THE TYPHOID BACILLUS 071 



phenomenon when some fresh culture of the typhoid bacillus on agar 

 is added to a small quantity of serum from an animal immunized 

 against typhoid bacilli and the mixture injected into the peritoneal cavity 

 of a non-immunized guinea-pig. After this procedure, if from time to 

 time minute drops of the liquid be withdrawn in a capillary tube and 

 examined microscopically, it is found that the bacteria, " previously 

 motile and vigorous and which remain so in control animals inoculated 

 without the specific serum, rapidly lose their motility and die. They 

 are first immobilized, then they become somewhat swollen and agglom- 

 erated into balls or clumps, which gradually become paler and paler, 

 until finally they are dissolved in the peritoneal fluid. This process 

 usually takes place in about twenty minutes, provided a sufficient 

 degree, of immunity be present in the animals from which the serum 

 was obtained. The animals injected with the mixture of the serum of 

 immunized animals and typhoid cultures remain unaffected, while 

 control animals treated with a fluid containing only the serum of non- 

 immunized animals mixed with typhoid cultures die. Pfeiffer claimed 

 that the reaction of the serum thus employed is so distinctly specific 

 that it could serve for the differential diagnosis of the cholera vibrion 

 or typhoid bacillus from other vibrions or allied bacilli, such as Finkler's 

 and Prior's or those of the colon group. 



In March, 1896, Pfeiffer and Kolle published an article entitled 

 "The Differential Diagnosis of Typhoid Fever by Means of the Serum 

 of Animals Immunized against Typhoid Infection," in which they 

 claimed that by the presence or absence of this reaction in the serum 

 of convalescents from suspected typhoid fever the nature of the dis- 

 ease could be determined. It was further found, if the serum of an 

 animal thoroughly immunized to the typhoid bacillus was diluted 

 with 40 parts of bouillon, and a similar dilution made of the serum of 

 non-immunized animals, and both solutions were then inoculated with 

 a culture of the typhoid bacillus and placed in the incubator at 37 C., 

 that after the expiration of one hour macroscopic differences in the 

 culture could be observed, which increased in distinctness for four 

 hours and then gradually disappeared. The reaction occurring is 

 described as follows: In the tubes in which the typhoid culture is 

 mixed with typhoid serum the bacilli are agglomerated in fine, whitish 

 flakes, which settle to the bottom of the tube, while the supernatant 

 fluid is clear or only slightly cloudy. On the other hand, the tubes 

 containing mixtures of bouillon with cholera or coli serum, or the 

 serum of non-immunized animals inoculated with the typhoid bacilli, 

 become and remain uniformly and intensely cloudy. These serum 

 mixtures, examined microscopically in a hanging drop, show distinct 

 differences. The typhoid serum mixture inoculated with the typhoid 

 bacilli exhibits the organisms entirely motionless, lying clumped together 

 in heaps; in the other mixtures the bacilli are actively motile. 



Similar observations were made independently by Grul>er and 

 Durham, who maintained, however, that the reaction described by 

 Pfeiffer was by no means specific, and that when the reaction is positive 



