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The growth of micro-organisms in vivo with particular reference to the relation between dose and latent period

Published online by Cambridge University Press:  15 May 2009

G. G. Meynell  and
Elinor W. Meynell
G. G. Meynell
Affiliation:
Department of Bacteriology, Postgraduate Medical School, Ducane Road, London, W. 12
Elinor W. Meynell
Affiliation:
Department of Bacteriology, London School of Hygiene and Tropical Medicine, Keppel Street, London, W. C. 1
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The growth of Salmonella typhimurium in mice was studied by performing viable counts on pooled viscera and, in the case of fatally infected mice, by determining the relation between size of dose and mean death time. The results suggested that this system conformed to a general model which postulates (a) that the organisms causing the response (death in the present experiments) increase in vivo at a rate which is constant for all doses, and (b) that the response is certain to occur when their number reaches a constant figure. It follows that logarithm of dose (for doses > 1 ED50) should be linearly related to mean latent period (the interval between inoculation and response). A search of the literature showed that this relation was observed in many reported infective systems.

The interpretation of the observations on partially resistant mice (LD50 = 102.5−106 organisms) was not straightforward for the hypothesis of independent action (Meynell & Stocker, 1957) states that only a random fraction of the inoculum usually initiates each response. Multiplication of this fraction is considered to cause a reduction in host resistance so that other organisms surviving in vivo began to increase in numbers and to contribute to the fatal infection. The observations showed that this could well occur as (i) the counts on all mice, whether fatally infected or not, increased exponentially for 2–3 days after inoculation; (ii) the growth curves of fatally infected mice showed exponential increase of the whole inoculum as postulated; and (iii) the length of the death time was found to be determined by the growth of the whole inoculum and not by the predicted random fraction. The viable count per fatally infected mouse at the time of death was approximately constant at 108.75 organisms. There was no evidence that the course of the infection was influenced by organisms which may have been killed in vivo as the requirements of the model were satisfied by the observed behaviour of the viable organisms alone. The rate of increase of organisms in a fatally infected animal was found to be less, the greater the LD50 of the host; which suggested that the degree of host resistance was determined by successive random events occurring after inoculation.

The latent period/log dose curve provides a new test of the hypothesis of independent action, since this predicts that most responses to doses equal to or less than 1 ED50 are each initiated by only one inoculated organism. Hence, the latent period should become approximately constant at such doses. This was found to be so in the present experiments.

The authors are grateful to the Medical Research Council for meeting part of the expenses of this work by a grant to G. G. M. They also wish to acknowledge the help of Dr W. R. Bryan, Dr B. Mandel, Dr D. B. W. Reid and Dr G. T. Stewart who provided unpublished data.

Type
Research Article
Information
Journal of Hygiene , Volume 56 , Issue 3 , September 1958 , pp. 323 - 346
Copyright
Copyright © Cambridge University Press 1958

