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Tuberculosis (TB) Diagnosis in Children — Structured Answer
(For PDU Medical College, Rajkot | Pediatrics University Practical/Theory Examination | 15 Marks)
INTRODUCTION
Diagnosis of childhood TB is challenging due to:
- Paucibacillary nature of disease (especially <5 years)
- Difficulty in obtaining sputum samples
- Non-specific symptoms overlapping with other illnesses
- Microbiological confirmation achieved in only 15–50% of pediatric cases
A stepwise diagnostic algorithm combining clinical, immunological, radiological, and microbiological criteria is therefore used.
(Treatment of Drug-Susceptible Tuberculosis, p. 29)
DIAGNOSTIC ALGORITHM — STEP BY STEP
✦ STEP 1 — HISTORY & CLINICAL EVALUATION
A. Contact History
- Close contact with a sputum smear-positive TB case (especially household contact) is one of the strongest risk factors in children
- Duration, proximity, and smear status of the index case must be documented
B. Symptoms (Cardinal Features — Think "3 P's + 1 F")
| Symptom | Duration Required |
|---|
| Persistent cough | >2 weeks (non-remitting) |
| Prolonged fever | >2 weeks (low-grade, evening rise) |
| Poor weight gain / Weight loss | Unexplained, not responding to nutrition |
| Fatigue / Lethargy | Chronic, progressive |
Other features: night sweats, anorexia, failure to thrive, lymphadenopathy
C. Predisposing Factors
- Malnutrition (severe acute malnutrition = high risk)
- HIV infection
- Immunosuppressive therapy
- Unvaccinated status (no BCG)
✦ STEP 2 — TUBERCULIN SKIN TEST (TST / MANTOUX TEST)
- Antigen: 2 TU of PPD-RT23 or 5 TU PPD-S injected intradermally on the volar aspect of the forearm
- Read at 48–72 hours — measure transverse induration (NOT erythema)
Interpretation in Children:
| Induration | Positive If |
|---|
| ≥5 mm | HIV-positive child, severely malnourished, close TB contact, immunosuppressed |
| ≥10 mm | All other children in high-burden settings (India) |
| ≥15 mm | Low-risk individuals in low-burden settings |
False Negatives (Anergy):
- Severe malnutrition, miliary TB, HIV, measles, steroid use, recent live viral vaccine, early disease
False Positives:
- BCG vaccination (usually <10 mm), NTM (Non-tuberculous mycobacteria) infection
Note: A positive TST indicates sensitization/infection, NOT necessarily active disease.
✦ STEP 3 — CHEST X-RAY (CXR)
Essential first-line investigation in all suspected cases.
Characteristic Findings in Primary Childhood TB:
| Finding | Significance |
|---|
| Hilar / mediastinal lymphadenopathy | Most common; pathognomonic of primary TB |
| Ghon's focus | Parenchymal opacity (usually mid/lower lobe) |
| Ghon's complex | Ghon focus + ipsilateral hilar lymphadenopathy |
| Ranke complex | Calcified Ghon complex (healed TB) |
| Lobar / segmental collapse | Lymph node compression of bronchus ("epituberculosis") |
| Miliary pattern | Uniform 1–2 mm nodules — hematogenous spread |
| Pleural effusion | Usually unilateral |
| Cavitation | Rare in young children; seen in adolescents (adult-type TB) |
(Tuberculosis, NICE Guidelines, p. 26)
✦ STEP 4 — MICROBIOLOGICAL CONFIRMATION
A. Sample Collection
| Age Group | Sample of Choice |
|---|
| Children ≥6 years | 3 spontaneous sputum samples (including 1 early morning) |
| Children <6 years | Induced sputum (preferred over gastric aspirate) or Nasopharyngeal aspirate |
| Hospitalized infants | Gastric aspirate — 3 consecutive early morning samples |
B. Tests Performed on Samples
| Test | Details |
|---|
| AFB Smear (ZN stain) | Rapid, cheap; low sensitivity in children (~10–40%) |
| Culture (LJ medium) | Gold standard; takes 6–8 weeks; sensitivity 30–40% |
| MGIT (liquid culture) | Faster results in 2–3 weeks |
| CBNAAT / Xpert MTB/RIF | Rapid PCR; detects MTB + RIF resistance in 2 hours; preferred in India (NTEP) |
| Line Probe Assay (LPA) | Detects MDR-TB; 1st and 2nd line drug resistance |
CBNAAT is recommended as the first-line diagnostic test under India's NTEP (National TB Elimination Programme) for all presumptive pediatric TB cases.
