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The need for a new tuberculosis (TB) vaccination strategy is clear when we consider the massive burden of TB disease in countries where universal infant bacille Calmette-Guérin (BCG) vaccination is practiced as part of the World Health Organization (WHO) Expanded Program on Immunization (EPI) (1). The lifetime risk for development of TB disease in these high-transmission settings is driven by multiple ongoing Mycobacterium tuberculosis exposure-re-exposure episodes, beginning in early childhood, leading to M. tuberculosis infection at an early age, and continuing throughout adulthood (Fig. 1). Infants and very young children not only have a higher risk of progression from infection to disease, but have a higher risk of severe disease, including miliary TB and tuberculous meningitis (2). Since BCG vaccine is thought to offer protective efficacy of about 74% against all forms of TB disease in children, BCG vaccination is firmly entrenched in the EPI (3). However, although BCG vaccination is thought to offer modest protection against M. tuberculosis infection as defined by interferon-gamma (IFN-?) release assay (IGRA) conversion, the majority of adults in high-TB-burden countries are M. tuberculosis-infected (4). In very high-transmission settings such as South Africa, more than three quarters of adolescents are M. tuberculosis-infected by the time they leave high school (5, 6). Given that the rate of infection in some African countries may exceed 10% per annum (7), it is not surprising that while Africa is responsible for only 28% of the world's new TB cases, 7 of the top 10 countries for TB incidence by population are in Africa, where HIV coinfection, a younger population demographic, and social disadvantage and disruption add susceptibility to TB disease (8). It is against this backdrop that we review the potential indications for TB vaccines, in search of a vaccination strategy that is safe and effective against all forms of TB disease in infants, children, and adults, including M. tuberculosis-infected and HIV-infected people.

Original publication





Book title

Tuberculosis and the Tubercle Bacillus: Second Edition

Publication Date



193 - 211