202 THE BACTERIOPHAGE 



passes into the circulation. This has not been demonstrated in 

 man for it is not practicable to carry out on man the repeated 

 blood examinations which such a study requires. 4 However, in 

 paratyphoid fever in the rat induced by the ingestion of a very 

 virulent strain of B. typhi murium a transitory appearance of the 

 ultramicrobe in the blood has been demonstrated by cardiac 

 puncture made between the fourth and sixth days after the inges- 

 tion of the infectious material. All of the rats in which this 

 phenomenon occurred were protected. At this time a bacterio- 

 phage active for the pathogenic bacillus was present in the 

 intestine and the rats resisted infection. 



In the third place we will see experimentally that the dissolved 

 products found in the cultures of the bacteriophage provoke, 

 after an incubation period, the development of an "organic im- 

 munity" so potent that it borders on a refractory state. These 

 dissolved products likewise form in the intestine of the patient, 

 and even within the body, since it is possible for the bacteriophage 

 to pass into the circulation in a septicemia. 



Twenty-eight more non-fatal cases of typhoid fever were studied 

 in order to determine the influence of the bacteriophage on the 

 course of the disease. Three fatal cases were observed. In these 

 three cases, at no period of the disease could the presence of a 

 bacteriophage be demonstrated active for B. typhosus, either for 

 a stock strain or for the bacillus from the patient. Furthermore, 

 examination of the strains from the intestinal contents from five 

 individuals who had died of typhoid failed to show any activity 

 for the typhoid bacillus. But the bacteriophage was not entirely 

 absent, since in six of these eight cases a bacteriophage of moder- 

 ate activity for the colon bacillus was found. This bacteriophage 

 did not, however, show any activity for the pathogenic organisms. 

 Death in typhoid fever results, usually, because of a failure of the 

 bacteriophage to adapt itself for the bacteriophagy of the in- 

 vading bacillus. 



May death occur because of the acquisition of a resistant con- 

 dition by the typhoid bacillus, which protects it from the action 



4 Beckerich and Hauduroy have very recently found it in blood cultures. 

 It is essential to examine them systematically for the bacteriophage; the 

 negative cultures in particular. 



