570 THE CHOLERA GROUP 
of a culture and contracted the disease. Hasterlik/ Metchnikoff,- 
Renvers,'' Kolle^ and ^"oges^ have also reported laboratory infections 
of man with cholera vibrios which resulted in typical disease in each 
instance, thus establishing beyond reasonable doubt the etiological 
relation of the cholera vibrio to the disease cholera. 
(b) Natural Infection. —The incubation period of the naturally 
acquired disease cholera may be very short; the patient may be 
infected and die within twelve hours, so-called cholera sicca.*' Ordi- 
narily the incubation period is from one to two days.^ 
The important, characteristic and distinctive clinical symptoms are 
extremely painful cramps, great withdrawal of water from the tissues, 
due to the violent diarrhea, resulting in shriveling of the skin of the 
extremities and increased viscosity of the blood. The urine after the 
first day is scanty in amount, the stools are very fluid, "rice-water 
stools," and there is profound collapse. The most noteworthy lesions 
postmortem are in the small intestine, particularly the lower half. The 
mucosa is swollen and congested particularly about Peyer's patches; 
the contents of the intestinal tract are fluid and contain shreds of mucus. 
There is parenchymatous degeneration of the liver, kidneys and spleen. 
The intestinal contents swarm wuth vibrios. In the markedly chronic 
cases there may be extensive necrosis and serofibrinous exudation on 
the surface of the intestinal mucosa. 
Immunity.— As a rule one attack confers lasting immunity. 
Artificial Immunity.— Attempts have been made to induce artificial 
active immunity: 
1. By subcutaneous inoculation of virulent cholera vibrios in man, 
either directly or after exaltation of their virulence for guinea-pigs 
or rabbits.^ (2) By the injection of autolyzed cultures of cholera 
vibrios, heated at 60° C. for an hour to kill them, then suspended in 
distilled water at 37° C. for three to four days, and filtered through 
porcelain.^ (3) Vaccines, (a) Killed cultures (Kolle);"' (6) sensitized 
cultures (Besredka) ;" (c) bacterial extractives. 
The only method thus far which has yielded encouraging results 
is that of Haffkine.^- This consists in the injection of from 0.25 to 0.5 
cc. of a suspension of an agar culture of cholera vibrios suspended 
in 5 cc. of sterile saline solution. This is introduced subcutaneously. 
The results reported from India are claimed to be favorable. ^'^ This 
1 Wien. klin. Wchnschr., 1893, 6, 167. 
2 Ann. Inst. Pasteur, 189.3, 7, 562; 1894, 8, 529. 
3 Deutsch. med. Wchnschr., 1894, 20, 52. * Ztschr. f. Hyg., 1894, 18, 17. 
' Centralbl. f. Bakteriol., 1895, 18, 629. 
6 Metchnikoff: Ann. Inst. Pasteur, 1893, 7, 562. 
' Banti: Lo Sperimentale, 1887. Gunther: Deutsch. med. Wchnschr., 1892, 18, 
841 (abstract). 
8 Haffkine: Wien. med. Blatter, 1895, No. 52. 
9 Haffkine: Bull, med., 1892, pp. 1084, 1113. 
10 Centralbl. f. Bakteriol., 1896, 19, 65. " Ann. Inst. Pasteur, 1902, 16, 918. 
'= Bull. Inst. Pasteur, 1906, 4, 697, 737. 
13 Deutsch. med. Wchnschr., 1909, 35, 2046. 
