A single dose of the BCG tuberculosis (TB) vaccine can provide protection for up to 60 years, according to a long-term follow-up study published in the May 5th edition of the Journal of the American Medical Association.
The Bacille Calmette-Guérin vaccine, abbreviated to BCG, is an attenuated strain of Mycobacterium bovis and is used in many countries as a TB vaccine. Meta-analysis has found that the vaccine reduces the risk of TB by 50%, but the durability of the vaccine’s protective effect had not been previously shown.
Accordingly, investigators from the US conducted a retrospective review of the medical records of 2,792 Native Americans and Alaskan Natives who participated in a placebo-controlled trial of the BCG vaccine between 1935-38. An earlier 20-year analysis had found that there was an 82% reduction in TB mortality attributable to the vaccine and at year eleven there was a 75% reduction in chest x-rays indicative of TB.
Between December 1935 and early 1938, over 3,000 Native Americans in three US states and Alaskan Natives aged between one and twenty years participated in a randomised placebo-controlled trial of the BCG vaccine. Follow-up took place between 1992 and 1998, and involved 1,483 individuals who received the BCG vaccine and 1,309 individuals who were provided with the placebo. Efficacy analysis was based on the time to first TB diagnosis or the end of the follow-up period in 1998.
There were a total of 102 cases of TB, 27 in the BCG group and 63 amongst individuals who received the placebo. This provided a case rate in the BCG arm of 66 per 100,000 person years, and a case rate of 138 per 100,000 person years in the placebo arm. This provided an adjusted vaccine efficacy of 55% (95% CI, 31%-77%).
The investigators found a slight, but not statistically significant, waning of the vaccine’s efficacy over time. There was also a difference in waning by sex, with a decline in the efficacy of the vaccine for men, but not for women (p=0.02 for the interaction), with men losing most of the benefits of the vaccine around 35-40 years after receiving their BCG dose.
Early trials had shown the BCG vaccine to be highly efficacious against extra-pulmonary TB, and this was confirmed by the investigators’ analysis. There were 35 cases of extra-pulmonary TB in the BCG arm, compared to 73 cases in the placebo arm (efficacy 52%). This meant that there were nine case of extra-pulmonary TB per 100,000 patient years amongst the BCG recipients and 25 cases per 100,000 person years amongst individuals who received the placebo.
A total of 44 patients had had more than one episode of TB, with a multiple episode rate of four per 100,000 person years seen in the BCG arm and 34 per 100,000 person years in the placebo arm.
The investigators excluded from their analysis individuals who had a serious infectious disease (although HIV was specified as an exclusion criteria, the investigators did not mention if any individuals were infected with HIV). It is known that the efficacy of the BCG vaccination declines in HIV-positive individuals.
However, the value of childhood BCG vaccination in communities that have a high prevalence of TB is suggested by a study conducted in South African gold mines. Investigators found that TB incidence increased in both HIV-positive and HIV-negative individuals, due to onward transmission of TB from HIV-positive individuals with weakened immunity.
The investigators of the BCG vaccine study conclude that “this placebo controlled trial of BCG vaccine is the only study… to demonstrate that its vaccine strains conferred a considerable degree of protection throughout most of the 60 years of follow-up.” They add that “these findings should provide encouragement to investigators aspiring to produce a vaccine with similar or improved characteristics.”
An editorial accompanying the article describes the results of the 60 year follow-up study as “remarkable”, and as “relevant to the well-being of millions who are still threatened by or who have TB. They provide important lessons for future TB vaccine development.”
Further information on this website
Old TB vaccine can improve immune response to TB in HIV patients - news story
BHIVA preparing HIV/TB treatment guidelines - comments sought - news story
HIV leads to rise in TB incidence in both HIV-positive and HIV-negative SA gold miners - news story
Aronson NE et al. Long-term efficacy of BCG vaccine in American Indians and Alaska natives: a 60 year follow-up study. Journal of the American Medical Association 291: 2086-2091, 2004.
Dye C. A booster for tuberculosis vaccine. Journal of the American Medical Association 291: 2127-2128, 2004.