BCG vaccine
The oldest in wide use across the world
The bacille Calmette-Guérin (BCG) vaccination is 90 years old. It was first used in humans in 1921 and is named after the two scientists, Calmette and Guérin, who developed the vaccine over the course of 13 years while working at the Pasteur Institute in Paris.
Albert Calmette, co-developer of the first effective TB vaccine
In 1974 the BCG vaccine was introduced globally as part of the WHO Expanded Program on Immunization. An estimated 1 billion people worldwide have since been vaccinated with BCG, and in 2002 approximately 100 million or 76% of infants born worldwide received the vaccine. BCG is the oldest vaccine that is still widely used around the world and currently the only vaccine against TB. However, much controversy surrounds BCG given varying estimates of its efficacy against TB. [WHO2004]
The BCG vaccine is live attenuated (weakened) Mycobacterium bovis. It is considered very safe and has a rare incidence of serious adverse events. The estimated incidence of fatal dissemination of BCG is 0.19-1.56 per million vacinees, and of disseminated BCG vaccine is less than 5 per million vacinees. The World Health Organization recommends intradermal administration of the vaccine, which frequently results in a minor local reaction. This local reaction commonly causes a small scar used as a marker for BCG vaccination, but not for protection against TB. [WHO2004]
The efficacy of the BCG vaccine is still highly debated. A recent review of the published literature found a strong and consistent protective effect of BCG in young children (non-HIV infected) against disseminated forms of TB. BCG reduced rates of TB meningitis by 73% (95% CI: 67-79%) and military disease by 77% (95% CI: 58-87%) [Trunz2006].
Reviews from 1995 to 2000 found a 50% reduction in risk of TB disease among young children. Despite the efficacy of the BCG vaccine against childhood TB, it does not offer any protection from primary TB infection or reactivation of latent TB. The protection offered by the BCG vaccine declines over 10-20 years. Resultantly, BCG offers no protection against TB disease in adulthood, and little protection against pulmonary TB, the most common manifestation of TB disease. [Colditz1995] [Brewer2000] [WHO2004]
Much has been written about why the efficacy of BCG differs widely between studies. Differences in efficacy are thought to depend on study design (randomized control trials, prospective cohorts and case-control studies) and the geographical location of the study, which influences participants’ exposure to environmental mycrobacteria. [WHO2004].
Current recommendations for including the BCG vaccine as part of routine childhood vaccine packages vary by country. In TB endemic countries and those with a high incidence of TB, it is recommended that children receive a single dose of BCG as close to the time of birth as possible. In developed countries were the incidence of TB is low, it is not part of routine vaccination schedules. Countries with a low incidence of TB largely work to control TB through other methods such as contact tracing and preventive therapy. However, some will still provide the BCG vaccine to high-risk populations. A searchable, open access, online database called the BCG World Atlas offers information on BCG vaccination policies and practices by country.
BCG is contraindicated for infants who are HIV-infected. This recommendation against the vaccination of HIV-positive children with BCG was made by the WHO in 2008 and supported by the BCG working group of the International Union against Tuberculosis and Lung Disease. Previous guidelines had been to immunize HIV infected asymptomatic infants at birth with BCG. However, these children were shown to be at an increased risk for disseminated TB and therefore the potential risks of BCG vaccination outweighed the benefits. [WHO2004] [Hesseling2008] [WHO2007]
Given the large global burden of TB, a number of new TB vaccines are under development. Recent advances in the field of mycobacterial genomics are assisting in the development of new vaccines. While the BCG vaccine is safe and used in many countries, the protection it confers is limited. As such, there is still a strong need for more vaccine research and development. [WHO2004]
References
[WHO2004]: World Health Organization (2004). "BCG vaccine. WHO position paper." Weekly Epidemiological Record 79(4): 27-38.
[Trunz2006]: Trunz, B. B., P. Fine, et al. (2006). "Effect of BCG vaccination on childhood tuberculous meningitis and miliary tuberculosis worldwide: a meta-analysis and assessment of cost-effectiveness." Lancet 367(9517): 1173-1180.
[Colditz1995]: Colditz, G. A., C. S. Berkey, et al. (1995). "The efficacy of bacillus Calmette-Guerin vaccination of newborns and infants in the prevention of tuberculosis: meta-analyses of the published literature." Pediatrics 96(1 Pt 1): 29-35.
[Brewer2000]: Brewer, T. F. (2000). "Preventing tuberculosis with bacillus Calmette-Guerin vaccine: a meta-analysis of the literature." Clin Infect Dis 31 Suppl 3: S64-67.
[Zwerling2011]: Zwerling, A., M. A. Behr, et al. (2011). "The BCG World Atlas: A Database of Global BCG Vaccination Policies and Practices." PLoS Med 8(3): e1001012.
[Hesseling2008]: Hesseling, A. C., M. F. Cotton, et al. (2008). "Consensus statement on the revised World Health Organization recommendations for BCG vaccination in HIV-infected infants." Int J Tuberc Lung Dis 12(12): 1376-1379.
[WHO2007]: World Health Organization (2007). "Revised BCG vaccination guidelines for infants at risk for HIV infection." Weekly Epidemiological Record 82(21): 193-196.
