Describe the BCG vaccine with its preparation, administration, efficacy and adverse effects.

Nature and Preparation

• BCG (bacille calmette-GUÉrin) is a live attenuated vaccine derived from Mycobacterium bovis
• Attenuated by Calmette and Guérin over 13 years and 231 subcultures on glycerine-potato-bile medium, during which it irreversibly lost its virulence
• Supplied freeze-dried with normal saline as diluent, because it is highly sensitive to light and heat; the vial must be protected from sunlight and discarded within 4 to 6 hours of reconstitution
• Dose and route — 0.1 mL intradermally (0.05 mL in newborns) over the left deltoid at the insertion, using a separate sterile syringe
• In India it is given AT birth or as early as possible, under the Universal Immunisation Programme

Normal Course and Adverse Effects

• Expected course — a papule appears at 2 to 3 weeks, becomes a small ulcer at 5 to 6 weeks, and heals over 6 to 12 weeks leaving a permanent scar of 4 to 8 mm. This is a normal reaction, not a complication, and parents must be told so or they will present alarmed and the lesion may be treated as an abscess
• Tuberculin conversion follows in 6 to 8 weeks
• Adverse effects — a persistent ulcer or abscess (usually from injection that was too deep or too large a dose); regional lymphadenitis, occasionally suppurative; keloid at the site; and rarely osteitis
• Disseminated BCG infection ("BCGosis") — rare but often fatal, occurring in infants with undiagnosed severe combined immunodeficiency or symptomatic HIV. This is the principal hazard of vaccinating at birth, before such conditions can be recognised

Efficacy, Contraindications and Other Uses

• Variable protection against adult pulmonary tuberculosis, attributed to differences in BCG strain, prior exposure to environmental mycobacteria (which may already confer or mask immunity), nutrition, genetics and latitude
• It does not prevent infection and does not prevent reactivation of existing latent infection; it limits haematogenous dissemination after infection
• Protection wanes over 10 to 20 years, and revaccination is not recommended, having shown no benefit
• Contraindications — symptomatic HIV and other cellular immunodeficiency, generalised eczema or infected dermatoses at the site, and pregnancy; it is a live vaccine
• Other uses — intravesical BCG for superficial bladder carcinoma, where it provokes a local immune response and is highly effective; and historically in leprosy prophylaxis
• The absence of a scar does not reliably indicate absence of vaccination, and a scar does not guarantee protection

Applied Aspects

• Explain the expected local reaction to parents before they leave; the ulcer at 6 weeks is normal and needs only to be kept clean and dry, with no dressing, antibiotic or incision
• Do not incise or drain a BCG lymphadenitis routinely; most resolve spontaneously, and incision produces a chronic discharging sinus
• Withhold BCG in a symptomatic HIV-positive infant, and consider a family history of unexplained infant deaths or severe infection, which may indicate undiagnosed combined immunodeficiency
• Give BCG intradermally, not subcutaneously; deep injection causes abscess and adenitis and is the commonest technical error
• BCG remains justified in India because the burden of childhood miliary disease and tuberculous meningitis is high, and it is against precisely these that protection is best
• BCG interferes with the tuberculin test but not with interferon-gamma release assays, which is a practical argument for the latter when screening a vaccinated population for latent infection