Long-term Efficacy of BCG Vaccine in American Indians and Alaska Natives

BACILLE CALMETTE-GUEIRIN (BCG) is an attenuated strain of Mycobacterium bovis that is used worldwide as a tuberculosis vaccine. 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. A meta-analysis of efficacy over time among randomized controlled trials reported a 5% to 14% annual decrease among 7 trials and an increase in efficacy of up to 18% among 3 others. More than 50 years ago, Townsend et al conducted a placebo-controlled trial of BCG vaccination among American Indians and Alaska Natives. Immunizations for this study occurred during 1935-1938, with prospective tuberculosis case finding through 1947. A 20-year analysis of tuberculosis mortality found an 82% reduction attributable to vaccination; there was a 75% reduction in radiographically diagnosed tuberculosis at 11 years. The original American Indian vaccine trial documents have been preserved over the intervening decades. Since study participants tend to obtain health care through a single system, the Indian Health Service (IHS), and to maintain ties to discrete communities, good follow-up is facilitated. We conducted a long-term follow-up of trial participants using medical record review and supplemental methods to address duration of tuberculosis protection by BCG vaccine. Author Affiliations: Department of Medicine, Infectious Disease Division, Uniformed Services University of the Health Sciences, Bethesda, Md (Dr Aronson); Department of Medicine, Infectious Diseases Service (Dr Aronson), and Department of Clinical Investigation (Ms Howard), Walter Reed Army Medical Center, Washington, DC; Center for American Indian and Alaska Native Health (Dr Santosham) and Departments of Epidemiology (Dr Comstock) and International Health (Dr Moulton), Johns Hopkins Bloomberg School of Public Health, Baltimore, Md; Native American Prevention Research Center, University of Oklahoma College of Public Health, Oklahoma City (Dr Rhoades); and Infectious Diseases Epidemiology Research Unit, University of Pittsburgh, Pittsburgh, Pa (Dr Harrison). Corresponding Author: Naomi E. Aronson, MD, Uniformed Services University of the Health Sciences, Infectious Diseases Division, Room A3058, 4301 Jones Bridge Rd, Bethesda, MD 20814 (naronson@usuhs.mil). Context The duration of protection from tuberculosis of BCG vaccines is not known.