BCG Vaccine Efficacy Persists for 50 to 60 Years

May 04, 2004

Yael Waknine

May 4, 2004 -- Bacille Calmette-Guérin (BCG) vaccine efficacy persists for 50 to 60 years, suggesting that a single vaccination can have a long duration of protection, according to results of a retrospective, placebo-controlled trial published in the May 5 issue of The Journal of the American Medical Association.

"BCG is an attenuated strain of Mycobacterium bovis that is used worldwide as a tuberculosis vaccine," write Naomi E. Aronson, MD, and colleagues from the Infectious Disease Division of the Uniformed Services University of the Health Sciences in Bethesda, Maryland. "Although the reported efficacy of BCG vaccines in controlled trials varies greatly, a meta-analysis found that overall, the vaccine reduced the risk of tuberculosis by 50% but that the duration of the protective effect could not be quantified."

To address duration of tuberculosis protection by BCG vaccine, the investigators followed up on data from 1948 to 1998 among American Indians and Alaska natives who participated in a placebo-controlled BCG vaccine trial from 1935 to 1938 and who were still at risk of developing tuberculosis.

In the original study, 3,025 adults and children aged 1 month to 20 years with normal chest radiographs and who did not respond to 250 TU of purified protein derivative of tuberculin were allocated to receive either a single dose of intravenous BCG vaccine (1 of 2 strains) or a saline placebo. In the follow-up study, the investigators identified 1,483 and 1,309 participants in the BCG and placebo groups, respectively.

Of a total 102 tuberculosis cases occurring since 1948, 36 were in the BCG group (incidence, 66 cases/100,000 person-years) and 66 in the placebo group (incidence, 138 cases/100,000 person-years). Unadjusted BCG vaccine efficacy was 52% (95% confidence interval [CI], 27% - 69%).

Vaccine efficacy was not substantially changed by adjustment for age at vaccination, additional BCG vaccine doses, chronic medical illness, subsequent isoniazid prophylaxis, tribal membership, or BCG strain or dose (efficacy, 55%; 95% CI, 31% - 77%).

A slight but not statistically significant waning of efficacy occurred over time. The decline was more pronounced in men than in women, with men losing most of the benefits of immunization after 35 to 40 years.

In those patients contracting tuberculosis, the BCG vaccine had an efficacy of 44% (95% CI, -22% to 75%) for preventing death. Likewise, the vaccine was efficacious in preventing multiple episodes of tuberculosis among those infected (efficacy, 89%; 95% CI, 53% - 99%).

The study was supported in part by a contract from the IHS, an award from the Armed Forces Infectious Disease Society, an award from the National Institute of Allergy and Infectious Diseases, and an award from the National Heart, Lung, and Blood Institute.

Explaining the limitations of the study in a related editorial, Christopher Dye, DPhil, from the World Health Organization in Geneva, Switzerland, notes that "the trial began when reinfection of vaccines was much more frequent than it would be today, possibly boosting the protection initially obtained from BCG."

In explaining why the efficacy rate was not higher, Dr. Dye writes, "Efficacy showed signs of waning in the later years of the trial, when tuberculosis incidence was lower and a higher proportion of cases would have arisen from reactivation of old infections rather than rapid progression of new ones. It is still unclear whether BCG vaccine is less efficacious in preventing disease due to reactivation or whether protection against any form of disease simply weakens with time," he concludes.

"This placebo-controlled trial of BCG vaccine is the only study, to our knowledge, to demonstrate that its vaccine strains conferred a considerable degree of protection throughout most of the 60-year follow-up period," Dr. Aronson and colleagues write. "These results should provide encouragement to investigators aspiring to produce a vaccine with similar or improved characteristics."

JAMA. 2004;291:2086-2091, 2127-2128

Reviewed by Gary D. Vogin, MD

Yael Waknine is a freelance writer for Medscape.


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