[Frontiers in Bioscience 3, c27-33, May 1, 1998] |
LURIE’S TUBERCLE-COUNT METHOD TO TEST TB VACCINE EFFICACY IN RABBITS
Departments of Environmental Health Sciences, Molecular Microbiology and Immunology, and Epidemiology, School of Hygiene and Public Health; and the Department of Pathology, School of Medicine, The Johns Hopkins University, Baltimore, Maryland 21205
Received 3/9/98 Accepted 3/14/98
10. TUBERCULOSIS IN DIFFERENT SPECIES
Rabbits and human beings are both rather resistant to tuberculosis. Guinea pigs are much more susceptible; and mice, although rather resistant, develop a somewhat different form of the disease. These species differences are compared in references 32 through 35.
Rabbit TB and human TB have these two characteristics in common: (a) Only a small percentage of inhaled virulent human-type tubercle bacilli is able to multiply and create at least a microscopic lesion, thereby converting the tuberculin skin test. (b) In both species, pulmonary cavities with bronchial spread readily occur, especially if the more virulent bovine-type of tubercle bacillus is used to infect the rabbits.
Guinea pigs usually develop a primary lesion for every unit of 1 to 3 bacilli that reaches the alveolar spaces (see 36-39), as do rabbits that inhale fully virulent bovine-type bacilli (1,6,8, see 5). Guinea pigs will develop cavities when infected with a low dose of bacilli (40), but bronchial spread of the disease rarely occurs in this species, because the disease spreads mainly by the hematogenous route.
Mice develop a slowly progressing form of tuberculosis (32,41) with less (caseous) necrosis and no cavity formation. We do not know how many tubercle bacilli must be inhaled by mice to produce one primary tubercle. However, unpublished preliminary experiments of Donald W. Smith (using methods described in reference 42) indicate that mice are just as susceptible as guinea pigs to H37Rv, i.e., about one unit of 1 to 3 tubercle bacilli in the pulmonary alveolar spaces will produce one primary lesion. Mice are much less sensitive to tuberculin than are humans, guinea pigs and rabbits (in that order), which is one of the reasons why their tubercles show less caseous necrosis than those of the other three species (32-34). Francis (33, see 34) states that pulmonary tubercles of mice contain more bacilli than do tubercles of rabbits and guinea pigs. If confirmed, this finding would be consistent with the less extensive caseous necrosis in mice, because the killing of macrophages in which the bacillus is proliferating stops such intracellular bacillary multiplication (13,14,17,18).
In human beings, the number of inhaled bacillary units required to generate one grossly visible primary pulmonary tubercle is unknown. Estimates vary from 20 to 200 units, depending on the native (genetic) resistance of the host and the virulence of the infecting bacillus. Most TB researchers agree that humans are much more resistant than guinea pigs to both human- and bovine-type virulent tubercle bacilli, and that humans are somewhat more susceptible than rabbits to the human-type. [Rabbits uniformly recover from infection with human-type tubercle bacilli, although many months are required to do so (1).]
Virulent bovine-type tubercle bacilli are apparently more infectious for rabbits than for humans: One inhaled unit of 1 to 3 fully virulent bovine-type bacilli in the alveolar spaces is sufficient to establish the disease in rabbits (1,6). Such bacilli in rabbits produce a cavitary disease with spread via the bronchial tree, which is quite similar to that found in immunocompetent human beings.
Humans, guinea pigs and mice (in contrast to rabbits) show no major differences in their susceptibility to human- and bovine-type tubercle bacilli (33, see 34). In humans, the main difference in the disease produced by these two bacillary types was due to the route of infection: The human type was usually inhaled, whereas the bovine type was usually ingested in milk from tuberculous animals (43).