402 BACTERIA PATHOGENIC TO MAN 



produced little effect. There appears to be, therefore, considerable 

 difference between the intracellular and the soluble extracellular 

 toxins. 



Cholera Immunity. Koch found in his animal experiments that 

 recovery from an intraperitoneal infection with small doses of living 

 cholera vibrios produced a certain immunity against larger doses, 

 though the animals inoculated were not very much more resistant to 

 the cholera poison than they were originally. In 1892 Lazarus observed 

 that the blood serum of persons who had recently recovered from an 

 attack of cholera possessed the power of preventing the development 

 in guinea-pigs of cholera bacilli, which in these animals are rapidly 

 fatal when injected intraperitoneally, while the serum of healthy indi- 

 viduals had no such effect. This specific change in the blood is observed 

 to take place from eight to ten days after the termination of an attack 

 of cholera, and reaches its maximum during the fourth week of con- 

 valescence, after which it declines rapidly and disappears entirely in 

 about two or three months. Similar antitoxic or bactericidal sub- 

 stances develop in the serum of guinea-pigs, rabbits, and goats, when 

 these animals are immunized artificially against cholera by subcuta- 

 neous or intraperitoneal injections of living or dead cultures. These 

 specific substances present in the blood of cholera-immune men and 

 animals act only upon organisms similar to those with which they were 

 infected; but, as Pfeiffer showed, this specific relation, which is found 

 to exist between the antibacterial and protective substances produced 

 during immunization and the bacteria employed to immunize the 

 animals, is not confined to cholera. The discovery, moreover, of this 

 specific reaction of the blood serum of immunized man and animals 

 when brought in contact with the spirilla, has given us an apparently 

 reliable means of distinguishing the cholera from all other vibrios, and 

 the disease cholera from other similar affections, both of which 

 have proved to be of great value, particularly in obscure or doubtful 

 cases, in which heretofore the only method of differential diagnosis 

 available viz., by cultural tests was often unsatisfactory. 



Anticholera Inoculations. Within the last few years Haffkine, in 

 India, has succeeded in producing an artificial immunity against cholera 

 infection by means of subcutaneous injections of cholera cultures. Two 

 or three injections are necessary to give the greatest amount of protec- 

 tion. Animals treated by this method are refractory to intraperitoneal 

 inoculations, but not to intestinal injections or feeding by Koch's method. 

 In the intestines the bacteria seem to be outside the influence of the 

 bactericidal properties of the blood, and the absorption of toxins is too 

 great to be neutralized by the small amount of antitoxin. In over 

 200,000 persons whom he has inoculated the results obtained would 

 undoubtedly seem to show a distinct protective influence in the pre- 

 ventive inoculations. 



Agglutinins. Five to ten days after infection (natural or experi- 

 mental) agglutinins appear in the blood of man or animal. These \ 

 are at least in part specific. Their presence in the blood is of diagnostic 



