Tuberculosis in Children

Introduction to Pediatric Tuberculosis

Tuberculosis (TB) in children remains a significant global health concern, particularly in developing countries. Pediatric TB presents unique challenges in diagnosis and management due to its often non-specific symptoms and the difficulty in obtaining diagnostic samples.

Key points:

Caused by Mycobacterium tuberculosis
Can affect various organ systems, but pulmonary TB is most common
Children are more likely to progress from infection to disease
Diagnosis is often based on clinical features, exposure history, and supportive investigations

Epidemiology of Pediatric Tuberculosis

Pediatric TB accounts for approximately 10-15% of the global TB burden. The epidemiology varies significantly across different regions and is influenced by socioeconomic factors.

Key epidemiological features:

Higher incidence in low- and middle-income countries
Children under 5 years of age are at highest risk
Close contact with an adult TB case is a major risk factor
HIV co-infection significantly increases the risk of TB disease
Malnutrition is an important predisposing factor

According to the WHO, in 2019:

An estimated 1.2 million children fell ill with TB globally
Over 200,000 children died from TB, including those with HIV-associated TB

Pathophysiology of Pediatric Tuberculosis

The pathophysiology of TB in children differs from adults due to their developing immune system and the rapid progression from infection to disease.

Key aspects of pathophysiology:

Primary infection usually occurs in the lungs
Formation of the Ghon focus: a small subpleural granulomatous lesion
Lymphatic spread to regional lymph nodes (usually hilar) forms the primary complex
Hematogenous dissemination can lead to miliary TB or extrapulmonary involvement
Children are more likely to develop progressive primary disease rather than latent infection
Risk of progression to disease is highest in infants and young children

Immunological factors:

Th1 cell-mediated immunity is crucial for controlling TB infection
Children may have a less robust Th1 response, contributing to disease progression
Tuberculin skin test (TST) and Interferon-Gamma Release Assays (IGRAs) may be less reliable in young children

Clinical Presentation of Pediatric Tuberculosis

The clinical presentation of TB in children can be highly variable and often non-specific, making diagnosis challenging.

Common symptoms:

Persistent cough (>2 weeks)
Fever
Weight loss or failure to thrive
Night sweats
Fatigue or reduced playfulness

Pulmonary TB:

Most common form in children
May present with cough, wheeze, or stridor due to airway compression
Chest X-ray may show hilar lymphadenopathy, lung infiltrates, or cavitation (rare in young children)

Extrapulmonary TB:

More common in children than adults
Common sites: lymph nodes, central nervous system, bones/joints, abdomen
TB meningitis: can present with headache, vomiting, altered mental status, and focal neurological deficits
Lymph node TB: usually cervical, presenting as painless, firm lymphadenopathy
Bone and joint TB: can cause chronic pain, swelling, and limited mobility

Disseminated TB:

More common in infants and immunocompromised children
Can present with severe systemic symptoms, hepatosplenomegaly, and respiratory distress
Miliary pattern on chest X-ray

Diagnosis of Pediatric Tuberculosis

Diagnosing TB in children is challenging due to the paucibacillary nature of the disease and difficulty in obtaining suitable specimens.

Diagnostic approach:

Detailed history, including TB exposure and risk factors
Thorough physical examination
Tuberculin skin test (TST) or Interferon-Gamma Release Assay (IGRA)
Chest X-ray
Microbiological confirmation when possible

Microbiological diagnosis:

Sputum smear microscopy: often negative in children due to paucibacillary disease
Culture: gold standard but can take several weeks
Xpert MTB/RIF assay: rapid molecular test, more sensitive than smear microscopy
Specimen collection: may include gastric aspirates, induced sputum, nasopharyngeal aspirates, or bronchoalveolar lavage

Imaging studies:

Chest X-ray: primary tool for pulmonary TB diagnosis
CT scan: may be helpful in complex cases or extrapulmonary TB
Ultrasound: useful for abdominal TB or peripheral lymphadenopathy

Other investigations:

Full blood count: may show anemia or elevated white cell count
HIV testing: recommended for all children with suspected TB
Tissue biopsy: may be necessary for certain forms of extrapulmonary TB

Treatment of Pediatric Tuberculosis

Treatment of pediatric TB follows similar principles to adult TB but requires careful consideration of dosing and potential side effects.

