Has BCG attenuated to impotence?

The magnitude of the global tuberculosis problem and the emergence of antibiotic-resistant organisms has resulted in a renewed need for tuberculosis vaccine development. An ideal vaccine would consistentlyconfer protection without confoundingthe interpretation of the tuberculin skin test. The current vaccine, Bacille Calmette-Guérin (BCG), provides inconsistent efficacy (0-80% in randomized control trials) yet usually induces tuberculin reactivity. This variability in observed efficacy has been attributed to differences in trial methodology, host genetics and immunity to a variety of environmental mycobacteria1. We hypothesize that the attributes of the current BCG have resulted from subtlepressures to minimize adverse reactions and maintain tuberculin reactivity during vaccine development and testing.