The relative immunogenicity of virulent and attenuated strains of tubercle bacilli.
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Biomedical subjects
Publications and source records attributed to F M Collins.
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Specific pathogen-free C57B1 mice are 100 to 1,000 times as sensitive as CD-1 mice to intravenous or oral challenge by Salmonella enteritidis or S. gallinarum. Resistance to infection by S. pullorum was unaffected. Growth of Listeria monocytogenes and Mycobacterium bovis (BCG) in intravenously infected C57B1 mice was similar to that seen in CD-1 mice. Quantitative counts of viable S. enteritidis in the walls of the stomach, small intestine, cecum, and large intestine and in the corresponding intestinal contents showed that most of the oral challenge inoculum was rapidly inactivated so that, by 24 hr, less than 1% was still viable. Overnight starvation and pretreatment with bicarbonate solution increased the relative survival of the challenge approximately 10-fold. Despite the rapid and extensive inactivation of the oral inoculum within the normal intestine, significant numbers of salmonellae reached the liver and spleen by 48 hr, and this systemic infection was subsequently responsible for the death of a high proportion of the challenged animals.
CD-1 mice were vaccinated intragastrically or intramuscularly with one or two doses of 200 mug of heat-killed Salmonella enteritidis 5694. Control mice were vaccinated with sublethal doses of living S. enteritidis Se795. The mice were challenged intragastrically with approximately 10(6)S. enteritidis 5694 SM(R) 7 to 14 days later, and the growth of the challenge population in the liver, spleen, mesenteric lymph nodes, lungs, and intestine was measured quantitatively. Mice receiving two doses of heat-killed vaccine by mouth were able to delay the systemic emergence of a gastrically introduced salmonella infection by 1 to 2 days. The corresponding liver and spleen populations were slightly lower than those seen in the normal controls. On the other hand, mice receiving the living, attenuated vaccine (either intravenously or intragastrically) developed an effective anti-salmonella immunity against subsequent reinfection.
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Mycobacterium tuberculosis strain Erdman, M. bovis (BCG), and M. phlei showed a 1- to 2-log drop in viability after exposure to ultraviolet light compared to a 5-log drop over the same period for Staphylococcus albus, Listeria monocytogenes, Escherichia coli, Pseudomonas aeruginosa, Salmonella enteritidis, and Serratia marcescens. L. monocytogenes showed an initial resistance to ultraviolet inactivation, but later the inactivation rate increased sharply. The significance of these findings with regard to the use of S. marcescens as a test organism for determining the bactericidal efficiency of ultraviolet lamps used to sterilize equipment contaminated with tubercle bacilli is discussed.
A total of 3,303 strains of Mycobacterium tuberculosis were tested for sensitivity to streptomycin (SM), isoniazid (INH), and p-aminosalicylic acid (PAS) by the Steenken modified minimal inhibitory concentration (MIC) test. A simultaneous double blind comparison was carried out on 277 selected strains by the Steenken MIC test and the Canetti proportion method. Agreement between the results for the two tests was 82% for SM, 95% for INH, and 89% for PAS. A small number of strains appeared to be sensitive when tested by one method but resistant by the other. MIC determinations were carried out on 83 strains by using Steenken-Smith, Lowenstein-Jensen, and Middlebrook 7H10 media containing a more extended range of concentrations of the test drugs. The MIC values for both SM and dihydrostreptomycin increased on Steenken-Smith medium compared with the other two. INH did not show any medium effect, whereas PAS showed increased MIC values in 7H10 agar. The significance of the comparisons of the MIC values on the various media is discussed in terms of possible changes in the drug sensitivity testing methods used at present in this laboratory.
Seven mycobacterial species were tested for their ability to immunize mice against subsequent tuberculous challenge. The phylogenetic relationships between the vaccine and challenge strains had little direct influence on the level of resistance; a better correlation was found between the ability of the vaccine to survive or multiply in vivo and the immunogenicity of the organism. Mycobacterium tuberculosis, M. bovis (except for an SM(R) variant), M. avium, two of three M. kansasii strains, and one strain of M. intracellulare all survived or multiplied in vivo. They induced an effective resistance against a subsequent M. tuberculosis (Erdman) or BCG challenge. The SM(R) BCG, the Bostrom strain of M. kansasii, M. scrofulaceum, three strains of M. intracellulare, and one of M. terrae and M. fortuitum were unable to survive in vivo and were nonallergenic and nonimmunogenic. No evidence was found for an interference phenomenon between the atypical mycobacteria and the BCG vaccine sufficient to explain the inadequate levels of immunization reported in some field trials.
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Specific pathogen-free CD-1 mice infected orally with sublethal doses (10(4) to 10(6) viable organisms) of Salmonella enteritidis rapidly developed extensive bacterial populations in the liver, spleen, and mesenteric lymph nodes. Although the pathogen did not multiply extensively in the gut, the infection persisted in the intestine at between 10(4) and 10(5) viable organisms throughout the experiment. S. gallinarum was less invasive than S. enteritidis when given by mouth; S. pullorum failed to survive in the intestine or to invade the tissues of orally infected mice. Vaccination with a sublethal dose of living S. enteritidis, either orally or intravenously, completely prevented the establishment of liver and spleen populations of a drug-resistant, virulent strain of S. enteritidis. Vaccination with an ethyl alcohol-killed vaccine given by various routes delayed the spread of the orally introduced challenge population to the liver and spleen by 1 to 2 days but was unable to prevent the subsequent growth of the pathogen in vivo, although the vaccinated mice survived the infection. The importance of these findings in relation to vaccination against typhoid fever in man is discussed.
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Salmonella enteritidis was injected intravenously, intraperitoneally, or subcutaneously into specific pathogen-free mice. The number of organisms in the blood, liver, spleen, peritoneal cavity, and draining inguinal lymph node was determined by daily enumeration. Opsonization of the organism with hyperimmune serum increased the rate of phagocytosis, resulting in rapid blood clearance together with an alteration in the relative numbers of organisms accumulating in the liver and spleen. Serum treatment also brought about a substantial increase in the number of bacteria killed during the first 60 min of the infection. However, the survivors of this initial period of inactivation then multiplied rapidly in the liver and spleen, ultimately resulting in the death of the animal from a generalized infection. Attempts to passively protect mice with hyperimmune serum were uniformly negative. The effects of treatment of the virulent S. enteritidis with hyperimmune serum were consistent with the general thesis that cellular rather than humoral factors play the major role in the expression of an effective antibacterial immunity against salmonella infections.