The variability of Mycobacterium tuberculosis in patients with cavitary pulmonary tuberculosis in the course of chemotherapy.

Inoculation of guinea pigs with membrane-filtered homogenates prepared from the walls of open cavities in the lungs of experimental animals allowed us to detect invisible (ultra-fine) forms of the tuberculosis agent. The ultra-fine forms of M. tuberculosis were detected directly by electron microscopy, and indirectly by culture on liquid semi-synthetic media and subsequent microscopy, and by injection of the pathological material into the experimental animals. Similar results were obtained in patients who, after 3 and 6 months of treatment with the triple drug chemotherapy, still had open cavities in the lungs although smear and culture examinations were negative. The proportion of detected ultra-fine forms increased during chemotherapy: by the third month of treatment they were detected in 82% of the patients with open cavities. The invisible forms of M. tuberculosis are able to revert to the typical bacterial forms. The initial stage of this process is accompanied by the formation of coccoid forms of mycobacteria that can be detected when the material is inoculated on to semi-synthetic medium with 10% plasma and by microscopy of the sediment. Inoculation of experimental animals with the filtrate of sputum or other pathological material containing these ultra-fine forms of mycobacteria is accompanied by development of a peculiar granulomatous inflammation characterised by macrophages, mononuclear cells and solitary epithelioid and giant cells.