PATHOGENESIS OF TUBERCULOSIS - PATHWAY TO APICAL LOCALIZATION

We have examined the published work of investigators which dealt with the pathogenesis of tuberculosis, especially the following: the infect ive dose, the yield of bacilli from the primary lesion and primary com plex, the predominant location of the minimal lesion, the hypotheses o f a vulnerable region in the lung and the specific pathways (endogenou s or exogenous) by which tubercle bacilli cause disease. More knowledg e of the pathogenic pathway to tuberculosis would provide clues to the development of new vaccines and drug regimens that can intervene at a specific stage in the pathogenesis. Based on the examination of the l iterature on pathogenesis of human tuberculosis and our findings in a guinea-pig model of experimental airborne tuberculosis, we have propos ed an hypothesis which integrates the endogenous and exogenous pathway s to tuberculosis. This hypothesis is based on the following observati ons: 1. The infectious dose is very low, usually 1-5 tubercle bacilli. 2. The first implant can occur anywhere in the lungs. 3. The cavitary lesion, characteristic of tuberculous disease, is often located in th e apical regions in the lungs. 4. Whereas the primary implant can occu r anywhere in the lungs, for the progression from infection to disease , the tubercle bacilli must gain access to the 'vulnerable' regions in the apex of the lungs. Our hypothesis states that in areas of the wor ld where there is a low risk of infection with tubercle bacilli low in cidence of vaccination or sensitization to environmental mycobacteria, or high incidence of high virulent isolates, the virulent tubercle ba cilli reach the vulnerable region via a bacillemia during the first in fection. In areas of the world where there is a high risk of infection with tubercle bacilli, high incidence of vaccination or sensitization to environmental mycobacteria or a high incidence of low virulent iso lates, the tubercle bacilli reach the vulnerable region via the airway , which requires repeated episodes of infection as the probability of a first implant occurring in the vulnerable regions is low.