Paediatric Tuberculosis

Tuberculosis in children differs fundamentally from adult disease: it is usually paucibacillary, more often extrapulmonary, harder to confirm bacteriologically, and progresses faster from infection to disease. A child is a sentinel event — it signals recent transmission from an infectious adult, almost always within the household.

Why paediatric TB is different

• Primary disease predominates (first exposure in a previously uninfected child), whereas adults usually have post-primary (reactivation) disease.
• Paucibacillary: low organism load → smear and culture are frequently negative → diagnosis is often clinical/composite.
• Rapid progression: the younger the child, the shorter the latent window and the higher the risk of disseminated forms (miliary TB, TB meningitis).
• Age-stratified risk of progression to disease after infection: highest in infants (<1 yr, up to 40–50%), lowest in the 5–10 yr "favoured age", rising again at adolescence.

High-yield: A child with TB = recent transmission. Always hunt for the adult index/source case (reverse contact tracing) and screen all household contacts.

Pathophysiology — the primary (Ghon) complex

After inhalation, bacilli are deposited in the subpleural well-ventilated zones (lower lobe, middle lobe, lower part of upper lobe). The sequence:

1. Ghon focus — the initial subpleural parenchymal lesion (caseating granuloma).
2. Lymphangitis — spread along draining lymphatics.
3. Regional lymphadenopathy — hilar/paratracheal nodes enlarge.

Ghon focus + lymphangitis + regional lymph nodes = Primary (Ghon) Complex.

When the Ghon focus heals and calcifies along with the calcified draining node, it becomes the Ranke complex (= healed/calcified primary complex).

High-yield (eponyms):

• Ghon focus = parenchymal lesion alone.
• Ghon / primary complex = focus + lymphangitis + lymph node (= "primary complex").
• Ranke complex = calcified (healed) primary complex (focus + node both calcified).
• Simon focus = apical metastatic focus seeded during primary haematogenous spread; later site of reactivation.
• Assmann focus = early reactivation infiltrate in the subclavicular region.

Term	What it is
Ghon focus	Single subpleural parenchymal granuloma
Primary (Ghon) complex	Ghon focus + lymphangitis + hilar node
Ranke complex	Calcified Ghon focus + calcified node (healed)
Simon focus	Apical seed from haematogenous spread (reactivation site)

In children, the enlarged lymph node, not the parenchymal focus, dominates the disease — nodes can compress bronchi (causing collapse/hyperinflation or "epituberculosis") or erode into a bronchus (endobronchial spread).

Clinical features

Pulmonary TB

• Persistent cough >2 weeks not improving, fever >2 weeks without an alternative cause.
• Documented weight loss / failure to thrive / faltering growth, fatigue, anorexia.
• A markedly positive contact history with a sputum-positive adult.

High-yield: The WHO/NTEP triad of suspicion = persistent fever >2 wk + persistent cough >2 wk + weight loss/no weight gain + fatigue, especially with a TB contact.

Common extrapulmonary forms in children

• Lymph node TB (tubercular lymphadenitis) — commonest extrapulmonary form; cervical nodes most common ("scrofula"). Matted, non-tender, may form cold abscess / collar-stud abscess and discharging sinus.
• TB meningitis (TBM) — most feared; basal meningitis with cranial nerve palsies (esp. CN VI, III, VII), hydrocephalus, vasculitic infarcts.
• Miliary TB — diffuse haematogenous dissemination.
• Skeletal TB — Pott's spine (gibbus), hip, knee.
• Abdominal TB — ascites, doughy abdomen, ileocaecal involvement.

Tuberculous meningitis (TBM)

Staged using the British Medical Research Council (MRC) staging:

Stage	Features
I	Non-specific (fever, irritability), no neuro deficit, GCS 15, fully conscious
II	Altered sensorium / signs of meningism / focal deficit / single cranial nerve palsy, GCS 11–14
III	Stupor/coma (GCS <10), dense deficits, multiple cranial nerve palsies

CSF in TBM (classic exam values):

Parameter	TBM finding
Appearance	Clear, may form a cobweb / spider-web clot on standing
Opening pressure	Raised
Cells	Lymphocytic pleocytosis (10–500/µL); neutrophils early
Protein	High (often very high, 100–500 mg/dL)
Glucose	Low (CSF:plasma ratio <0.5)
Chloride	Low (classic but non-specific)
ADA	Raised (>10 U/L supportive)

High-yield: TBM CSF = clear fluid, lymphocytosis, very high protein, low sugar, cobweb clot. CT brain: basal meningeal enhancement, hydrocephalus, infarcts (basal ganglia), tuberculomas.