General principles:

Multi-drug regimen to prevent drug resistance
Prolonged treatment duration (usually 6-12 months)
Directly Observed Therapy (DOT) recommended to ensure adherence
Regular monitoring for treatment response and adverse effects

First-line drugs:

Isoniazid (INH)
Rifampicin (RIF)
Pyrazinamide (PZA)
Ethambutol (EMB)

Treatment regimens:

Drug-susceptible pulmonary TB: 2 months of INH, RIF, PZA, EMB followed by 4 months of INH and RIF
Extrapulmonary TB: may require longer treatment duration (9-12 months)
TB meningitis: 12 months of treatment, often with the addition of corticosteroids

Drug-resistant TB:

Requires specialized regimens based on drug susceptibility testing
May include second-line drugs such as fluoroquinolones, aminoglycosides, and newer agents like bedaquiline
Treatment duration is typically longer (18-24 months)

Monitoring and follow-up:

Regular clinical assessment for treatment response
Monitoring of growth and development
Liver function tests to assess for drug-induced hepatotoxicity
Follow-up chest X-rays to evaluate radiological improvement

Prevention of Pediatric Tuberculosis

Prevention strategies are crucial in reducing the burden of pediatric TB, particularly in high-risk populations.

Key prevention strategies:

BCG vaccination
Contact tracing and screening
Isoniazid Preventive Therapy (IPT)
Infection control measures

BCG vaccination:

Recommended in high TB burden countries
Provides protection against severe forms of TB in young children
Efficacy varies, particularly for pulmonary TB

Contact tracing and screening:

Systematic screening of household contacts of TB cases
Includes symptom screening, TST/IGRA, and chest X-ray as appropriate
Early identification of infected children for preventive therapy or treatment

Isoniazid Preventive Therapy (IPT):

Recommended for children <5 years who are close contacts of TB cases
Typically 6-9 months of daily isoniazid
Alternative regimens include 3 months of isoniazid plus rifampicin

Infection control measures:

Early diagnosis and treatment of infectious TB cases
Proper cough hygiene and use of masks for infectious patients
Adequate ventilation in healthcare settings and households

General Principles of Pediatric TB Treatment

The treatment of pediatric TB follows several key principles:

Multi-drug regimen: To prevent the development of drug resistance and ensure effective treatment
Prolonged duration: Usually 6-12 months, depending on the site and severity of disease
Weight-based dosing: Medication doses are calculated based on the child's weight
Directly Observed Therapy (DOT): Recommended to ensure adherence to the treatment regimen
Family-centered approach: Involving caregivers in the treatment process
Regular monitoring: For treatment response and adverse effects

The goals of treatment are to:

Cure the patient and restore quality of life
Prevent death from active TB or its late effects
Prevent relapse of TB
Reduce transmission of TB to others
Prevent the development and transmission of drug resistance

First-Line Drugs for Pediatric TB

The main first-line drugs used in pediatric TB treatment are:

Isoniazid (INH):
- Dosage: 10-15 mg/kg/day (maximum 300 mg/day)
- Mechanism: Inhibits mycolic acid synthesis in the mycobacterial cell wall
- Side effects: Hepatotoxicity, peripheral neuropathy (can be prevented with pyridoxine supplementation)
Rifampicin (RIF):
- Dosage: 10-20 mg/kg/day (maximum 600 mg/day)
- Mechanism: Inhibits bacterial RNA synthesis
- Side effects: Hepatotoxicity, orange discoloration of body fluids, drug interactions
Pyrazinamide (PZA):
- Dosage: 30-40 mg/kg/day (maximum 2000 mg/day)
- Mechanism: Active against intracellular bacilli in acidic environments
- Side effects: Hepatotoxicity, arthralgia
Ethambutol (EMB):
- Dosage: 15-25 mg/kg/day (maximum 1000 mg/day)
- Mechanism: Inhibits arabinogalactan synthesis in mycobacterial cell wall
- Side effects: Optic neuritis (rare in children at recommended doses)

These drugs are typically well-tolerated in children, but regular monitoring for adverse effects is essential.

