Tuberculosis in Children

Background

• In 2017, there were an estimated 1 million cases of pediatric tuberculosis (TB) globally, representing about 10% of the 10 million incident cases overall.
• In the United States, 460 cases of TB in children ≤ 14 years old were reported during 2014, with an incidence of 0.8 cases per 100,000 children, a rate lower than any other age group.
• Major risk factors for acquisition of infection include birth or residence in an endemic area, exposure to adults with active TB, and exposure to second hand smoke.
• Factors associated with increased risk of progressing from latent infection to active disease include recent acquisition of infection, younger age, immunocompromise, particularly HIV infection, and chronic comorbidities such as diabetes mellitus.
• The most common clinical presentation of tuberculosis in children is pulmonary parenchymal disease with associated intrathoracic lymphadenopathy.
• Extrapulmonary disease is also more common in children than in adults, most often manifesting as tuberculous lymphadenitis or pleural disease.
• Less common extrapulmonary manifestations include pericardial, central nervous system, skeletal, and miliary disease.
• Congenital TB is very rare, but reported, and may present with fever, respiratory distress, hepato/splenomegaly, or with nonspecific symptoms such as poor feeding or lethargy.

Evaluation

• Consider the diagnosis of tuberculosis (TB) in children born in endemic areas or with known exposure to an adult with active TB, presenting with cough and/or fever, weight loss or failure to thrive, lymphadenopathy, hepato- or splenomegaly, meningitis or ascites, or other suggestive signs and symptoms.
• Screen children with suspected latent or active infection using either a tuberculin skin test (TST) or interferon gamma release assay (IGRA).
  • TST is preferred in children < 5 years old, but IGRA is preferred in children ≥ 5 years old with history of bacille Calmette-Guérin (BCG) vaccination.
  • Either test is acceptable in children > 5 years old who lack a history of BCG vaccination.
• In children who screen positive, perform a thorough physical examination, including a careful neurologic assessment and a chest x-ray.
• In children who screen negative, consider additional evaluation in those who remain at increased risk for TB, as a negative result does not rule out active disease.
• Detection of the organism in affected tissue by acid-fast staining, culture, or nucleic acid amplification testing is required for confirmation of diagnosis but is not always possible.
• For children with suspected pulmonary disease, obtain a sputum sample, but note that diagnostic yield is low, as disease in children tends to be paucibacillary, and high-quality samples may be difficult to obtain due to absence of cough, decreased sputum production, or lack of tussive force needed to produce an adequate sample.
• In the absence of bacterial confirmation, the diagnosis can be made clinically based on risk factors, signs and symptoms and/or characteristic chest x-ray findings.
• Due to the association between HIV infection and TB, consider HIV testing in all children with suspected or confirmed TB.

Management

• Report all cases of pediatric tuberculosis to local health authorities for coordination of management.
• The diagnosis in children often represents a recent transmission and should trigger a source case investigation.
• American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America (ATS/CDC/IDSA)-recommended empiric treatment for tuberculosis in children with pulmonary tuberculosis caused by Mycobacterium tuberculosis known or suspected to be susceptible to all first-line drugs is a 2-month initial phase followed by a 4-month continuation phase (Strong recommendation).
  • The 2-month initial phase includes:
    • isoniazid 5 mg/kg/day (maximum 300 mg/day, 10 mg/kg/day in children) orally, IV, or intramuscularly
    • rifampin 10 mg/kg/day (maximum 600 mg/day, 15 mg/kg/day in children) orally or IV
    • pyrazinamide 25 mg/kg/day (maximum 2 g/day, 15-30 mg/kg/day in children) orally
    • ethambutol 15 mg/kg/day (maximum 1.6 g/day, 20 mg/kg/day in children) orally
  • The 4-month continuation phase includes:
    • isoniazid 5 mg/kg/day (maximum 300 mg/day, 10 mg/kg/day in children) orally, IV, or intramuscularly
    • rifampin 10 mg/kg/day (maximum 600 mg/day, 15 mg/kg/day in children) orally or IV
  • Extend the continuation phase for patients with cavitation on initial chest radiograph and positive sputum cultures after 2 months of therapy, tuberculous meningitis, or skeletal tuberculosis.
  • The CDC has issued guidance regarding use of rifampin and rifapentine for treatment of active and latent TB infection after some manufacturers detect nitrosamine impurities in their products.
• Adjunctive corticosteroids are recommended for all children with tuberculous meningitis, airway impingement from lymphadenopathy, and can be considered for those with pleural, pericardial, abdominal, or severe miliary disease.