Imaging

• Hilar / mediastinal lymphadenopathy is the hallmark of childhood pulmonary TB (more than the parenchymal focus).
• Miliary TB: chest X-ray shows innumerable uniform 1–2 mm "millet seed" nodules evenly distributed in both lung fields.
• Other patterns: segmental collapse-consolidation, cavitation (rare in young children, common in adolescents — adult-type disease), pleural effusion (older children).

High-yield: Miliary = "millet seed" 1–2 mm diffuse nodules. Most consistent paediatric CXR finding overall = persistent hilar/mediastinal lymphadenopathy.

Diagnosis & investigation of choice

Because confirmation is hard, paediatric TB diagnosis is a composite: contact + symptoms + tuberculin test + imaging + microbiology.

1. Tuberculin Skin Test (Mantoux / TST)

• 0.1 mL of 5 TU PPD injected intradermally on the flexor forearm → read at 48–72 h, measure the transverse diameter of induration (not erythema) in mm.
• Type IV (delayed hypersensitivity) reaction.

Interpretation cut-offs (induration):

Cut-off	Considered positive in
≥5 mm	HIV-positive, severe malnutrition, immunosuppressed, recent close contact of infectious TB, fibrotic CXR changes
≥10 mm	All other children (immunocompetent, irrespective of BCG)

• False negatives: miliary/disseminated TB, TBM, severe malnutrition, measles/other viral infections, recent live vaccine, HIV, very young infants, faulty technique, steroids.
• A positive Mantoux indicates infection, not necessarily disease, and cannot distinguish the two.

High-yield: Mantoux = 5 TU PPD intradermal, read 48–72 h, measure induration. ≥10 mm positive in normal child; ≥5 mm in HIV/malnourished/close contact. BCG does not invalidate a strongly positive test.

2. Microbiological confirmation

• Specimens: young children cannot expectorate → use gastric aspirate (3 early-morning, fasting, on consecutive days), induced sputum, or nasopharyngeal aspirate.
• CBNAAT / GeneXpert MTB/RIF (NAAT) is now the first-line/initial diagnostic test of choice — detects M. tuberculosis DNA and rifampicin resistance within ~2 hours; far more sensitive than smear.
• Culture (LJ medium / liquid MGIT) = gold standard but slow (LJ 6–8 weeks).
• AFB smear (ZN stain) — low yield (paucibacillary).
• Lymph node TB: FNAC/biopsy → caseating granuloma with Langhans giant cells; send for CBNAAT.

High-yield: CBNAAT (GeneXpert) on gastric aspirate / induced sputum is the recommended initial diagnostic test in a child with presumptive TB — gives diagnosis + rifampicin resistance status quickly.

3. IGRA

• Interferon-gamma release assays (QuantiFERON, T-SPOT) — measure IFN-γ to TB-specific antigens; not affected by BCG, but like TST cannot distinguish infection from disease and are not superior to TST in young children.

WHO / Kenneth Jones scoring (resource-limited settings)

A weighted clinical scoring chart historically used to support diagnosis when bacteriology is unavailable, combining:

• Duration of illness, nutritional status / weight,
• Family history of TB / contact,
• Mantoux reaction,
• Suggestive findings on examination/X-ray.

A total score ≥7 supports starting anti-TB treatment. (Modern NTEP relies more on CBNAAT + composite criteria, but the scoring concept remains examinable.)

