An experimental basis for estimating the virulence of tubercle bacilli

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Abstract
1. Mice infected intracerebrally with M. tuberculosis H 37 Rv in doses of 400,000–1,300,000 bacillary units gave a graduated series of responses whose regression provided an arbitrary 100% standard of mouse virulence for human tubercle bacilli.2. Under certain experimental conditions this standard remained stable and its confidence limits could be defined.3. The relative virulence of other strains of tubercle bacilli could be assessed quantitatively in relation to this standard, and expressed as a (percentage) virulence ratio.4. 100% virulence was defined as that of a strain showing a threshold of response of 600,000–1,300,000 bacillary units, lethal cerebral lesions at 8–20 days or necrotic pulmonary lesions at 20–30 days, and a mean 50% mortality time of less than 36 days.5. Qualitative and quantitative responses characteristic of intermediate and very low virulence were also defined.6. Higher proportions of virulent cells were obtained from 3 to 7 days than from older cultures in Tween-albumin liquid media, but inocula were more suitably standardized by obtaining cells from 11 to 12-day cultures.7. Passage in the mouse and guinea-pig failed to alter the virulence of H 37 Rv. A slight increase was effected by passage in the lung of the rabbit.8. The technique employed was a measure essentially of the ability of the organism to multiply in, and damage, resistant tissues.