An analysis of some hypotheses related to the Chingelput Bacille Calmette-Guerin Trial

Investigation of several hypotheses related to the outcome of the Chingelpu t Bacille Calmette-Guerin (BCG) Trial suggests at least 2 factors that migh t explain the major scientific puzzle of a protective effect expected of 80 % and a protective effect observed of 0% (i.e., equivalent protection for B CG and placebo). One factor that explains some of the low efficacy observed for BCG in this trial is the virtual saturation level of exposure to envir onmental mycobacteria (EM). Studies in animal models demonstrated that the protection afforded by infection with EM was equivalent to the protection t hat resulted from BCG vaccination. The second factor, pathogenetic pathway, explains why there was still a high case rate for tuberculosis, even thoug h the population was fully vaccinated by EM. This hypothesis states that tu berculosis in India, as well as in most developing countries, results prima rily from exogenous reinfection, a pathway against which BCG (or EM) exerts no protective effect beyond that induced by the first episode of infection with Mycobacterium tuberculosis.