434 THE DIPHTHERIA BACILLUS GROUP 
T&thogenesis. — Experimental Evidence of Pathogenesis.— Loffier^ ap- 
pears to have been the first to attempt to estabhsh the etiological 
relationship of the diphtheria bacillus to the disease. He succeeded 
in producing diphtheritic membranes on the mucous surfaces of 
animals by rubbing cultures on the previously injured surface. Num- 
erous laboratory accidents, where the organisms have been inadver- 
tently swallowed with the subsequent development of typical clinical 
diphtheria, complete the proof of the etiological relationship of the 
organism to the disease. 
Animal Pathogenesis. — LahorsLtory animals, excepting mice and 
rats, are very susceptible to the diphtheria toxin. Guinea-pigs are 
particularly susceptible, and the subcutaneous injection of fatal or 
nearly fatal doses of broth cultures is followed after one to three days 
by the appearance at the site of inoculation of a membrane, edema, 
and a serosanguineous exudate. A pleuritic, and frequently a peri- 
cardial exudate is found as well. There is hyperemia of the abdom- 
inal organs and a very characteristic swelling and hyperemia of the 
adrenals. The kidneys are also usually hyperemic. Often there are 
ecchymoses and even ulcers in the gastric mucosa. No bacilli are 
found in the internal organs. Intraperitoneal injections are less severe 
as a rule than subcutaneous inoculations of the same dose. There 
is usually some peritoneal effusion which frequently contains diph- 
theria bacilli. Intratracheal inoculation after mechanical injury is 
commonly followed by the appearance of a false membrane and the 
animal dies of toxemia;- intra vaginal injection after injury of the 
mucosa frequently leads to a necrotic inflammation with membrane 
formation.^ Repeated applications of diphtheria toxin to the con- 
junctiva of rabbits cause a marked conjunctivitis with membrane 
formation.^ 
Human. — \n man diphtheria bacilli are usually localized in the 
false membranes, chiefly on the tonsils or pharynx, and these mem- 
branes may extend to the nose, larynx, and mouth. The organisms 
occasionally invade the blood stream. They may even extend into 
the lungs causing a true bronchial pneumonia. Occasionally diph- 
theria bacilli may cause rhinitis fibrinosa or simple rhinitis.'^ They 
also are found in occasional cases of vulvitis gangrenosa and noma 
faciei.'' Rarely, false membranes are found on the genitalia or in 
cutaneous wounds, in the latter case producing a true wound diph- 
theria.'' The association with certain other organisms, particularly the 
streptococcus, the staphylococcus, and B. coli, appears to increase the 
virulence of the diphtheria bacillus.^ 
• Loc. cit. - Fraenkel: Deutsch. med. Wchnschr., 1895, 21, 172. 
3 Roux and Martin: Ann. Inst. Pasteur, 1894, 8, 609. 
* Morax and Elmassian: Ann. Inst. Pasteur, 1898, 12, 210. 
£■ Neumann: Centralbl. f. Bakteriol., orig., 1902, 31, 33. 
^ Freymouth and Petruschky: Deutsch. med. Wchnschr., 1898, 24, 232. 
' Schottmuller: Deutsch. med. Wchnschr., 1895, 21, 272. 
8 Theobald Smith: Med. Rec, 1896, 49, 666. 
