approach 40-50% in this population 1
• Multiple specimen types should be tested: sputum, gastric aspirate, urine, bronchial washings, and tissue biopsies when feasible 4
• Culture remains mandatory in suspected miliary TB despite CB-NAAT results, as culture detects 76% of cases from sputum alone 1, 4

Extrapulmonary Specimen Considerations

• For specimens from extrapulmonary sites (relevant in miliary TB), CB-NAAT sensitivity ranges from only 56-62% for pleural fluid and CSF, with specificity of 98% 1
• A positive CB-NAAT from any site provides strong evidence (>95% specificity) and should prompt immediate treatment initiation 1
• However, negative results are "exceedingly common" (38-44% false-negative rate) and must not delay treatment when clinical suspicion is high 1

Practical Algorithm for Miliary TB Diagnosis

When Miliary TB is Suspected:

1. Collect multiple specimen types immediately: at least 3 sputum samples, gastric aspirate, urine, and blood cultures 4
2. Send all specimens for both CB-NAAT and mycobacterial culture—never rely on CB-NAAT alone 1, 6
3. Perform fundoscopic examination for choroid tubercles, which are pathognomonic when present 5
4. Consider transbronchial biopsy, liver biopsy, or bone marrow biopsy for histopathology and culture 1, 4

Result Interpretation:

• If any CB-NAAT is positive: Presume miliary TB and initiate treatment immediately 1, 2
• If all CB-NAAT tests are negative but clinical suspicion remains high: Do NOT withhold treatment—initiate empiric therapy while awaiting cultures 1
• Cultures take 2-6 weeks but remain the gold standard, detecting cases CB-NAAT misses 6

Common Pitfalls to Avoid

• Never exclude miliary TB based on negative CB-NAAT alone—this is the single most dangerous error 1
• Do not assume respiratory specimens will be adequate; miliary TB requires sampling multiple sites 4
• Miliary TB is uniformly fatal if untreated, so err on the side of treatment when clinical presentation is consistent 5
• Remember that elderly and immunocompromised patients (the typical miliary TB population) have even lower diagnostic yields from all tests 4, 5