380 THE TYPHOID BACILLUS 



5. Vaccination. 



A. Immunization of the lower animals. 



(i) Beumer and Peipper immunized white mice by inoculating them daily 

 for several days with increasing doses of living cultures. Guinea-pigs, rabbits, 

 and especially goats and dogs may be vaccinated in a similar manner (Pfeiffer, 

 Lceffler and Abel). Vincent immunized dogs and rabbits by inoculating them 

 first with cultures heated to 60 C., then with living cultures 16 hours old, 

 and finally with more toxic cultures 15-20 days old. The serum of animals 

 so treated has both immunizing and agglutinating properties : immunized 

 animals are however not immune to an mtra-cerebral inoculation of typhoid 

 toxin. 



(ii) Brieger, Wassermann and Kitasato used for their immunizing experi- 

 ments organisms attenuated by being grown in thymus broth (p. 34). 

 Inoculations of a culture of a virulent bacillus grown in thymus broth and 

 heated to 60 C. produced immunity in guinea-pigs and mice. 



(iii) Sanarelli, Chantemesse and Widal, Beumer and Peipper immunized 

 animals by inoculating them with cultures sterilized by heat. 



(a) Sanarelli incubated a culture of a bacillus of increased virulence in 

 peptone broth for a week at 37 C. and sterilized the growth at 120 C. ' The 

 sterilized product possessed vaccinating properties. 



Generally, it may be said that to immunize guinea-pigs weighing 400 grams it is 

 only necessary to inoculate them several times over a period of 5 days with 16-18 c.c. 

 of sterilized cultures. The animals are immune 4 days after the last inoculation 

 and will then resist the inoculation of a virus of exalted virulence. During the 

 process of immunization the animals lose a certain amount of weight but quickly 

 recover. 



It is very difficult to immunize rabbits for they are far more susceptible than 

 guinea-pigs and death often takes place during the immunizing process ; but animals 

 which survive the treatment are immune in a high degree. 



(6) Chantemesse and Widal used broth cultures incubated at 37 C. for 

 15 days and then sterilized at 100 C. 



Twenty c.c. are necessary to immunize a guinea-pig : the toxin should be inocu- 

 lated in four doses allowing a few days to elapse between each inoculation. 

 Immunization takes a fortnight ; after the lapse of another 8 days the test inocula- 

 tion may be performed (2 c.c. of a virulent culture into the peritoneum). Not 

 infrequently the animals die either during the immunizing process or as the result 

 of the test inoculation. 



Rabbits may be immunized in a similar manner but in these animals the process 

 is even more difficult. 



(c) Beumer and Pfeiffer immunized sheep in a like manner with cultures 

 heated to 60 C. for an hour. 



For immunizing horses Funck prefers to use cultures sterilized with carbolic 

 acid. 



(iv) Chantemesse immunized horses by injecting them with gradually 

 increasing doses of his toxin (vide supra). 



The immunization of horses is very difficult ; the inoculations whether made 

 sub-cutaneously or intra-venously have frequently to be interrupted on account 

 of the violence of the reaction, and it takes several years to produce a lasting 

 immunity. 



B. Human vaccination. 



For many years the problem of the vaccination of the human subject 

 against enteric fever has been under investigation. In 1896, Pfeiffer and 

 Kolle showed that as a result of inoculating man with a small quantity of 



