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SHORT ESSAY: TUBERCULOSIS IN CHILDREN (Pediatric TB)

Definition

• TB Infection (TBI) / Latent TB: positive TST or IGRA, no symptoms, normal or healed-pattern chest X-ray
• TB Disease: active clinical/radiological disease

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Epidemiology

• Children are usually infected by a close adult contact (source case) with active pulmonary TB
• Young children (<5 years) and immunocompromised children are at highest risk for rapid progression and disseminated disease
• Incidence is highest in resource-limited settings; in the US, most cases occur in immigrants and minority populations

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Pathogenesis

1. Primary complex forms: lung parenchymal focus (Ghon focus) + draining hilar lymph node = Ghon complex
2. Usually contained by cell-mediated immunity (TBI state)
3. In young/immunocompromised children: hematogenous spread → miliary TB, meningitis, or extrapulmonary disease
4. Tuberculin skin test becomes positive 2–10 weeks after infection (median 3–4 weeks)

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Clinical Features

Pulmonary TB

• Often asymptomatic, especially in young children — frequently identified only through contact tracing or screening
• Older children: fever, weight loss/poor weight gain, cough, night sweats, chills
• Children <5 years: may present as miliary TB, meningitis, or persistent pneumonia not responding to antibiotics
• Cavitation is uncommon in childhood TB (unlike adults); bony involvement is more common than in adults

Extrapulmonary TB (most common: cervical lymphadenitis)

• Congenital TB: mimics neonatal sepsis; presents in first 90 days with bronchopneumonia and hepatosplenomegaly

Miliary TB

• Hematogenous dissemination during primary or reactivation disease
• Features: fever, anorexia, night sweats, cough, weight loss, hepatosplenomegaly, lymphadenopathy
• Choroidal tubercles on fundoscopy — pathognomonic
• Diffuse 1–3 mm nodular infiltrates on chest X-ray (millet seed pattern)

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Diagnosis

Tuberculin Skin Test (TST / Mantoux)

• 5 TU PPD (0.1 mL) injected intradermally into volar forearm
• Read at 48–72 hours — measure induration in mm (transversely)
• Interpretation (by risk):

• False negatives: ~10–40% of culture-proven TB in children; caused by young age, malnutrition, immunosuppression, viral infections (measles, varicella), disseminated TB

IGRA (Interferon-Gamma Release Assay)

• QuantiFERON-TB Gold Plus, T-SPOT.TB
• Not recommended for children <2 years (immune response unreliable); used with caution <5 years
• Advantage: not affected by BCG vaccination (unlike TST)
• Cannot distinguish TBI from active TB disease

Microbiological Confirmation

• Culture from: sputum, gastric aspirate (best specimen in young children — 3 consecutive early morning aspirates), bronchial washings, pleural fluid, CSF, urine, tissue biopsy
• Culture confirmation achieved in only 30–40% of children due to paucibacillary nature and difficulty obtaining specimens
• NAATs (e.g., Xpert MTB/RIF): FDA-cleared for rapid detection; doesn't replace culture
• AFB smear: low yield in children

Chest Radiology

• Hilar/mediastinal lymphadenopathy (most characteristic)
• Segmental/lobar atelectasis or infiltrate
• Pleural effusion
• Miliary pattern
• CT chest: useful when plain film is nonspecific

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Treatment (Red Book 2021 / AAP)

TB Infection (Latent TB)

Active TB Disease

• Intensive phase: RIPE (Rifampin + Isoniazid + Pyrazinamide + Ethambutol) × 2 months
• Continuation phase: Isoniazid + Rifampin × 4 months
• Total = 6 months; DOT (Directly Observed Therapy) is strongly recommended

• Initial 2 months: INH + RIF + PZA + ethionamide (or aminoglycoside)
• Continuation: INH + RIF × 7–10 months → Total 9–12 months
• Adjunctive corticosteroids (dexamethasone) reduce morbidity/mortality

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Prevention

• BCG vaccine: widely used globally; protects against miliary TB and TB meningitis in children but has variable efficacy against pulmonary TB
• Contact tracing and treatment of all household contacts
• Isolation of infectious adults

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SHORT ESSAY: ENTERIC FEVER IN CHILDREN (Typhoid/Paratyphoid)

Definition

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Etiology

• Gram-negative bacilli, family Enterobacteriaceae
• S. Typhi belongs to O serogroup 9
• Exclusively a human pathogen — no animal reservoir
• Reservoir: chronic human carriers (gallbladder infection); occasionally urinary tract

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Epidemiology

• Highly endemic in South/Southeast Asia, sub-Saharan Africa, Latin America
• Transmission: feco-oral route — ingestion of food/water contaminated by a carrier or acute case
• In the US: ~300–400 cases/year, mostly in returned travelers from South Asia
• Chronic carrier state: more common in adults, females, and those with cholelithiasis; uncommon in children
• Incubation period: 7–14 days (range 3–60 days)

