270 BACTERIA PATHOGENIC TO MAN 



experiments already referred to would seem to indicate, has not yet 

 been conclusively proven; nor do Pettenkofer's investigations into the 

 relation of the frequency of typhoid fever to the ground-water level 

 satisfactorily explain the occurrence of the disease in most cases, whether 

 sporadically or in epidemics. 



Immunization. After recovery from typhoid fever a considerable 

 immunity is present which lasts for years. This is not absolute, as 

 about 2 per cent, of those having typhoid fever have a second attack. 

 This attack is usually a mild one. Specific immunization against experi- 

 mental typhoid infection has been produced in animals by the usual 

 method of injecting at first small quantities of the living or dead typhoid 

 bacilli and gradually increasing the dose. The blood serum of animals 

 thus immunized has been found to possess bactericidal and feeble antitoxic 

 properties against the typhoid bacillus. These characteristics have also 

 been observed in the blood serum of persons who are convalescent from 

 typhoid fever. The attempt has been made to employ the typhoid 

 serum for the cure of typhoid fever in man, but although a number of 

 individual observers have reported good results with one or another of 

 the sera most consider that little or no good is derived from the serum. 



VACCINATION AGAINST TYPHOID. The use of killed typhoid bacilli 

 as vaccines has been advocated by Wright and tried upon some 8000 

 persons who expected to be subjected to danger of infection. 



About 2 mg. of an agar tube culture which had been suspended in 

 bouillon and heated was used at first, but now 0.3 to 0.1 c.c. of a bouillon 

 culture according to the density of suspension is heated to 60 C. for five 

 minutes. For a day or two the injection produces a slight fever and local 

 pain, followed in a few days by the development of bactericidal substances 

 in the blood, apparently sufficient in amount to give some immunity 

 lasting for a year or more. A second injection adds to the degree of 

 immunity. In 49,600 individuals under observation in India and Africa, 

 8600 were thus treated. The disease appeared in them to the extent of 

 2.25 per cent., with a case mortality of 12 per cent. In the 41,000 

 uninoculated there was a case percentage of 5.75 per cent., and a 

 mortality of 26 per cent. The use of a protective serum, or, when 

 this cannot be obtained, of dead cultures, would, therefore, seem to be 

 advisable where great danger of typhoid infection exists. 



Diagnosis by Means of the Widal or Serum Reaction. 



The chief practical application of our knowledge of the specific 

 substances developed in the blood of persons sick with typhoid fever 

 has been as an aid to diagnosis. 



In 1894-95 Pfeiffer showed that when cultures containing dead or 

 living cholera spirilla or typhoid bacilli are injected subcutaneously 

 into animals or man, specific protective substances are formed in the 

 blood of the individuals thus treated. These substances confer a more 

 or less complete immunity against the invasion of the living germs of 

 the respective diseases. He also described the occurrence of a peculiar 



