SERUM THERAPY 383 



slow and irregular, it has been suggested by several observers (Leclainche, 

 Calmette, Salimbeni) that mixtures of specific serum and micro-organisms 

 might prove more effective. The results so far obtained have been only 

 moderately encouraging, probably because there has been too much serum 

 in the mixtures used for inoculation. 



Bearing in mind the property possessed by organisms of fixing the immune 

 body present in their specific serums, Besredka sensitizes bacilli with anti- 

 typhoid serum and uses the sensitized organisms for vaccinating purposes. 

 An emulsion of bacilli from a forty-eight-hour culture on agar is made in 

 normal saline solution, mixed with antityphoid serum and left at 37 C. for 

 24 hours. The agglutinated bacilli are then centrifuged and washed several 

 times with normal saline solution until all traces of serum have disappeared ; 

 the emulsion is then heated in a water bath at 58 C. for half an hour. 



Guinea-pigs can be rendered highly immune in about 20 hours by inocu- 

 lating them sub-cutaneously with the vaccine. The immunity lasts for 

 several months (Besredka, Paladino-Blandini) and the serum of the animals 

 is bactericidal and prophylactic. 



In man, inoculation with Besredka's vaccine produces only a very slight 

 tenderness locally, and there is ground for hoping that this method, which 

 confers immunity within 24 hours, will in future play an important part in 

 the prophylaxis of enteric fever. 



6. Serum therapy. 



Brieger, and Wassermann and Kitasato, whose experiments have been con- 

 firmed by Sanarelli, Chantemesse and Widal and others, have shown that 

 laboratory animals can be immunized against experimental infection by 

 inoculating them with the serum of a vaccinated animal, and that such a 

 serum possesses curative as well as prophylactic properties. 



If a fatal dose of a culture of the typhoid bacillus be mixed with 0'5 c.c. of the serum 

 and inoculated into the peritoneal cavity or beneath the skin of a guinea-pig the 

 animal remains unaffected. 



Guinea-pigs can be immunized in a few hours by inoculating them with 2 c.c. of 

 the serum of a vaccinated animal. Subsequent inoculation of a dose of a virus 

 of exalted virulence sufficient to kill a control animal is without effect on the treated 

 animal. 



Similarly, animals inoculated with an ordinarily fatal dose of culture recover if, 

 within 3 hours of the inoculation, 1-2 c.c. of antityphoid serum be administered 

 to them. 



Chantemesse and Widal have shown that the serums of patients who have 

 recovered from an attack of enteric fever exhibit both prophylactic and 

 curative properties. These properties are not very well marked, and to 

 immunize a guinea-pig about 10 c.c. of serum are necessary. Attempts to 

 use the serum in the treatment of human enteric fever have not given conclusive 

 results. 



Artificial animal serums have been used by a great many observers in the 

 treatment of enteric fever, but with little result (Beumer and Peipper, Shaw, 

 Tavel, Aronson, arid others). 



Chantemesse and Besredka however have prepared serums which un- 

 doubtedly possess therapeutic powers. 



A. Chantemesse s serum. 1. Preparation. Chantemesse immunizes horses 

 by repeated sub-cutaneous inoculations of his soluble toxin (p. 377) and intra- 

 venous inoculations of virulent typhoid bacilli. The process of immuniza- 

 tion is very lengthy ; small doses should be used to begin with, and the animals 

 must be carefully handled. 



2. Properties. Chantemesse's antityphoid serum may be repeatedly 



