G. HOWARD BAILEY 805 



an analysis of much clinical and laboratory data Courmont' arrived at the following 

 conclusions concerning the relation of agglutinins to prognosis in typhoid fever: (i) 

 a large quantity of agglutinins present in the blood is always favorable (the larger it 

 is the better), especially if this coincides with a remission of the temperature; (2) a 

 small quantity of agglutinins with a rise of temperature is always unfavorable; (3) a 

 strong agglutinating power is good at all times in the course of the disease; a low ag- 

 glutinating power is usually bad as the latter condition is found in light forms of the 

 disease with a tendency to relapse or in very severe cases. Exactly the same conclu- 

 sions were reached by Birt and Lamb' in regard to Malta fever. It is well known that 

 during the early stages of typhoid fever the bacilli may be found in the blood stream, 

 later to localize particularly in the lymphoid tissues of the intestine and spleen. Wright 

 and Lamb^ have shown that in cases of typhoid fever examined postmortem the fluids 

 of these tissues are always much poorer in agglutinins than the heart blood, and they 

 thus explained the ultimate localization of the organisms. It was believed that the 

 continued growth in these situations was made possible by the absorption of agglu- 

 tinins from the surrounding plasma or lymph and the agglutinative power thus re- 

 duced below a certain minimum. One hypothesis which has been advanced as an ex- 

 planation of relapses in this disease in the presence of a relatively high agglutinin titre 

 of the blood is the decrease in agglutinability of the typhoid bacillus after long culti- 

 vation in vivo. This phenomenon has not yet been fully explained, but it may depend 

 on an active immunity of the bacteria against the agglutinins, for it can be developed 

 in agglutinable strains by cultivatmg them in serum containing agglutinins. ■< 



EXPERIMENTAL OBSERVATIONS ON AGGLUTINATION in vivO 



Following the interesting clinical and experimental observations of Sawtschenko 

 and Melkich concerning the relation of agglutinins to immunity in recurrent fever, 

 already referred to, a further observation bearing on the question of the influence 

 which is exerted by agglutinins in the infected organism was made by Wright and 

 Lamb.5 It was shown that in plague-infected guinea pigs- which had received a suf- 

 ficient quantity of antiplague serum the plague bacilli were to be found only in dis- 

 crete clumps or colonies, especially in the spleen. In control animals the bacilli were 

 found in countless numbers uniformly distributed all over the body. 



The first extensive experimental investigation, however, on agglutination in vivo 

 was made by Bull.'' Working with rabbits and dogs a technique was employed by which 

 specimens of blood were taken from the heart at closely spaced intervals following 

 the intravenous injection of a uniform suspension of bacteria into normal or actively 

 or passively immunized animals. It was found that not only may agglutination occur 

 in the circulation of such animals, but in contradistinction to the slowness with which 



' Courmont, P.: Fresse mid., 1, No. 2, 8. 1898. 



^ Birt, C, and Lamb, G.: Lancet, 2, 701. 1899. 



3 Wright, A. E., and Lamb, G.: ibid., p. 1727. 1899. 



"Walker, E. W. A.: /. Path, dr BacL, 8, 34. 1903. 



5 Wright, A. E., and Lamb, G.: loc. cil. 



^Bull, C. G.: /. Exper. Med., 20, 237. 1914; ibid., 22, 457, 466, 475, 484. 1915; ibid., 24, 7, 25 

 1916. 



