What are the recommended indications, dosing, contraindications, and adverse effects of the Bacillus Calmette‑Guérin (BCG) vaccine for tuberculosis prevention and intravesical bladder cancer therapy?

BCG Vaccine: Indications, Dosing, Contraindications, and Adverse Effects

Indications for BCG Vaccination

BCG vaccination is NOT routinely recommended in the United States for tuberculosis prevention, and should only be considered in highly specific circumstances where other TB control measures have failed. 1

Tuberculosis Prevention (Extremely Limited Use)

BCG vaccination may be considered only for tuberculin-negative children (<5 mm induration with 5 TU PPD) in the following situations: 1

• Children with continuous exposure to persons with active TB who cannot be placed on isoniazid preventive therapy 1
• Children with continuous exposure to patients with organisms resistant to both isoniazid and rifampin 1
• Children belonging to groups with exceptionally high annual rates of new TB infection (>1% per year) 1

BCG is no longer recommended for healthcare workers or other adults at high risk for acquiring TB infection in the United States. 1

Bladder Cancer Therapy

Intravesical BCG instillation is the most effective treatment for non-muscle invasive bladder cancer, particularly for carcinoma in situ, and is FDA-approved as first-line therapy. 2, 3 This represents a distinct therapeutic application separate from vaccination.

Dosing and Administration

Pre-Vaccination Requirements

• Tuberculin skin testing with 5 TU PPD must be performed first 1, 4
• BCG should only be administered to persons with <5 mm induration on tuberculin testing 1, 4

Vaccine Preparation and Dose

The Tice strain (Organon, Inc.) is the only BCG vaccine currently licensed in the United States for tuberculosis prevention. 1

Standard dosing: 1, 4

• Adults and children ≥1 month: 0.3 mL of reconstituted vaccine administered percutaneously
• Infants <30 days: One-half the usual dose (prepared by increasing diluent volume)
• Infants who received half-dose should receive full dose after age 1 year if tuberculin testing remains <5 mm 1

Administration Technique

Percutaneous administration via multiple-puncture disc: 1, 4

• Clean the lower deltoid area with alcohol or acetone swab in circular motion from center outward 4
• Allow skin to dry thoroughly 4
• Place 0.3 mL of reconstituted vaccine on the skin 1
• Deliver through multiple-puncture disc 1
• Reconstituted vaccine must be protected from light, refrigerated when not in use, and used within 8 hours 1

Post-Vaccination Follow-up

Expected reaction timeline: 1, 4

• Bluish-red pustule forms within 2-3 weeks 1, 4
• Ulceration occurs at approximately 6 weeks, forming a lesion ~5 mm in diameter 1
• Scabs form and heal within 3 months, typically leaving a permanent scar 1, 4
• Draining lesions should be kept clean and bandaged 1, 4

Tuberculin skin testing should be performed 3 months after BCG administration to document tuberculin reactivity, with results recorded in millimeters of induration. 1

Contraindications

Absolute Contraindications

BCG vaccination is absolutely contraindicated in immunocompromised persons: 1

• HIV infection (both symptomatic and asymptomatic in the United States) 1
• Congenital immunodeficiency 1
• Leukemia 1
• Lymphoma 1
• Generalized malignancy 1
• Immunosuppression from corticosteroids 1
• Immunosuppression from alkylating agents 1
• Immunosuppression from antimetabolites 1
• Immunosuppression from radiation therapy 1

Pregnancy

BCG vaccination is not recommended during pregnancy, although no harmful effects to the fetus have been documented. 1

Relative Contraindications

• History of severe local or systemic reaction after a previous BCG dose 1
• Positive tuberculin skin test (≥5 mm induration) 1

Adverse Effects and Complications

Common Local Reactions (Expected)

Mild to moderate local reactions occur frequently and are considered normal: 1

• Muscular soreness at injection site 1
• Erythema 1
• Induration 1
• Purulent drainage 1
• Ulceration at vaccination site (expected within 6 weeks) 1

Higher rates of local reactions result from subcutaneous injection compared to intradermal injection. 1

Severe Local Reactions

Severe ulceration and regional adenitis occur in approximately 1-10% of vaccinees: 1

• Prolonged ulceration at vaccination site 1
• Regional suppurative lymphadenitis 1
• Adherent or fistulated lymph nodes 1

Management of BCG adenitis: 1

• Nonadherent lesions heal spontaneously without treatment 1
• Adherent or fistulated lymph nodes may require drainage and direct instillation of anti-TB drug into the lesion 1

Serious Complications (Rare)

Disseminated BCG infection is the most serious complication: 1

• Fatal disseminated BCG disease occurs at a rate of 0.06-1.56 cases per million doses 1
• Deaths occur primarily among immunocompromised persons 1
• All BCG strains are resistant to pyrazinamide, which must never be used for treatment 1

BCG osteitis: 1

• Affects epiphyses of long bones, particularly the leg 1
• Occurs 4 months to 2 years after vaccination 1
• Risk varies by country: 0.01 cases per million (Japan) to 32.5-43.4 cases per million (Sweden/Finland) 1
• Treated effectively with anti-TB medications, though surgery may be necessary 1

Other severe reactions reported in adults: 1

• Erythema multiforme 1
• Pulmonary tuberculosis 1
• Meningitis 1

Abnormal Scar Formation

• Hypertrophic scars occur in 28-33% of vaccinees 1
• Keloid scars occur in approximately 2-4% 1

HIV-Specific Risks

HIV-infected persons are at significantly increased risk for complications: 1

• Disseminated BCG disease has been documented in HIV-infected children and adults 1
• Possibly greater risk for lymphadenitis and other complications compared to HIV-negative persons 1
• BCG-related lymphadenitis, local ulceration, and disseminated disease may occur several years after vaccination in symptomatic HIV infection 1

Critical Clinical Pitfalls

Key considerations before BCG vaccination: 1

• Variable protective efficacy of BCG vaccine, especially in adults 1
• Difficulty interpreting tuberculin skin-test results after BCG vaccination 1
• Possible risks for exposure of immunocompromised persons to the vaccine 1
• Other public health or infection-control measures known to be effective may not be implemented 1

Physicians considering BCG vaccination should discuss this intervention with personnel in local TB control programs before proceeding. 1

Tuberculin reactivity from BCG vaccination wanes over time and is unlikely to persist >10 years after vaccination in the absence of M. tuberculosis exposure. 1 The size of a tuberculin skin-test reaction in a BCG-vaccinated person does not predict vaccine protection and is not a factor in determining whether the reaction is caused by M. tuberculosis infection or prior BCG vaccination. 1