Disseminated Bacillus Calmette-Guérin and Susceptibility to Mycobacterial Infections—Implications on Bacillus Calmette-Guérin Vaccinations

Abstract

Bacillus Calmette-Guérin (BCG) is a live vaccine and has the potential to cause local disease and systemic dissemination in immunocompromised hosts, including infants who are infected with human immunodeficiency virus (HIV) through vertical transmission, and patients with primary immunodeficiencies (PID) such as severe combined immunodeficiency (SCID), chronic granulomatous disease (CGD), hyper-IgM syndrome, and defects of the IL12-IFNγ axis (Mendelian susceptibility to mycobacterial diseases, MSMD). Disseminated BCG is extremely difficult to treat. The chance of complete eradication is low unless functional immune response is restored by haematopoietic stem cell transplant. Prolonged use of anti-mycobacterial drugs often causes organ toxicities and drug resistance. Inflammatory complications which develop upon immunoreconstitution post-transplant may necessitate immunosuppressive treatment, which adversely affect immune recovery and increases risks of opportunistic infections. Multiple BCG reactivations can occur in patients with CGD and MSMD, and BCG can remain latent until reactivations take place in adulthood and manifest as disease. It is important for neonatologists, general practitioners, primary care clinicians and nurses working in maternal and child care centers to be aware of BCG-related complications, which may be the first sign of an underlying immunodeficiency. As neonatal BCG is included in standard vaccination schedule in many countries, it is a challenge to identify and avoid administration of BCG to infants who potentially have PIDs. Deferring BCG vaccination is recently advocated to protect highly vulnerable populations, but the appropriate strategy is yet to be determined. Newborn screening for SCID offers a potential to avoid this complication, if an integrated system of screening and vaccination can be organised. Key words: BCG, Newborn screening, Primary immunodeficiency