CAVITARY TUBERCULOSIS PRODUCED IN RABBITS BY AEROSOLIZED VIRULENT TUBERCLE-BACILLI

Liquefaction of solid caseous tuberculous lesions and the subsequent c avity formation are probably the most dangerous processes in the patho genesis of human pulmonary tuberculosis, In liquefied caseum, the tube rcle bacilli grow extracellularly for the first time since the onset o f the disease and can reach such large numbers that mutants with antim icrobial resistance may develop, From a cavity, the bacilli enter the bronchial tree and spread to other parts of the lung and also to other people, Of the commonly used laboratory animals, the rabbit is the on ly one in which cavitary tuberculosis can be readily produced, This re port is the first to describe and analyze the complete course of cavit ary tuberculosis, produced by aerosolized virulent bovine-type tubercl e bacilli in commercially available New Zealand white rabbits, after t he inhalation of 220 to 880 bacillary units, all of the rabbits were o vertly well until they were sacrificed at 33 weeks, After the inhalati on of 3,900 to 5,800 bacillary units, half of the rabbits died of prog ressive tuberculosis between 5 and 9 weeks and the other half lived un til they were sacrificed at 18 weeks. Pulmonary cavities developed in both low- and high-dose groups, some beginning as early as 6 weeks. Ba cilli from primary cavities sometimes caused nearby secondary cavities , but more frequently, they ascended the bronchial escalator, were swa llowed, and caused secondary tubercles in the lymphoid tissue of the a ppendix and ileocecal junction, Histologically, and by culture, the nu mber of bacilli found in the liquefied caseum varied from many to comp aratively few, Strong tuberculin reactions at 4 weeks after infection were associated with fewer primary lesions, while strong tuberculin re actions at 33 weeks were associated with more cavitary lesions, In the tuberculous granulation tissue surrounding caseous and liquefied pulm onary foci and cavities, we found many mature epithelioid macrophages that contained high levels of the proteinase cathepsin D, Therefore, c athepsin D probably plays a major role in the liquefaction of solid ca seous material and in the subsequent cavity formation.