References

Bacon, G. A., Burrows, T. W. & Yates, M. (1951). The effects of biochemical mutation on the virulence of Bacterium typhosum: the loss of virulence of certain mutants. Brit. J. exp. Path. 32, 85.Google ScholarPubMed
Beard, J. W., Sharp, D. G. & Eckert, E. A. (1955). Tumour viruses. Advanc. Virus Res. 3, 149.CrossRefGoogle Scholar
Bell, J. F., Owen, C. R. & Larson, C. L. (1955). Virulence of Bacterium tularense. I. A study of the virulence of Bacterium tularense in mice, guinea pigs and rabbits. J. infect. Dis. 97, 162.CrossRefGoogle Scholar
Berry, L. J., Ropp, M. K. DE, Fair, M. H. & Schur, E. M. (1956). Dynamics of bacterial infections in mice under conditions known to alter survival time. J. infect. Dis. 98, 198.CrossRefGoogle ScholarPubMed
Bonezzi, G., Cavalli, L. & Magni, G. (1943). Quantitative Untersuchungen über die Virulenz. I. Eine Virulenzgleichung und ihre biologische Deutung. Zbl. Bakt. (Abt. 1, Orig.) 150, 17.Google Scholar
Bryan, W. R. (1956). Biological studies on the Rous Sarcoma virus. IV. Interpretation of tumour-response data involving one inoculation site per chicken. J. nat. Cancer Inst. 16, 843.Google Scholar
Bryan, W. R. & Beard, J. W. (1939). Estimation of purified papilloma virus protein by infectivity measurements. J. infect. Dis. 65, 306.CrossRefGoogle Scholar
Bryan, W. R. & Beard, J. W. (1940). Correlation of frequency of positive inoculations with incubation period and concentration of purified papilloma protein. J. infect. Dis. 66, 245.CrossRefGoogle Scholar
Bryan, W. R., Calnan, D. & Moloney, J. B. (1955). Biological studies on the Rous Sarcoma virus. III. The recovery of virus from experimental tumours in relation to initiating dose. J. nat. Cancer Inst. 16, 317.Google ScholarPubMed
Cavalli, L. & Magni, G. (1943). Quantitative Untersuchungen über die Virulenz. II. Die bakteriostatische Wirkung der Sulfanilamide in vivo. Zbl. Bakt. (Abt. 1, Orig.) 150, 25.Google Scholar
Cavalli, L. & Magni, G. (1947). Methods of analysing the virulence of bacteria and viruses for genetical purposes. Heredity, 1, 127.CrossRefGoogle Scholar
Crocker, T. T. (1954). The number of elementary bodies per 50% lethal dose of meningo-pneumonitis virus as determined by electron microscopic counting. J. Immunol. 73, 1.CrossRefGoogle Scholar
Crocker, T. T. & Bennett, B. M. (1955). The slope assay for measurement of the lethal potency of meningo-pneumonitis virus in the chick embryo. J. Immunol. 75, 239.CrossRefGoogle ScholarPubMed
Epstein, M. A. (1956). The identification of the Rous virus; a morphological and biological study. Brit. J. Cancer, 10, 33.CrossRefGoogle Scholar
Faine, S. (1957). Virulence in Leptospira. II. The growth in vivo of virulent Leptospira icterohaemorrhagiae. Brit. J. exp. Path. 38, 8.Google ScholarPubMed
Felix, A. (1938). The titration of therapeutic anti-typhoid serum. J. Hyg., Camb., 38, 750.Google ScholarPubMed
Gard, S. (1940). Encephalomyelitis of mice. II. A method for the measurement of virus activity. J. exp. Med. 72, 69.CrossRefGoogle Scholar
Gard, S. (1943). Purification of poliomyelitis viruses. Experiments on murine and human strains. Acta med. scand. (Suppl.) 143.Google Scholar
Gledhill, A. W. (1956). Quantitative aspects of the enhancing action of Eperythrozoa on the pathogenicity of Mouse Hepatitis Virus. J. gen. Microbiol. 15, 292.CrossRefGoogle ScholarPubMed
Gogolak, F. M. (1953). A quantitative study of the infectivity of murine pneumonitis virus in mice infected in a cloud chamber of improved design. J. infect. Dis. 92, 240.CrossRefGoogle Scholar
Goldberg, L. J., Watkins, H. M. S., Dolmatz, M. S. & Schlamm, N. A. (1954). Studies on the experimental epidemiology of respiratory infections. VI. The relationship between dose of micro-organisms and the subsequent infection or death of a host. J. infect. Dis. 94, 9.CrossRefGoogle ScholarPubMed
Golub, O. J. (1948). A single-dilution method for the estimation of LD50 titers of the psittacosis-LGV group of viruses in chick embryos. J. Immunol. 59, 71.CrossRefGoogle ScholarPubMed
Gonnert, R. (1942). Ueber einige Eigenschaften des Bronchopneumonievirus der Maus. Zbl. Bakt. (Abt. 1, Orig.) 148, 331.Google Scholar
Hobson, D. (1956). The chemotherapy of experimental mouse typhoid with furazolidone. Brit. J. exp. Path. 37, 20.Google ScholarPubMed
Hobson, D. (1957). Chronic bacterial carriage in survivors of experimental mouse typhoid. J. Path. Bact. 73, 399.CrossRefGoogle Scholar
