Tuberculosis (Pediatrics: Learning Outcomes)

1. Define the term "Tuberculosis"

Definition: Tuberculosis (TB) is an infectious disease caused by pathogens of the Mycobacterium tuberculosis complex (most commonly Mycobacterium tuberculosis). It primarily manifests as pulmonary disease but can affect any organ system.
Differential: The student distinguishes between Tuberculosis and Nontuberculous Mycobacteriosis (NTM). NTM (e.g., M. avium) represents an etiologically distinct group with different clinical presentations, diagnostic protocols, and therapeutic management.

Global Burden: TB remains a leading cause of infectious disease morbidity and mortality worldwide (a "top killer" according to the WHO), with over 10 million new cases and approximately 1.5 million deaths annually.
High-Incidence Areas: Sub-Saharan Africa, India, Southeast Asia, China, and the former Soviet Union states.
Czech Republic: Incidence remains very low (fewer than 500 cases per year, including ~25 children), despite a recent uptick associated with migration from Ukraine.

Global perspective: Poverty, malnutrition, HIV infection.
Low-incidence countries: Close contact with an individual with active pulmonary TB, origin from or long-term stay in a high-incidence country, Roma ethnicity, and secondary immunodeficiencies (HIV, long-term systemic corticosteroid therapy, biological therapy/TNF inhibitors, or organ transplantation).

Tuberculous Infection (TBI / Latent TB): Positive Tuberculin Skin Test (TST/MxII) and/or IGRA (e.g., QuantiFERON), but without clinical symptoms and with normal findings on imaging.
Tuberculosis (Active TB Disease): Positive TST and/or IGRA, often with abnormal findings on Chest X-ray (CXR), clinical symptoms, and potential microbiological confirmation.

Age-related risk: The youngest children face the highest risk; infants (<1 year) have up to a 40% chance of developing active disease following exposure.
Bimodal distribution (in low-incidence countries): Peaks occur in children under 5 years and in adolescents; school-age children are rarely affected.
Presentation:
- Under 5 years: Often asymptomatic; cases are typically identified through active contact tracing (screening).
- Adolescents: Present with "adult-type" symptoms: chronic cough, low-grade fever, night sweats, weight loss, and anorexia.
- Extrapulmonary TB: Manifestations depend on location (cervical lymphadenitis, TB meningitis, osteoarticular TB) or route of spread. The most severe is hematogenous dissemination, manifesting as acute miliary TB or basilar meningitis.

Most pediatric cases are diagnosed via active screening (contact tracing) rather than passive presentation due to minimal symptomatology.

The 3 Main Diagnostic Pillars:

Epidemiological link: History of contact with an infected individual.
Immunological tests: TST and/or IGRA (a combination is optimal, especially in children >5 years).
Imaging: Chest X-ray (parenchymal lesions, lymphadenopathy, pleural effusion, miliary pattern). CT is indicated if CXR is unclear or in children <10 years with positive epidemiology/immunology but negative CXR.

Labs: Inflammatory markers are usually minimal (mildly elevated ESR, typically no leukocytosis or high CRP); microcytic anemia may be present.

Microbiological Diagnosis Principles:

Microscopy: Ziehl-Neelsen staining. Children often have paucibacillary forms; microbiological positivity is found in only 10–25% of pediatric cases.
Culture: Solid and liquid media (Bactec). Solid media results take 6–9 weeks for a definitive result.
PCR (NAAT): DNA detection of M. tuberculosis (e.g., GeneXpert). Results within 24–48 hours, including detection of resistance genes (e.g., Rifampin).
Specimens: Most commonly gastric lavage (since children swallow sputum), followed by bronchoalveolar lavage (BAL), induced sputum, or biopsies.

Setting: Pediatric TB patients belong in specialized centers (in the Czech Republic: Thomayer University Hospital). Treatment is managed by a pediatric pulmonologist.
Pharmacotherapy: A combination of 4 anti-tuberculosis drugs: Isoniazid (INH), Rifampicin (R), Pyrazinamide (Z), and Ethambutol (E).
Standard Regimen (Pulmonary TB):
- Initial phase (2 months): INH + R + Z + E.
- Continuation phase (4 months): INH + R.
Complicated forms: (Meningitis, bone TB, disseminated TB) require treatment for 9–12 months.
Drug-Resistant TB: Requires 2nd and 3rd line antituberculotics; treatment is longer, more complex, and more expensive.

Vaccination (BCG): Targeted in the CR for high-risk groups (based on a risk-definition questionnaire: family history, high-incidence country origin, or contact).
Isolation and Mandatory Treatment: Ensuring active cases are treated to stop transmission.
Contact Tracing & TBI Treatment: Identifying exposed individuals and treating latent infection to prevent progression to active disease.