394 HOST-PARASITE RELATIONSHIPS 



enteritidis picks out the mice of the susceptible strain from those of the resistant. In this 

 sense, each of the tests is accomplishing its purpose. The second conclusion is that the 

 intrastomachal instillation of the bacteria requires 100 times the dose of the pathogen 

 to cause the disease than the intraperitoneal, subcutaneous, or intravenous routes. 

 Conclusions from this fact may be opposed. (1) It may be supposed that the intra- 

 stomachal route is the natural route of infection and as such has had most of the natural 

 resistance mechanisms built up around it. If this were true, the numbers of bacteria 

 immobilized would be large and a higher initial dose be required to cause the typhoid 

 disease. (2) On the other hand, the stomach and contents furnish much material 

 in which large numbers of bacteria may be lost through chance and thus never get an 

 opportunity to reach the vital centers and cause death. The inoculation routes are 

 closer to these centers so there is less chance of loss and fewer organisms are required. 

 Of all the inoculation routes, it is a little surprising perhaps that the intravenous is 

 least efficient, the subcutaneous is next, and the intraperitoneal is the most effective. 

 S. enteritidis parasitizes the liver and spleen. In that sense, intraperitoneal inoculation 

 places the bacteria near these organs and so could facilitate immediate infection possibly 

 at the vital organ. On the other hand, at one stage the disease is a septicemia with 

 large numbers of bacteria in the bloodstream. Should the septicemia be a funda- 

 mental part of the disease, it would also seem that the intravenous injection should 

 be more helpful in reaching the vital organs than subcutaneous inoculations which dis- 

 tribute the bacteria more widely and also give them more chance for loss before their 

 effects may reach the vital center. However, the data show that this is not the result. 

 In any case, the large dose required by the intrastomachal routes is subject to at 

 least two interpretations having opposite significance. 



Another test of this matter came in our own research some 30 years ago while 

 studying genetic resistance to poisons as distinct from reproducing pathogens. The 

 dose of ricin for the mice was 0.002 mg. The mice were of a single inbred strain and 

 were 60 days of age. The routes of instillation were subcutaneous, intraperitoneal, and 

 intravenous (into the tail vein) . One hundred and sixteen mice were used in the tests, 

 figure 53. 



The data of figure 53 are in order of the susceptibilities of the mice, the subcu- 

 taneous route being least toxic, the intraperitoneal route noticeably more lethal, and 

 the intravenous being completely lethal. The order of effect is that which our pre- 

 conceptions might lead us to expect. There should be more wastage of poison when 

 introduced subcutaneously than when placed near the vital organs in the peritoneal 

 cavity. Introduction into the circulation would seem to give the means to carry the 

 toxic chemical most directly to the organs vulnerable to its effects. 



The order of effectiveness of the routes of entry into the body is not the same as 

 that for disease due to S. enteritidis. It appears quite likely it will not be the same for 

 other pathogens. In any case the evidence is equivocal on whether or not a given 

 route for introducing a pathogen in testing for natural resistance of a host is better 

 than another. 



