APPLICATION OF THE PHENOMENON 405 



obtained that exceeds the sera presently employed in the nimiber 

 of neutralizing units capable of consistent neutralizations. 



4. The seriun should neutralize to a high degree not only re- 

 acting factors derived from the stock strains of the different 

 serological groups, but also tlie reacting factors of the "variants" 

 of the same groups. 



5. The serum if purified should be sho^vn to contain the neces- 

 sary neutralizing antibodies in higher concentration than the 

 crude serum. 



STUDIES ON PHENOMENON-NEUTRALIZING ANTITYPHOID HORSE SERA 

 AND THEIR USE IN TYPHOID FEVER PATIENTS 



Previous observations on therapeutic effect of anti-typhoid 

 sera: 



Attempts to develop specific serum therapy for typhoid fexer 

 have been made by numerous in\estigators. The difficulties en- 

 cotmtered in the past ^vere mainly due to lack of a specific bio- 

 logical reaction for meastiring the potency of the therapeutic sera 

 employed (horse, goat, and sheep) . Estimation of their thera- 

 peutic potency was mainly based on the agglutination titer of 

 the serum. In some instances (Berner Institute Serum, Tavel, 

 used by Spirig, 1898, and du Mesnil, 1902) bacteriolysis and 

 anti-endotoxic tests (Chantemesse, i8g8; Kraus and von Stenitzer, 

 1907, 1911; and Besredka, igoGrt) were employed as well as pro- 

 tection tests against \i\e B. typJiosus ctiltures in guinea pigs 

 (Klemperer and Levy, 1895; Rodet, 1914; Gory and Grasset, 

 1928, 19^30; and Ltidke, 1912) . Favorable therapeutic results were 

 reported ^vith some of the sera (Chantemesse and Widal, Kraus 

 and von Stenitzer, Rodet, Berner Institute Serum, Burroughs and 

 \Vellcome, Gory and Grasset, Besredka sertim used by Andriescu 

 and Ciuca) , especially if they ^vere administered in the early 

 stages of the disease, usually the first t^vo weeks. The reports of 

 stibsequent investigators seem to have discredited some of these 

 claims (Bertoye and Martin, 1929; Rodet's serum) . 



The therapeutic value of these anti-typiioid immune sera has 

 also been discredited on other grounds. The antibodies which 

 were demonstrable in the sera (bacteriolytic, agglutinating, com- 

 plement fixing antibodies) , apparently have no bearing upon the 

 processes of recovery from acute infectious diseases. The so-called 

 anti-endotoxic sera fail to neutralize these endotoxins specifically 



