THE PRODUCTION OF EXPERIMENTAL TYPHOID FEVER IN THE GUINEA PIG WITH AN IN VIVO PREPARED TOXIC FILTRATE OF B. TYPHOSUS.

When the typhoid bacillus is injected into the peritoneal cavity of guinea pigs acute peritonitis and death are produced. The character of the exudate is variable as to the elements present but is usually of a serous type with slight clouding due to the presence of polymorphonuclear neutrophils, mononuclear cells and bacteria. When the Berkefeld filtrate of this exudative material is inoculated into normal guinea pigs either subcutaneously, intraperitoneally or intracardially, the character of response obtained on the part of the host is quite at variance with that produced by the inoculation of the living typhoid bacillus. A febrile reaction and marked leucopenia, as a rule, are persistent and are accentuated after each injection the latter often reaching below 1000 cells per c. mm. There is a loss of weight of a variable extent in all animals and in some the emaciation is extreme. The animals were given four such inoculations and all succumbed in from 2 to 4 weeks. The intracardiac route produces death more quickly and the reactions are more clear-cut when this route is employed. At autopsy a general tumefaction and congestion of the lymphoid structures more especially of the abdominal cavity are found. Peyer's patches and the solitary follicles of the intestinal tract are likewise involved and in some of the patches slight ulceration is noted; occasionally, there occur extreme ulceration and necrosis of the patch. The spleen is enlarged and usually softened. Microscopically, marked endothelial cell proliferation is noted especially in the lymphoid structures and in many instances the phagocytic cells of Mallory are found. These cells include within their cytoplasm elements of the surrounding structures. In the spleen there are present congestion, and hemorrhages with many "shadow" red blood cells. Phagocytosis of the red cells by the endothelial cells is present. In the liver, areas of focal necrosis are found and phagocytic cells are seen. In the animals inoculated subcutaneously, localized degenerative changes are observed especially in the muscular structures. From these results it can be seen that the reactions and injury of the animal body by the toxic filtrate employed, are quite similar to the changes produced by the specific toxin in human typhoid fever.