What is the BCG (Bacillus Calmette-Guérin) vaccine?

What is the BCG Vaccine?

BCG (Bacillus Calmette-Guérin) is a live attenuated vaccine derived from Mycobacterium bovis that was developed in 1921 and remains the only licensed vaccine against tuberculosis, primarily used to prevent severe forms of TB in children, particularly tuberculous meningitis and miliary TB. 1

Origin and Development

• BCG was created by Albert Calmette and Camille Guérin at the Pasteur Institute in Lille, France, through attenuation of a Mycobacterium bovis strain 1
• First administered to humans in 1921, making it one of the oldest vaccines still in use 1, 2
• Multiple BCG vaccine strains exist worldwide, all derived from the original strain but with variations due to genetic changes over time and different production techniques 1
• In the United States, the Tice strain (developed at the University of Illinois) is the only currently licensed BCG vaccine 1, 3

Mechanism and Protection

The vaccine provides strong protection (52-100% efficacy) against severe disseminated forms of tuberculosis in children, including tuberculous meningitis and miliary TB, but offers variable and limited protection (2-80% efficacy) against pulmonary tuberculosis, especially in adults. 1

• Meta-analyses confirm approximately 86% protective efficacy against meningeal and miliary TB in children 1
• Protection against pulmonary TB in adolescents and adults remains equivocal and highly variable 1
• The largest community trial in southern India (1968-1971) showed no protective efficacy in adults and only 17% efficacy in children after 15 years 1

Current Use in the United States

BCG vaccination is NOT recommended as a routine TB control strategy in the United States because the overall risk of M. tuberculosis infection is low, and the vaccine interferes with tuberculin skin testing used for TB surveillance. 1, 3

Limited Indications for BCG in the U.S.:

• Children with negative tuberculin skin tests who have continuous exposure to persons with active TB and cannot be placed on isoniazid preventive therapy 1
• Children with continuous exposure to patients with organisms resistant to both isoniazid and rifampin 1
• Children in groups with exceptionally high annual rates of new infection (>1% per year) 1
• Healthcare workers may be considered only in settings with high likelihood of transmission of multidrug-resistant TB strains, and only after comprehensive infection-control measures have failed 1, 3

Administration and Expected Reactions

• The vaccine can be administered intradermally or percutaneously (multiple puncture technique), depending on the specific product 1
• Pre-vaccination requires tuberculin skin testing showing <5mm induration to confirm no prior TB infection 3
• Normal reaction includes formation of a bluish-red pustule within 2-3 weeks, which ulcerates and heals within 3 months, leaving a permanent scar 3
• Follow-up tuberculin skin testing should be performed 3 months after vaccination to document tuberculin reactivity 3

Contraindications and Safety Concerns

BCG is absolutely contraindicated in immunocompromised persons, including those with HIV infection, due to risk of disseminated BCG infection. 1, 3

• Should be avoided during pregnancy, though no harmful fetal effects have been documented 1, 3
• Not recommended for children under 6 years of age when using oral formulations 1
• Adverse reactions include severe ulceration and regional adenitis (1-10% of vaccinees), with rare disseminated infections and osteitis (1-10 per million doses) 1

Non-Tuberculosis Applications

• BCG has demonstrated non-specific immune benefits against non-tuberculous infections in newborns and older adults through "trained immunity" mechanisms 2, 4
• Widely used as immunotherapy for non-muscle invasive bladder cancer 2
• Global coverage at birth approaches 90% worldwide, with approximately 130 million infants vaccinated yearly in TB-endemic countries 5, 4

Key Clinical Pitfall

The major limitation of BCG vaccination in the U.S. is that it causes tuberculin skin test reactivity, which interferes with the primary TB control strategy of identifying and treating latent TB infection with isoniazid preventive therapy. 1 This is why physicians considering BCG vaccination should consult with local TB control programs before proceeding 1, 3.