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Inhalation Experiments on Mice with Pneumococci

Published online by Cambridge University Press:  15 May 2009

Fred Griffith
Affiliation:
(From the Pathological Laboratory of the Ministry of Health.)
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Fatal general infection can be readily production in mice by spraying with pneumococcal culture in a closed chamber without resorting to any artificial means of lowering the animal's resistance.

In the experiments recorded the proportion of unprotected mice which developed septicaemia varied considerably, the highest being nine out of ten. These irregularities may be partly attributable to variations in (1) the fineness of the spray, and (2) the virulence of the culture.

In unprotected mice death from septicaemia rarely occurs before the 3rd day after spraying and may be delayed for a week or more.

Vaccination by subcutaneous and intraperitoneal inoculation with heated cultures afforded protection against infection by inhalation to 11 out of 13 mice. Two succumbed to septicaemia although they had resisted 14 days earlier an intraperitoneal dose of 0·0001 c.c. of culture. The culture used for spraying was evidently in a highly virulent state since nine out of the ten controls died of septicaemia.

The above experiments were with homologous cultures but tests have also been made of the efficacy of vaccination against heterologous strains. For example, vaccination with Types I and II cultures gave apparently a certain amount of protection against infection by spraying with a mixture of Type III and Group IV strains.

Passive immunity induced by an injection of antipneumococcal serum immediately before spraying was effective against the homologous types in all of a batch of 13 mice. The resistance showed a tendency to diminish with the lapse of time, since on re-spraying the same lot of mice 3 weeks later one mouse developed septicaemia.

In unprotected mice where death was delayed for some days after spraying there was generally no evidence to the naked eye of any local pulmonary lesions. Rarely typical grey consolidation of portions of the lungs was found. A pneumonic condition occurred more frequently in mice in which a slight degree of immunity had been produced. For example, a Type II pneumonia was found in a mouse which had been immunised against Type I.

The production of the carrier state is a regular sequel to spraying even with the most virulent cultures of pneumococci. A large proportion of the mice which survived spraying were nasopharyngeal carriers a fortnight later and the condition persisted in one mouse for 99 days. A carrier of pneumococci may succumb to septicaemia 15 days after the date of infection; it is not known whether any immunity develops in carriers.

The presence, about the pharynx of mice, of Gram-negative bacilli which grow rapidly in culture and are of high virulence when introduced parenterally is a source of difficulty in attempts to demonstrate pneumococci.

An attempt was made to ascertain whether, after spraying, nasopharyngeal carriers of pneumococci were more numerous among normal or among protected mice. The results were inconclusive, but there was no marked indication in the experiments recorded that the state of immunity influenced the carrier condition.

Type
Research Article
Copyright
Copyright © Cambridge University Press 1926

References

page 1 note 1 Stillman, E. G. and Branch, A. (1924). Experimental production of Pneumococcus pneumonia in mice by the inhalation method. Journ. Exp. Med. xl. 733752.CrossRefGoogle Scholar

page 6 note 1 Stillman, and Branch, (loc. cit. p. 733) have made experiments which show that this is feasible (see footnote, p. 1).Google Scholar