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Clinical Features

In Older Children

• Week 1: Fever (rises in stepladder pattern), headache, malaise, anorexia, lethargy, abdominal pain
• Week 2: High sustained fever, hepatomegaly, splenomegaly, rose spots (salmon-colored maculopapular rash on trunk, present in ~30%), relative bradycardia (pulse-temperature dissociation — less reliable in children)
• Week 3: Complications — intestinal hemorrhage (~10%), intestinal perforation, altered consciousness (delirium, stupor, coma), shock

In Infants and Toddlers

• May present as a mild, nonspecific febrile illness with self-limited bacteremia
• Or as severe invasive infection with sustained bacteremia and meningitis
• Diarrhea (pea-soup consistency) or constipation can be early features

Complications

• Intestinal perforation and hemorrhage
• Encephalopathy (severe: delirium, coma, shock)
• Myocarditis (rare)
• Cholecystitis, hepatitis
• Relapse: up to 17% within 4 weeks (higher in immunocompromised)

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Diagnosis

Blood Culture

• Gold standard for enteric fever
• Sensitivity ~60% in children
• Best in first week of illness (bacteremic phase)

Bone Marrow Culture

• Sensitivity ~90% — highest yield, even after antibiotics started
• Useful when blood culture is negative

Stool Culture

• Positive in ~30% of cases
• More useful in later weeks of illness

Bile (Duodenal String) Culture

• Blood culture + bile culture together: 90% sensitive in children with clinical enteric fever

Widal Test

• Measures agglutinating antibodies to O and H antigens
• Not recommended by CDC for diagnosis — poor sensitivity and specificity, difficult to interpret in endemic populations and with prior vaccination/infection

PCR/Molecular Testing

• Emerging, not yet standard
• Multiple stool PCR platforms are FDA-cleared for Salmonella detection

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Treatment

Drug Choice (guided by susceptibility)

Duration

• Uncomplicated disease: 7–10 days (most antibiotics)
• If TMP-SMX or amoxicillin: 14 days
• MDR S. Typhi (not XDR): ceftriaxone or azithromycin
• XDR S. Typhi (Pakistan outbreak, resistant to ceftriaxone + ampicillin + ciprofloxacin + TMP-SMX): azithromycin or carbapenems only

Corticosteroids

• Reserved for severe enteric fever (delirium, stupor, coma, shock)
• Regimen: Dexamethasone IV 3 mg/kg initial dose, then 1 mg/kg every 6 hours × 48 hours total

Chronic Carrier Treatment

• 4 weeks oral ciprofloxacin or norfloxacin (concentrated in bile)
• Cholecystectomy if antibiotic therapy fails

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Isolation & Infection Control

• Contact precautions for diapered/incontinent children for duration of illness
• In enteric fever: continue until 3 consecutive negative stool cultures (obtained ≥48 hours after last antibiotic dose)
• For XDR typhoid: contact precautions throughout hospitalization

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Prevention

• Typhoid vaccines:
  • Vi polysaccharide vaccine (Typhim Vi): IM, approved ≥2 years, single dose, efficacy ~70%
  • Ty21a oral live attenuated vaccine (Vivotif): ≥6 years, 4 doses on alternate days
  • Neither protects against paratyphoid
• Safe water, food hygiene, handwashing
• Surveillance and treatment of chronic carriers

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Key Exam Points to Remember

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• Definition (TBI vs active disease), pathogenesis (Ghon complex → hematogenous spread)
• Clinical features unique to children (often asymptomatic, rare cavitation, cervical adenitis most common extrapulmonary, miliary/meningitis in <5 years, congenital TB)
• Diagnosis: TST interpretation table (≥5/10/15 mm thresholds), IGRA limitations in young children, gastric aspirate as best specimen, NAATs, CXR findings
• Treatment tables: Latent TB regimens (3HP, 4R, 9H) and Active TB (RIPE 2 months → HR 4 months; meningitis 9–12 months with dexamethasone)
• Prevention: BCG, contact tracing

• Etiology, epidemiology (human-only reservoir, feco-oral, XDR outbreak in Pakistan)
• Clinical features by age: stepladder fever/rose spots/relative bradycardia in older children; nonspecific/meningitis in infants
• Diagnosis: blood culture 60% vs bone marrow 90% sensitivity, string culture combination 90%, why Widal test is discouraged
• Treatment: ceftriaxone/azithromycin as empiric; fluoroquinolones avoided; dexamethasone for severe disease (3 mg/kg then 1 mg/kg q6h × 48h)
• XDR typhoid management, vaccines