BCG: the challenge continues

It is widely recognized that BCG provides inconsistent and often inadequate protection against tuberculosis; however, simple estimates of efficacy fail to reflect the complexity of protection within, let alone between, populations. A decline in protection with an increase in age at vaccination has been seen in many studies. This may reflect 2 things: (i) that as people age they are exposed to a variety of mycobacterial challenges which may interfere with, or mask, the protection of BCG; and/or (ii) that the vaccine is better at protecting against primary disease than against either reactivation- or reinfection-type disease. These factors need to be taken into consideration when interpreting the results obtained with screening vaccines in animal models, as most of these models mimic acute primary-type disease. In addition, we have no evidence that the protection induced by BCG lasts for > 15 y, in any population. Recent data from South India indicate a complex interaction of age and time effects: BCG imparted consistent protection in children, but no protection for subjects > 15 y old, and may even have imparted negative protection among these older individuals. If true, these findings have important implications for efforts to develop a vaccine against adult pulmonary tuberculosis.