PATHOGENICITY OF C. DIPHTHERIA 457 



serum and will give rise to antibody production in animals, but is no longer toxic. 

 It appears to be produced within the bodies of the bacilli, since toxin is liberated 

 in bacterial suspensions submitted to treatment with sonic vibration (Morton and 

 Gonzalez 1942). 



The classical paper in which Loeffler (1884) first described the isolation and 

 characters of the diphtheria bacillus, and the report by Roux and Yersin (1888) 

 of the separation of the filtrable toxin, contain descriptions of the lesions produced 

 by the living organism, or by its separated toxin, in a variety of laboratory animals. 

 These original observations have since been extended by a host of experimental 

 studies. It will suffice to note here that, among laboratory animals, the guinea-pig 

 and the rabbit are the most susceptible, while rats and mice are extremely resistant. 

 Dogs, cats, pigeons, and other birds appear to occupy an intermediate position. 

 (See Loeffler 1884, 1890, Eoux and Yersin 1888, Wernicke 1893, Goodman 1907, 

 Coca et al. 1921, Glenny and Allen 1922, Andrewes et al. 1923). It may be noted 

 that the bacillus appears to have little power of tissue invasion ; whether the 

 inoculum consists of a living culture, or of a toxic filtrate, death occurs as the result 

 of a toxaemia in the strict sense. This general statement may require minor 

 modification in regard to certain varieties of the diphtheria bacillus (see below). 

 For our immediate purpose it will suffice to note the sequence of events that follow 

 the injection of a living culture, or of a toxic filtrate, into the guinea-pig. 



If a guinea-pig is inoculated subcutaneously into the flank with a dose of a virulent 

 culture or of a toxic filtrate, of a size which will produce death within a few days, a soft 

 oedematous swelling usually appears at the site of inoculation within 12 to 18 hours, and 

 gradually extends. About the time the swelling appears, or shortly thereafter, the animal 

 becomes obviously ill, developing a staring coat and sitting crouched in its cage. Death 

 usually occurs between 18 and 96 hours, according to the size of the dose of culture or 

 filtrate inoculated. With very large doses the time to death may be even shorter, but is 

 never less than 10 to 14 hours (see Glenny 19256). Animals that survive beyond the 4th 

 day may develop cachexia and paralysis, and die at some later period ; but the pathogenesis 

 of this condition appears to be essentially different from that of the acutely fatal toxaemia, 

 and it is with the latter that we are here concerned. When a guinea-pig that has died 

 within 4 days after a subcutaneous inoculation is examined post mortem, the typical 

 findings are as follows : 



At the site of inoculation is found an exteiisive area of gelatinous hsemorrhagic oedema, 

 extending to the skin superficially, and deeply to the muscles or to the parietal peritoneal 

 membrane. If the animal has survived for several days, the tissues in the more central 

 parts of the oedematous area may be obviously necrotic. The regional l3Tnph glands are 

 usually swollen and congested. The peritoneum may contain a varying amount of fluid, 

 which may be clear, cloudy or blood-stained. The abdominal viscera as a whole are 

 congested ; but the most striking lesion is the marked swelling and congestion of the 

 adrenal glands. On macroscopical section there are seen to be scattered haemorrhages, 

 situated in the medulla, in the cortex, or in both. Sometimes aU naked-eye distinction 

 between cortex and medulla is lost. On opening the thorax a serous exudate will often be 

 found in the pleural cavities, usually clear, sometimes cloudy or blood-stained. A peri- 

 cardial efi"usion may or may not be present. Films prepared from such effusions reveal a 

 marked preponderance of mononuclear cells. 



It is of some interest to note the relative frequency of the more important lesions 

 associated with acute diphtheritic toxaemia in the guinea-pig. Wright (1894) records the 

 findings in 160 necropsies : a local lesion was present in 90 per cent, of the animals ; con- 

 gestion of the adrenals in 81-2 per cent. ; and a pleural effusion in 42-5 per cent. Barratt 

 (1923) records the post-mortem findings in 50 guinea-pigs which died within 72 hours after 



