Variation in protection by BCG: implications of and for heterologous immunity

Besides being the world's most widely used vaccine, and being directed against the world's leading cause of infectious disease mortality, BCG is the most controversial vaccine in current use.1,2 Estimates of protection imparted by BCG against pulmonary tuberculosis vary from nil to 80%. This variability has been attributed to strain variation in BCG preparations, to genetic or nutritional differences between populations, and to environmental influences such as sunlight exposure, poor cold-chain maintenance, or exposure to environmental mycobacterial infections. Evidence accumulated to date indicates that regional differences in environmental mycobacteria are responsible for much of the variation observed between populations in the efficacy of BCG against pulmonary tuberculosis. This paper reviews the evidence, and notes its broader implications for the epidemiology and control of mycobacterial diseases as well as for other infections and vaccines.