BCG vaccine demonstrates effectiveness after 40 years

Issue: February 2016

Recent data showed the bacille Calmette-Guérin vaccine reduced the risk for tuberculosis after 40 years of vaccination, suggesting the vaccine may be more cost-effective than previously estimated.

“This finding could be relevant if countries revise their BCG vaccination policies in response to changing tuberculosis [(TB)] epidemiology, especially in low-incidence countries,” Patrick Nguipdop-Djomo, MD, from the department of infectious disease epidemiology at the London School of Hygiene & Tropical Medicine, and colleagues wrote.

BCG is one of the most common vaccines; however, the duration of vaccine effectiveness is unclear, according to researchers. Results from a prior study of American Indians and Alaska Natives demonstrated significant BCG effectiveness up to 40 years after vaccination; however, the findings have not been confirmed in other trials.

A systematic review conducted in 2012 found that BCG was effective against TB for 10 to 15 years. The investigators concluded the vaccine was 60% (95% CI, 37-74) effective for less than 5 years, 56% (95% CI, 17-76) effective between 5 and less than 10 years, and 46% (95% CI, 18-64) effective for up to 15 years. In addition, three observational studies observed persisting but waning patterns of BCG protection up to 20 years after vaccination.

For the current retrospective study, Nguipdop-Djomo and colleagues evaluated TB incidence in Norwegians who accepted or declined the BCG vaccine during a mass TB screening and vaccination program from 1962 to 1975. The participants were followed up to Dec. 31, 2011 or until their first TB diagnosis, emigration or death. Results were adjusted for age-specific TB risk as well as demographic and socioeconomic factors.

Median follow-up was 44 years for vaccinated participants (n = 297,905) and 41 years for unvaccinated participants (n = 83,421). TB rates were 3.3 (95% CI, 2.7-4) per 100,000 person-years in unvaccinated participants vs. 1.3 (95% CI, 1.1-1.5) per 100,000 person-years in vaccinated participants. The vaccine was 49% (95% CI, 26-65) effective after 40 years of vaccine receipt (adjusted HR = 0.51; 95% CI, 0.35-0.74); however, the findings were not significant after 20 years, the researchers wrote.

They performed a sensitivity analysis to exclude participants who developed TB after 2 years of vaccination and may have been infected before receiving the vaccine. BCG was 61% (95% CI, 24-80) effective up to 9 years, 58% (95% CI, 27-76) effective between 10 and 19 years, 38% (95% CI, –32 to 71) effective between 20 and 29 years, and 42% (95% CI, –24 to 73) effective after 30 to 40 years.

For pulmonary TB, the vaccine was 57% (95% CI, 8-80) effective up to 9 years, 63% (95% CI, 32-80) effective between 10 and 19 years, 50% (95% CI, –19 to 79) effective between 20 and 29 years, and 40% (95% CI, –46 to 76) effective between 30 and 40 years.

“The vaccine seemed to reduce the risk of pulmonary tuberculosis, the infectious form of the disease, more than it did of all tuberculosis,” Nguipdop-Djomo and colleagues wrote. “Our results are consistent with long-lived BCG-derived immunity, adding to the evidence that BCG vaccination of individuals not yet infected by [Mycobacterium tuberculosis] infection itself nor sensitized by environmental mycobacteria might confer some protection against tuberculosis for at least 20 years.” – by Stephanie Viguers

References:
Abubakar I, et al. Health Technol Assess. 2013;doi:10.3310/hta17370.
Aronson NE, et al. JAMA. 2004;doi:10.1001/jama.291.17.2086.
Nguipdop-Djomo P, et al. Lancet Infect Dis. 2015;doi:10.1016/S1473-3099(15)00400-4.

Disclosure: Nguipdop-Djomo reports no relevant financial disclosures. Please see the full studies for lists of all other authors’ relevant financial disclosures.