✦ STEP 5 — IGRA (Interferon Gamma Release Assay)
- Tests: QuantiFERON-TB Gold Plus (QFT-Plus), T-SPOT.TB
- Measures IFN-γ release from T-cells sensitized to ESAT-6 and CFP-10 antigens
- Not affected by BCG vaccination — more specific than TST
- Limitations in children <5 years: higher indeterminate results; not routinely recommended for young children in India
- Used as adjunct to TST, not a replacement in most Indian settings
✦ STEP 6 — ADDITIONAL INVESTIGATIONS
| Investigation | Indication / Finding |
|---|
| CBC | Lymphocytosis, anemia of chronic disease, raised ESR |
| ESR | Non-specific; elevated (>20 mm/hr) in active TB |
| CRP | Elevated, non-specific |
| LFT / KFT | Baseline before starting anti-TB therapy |
| HIV testing | Mandatory in all children with TB |
| CECT Chest | Lymphadenopathy not clear on plain X-ray |
| USG Abdomen | Abdominal TB — mesenteric lymph nodes, ascites |
| FNAC / Biopsy | Lymph node TB — shows caseating granuloma with Langhans giant cells |
| CSF analysis | TBM — lymphocytic pleocytosis, low sugar, high protein, spider web clot |
| Bone Marrow Biopsy | Miliary TB |
| Adenosine Deaminase (ADA) | Elevated in TB pleural effusion (>40 U/L), TB meningitis, peritonitis |
✦ STEP 7 — SCORING SYSTEMS / DIAGNOSTIC SCORING
Indian Academy of Pediatrics (IAP) Diagnostic Score / WHO Symptom-Based Criteria
Used when microbiological confirmation is not possible (common in India):
| Parameter | Score |
|---|
| Close TB contact | +2 |
| Positive TST (≥10 mm) | +2 |
| Suggestive CXR | +2 |
| Symptoms >2 weeks (fever/cough/wt loss) | +1 each |
| Lymphadenopathy | +1 |
| Not responding to 2 weeks of broad-spectrum antibiotics | +1 |
Score ≥6 → Probable TB → Start anti-TB treatment
Score 3–5 → Possible TB → Investigate further / trial of ATT considered
Score <3 → TB unlikely
✦ STEP 8 — THERAPEUTIC DIAGNOSTIC TRIAL
- When microbiological confirmation is unavailable and score is borderline:
- Start 2-month trial of anti-TB therapy (HRZE)
- Positive response (weight gain, fever resolution, radiological improvement) supports diagnosis
- Widely practiced in India per NTEP guidelines for paucibacillary childhood TB
FLOWCHART SUMMARY
Child with suspected TB
↓
History: Contact + Symptoms >2 weeks + Risk factors
↓
Mantoux Test + Chest X-ray (SIMULTANEOUSLY)
↓
┌──────────────────────┐
│ CBNAAT / Sputum / │
│ Gastric aspirate │
└──────────────────────┘
↓
Microbiologically CONFIRMED?
Yes → Start ATT (RNTCP/NTEP protocol)
No → Apply Diagnostic Score (IAP/WHO criteria)
↓
Score ≥6 → Probable TB → Start ATT
Score 3–5 → Additional tests (HRCT/IGRA/FNAC/Biopsy)
Score <3 → Alternative diagnosis
↓
Always: HIV test + Baseline LFT + Drug sensitivity testing
SPECIAL SITUATIONS
| Situation | Key Points |
|---|
| TB + HIV | TST may be falsely negative; use IGRA + CBNAAT; lower threshold for treatment |
| Miliary TB | CXR (miliary pattern) + bone marrow biopsy + fundoscopy (choroidal tubercles) |
| TB Meningitis | CSF — lymphocytosis, high protein, low glucose, AFB smear/culture/Xpert MTB |
| Abdominal TB | ADA in ascitic fluid, USG, CT abdomen, peritoneal biopsy |
| MDR-TB suspicion | If contact is MDR-TB patient or no response to 1st line — LPA / DST |
IMPORTANT POINTS FOR VIVA
- Gold standard for TB diagnosis = Culture on LJ medium
- Rapid molecular test of choice in India = CBNAAT (Xpert MTB/RIF)
- Most common CXR finding in childhood TB = Hilar lymphadenopathy
- Confirmatory test for lymph node TB = FNAC / Biopsy — caseating granuloma with Langhans giant cells
- Mantoux is read at 48–72 hours — induration, not erythema
- BCG scar does not exclude TB; BCG-induced Mantoux reaction is usually <10 mm
- ADA >40 U/L in pleural/CSF/ascitic fluid is supportive of TB
- IGRA is not affected by BCG — preferred in BCG-vaccinated children when differentiating infection from BCG response
REFERENCES
- Treatment of Drug-Susceptible Tuberculosis — WHO Guidelines (p. 29)
- Tuberculosis — NICE Clinical Guidelines (p. 26)
- IAP Standard Treatment Guidelines — Pediatric TB
- NTEP (National TB Elimination Programme) — India, 2023
- Nelson Textbook of Pediatrics, 21st Edition — Chapter on Tuberculosis
- WHO Operational Handbook on Tuberculosis — Module 2 (Diagnosis), 2022
Examiner's Tip: For a 15-mark answer at PDU Medical College, cover at minimum — (i) clinical criteria, (ii) Mantoux interpretation, (iii) CXR findings, (iv) microbiological tests including CBNAAT, (v) diagnostic scoring, and (vi) special situations (TB+HIV / miliary TB). This answer covers all of them with appropriate depth.