Tuberculosis (TB) kills or debilitates more adults aged between 15 and 59 years than any other disease in the world. TB is caused by Mycobacterium tuberculosis, an intracellular pathogen of the genus Mycobacterium that includes some 55 species, half of which may cause disease in humans. M. tuberculosis is spread from person to person by respiratory secretions. In most cases, the asymptomatic primary infection in the lungs is resolved, usually leaving the infected person unaware of the event. However, M. tuberculosis may spread from the site of the primary infection to other parts of the body particularly in younger children, resulting in severe primary disease. Following infection, M. tuberculosis usually remains for life in a dormant state in the host tissue, where months to decades later, it can be reactivated.
Clinical symptoms of TB include chronic cough, fever, and weight loss; tubercules (granulomas) usually located in the lungs may subsequently become cavities that rupture into the bronchi, disseminating large numbers of the mycobacteria throughout the respiratory system. Reactivation of dormant bacilli is often associated with immunodeficiency, such as in patients co-infected with HIV, and in some areas nearly 50% of the HIV-infected population is co-infected with M. tuberculosis and more than two-thirds of patients with TB are infected with HIV. In the past two decades the development of microbial resistance to several first-line antimyobacterial drugs has complicated TB control significantly.
BCG Vaccines (Tuberculosis)
All current vaccine strains are descendants of an M. bovis bacillus strain isolated and extensively attenuated by cultivation by Calmette and Guérin to increase acceptability as a human vaccine. In order to prevent further deviation from the original BCG, lyophilized seed lots of the vaccine strains have been kept by WHO since 1956. Vaccine strains are prepared from seed-lot material by growing the bacilli in an artificial medium, harvesting, concentrating, homogenizing, and the preparation is then lyophilized. Reconstituted vaccine, for which WHO recommends intradermal administration, contains both living and dead bacilli.
BCG was first used to immunize humans in 1921, and following its introduction into the WHO Expanded Programme on Immunization in 1974, BCG soon reach global coverage rates exceeding 80% in countries endemic for TB. Extensive clinical trials have been conducted to assess the protective efficacy of BCG against pulmonary TB, but a wide range of vaccine efficacy values have been observed probably due in part to differences in study design and geographical location. BCG vaccination does not prevent reactivation of latent TB, the main source of bacillary dissemination in the community. Despite these limitations, and particularly in light of the growing HIV/AIDS pandemic and the appearance of multidrug-resistant M. tuberculosis strains, BCG vaccines will continue to represent an important tool in the global fight against TB until new vaccines are available.
BCG Vaccine Standardization
WHO adopted requirements for BCG vaccine in 1965 and these were updated in 1978 to reflect the increased knowledge concerning the dose of vaccine to administer and the change to freeze-dried preparations. These were modified slightly in 1985 to update production and testing requirements, and amended again in 1987 to amend requirements concerning the expiry date.
Recommendations to assure the quality, safety and efficacy of BCG vaccines, Annex 3, Technical Report Series 979
WHO reference materials for BCG vaccine, BCG vaccine substrains (Tokyo 17, Danish 1331 and Russian BCG-I) are available to qualified applicants:
WHO Informal Consulttaion on Standardization and Evaluation of BCG Vaccines, 22-23 September 2009, WHO, Geneva, Switzerland
WHO discussion on the improvement of the quality control of BCG vaccines, Pasteur Institute, Paris, France, 7 June 2005
WHO Consultation on the characterization of BCG vaccines, WHO, Geneva, Switzerland, 8-9 December 2004
WHO Consultation on the characterization of BCG strains, London, UK, 15-16 December 2003
Prequalified BCG vaccines
BCG vaccines are prequalified for procurement by UN organizations: