436 Diphtheria 



the poisonous quaUty is lost though the power of combining with 

 antitoxin remains. 



The toxin is extremely poisonous, and a filtered bouillon con- 

 taining it may be fatal to a 300-gram guinea-pig in doses of only 

 0.0005 cc. It is thought not to be an albuminous substance, as 

 it can be elaborated by the bacilli when grown in non-albuminous 

 urine, or, as suggested by Uschinsky, in non-albuminous solutions 

 whose principal ingredient is asparagin. The toxic value of the 

 cultures is greatest in the second week. 



This soluble toxin so well known in bouillon cultures is probably only 

 one of the poisonous substances produced by the bacillus. An 

 intracellular, insoluble toxic product seems to have been discovered 

 by Rist,* who found it in the bodies of dried bacilli, and observed 

 that it was not neutralized by the antitoxin. 



Pathogenesis. — The Bacillus diphtherise is pathogenic for man, 

 monkeys, guinea-pigs, rabbits, dogs, cats, cows, and horses. Spar- 

 rows, pigeons and fowls are susceptible to experimental mfection; 

 rats and mice are immune. Spontaneous or natural infection is pretty 

 well limited to man. The effects of artificial experimental infection 

 vary with the avenue of infection, the quantity of culture and its 

 virulence. 



1. Subcutaneous inoculation in rabbits and guinea-pigs is usually 

 fatal in from seventy-two hours to five days. The animal suffers 

 some rise of temperature in twelve to twenty-four hours, soon is 

 depressed, weak, loses flesh, remains quiet and dies. At the seat 

 of infection there is a swelling caused by combined edema, hemor- 

 rhage and fibrinous exudation. If the culture be of feeble viru- 

 lence so that death does not occur, this area sloughs, and then 

 heals slowly. 



2. Intraperitoneal and Intrapleural Infection. — This is not so 

 serious in its results as might be supposed. Some animals recover 

 from doses that might be fatal under the skin. Death does not 

 occur until after a week or twelve days. Fluid of slightly turbid 

 character with flakes of fibrin is found in the peritoneum. 



3. Mucous Membrane Inoculations. — When implanted upon the 

 scarified surface of the mucous membranes, the bacillus causes the 

 formation of a fibrinous and necrotic pseudo-membrane. Such con- 

 ditions may recover or death may follow after some days. 



In all cases the bacilli remain fairly .well-locaHzed at or near the 

 seat of inoculation and only rarely invade the blood. Death and 

 illness result from toxemia, not from bacteremia. 



When examined post-mortem, the liver is found to be enlarged and 

 sometimes shows minute whitish points, which upon microscopic . 

 examination prove to be necrotic areas in- which the cells are com- 

 pletely degenerated, and the chromatin of their nuclei scattered 

 about in granular form. Similar necrotic foci, to which attention 

 *"Soc. de Biol. Paris," 1903 No. 25. 



