4i 8 Diphtheria 



and found to be extremely complex. As it exists in cultures it is 

 composed of equal parts of toxin and toxoid. Of these, the former 

 is poisonous, the latter harmless for animals or at least not fatal 

 to them. The toxoids have equal or greater affinity for combining 

 with antitoxin than the toxin and cause confusion in testing the 

 unit value or strength of the antitoxin. In old or heated toxin all 

 of the toxin molecules become changed into toxons or toxoids and 

 the poisonous quality 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 3oo-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 diphtherias is pathogenic for man, 

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

 rows, pigeons and fowls are susceptible to experimental infection; 

 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 surfaces 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-localized at or near the 

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



