THE BACTERIOPHAGE IN DISEASE 203 



of the bacteriophage, as we have seen in the case of dysentery? 

 There has been no opportunity to establish this up to the present 

 but it is the more probable, since, in vitro as in vivo, the tendency 

 toward resistance is certainly more marked for the typhoid bacillus 

 than for B. dysenteriae. In any case, this cause of death is cer- 

 tainly the exception, even in typhoid. It must necessarily 

 accompany a septicemia when it occurs. 



In typhoid, as in dysentery, the investigation of the virulence 

 of the bacteriophage is of prognostic significance. It is sufficient 

 to verify simultaneously the virulence of the intestinal bacterio- 

 phage of the patient toward B. coli, toward the pathogenic bacillus 

 taken from the patient, and toward a stock culture of B. typhosus. 

 A comparison of these three results furnishes the information 

 desired. The detection of resistance in the pathogenic bacterium 

 would indicate a poor prognosis, and that in proportion as the 

 resistance is the more pronounced. The establishment of a re- 

 fractory state in the bacterium, resulting in the formation of a 

 mixed culture in the intestine accompanying a septicemia, im- 

 plies a fatal outcome with a quick maturity. 



To summarize: in all of the cases of typhoid fever studied, 

 whatever may have been their severity, the appearance in the 

 bacteriophagous ultramicrobe of virulence for the pathogenic 

 bacillus has been preceded by an increase in virulence for B. coli, 

 which has always begun in the course of the second week and has 

 rapidly attained great intensity. This activity is maintained 

 during the entire course of the infection and appreciably decreases 

 only during convalescence, sometimes even later. On the con- 

 trary, the development of virulence for the pathogenic bacillus 

 has varied according to the severity of the disease. In cases that 

 were mild or of average severity the activity of the bacteriophage 

 for this bacillus appears before the end of the second week and 

 disappears toward the end of convalescence. The activity for 

 B. coli and for B. typhosus is there parallel. In the severe cases 

 the activity for the typhoid bacillus only commences to manifest 

 itself in an energetic manner towards the beginning of definite 

 improvement. It persists for a greater or less length of time, in 

 some cases up to the middle of the period of convalescence. 



In the forms with relapse and recrudescence the struggle is 

 complicated by the fact of the acquisition of a resistance by the 



