Studies on the Experimental Epidemiology of Respiratory Infections: VI. The Relationship between Dose of Microorganisms and Subsequent Infection or Death of a Host

Goldberg, L. J.; Watkins, H. M. S.; Dolmatz, M. S.; Schlamm, N. A.

doi:10.1093/infdis/94.1.9

Cited by 25 publications

(8 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is possible that the later deaths result from the asynchronous breakdown of localized lesions, each of which may have resulted from the multiplication of only one of the inoculated bacteria; it is to be noted that the abscesses found in survivors appear from their bacterial compositions to have originated in this way. Our data do not exclude this hypothesis but, for reasons given elsewhere, we consider that the hypothesis of independent action is more convincing than its alternatives because it has to be modified by fewer and less restricted assumptions to explain the results of these and of other experiments (see, for example, the discussion of the doseresponse curve given below and experiments by Goldberg, Watkins, Dolmatz & Schlamm, 1954).…”

Section: Discussionmentioning

confidence: 65%

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

Meynell

Stocker

1957

Journal of General Microbiology

110

View full text Add to dashboard Cite

SUMMARY:Some hypotheses are considered which describe the aetiology of a fatal infection in a partially resistant host ; i.e. a host which does not invariably die after inoculation with one bacterium. The hypothesis of independent action postulates that the mean probability per inoculated bacterium of multiplying to cause (or help to cause) a fatal infection is independent of the number of bacteria inoculated and, for a partially resistant host, is less than unity ( 1 > p > 0). It predicts : (1) that the slope, b, of the probit-mortality/log-dose curve will be 2.0 or less a t the LD 50 point ; (2) that, while hosts dying after inoculation with many LD 50 die as a result of the multiplication of many of the inoculated bacteria, most of those dying from 1 LD 50 or less do so following the multiplication of only one of the inoculated bacteria, regardless of the total number of bacteria inoculated. When a mixture of several equally virulent, distinguishable variants of a given pathogen are inoculated, fatal infections caused by the growth of one bacterium should result in the predominance of only one variant a t post mortem. The hypotheses of maximum and of partial synergism postulate that inoculated bacteria co-operate so that the value of p increases as the size of the dose increases. They predict : (1) that the slope of the dose-response curve may be more than 2.0 a t the LD50 point ; (2) that all observed fatal infections will be initiated by more than one bacterium and that consequently the inoculation of a mixed inoculum will lead to the predominance of several variants at post mortem.Variants of Salmonella paratyphi-B which carried one of the three flagellar antigens, b, i, or e,h, were prepared by transduction. Variants of S. typhimurium which either fermented or did not ferment xylose were also prepared. In each case, the variants did not differ detectably in growth rate in vivo, or in virulence. The value of b was 1.8 for mice inoculated with S. paratyphi-B by intraperitoneal injection (LD50 = 74' x lo6 organisms). As predicted by the hypothesis of independent action, the relative frequencies of the variants in samples of heart blood obtained post mortem varied greatly from mouse to mouse when the dose was 1 LD50 or less, and became progressively more uniform (and similar to the inoculum) as the size of the dose increased. The value of b was 0.66 for mice challenged by S. typhimurium by subcutaneous injection (LD 50 = 2 x lo8 organisms) ; and challenge with a mixed inoculum gave similar results.Despite this general conformity with prediction, far fewer mice than expected yielded only one variant at post mortem. This discrepancy possibly resulted from * Present address.

show abstract

Section: Discussionmentioning

confidence: 65%

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

Meynell

Stocker

1957

Journal of General Microbiology

110

View full text Add to dashboard Cite

show abstract

“…experiments is susceptible to infection with 2 to 5 virulent P. pestis. Subcutaneous LD5o values were derived by correlating percentage mortality and estimated dose per animal (EDA) data upon the Linearized Mortality Grid devised by Goldberg et al (1954). Usually 4 groups of 8 mice each were injected with 0.1 ml amounts of appropriate decimal serial concentrations of organisms.…”

Section: Methodsmentioning

confidence: 99%

COLONIAL MORPHOLOGY AND VIRULENCE OF PASTEURELLA PESTIS

1958

View full text Add to dashboard Cite

“…This point has been discussed by Meynell & Stocker (1957), who suggested that the proportion could be predicted from a general hypothesis (the hypothesis of independent action) which relates several other features of infective systems. These are, the increasing probability of a response with increase in dosage, and the isolation of pure clones of organisms from hosts inoculated with limiting dilutions (Kunkel, 1934;Meynell & Stocker, 1957;Meynell, 1957 a); the shape of the dose-response curve and the relatively high variability in response observed in infectivity titrations using an all-or-none response (Meynell, 1957 b); the effect on response of subdivision of the total number of organisms inoculated (Goldberg, Watkins, Dolmatz & Schlamm, 1954); and the approximate constancy of the latent period reported below for doses equal to or less than the ED50. The latter provides a new test of the hypothesis.…”

Section: Introductionmentioning

confidence: 99%

The growth of micro-organismsin vivowith particular reference to the relation between dose and latent period

Meynell

1958

J. Hyg.

View full text Add to dashboard Cite

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.

show abstract

Studies on the Experimental Epidemiology of Respiratory Infections: VI. The Relationship between Dose of Microorganisms and Subsequent Infection or Death of a Host

Cited by 25 publications

References 5 publications

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

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

COLONIAL MORPHOLOGY AND VIRULENCE OF PASTEURELLA PESTIS

The growth of micro-organismsin vivowith particular reference to the relation between dose and latent period

Contact Info

Product

Resources

About