Diagnostic approach (stepwise)

Presumptive TB (cough/fever >2 wk + weight loss ± contact) → CXR + Mantoux → collect gastric aspirate/induced sputum for CBNAAT → CBNAAT positive → confirmed TB, check Rif resistance → CBNAAT negative but strong clinical + CXR + Mantoux + contact → clinically diagnosed TB, treat → always do contact tracing + HIV test + nutritional assessment.

Management — NTEP (RNTCP) paediatric regimen

India follows daily fixed-dose combination (FDC) therapy under NTEP (the National TB Elimination Programme, formerly RNTCP), weight-band based, given under DOTS.

Standard drug-sensitive regimen:

• Intensive Phase (2 months): HRZE — isoniazid (H) + rifampicin (R) + pyrazinamide (Z) + ethambutol (E).
• Continuation Phase (4 months): HRE (ethambutol now retained in the daily regimen).

So uncomplicated TB = 2HRZE + 4HRE (total 6 months).

Paediatric daily doses (mg/kg):

Drug	Dose (mg/kg/day)	Key toxicity
Isoniazid (H)	10 (7–15)	Peripheral neuropathy (give pyridoxine), hepatitis
Rifampicin (R)	15 (10–20)	Orange secretions, hepatitis, enzyme induction
Pyrazinamide (Z)	35 (30–40)	Hepatotoxicity, hyperuricaemia/arthralgia
Ethambutol (E)	20 (15–25)	Optic neuritis (dose-related, reversible)

High-yield: Drug-sensitive paediatric TB = 2HRZE + 4HRE daily, weight-band FDCs under NTEP. Always add pyridoxine in malnourished/HIV/breastfed infants to prevent INH neuropathy.

Extended duration / steroid use:

• TB meningitis & osteoarticular (spinal) TB → continuation phase extended to 10 months (total 12 months: 2HRZE + 10HRE).
• Adjunctive corticosteroids (prednisolone) are indicated in TBM (reduces mortality/disability), TB pericarditis, and airway compression by nodes / endobronchial TB.
• In TBM, ethionamide is often substituted for ethambutol owing to better CSF penetration in NTEP paediatric TBM regimens.

Drug-resistant TB: MDR-TB (resistance to H + R) is treated with longer regimens including newer drugs (bedaquiline, delamanid) per NTEP DR-TB guidelines; CBNAAT rifampicin resistance triggers referral.

High-yield: TBM and spine TB → treat for 12 months total and add steroids in TBM. Optic neuritis = ethambutol; peripheral neuropathy = isoniazid (prevent with pyridoxine).

BCG vaccine

• Bacille Calmette–Guérin = live attenuated Mycobacterium bovis.
• Dose: 0.1 mL intradermal (0.05 mL in neonates <1 month) over left deltoid (insertion).
• Given at birth in the Indian National Immunization Schedule.
• A papule → ulcer → scar develops over 4–6 weeks (normal evolution).

What BCG protects against:

• Strongly protects infants/young children against severe disseminated forms — miliary TB and TB meningitis.
• Does not reliably prevent primary infection or adult pulmonary TB.

High-yield: BCG's proven benefit = prevention of miliary TB and TBM in young children. Given intradermally over the left deltoid at birth.

BCG complications: local abscess, BCG lymphadenitis (regional axillary adenitis), keloid; disseminated BCG-osis in severe immunodeficiency (SCID) — hence BCG is contraindicated in symptomatic HIV / known severe combined immunodeficiency.

BCG and Mantoux: prior BCG may cause a small (<10 mm) reaction but does not account for strongly positive (≥10 mm) results — do not dismiss a positive Mantoux as "due to BCG."

TB Preventive Therapy (TPT / chemoprophylaxis)

Indicated to prevent progression of infection to disease:

• All household child contacts <5 years of a pulmonary TB case (after ruling out active disease).
• HIV-infected children (any age) exposed/infected.
• TST-positive children on immunosuppression.

Regimens (NTEP): 6 months of isoniazid (6H, 10 mg/kg/day) is classic; shorter rifapentine-based (3HP) and 3HR regimens are now preferred where available.

High-yield: Asymptomatic child <5 yr in contact with a sputum-positive adult, active TB excluded → give isoniazid preventive therapy (6H) ± pyridoxine.

