What are the indications, dosing, contraindications, and alternative management for Bacillus Calmette‑Guérin (BCG) vaccination in children and adults at risk for tuberculosis?

BCG Vaccine: Indications, Dosing, Contraindications, and Alternatives

Primary Recommendation

BCG vaccination in the United States is reserved for highly selective situations only: infants and children in settings with high likelihood of M. tuberculosis transmission where no other protective measures can be implemented, and potentially for healthcare workers exposed to multidrug-resistant TB strains when comprehensive infection control has failed. 1

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Indications for BCG Vaccination

Pediatric Indications

• Consider BCG for infants and children residing in settings with high likelihood of M. tuberculosis transmission and subsequent infection, provided no other measures (such as removing the child from the source of infection) can be implemented. 1
• BCG provides >80% protection against severe forms of TB including meningitis and miliary TB in young children, though protection against pulmonary TB is variable (0-80% efficacy). 1, 2
• The vaccine demonstrates 86% protective effect against meningeal and miliary TB in children based on meta-analysis of clinical trials. 1

Healthcare Worker Indications

• BCG may be considered for healthcare workers employed in settings with high likelihood of transmission of isoniazid and rifampin-resistant M. tuberculosis strains, only after comprehensive TB infection-control precautions have been implemented and proven unsuccessful. 1
• BCG is generally not recommended for most healthcare workers because it interferes with tuberculin skin testing for latent TB infection detection and the protective efficacy against pulmonary TB in adults is uncertain. 1

When BCG is NOT Recommended

• BCG vaccination is not recommended for inclusion in routine immunization or TB control programs in the United States. 1
• The overall risk for acquiring M. tuberculosis infection is low for the total U.S. population, making national vaccination policy unnecessary. 1
• Physicians considering BCG should consult local TB control programs before proceeding. 1

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Absolute Contraindications

Immunocompromised Patients

• BCG vaccination is absolutely contraindicated in all immunocompromised infants and adults, including those with HIV infection, as disseminated BCG disease can be fatal. 3
• Fatal disseminated BCG disease occurs at 0.06-1.56 cases per million doses, primarily in immunocompromised persons. 4
• Disseminated BCG infection risk is greatly increased in patients with severe combined immunodeficiency disease (SCID). 5

HIV-Specific Considerations

• If maternal HIV status is unknown or positive, confirm infant HIV testing before vaccination. 3
• BCG is not recommended for children and adults infected with HIV because of potential adverse reactions. 1
• HIV infection significantly increases risk for lymphadenitis and disseminated complications. 4

Maternal Biologic Therapy Exposure

• If the mother received anti-TNF biologics (infliximab, adalimumab, golimumab) during the second half of pregnancy, BCG vaccination MUST be delayed until at least 6 months of age. 3
• Certolizumab has minimal transplacental transfer and does not require vaccination delay. 3

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Dosing and Administration

Pre-Vaccination Requirements

• Tuberculin skin testing should be negative (<5mm induration) before vaccination. 3
• Perform Mantoux tuberculin skin test using 0.1 mL of 5 TU PPD. 1, 2

Administration Technique

• Intradermal injection is required; subcutaneous injection increases rates of local reactions. 4
• The Tice strain is currently available for immunization in the United States. 1

Special Populations

• Preterm infants (26-37 weeks gestational age) and low birth weight infants (0.69-2.5 kg) can safely receive BCG once medically stable. 3

Post-Vaccination Monitoring

• Perform tuberculin skin testing 3 months post-vaccination to document reactivity. 3
• Standard local reactions (induration, pustule formation, lymphadenopathy) typically persist for up to 3 months after vaccination. 4

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Complications and Management

Expected vs. Abnormal Reactions

• Reactions beyond 3-4 months warrant evaluation for BCG osteitis or disseminated infection. 3, 4
• Ulceration at vaccination site, regional suppurative lymphadenitis, caseous lesions, or purulent drainage can occur within 5 months and persist for several weeks. 4

BCG Osteitis

• BCG osteitis affecting epiphyses of long bones can occur from 4 months to 2 years after vaccination. 4
• Evaluate for systemic symptoms including fever, bone pain, or joint swelling. 4

Lymphadenitis Management

• For isolated local reactions with nonadherent lymph nodes, observe as they heal spontaneously without treatment. 4
• For adherent or fistulated lymph nodes, drainage with direct instillation of anti-TB drug into the lesion may be required. 4

Disseminated BCG Disease

• If disseminated BCG disease is suspected, initiate anti-TB therapy immediately but NEVER use pyrazinamide, as all BCG strains are universally resistant. 3, 4
• Consider HIV testing in any patient with prolonged or severe BCG reactions, as immunocompromised status dramatically increases complication risk. 4

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Alternative Management Strategies

Primary TB Prevention in the United States

• TB prevention and control efforts focus on interrupting transmission from active infectious TB patients and skin testing high-risk individuals with preventive therapy for positive results. 1
• The preferred method is Mantoux tuberculin skin test using 0.1 mL of 5 TU PPD. 1

Management of TB-Exposed Children

• For a child exposed to open pulmonary TB, perform tuberculin skin testing immediately and begin isoniazid preventive therapy regardless of BCG vaccination status. 2
• If tuberculin skin test is positive (≥10 mm), initiate isoniazid preventive therapy at 10-15 mg/kg daily (up to 300 mg) for 9 months after ruling out active TB disease. 2
• If tuberculin skin test is negative, begin isoniazid preventive therapy immediately and repeat testing in 8-10 weeks to detect conversion during the window period. 2
• A positive tuberculin skin test (≥10 mm induration) in a BCG-vaccinated child who is a TB contact should be interpreted as true M. tuberculosis infection, not vaccine effect. 2

Drug-Resistant TB Exposure

• If the source case has isoniazid-resistant TB, use rifampin for preventive therapy instead. 2
• If the source case has multidrug-resistant TB (resistant to both isoniazid and rifampin), consult a TB specialist immediately. 2

Source Control

• The infectious source must be treated immediately with directly observed therapy (DOT) to prevent prolonged infectiousness. 2
• If the adult source fails to cooperate with treatment, remove the child from contact until the patient is no longer infectious. 2

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Critical Clinical Pitfalls

• Never delay preventive therapy while waiting for tuberculin skin test results in household contacts, as risk of progression to active TB is highest in the first 2 years after infection. 2
• BCG vaccination status should not influence the decision to provide preventive therapy to exposed contacts. 2
• Persistent reactions at 4 months should not be dismissed as normal and require evaluation for complications. 4
• Pyrazinamide should never be used in BCG-related infections due to universal resistance. 4
• Children <2 years are at particularly high risk for tuberculous meningitis or miliary TB. 2