Horsfall, F. L. & Ginsberg, H. S. (1951). The dependence of the pathological lesion upon the multiplication of pneumonia virus of mice (PVM). Kinetic relation between the degree of viral multiplication and the extent of pneumonia. J. exp. Med., 93, 139.CrossRefGoogle ScholarPubMed
Ipsen, J. (1944). Quantitative Studien über maüsepathogene Fleckfieberrickettsien. Schweriz. Z. Path. 7, 129.Google Scholar
Kunkel, L. O. (1934). Tobacco and aucuba-mosaic infections by single units of virus. Phytopathology, 24, 13.Google Scholar
Maaløe, O. (1948). I. Pathogenic-apathogenic transformation of Salmonella typhimurium. Acta path. scand. microbiol. 25, 414.CrossRefGoogle Scholar
MacDowell, E. C. (1936). Genetic aspects of mouse leukaemia. Amer. J. Cancer. 26, 85.CrossRefGoogle Scholar
McKee, C. M., Rake, G., Donovick, R. & Jambor, W. P. (1949). The use of the mouse in a standardized test for antituberculous activity of compounds of natural or synthetic origin. I. Choice and standardization of culture. Amer. Rev. Tuberc. 60, 90.Google ScholarPubMed
Magnuson, H. J., Rosenau, B. J. & Greenberg, B. G. (1951). The effects of sex, castration, and testosterone upon the susceptibility of rabbits to experimental syphilis. Amer. J. Syph. 35, 146.Google Scholar
Mandel, B. & Racker, E. (1953). Inhibition of Theiler's encephalomyelitis virus (GDVII strain) of mice by an intestinal mucopolysaccharide. J. exp. Med. 98, 399.CrossRefGoogle ScholarPubMed
Meynell, G. G. (1957 a). The applicability of the hypothesis of independent action to fatal infections in mice given Salmonella typhimurium by mouth. J. gen. Microbiol. 16, 396.CrossRefGoogle ScholarPubMed
Meynell, G. G. (1957 b). Inherently low precision of infectivity titrations using a quantal response. Biometrics, 13, 149.CrossRefGoogle Scholar
Meynell, G. G. & Stocker, B. A. D. (1957). Some hypotheses on the aetiology of fatal infections in partially resistant hosts and their application to mice challenged with Salmonella paratyphi-B or Salmonella typhimurium by intraperitoneal injection. J. gen. Microbiol. 16, 38.CrossRefGoogle ScholarPubMed
Mims, C. A. (1956). Rift Valley Fever virus in mice. III. Further quantitative features of the infective process. Brit. J. exp. Path. 37, 120.Google ScholarPubMed
Ormsbee, R. A., Lackman, D. B. & Pickens, E. G. (1951). Relationships between complement-fixing values, infectious endpoints, and death curves in experimental Coxiella burneti infection. J. Immunol. 67, 257.CrossRefGoogle Scholar
Pierce, C. H., Dubos, R. J. & Schaefer, W. B. (1953). Multiplication and survival of tubercle bacilli in the organs of mice. J. exp. Med. 97, 189.CrossRefGoogle ScholarPubMed
Prince, A. M., Littell, A. S. & Ginsberg, H. S. (1957). Methods for quantitative bioassay of Ehrlich ascites-tumour cells. J. nat. Cancer Inst. 18, 487.Google Scholar
Reinhard, M. C., Goltz, H. L. & Warner, S. G. (1945). Further studies on the quantitative determination of the growth of a transplantable mouse adenocarcinoma. Cancer Res. 5, 102.Google Scholar
Rowley, D. (1954). The virulence of strains of Bacterium coli for mice. Brit. J. exp. Path. 35, 528.Google ScholarPubMed
Schneider, H. A. & Zinder, N. D. (1956). Nutrition of the host and natural resistance to infection. V. An improved assay employing genetic markers in the double strain inoculation test. J. exp. Med. 103, 207.CrossRefGoogle Scholar
Smith, C. E. G. & Westgarth, D. R. (1957). The use of survival time in the analysis of neutralization tests for serum antibody surveys. J. Hyg., Camb., 55, 224.CrossRefGoogle ScholarPubMed
Stewart, G. T. & Tamargo-Sanchez, M. (1952). An experimental basis for estimating the virulence of tubercle bacilli. J. Hyg., Camb., 50, 37.CrossRefGoogle ScholarPubMed
Thompson, W. R. (1947). Use of moving averages and interpolation to estimate median-effective dose. I. Fundamental formulas, estimation of error, and relation to other methods. Bact. Rev. 11, 115.CrossRefGoogle ScholarPubMed
Weiss, E. (1950a). Multiplication of the agent of feline pneumonitis in the yolk sacs of dead chick embryos. J. infect. Dis. 86, 27.CrossRefGoogle ScholarPubMed
Weiss, E. (1950b). The effect of antibiotics on agents of the psittacosis-lymphogranuloma group. I. The effect of penicillin. J. infect. Dis. 87, 249.CrossRefGoogle Scholar
Youmans, G. P. & Youmans, A. S. (1951). The relation between the size of infecting dose of tubercle bacilli and the survival time of mice. Amer. Rev. Tuberc. 64, 534.Google ScholarPubMed