ASIATIC CHOLERA AND THE CHOLERA ORGANISM 589 



is endemic, but its significance in producing epidemics is limited owing to 

 the fortunately low resistance of the spirillum to desiccation. The 

 sudden appearance of cholera in a place far distant from the seat of a 

 prevalent epidemic may be explained by the occasional presence of 

 cholera spirilla in the dejecta of convalescents as late as two or three 

 weeks after apparent recovery from the disease and consequent release 

 from quarantine. 



Cholera Toxin. The absence of the cholera spirilla from the in- 

 ternal organs of fatal cases, in spite of the severe general symptoms 

 of the disease, points distinctly to the existence of a strong poison pro- 

 duced in the intestine by the microorganisms and absorbed by the 

 patient. It was in this sense, indeed, that s Koch first interpreted the 

 clinical picture of cholera. Numerous investigations into the nature of 

 these toxins have been made, the earlier ones defective in that definite 

 identification of the cultures used for experimentation were not carried 

 out. 



Pfeiffer, 1 in 1892, was able to show that filtrates of young bouillon 

 cultures of cholera spirilla were but slightly toxic, whereas the dead 

 bodies of carefully killed agar cultures were fatal to guinea-pigs even in 

 small quantities. In consequence, he regarded the cholera poison as 

 consisting chiefly of an endotoxin. 2 The opinion as to the endotoxic 

 nature of the cholera poison is not, however, shared by all workers. 

 Metchnikoff, Roux, and Salimbeni, 3 in 1896, succeeded in producing 

 death in guinea-pigs by introduction into their peritoneal cavities of 

 cholera cultures enclosed in celloidin sacs. Brau and Denier, 4 and, 

 more recently, Kraus, 5 claim that they have succeeded not only in 

 demonstrating a soluble toxin in alkaline broth cultures of cholera 

 spirilla, but in producing true antitoxins by immunization with such 

 cultures. It appears, therefore, that the poisonous action of the cholera 

 organisms may depend both upon the formation of true secretory toxins 

 and upon endotoxins. Which of these is paramount in the produc- 

 tion of the disease can not be at present definitely stated. In favor 

 of the great importance of the endotoxic elements is the failure, 

 thus far, to obtain successful therapeutic results with supposedly 

 antitoxic sera. 



1 Pfeiffer, Zeit. f. Hyg., xi, 1892. 



2 Pfeiffer und Wassermann, Zeit. f. Hyg., xiv, 1893. 



3 Metchnikoff, Roux, et Salimbeni, Ann. de 1'inst. Pasteur, 1896. 



4 Brau et Denier, Comptes rend, de 1'acad. des sci., 1906. 

 6 R. Kraus, Cent. f. Bakt., 1906. 



