INFECTIOUS DISEASES OF MICE 383 



later (280, 281, 283). All degrees between these extremes are met with, 

 depending upon such variables as the dosage, resistance of the individual 

 mouse or strain of mice, virulence of the organism, and external environ- 

 mental factors such as temperature (129), and diet (329, 172). 



The experimental disease. — In part because of its similarity to human 

 typhoid fever, the pathogenesis of Salmonella infection in mice has been 

 extensively studied experimentally (247, 336, 177, 139, 300, 190, 192, 191, 

 255). After oral administration, a transitory excretion of the bacilli occurs 

 in the feces. The organisms do not multiply and many are excreted from 

 or destroyed in the gastro-intestinal tract, since a period follows in which no 

 organisms can be recovered from the stools. Invasion of the lymphatic 

 system then occurs, with involvement of the intestinal lymph follicles, 

 mesenteric lymph nodes, and less often the tracheobronchial and cervical 

 nodes. Here multiplication presumably occurs, bacteria are carried by 

 lymphatic channels such as the thoracic duct to the blood stream, and a 

 transitory bacteremia ensues (second to fourth day), terminated by removal 

 of the bacilli through action of the reticulo-endothelial cells, particularly in 

 the liver and spleen. Bacterial proliferation occurs in the lymph nodes, 

 liver, and spleen for the next 2 to 4 days, as evidenced by the increase in 

 numbers of bacilli found in these organs, but the blood remains sterile. 

 Finally, a progressive re-invasion of the blood stream occurs with generaliza- 

 tion of the infection throughout the body and secondary invasion of the 

 intestine. Bacilli are found in such tissues as muscle, gall bladder, bile, and 

 urine after the septicemia has become established. Direct invasion of the 

 blood stream occurs only when the infecting strains are of highest virulence 

 and toxicity or when an overwhelming dose is given. Following the second 

 bacteremia, the bacilli multiply rapidly in the intestine and may over- 

 whelm the normal flora (307). In cases of chronic infection, such as is 

 present in mice which have survived natural or experimental infection, 

 organisms persist in the spleen, liver, lymph nodes, and gall bladder for 

 months, and are intermittently or continuously discharged in the feces (see 

 work of Amoss, Neufeld, Topley, and Webster). The various strains of 

 Salmonella behave similarly (177, 5, 6). Fatal infections may also be pro- 

 duced by applying bacilli to the depilated intact or lightly scarified skin, to 

 the mucous membranes of the conjunctiva by dropping a liquid suspension 

 into the eye, or by inhalation. 



The role played by ''toxins," lytic products, or specific substances derived 

 from the bacteria is difficult to define, but presumably such products of 

 the organism account for the leukopenia and focal necrosis in the liver. 



