What is the approach to diagnosing tuberculosis (TB) in children?

Diagnosing Tuberculosis in Children

The diagnosis of pediatric TB is most reliably established through the triad of: (1) a positive tuberculin skin test, (2) abnormal chest radiograph or physical examination, and (3) discovery of a link to a known or suspected case of contagious pulmonary TB. 1

Clinical Approach to Diagnosis

Diagnostic Challenges

• Children with TB often present differently from adults:
  • Rarely produce sputum voluntarily
  • Typically have low bacterial load (culture-positive in only ~50% of cases)
  • Often present with non-specific symptoms
  • Radiographic findings differ from adult patterns 1

Essential Diagnostic Components

1. Tuberculin Skin Testing (TST)

   • Recommended interpretation thresholds:
     • ≥5 mm induration: HIV-infected children, close contacts of infectious TB cases, immunosuppressed children 2
     • ≥10 mm induration: Children <4 years, immigrants from high-prevalence countries, children with certain medical conditions 2
     • ≥15 mm induration: Children with no known risk factors 2
   • Important limitations:
     • ~10% of children with culture-positive TB may have negative TST initially 1
     • Up to 50% with miliary TB or meningitis may have initially negative TST 1
     • Children <2 years and those with HIV are more likely to have false-negative results 1

2. Interferon-Gamma Release Assays (IGRAs)

   • Higher specificity than TST, especially in BCG-vaccinated children 2
   • Not affected by prior BCG vaccination
   • Preferred for immunocompromised patients 2
   • Like TST, cannot distinguish between active TB and latent TB infection 2

3. Microbiological Testing

   • Early morning gastric aspirates: Culture-positive in approximately 50% of children with TB disease 1
   • Acid-fast stains: Positive in only 0-20% of children with TB 1
   • Molecular tests (e.g., GeneXpert MTB/RIF): Higher sensitivity than conventional methods 2
   • Collection of multiple specimens on different days is recommended 2

4. Radiographic Evaluation

   • Common findings in children:
     • Localized pulmonary infiltrate with hilar lymphadenopathy
     • Multiple lobe involvement in up to 25% of cases
     • Atelectasis from hilar adenopathy compressing bronchi 1
   • Differs from adult pattern (typically apical infiltrates with cavitation) 1

5. Source Case Investigation

   • Critical for diagnosis and determining drug susceptibility
   • Parents and other close contacts should be evaluated for TB disease 1
   • Particularly important since TB in young children usually occurs within weeks to months of infection 1
   • Helps establish likely drug susceptibility pattern when cultures from child are negative 1

Special Considerations

HIV-Infected Children

• Clinical presentation similar to HIV-negative children but with higher risk of treatment failure and mortality 1
• TST reactivity further decreased by HIV infection 1
• Annual TST recommended beginning at age 3-12 months 1
• Consider IGRAs due to better performance in immunocompromised patients 2

Young Infants

• May present with progressive respiratory distress, apnea, jaundice, and abdominal distention 1
• TST may take 2-3 months after infection to become positive 1
• Incubation period for severe TB (meningitis, disseminated disease) may be only 4-6 weeks 1
• Empiric treatment should be considered for exposed infants with negative TST, particularly those <3 years 1

Drug-Resistant TB

• Diagnosis is either confirmed (isolation of resistant M. tuberculosis) or presumed (clinical evidence plus risk factors) 1
• Risk factors include contact with confirmed/presumed DR-TB source or failure to respond to first-line regimen 1
• Extensive efforts should be made to confirm diagnosis with intensive sampling 1

Diagnostic Algorithm

1. Initial Assessment

   • Evaluate for TB symptoms: persistent cough, fever, weight loss/failure to thrive
   • Identify risk factors: TB contact, HIV status, immigration from high-prevalence area
   • Perform TST or IGRA

2. If Positive TST/IGRA or Strong Clinical Suspicion:

   • Obtain chest radiograph
   • Attempt microbiological confirmation:
     • Collect early morning gastric aspirates (3 consecutive days)
     • For older children who can produce sputum: collect sputum samples
     • Consider alternative specimens based on suspected site of disease
   • Identify potential source case and determine drug susceptibility pattern

3. Diagnostic Decision Making:

   • Confirmed TB: Positive culture or molecular test
   • Presumptive TB: Based on positive TST/IGRA, compatible clinical/radiographic findings, and TB contact history
   • If microbiological confirmation not possible, use the diagnostic triad approach 1

Common Pitfalls to Avoid

• Relying solely on TST results (false negatives occur, especially in young or immunocompromised children)
• Waiting for bacteriological confirmation before initiating treatment in severely ill children
• Failing to investigate potential source cases
• Overlooking extrapulmonary manifestations (lymph nodes, CNS, bone, etc.)
• Using adult diagnostic criteria for children
• Mass testing of low-risk children (leads to false positives and unnecessary treatment) 1

By following this structured approach to diagnosis, clinicians can improve the detection and management of TB in children, leading to better outcomes and reduced morbidity and mortality.