A 38-year-old woman with no prior history of tuberculosis undergoes tuberculin skin test (TST) screening at her workplace. The TST is positive (induration ≥5 mm). The TST has a sensitivity of 85% and specificity of 90% in the general population. The prevalence of active TB in her region is 1%. Which investigation is the most appropriate next step to confirm active tuberculosis?

Question

Accepted Answer

B. Chest X-ray and sputum smear microscopy. ## Clinical Scenario Analysis
A positive TST in a low-prevalence population (1% active TB) has a low positive predictive value (PPV). The TST detects both active TB and latent TB infection, making it a screening test, not a diagnostic test.

## Calculating PPV for TST
$$PPV = \frac{0.85 	imes 0.01}{(0.85 	imes 0.01) + (0.10 	imes 0.99)} = \frac{0.0085}{0.0085 + 0.099} \approx 0.079 	ext{ or } 7.9\%$$

**Key Point:** A positive TST with PPV of ~8% means 92% of positive tests are false positives (latent TB infection, not active disease). Confirmatory testing is mandatory.

## Investigation Hierarchy for TB Diagnosis

```mermaid
flowchart TD
  A[Positive TST]:::outcome --> B{Clinical symptoms?}:::decision
  B -->|Yes or Suspicious CXR| C[Chest X-ray + Sputum smear]:::action
  B -->|No symptoms| D[IGRA or repeat TST]:::action
  C --> E{AFB positive?}:::decision
  E -->|Yes| F[Confirm TB diagnosis]:::outcome
  E -->|No| G[Culture, GeneXpert MTB/RIF]:::action
  D --> H{IGRA positive?}:::decision
  H -->|Yes + symptoms| I[Chest X-ray]:::action
  H -->|No| J[Latent TB, no active disease]:::outcome
```

## Why Chest X-ray and Sputum Smear Microscopy?

| Investigation | Sensitivity | Specificity | Purpose | Diagnostic? |
|---|---|---|---|---|
| **TST** | 85% | 90% | Screening | No |
| **Chest X-ray** | 80–90% | 70–80% | Detect infiltrates | Presumptive |
| **Sputum smear microscopy** | 50–80% | 95–99% | Confirm active TB | Yes (if AFB+) |
| **GeneXpert MTB/RIF** | 98% | 99% | Confirm + detect rifampicin resistance | Yes |
| **IGRA** | 90% | 96% | Differentiate latent from active | No |

**High-Yield:** In a patient with a positive TST and clinical suspicion of active TB, the next investigation is **chest X-ray + sputum smear microscopy** because:
1. Chest X-ray identifies infiltrates consistent with TB
2. Sputum smear microscopy (AFB staining) directly detects *Mycobacterium tuberculosis*
3. Together they provide presumptive diagnosis and infectivity assessment
4. This is the WHO-recommended algorithm for TB diagnosis in resource-limited settings

**Clinical Pearl:** TST positivity alone does NOT diagnose active TB. It indicates TB infection (active or latent). Confirmation requires evidence of disease: symptoms, imaging findings, and/or microbiological confirmation (AFB smear or culture).

**Mnemonic:** **AFB-CXR-TST** — After a positive screening Test, check Sputum for AFB and get a Chest X-Ray to confirm active disease.

[cite:Park 26e Ch 5]

Answer

A. Repeat tuberculin skin test after 2 weeks

Answer

C. Start anti-tuberculosis therapy immediately

Answer

D. Interferon-gamma release assay (IGRA)

Explanation

Clinical Scenario Analysis

Calculating PPV for TST

Investigation Hierarchy for TB Diagnosis

Why Chest X-ray and Sputum Smear Microscopy?

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Investigation	Sensitivity	Specificity	Purpose	Diagnostic?
TST	85%	90%	Screening	No
Chest X-ray	80–90%	70–80%	Detect infiltrates	Presumptive
Sputum smear microscopy	50–80%	95–99%	Confirm active TB	Yes (if AFB+)
GeneXpert MTB/RIF	98%	99%	Confirm + detect rifampicin resistance	Yes
IGRA	90%	96%	Differentiate latent from active	No