Complications

• TB meningitis: hydrocephalus, infarcts, blindness, deafness, SIADH, neurological sequelae, death.
• Miliary spread with multiorgan involvement, ARDS.
• Bronchial obstruction by enlarged nodes → lobar collapse, obstructive emphysema, bronchiectasis.
• Pott's spine: cold (psoas) abscess, gibbus deformity, paraplegia (Pott's paraplegia).
• Pleural effusion / empyema, constrictive pericarditis.
• Drug toxicity: hepatitis (H/R/Z), optic neuritis (E), neuropathy (H).

Key differentials

Presentation	Differentials to consider
Chronic cough + hilar nodes	Sarcoidosis, lymphoma, fungal infection, recurrent bacterial pneumonia
Cervical lymphadenitis	Reactive/pyogenic adenitis, atypical (non-tuberculous) mycobacteria, Kikuchi, lymphoma, HIV
Lymphocytic CSF, low sugar	Partially treated bacterial meningitis, fungal (cryptococcal) meningitis, viral, malignancy
Miliary CXR pattern	Miliary fungal disease, hypersensitivity pneumonitis, metastases, sarcoid, varicella pneumonia
FTT + fever	Malignancy, HIV, chronic infection, immunodeficiency

Recently asked / exam angle

• Eponym matching is a perennial favourite: Ghon focus vs primary complex vs Ranke (calcified/healed) vs Simon focus (apical reactivation).
• Mantoux specifics: dose 5 TU PPD, read at 48–72 h, measure induration, cut-offs ≥5 / ≥10 mm; reaction is type IV hypersensitivity; causes of false-negative Mantoux (miliary, TBM, malnutrition, measles, HIV).
• CBNAAT/GeneXpert as the initial test of choice + its ability to detect rifampicin resistance.
• TBM CSF picture (lymphocytic, high protein, low glucose, cobweb clot) and MRC staging.
• NTEP regimen: 2HRZE + 4HRE; 12 months for TBM/spine; steroids in TBM; pyridoxine prophylaxis.
• BCG: protects against miliary TB & TBM, intradermal left deltoid at birth, complications (BCG adenitis), contraindicated in SCID/symptomatic HIV.
• Commonest extrapulmonary site in children = lymph node (cervical); commonest CXR finding = hilar lymphadenopathy.
• Specimen of choice in non-expectorating child = gastric aspirate (early morning, fasting).

Rapid revision

1. A child with TB = recent transmission → trace the adult source case and screen contacts.
2. Childhood TB is paucibacillary, often extrapulmonary, and progresses fast (infants highest risk).
3. Ghon focus = parenchymal lesion; primary complex = focus + lymphangitis + node; Ranke = calcified/healed; Simon = apical reactivation focus.
4. Hilar/mediastinal lymphadenopathy is the hallmark CXR finding; miliary = "millet-seed" 1–2 mm diffuse nodules.
5. Mantoux = 0.1 mL of 5 TU PPD intradermal, read 48–72 h, measure induration; ≥10 mm positive (≥5 mm if HIV/malnourished/close contact); type IV reaction.
6. False-negative Mantoux: miliary TB, TBM, malnutrition, measles, HIV, steroids.
7. CBNAAT (GeneXpert) on gastric aspirate/induced sputum = initial diagnostic test of choice (also detects rifampicin resistance); culture (MGIT/LJ) = gold standard.
8. TBM CSF: clear with cobweb clot, lymphocytic, high protein, low glucose; CT → basal enhancement, hydrocephalus, infarcts.
9. Drug-sensitive TB = 2HRZE + 4HRE daily under NTEP/DOTS; TBM & spine = 12 months + steroids in TBM.
10. Toxicities: ethambutol → optic neuritis, isoniazid → neuropathy (give pyridoxine), pyrazinamide → hepatitis/hyperuricaemia.
11. BCG (live attenuated M. bovis) at birth, intradermal left deltoid → protects against miliary TB and TBM; contraindicated in SCID/symptomatic HIV.
12. Asymptomatic child <5 yr contact of smear-positive case, active disease excluded → isoniazid preventive therapy (6H).