COMPARISON OF GRADED AND QUANTAL VIRULENCE TESTS FOR BACILLUS ANTHRACIS SPORES

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Abstract
Good correlation between a quantal (LD50) and a graded (median-time-to-death) response method was shown by 2 challenge routes in the mouse using 4 strains of Bacillus anthracis with characteristics of high virulence and 4 with low virulence. To emphasize the importance of the time-to-death response and its association with mode of action all data were combined, by use of reciprocal death time, into continuous response curves over several log doses of the organism. It is theorized that the time-to-death of an animal is an accumulation of the time periods required for in vivo (a) germination and conditioning of spores to initiate vegetative growth, (b) rate of cell division or generation time, and (c) the number of cell divisions necessary to produce a critical number of vegetative organisms or sufficient toxin to cause death of the host. These concepts are formulated in an equation and are illustrated in a schematic diagram.