Treatment Regimens for Pediatric TB

Treatment regimens vary based on the site and severity of disease:

1. Drug-susceptible Pulmonary TB:

Intensive phase: 2 months of daily INH, RIF, PZA, and EMB
Continuation phase: 4 months of daily INH and RIF

2. Extrapulmonary TB:

Most forms: Same as pulmonary TB
TB meningitis or osteoarticular TB: Extended to 12 months total duration

3. HIV co-infection:

Similar regimens, but potential for drug interactions with antiretroviral therapy
May require longer treatment duration in some cases

4. Latent TB Infection (LTBI):

6-9 months of daily INH
Alternative: 3 months of daily INH and RIF
Newer regimen: 3 months of weekly INH and Rifapentine (for children ≥2 years)

The choice of regimen should be based on local guidelines, drug susceptibility patterns, and individual patient factors.

Treatment of Drug-Resistant TB in Children

Drug-resistant TB poses significant challenges in pediatric patients:

1. Multidrug-Resistant TB (MDR-TB):

Requires specialized regimens based on drug susceptibility testing
Treatment duration typically 18-24 months
May include drugs such as:
- Fluoroquinolones (e.g., Levofloxacin, Moxifloxacin)
- Injectable agents (e.g., Amikacin, Capreomycin) - now less preferred due to toxicity
- Bedaquiline (for children ≥6 years)
- Linezolid
- Cycloserine
- Ethionamide or Prothionamide

2. Extensively Drug-Resistant TB (XDR-TB):

Requires highly individualized regimens
May include newer drugs like Delamanid and Bedaquiline
Often necessitates expert consultation

Treatment of drug-resistant TB in children requires careful consideration of efficacy, safety, and the limited data available on many second-line drugs in pediatric populations.

Special Considerations in Pediatric TB Treatment

Several factors require special attention in managing pediatric TB:

1. Age-related considerations:

Neonates: Higher risk of disseminated disease, may require longer treatment
Infants and young children: More prone to severe forms of TB, careful monitoring essential
Adolescents: Risk of poor adherence, may benefit from peer support programs

2. Nutritional support:

Malnutrition is common and can affect treatment outcomes
Nutritional assessment and support should be integrated into TB care

3. Fixed-dose combinations (FDCs):

Can improve adherence and prevent monotherapy
Pediatric FDCs are now available and recommended by WHO

4. Central Nervous System TB:

Requires drugs with good CNS penetration (e.g., INH, PZA, Ethionamide)
Adjunctive corticosteroids are recommended

5. Pregnancy and breastfeeding:

Most first-line TB drugs are safe in pregnancy and during breastfeeding
Streptomycin should be avoided in pregnancy

Monitoring and Follow-up

Regular monitoring is crucial for ensuring treatment success and detecting complications early:

1. Clinical monitoring:

Monthly weight checks to adjust drug dosages
Assessment of treatment adherence and tolerability
Evaluation of symptom resolution

2. Laboratory monitoring:

Baseline liver function tests, especially for children with risk factors for hepatotoxicity
Monthly liver function tests if baseline tests are abnormal or there are ongoing risk factors
HIV-infected children require more frequent laboratory monitoring

3. Radiological follow-up:

Chest X-rays at 2-3 months and at treatment completion for pulmonary TB
More frequent imaging may be needed for complicated cases

4. Microbiological follow-up:

Not routinely required in uncomplicated cases due to paucibacillary nature of pediatric TB
May be necessary in drug-resistant TB or treatment failure

5. Post-treatment follow-up:

Clinical evaluation at 3, 6, and 12 months after treatment completion
Assess for possible relapse or sequelae of TB

Adjunctive Therapies in Pediatric TB

Several adjunctive therapies may be used in specific situations:

1. Corticosteroids:

Recommended in TB meningitis and pericarditis
May be beneficial in severe lymph node disease with airway compression
Typically prednisone or dexamethasone, tapered over 6-8 weeks

2. Pyridoxine (Vitamin B6) supplementation:

Recommended for all infants, children with malnutrition, and HIV-infected children receiving INH
Prevents INH-induced peripheral neuropathy

3. Immunomodulatory therapies:

Still experimental, but being studied for use in severe TB
Examples include host-directed therapies targeting inflammatory responses

4. Nutritional support:

Micronutrient supplementation, especially Vitamin D and Zinc
High-protein, high-calorie diets for malnourished children

5. Physiotherapy and occupational therapy:

Important in cases of osteoarticular TB or TB meningitis with neurological sequelae

These adjunctive therapies should be considered on a case-by-case basis, taking into account the specific clinical presentation and complications of TB in each child.