BACILLUS DIPHTHERIA 527 



surrounded by a red areola, one to two cm. in diameter. A negative 

 reaction indicates that sufficient natural antitoxin is present to pro- 

 tect the individual against diphtheria, although he may nevertheless 

 harbor the bacilli as a carrier. It has been found unnecessary to give 

 prophylactic injections of antitoxin to individuals with a negative 

 Shick reaction. Park and Zingher 1 have found that negative reactions 

 were obtained in 93 per cent of the new-born, and became less fre- 

 quent up to the second or fifth year, when 37 per cent were negative. 

 In older children negative reactions were more frequently met with, 

 and about 90 per cent of adults were negative. A pseudoreaction 

 which appears earlier than the true reaction and which disappears in 

 twenty-four to forty-eight hours is occasionally seen in individuals 

 who have natural antitoxin. This is due to sensitiveness 'to some of 

 the proteins used in the injection, and may be reproduced in the same 

 individual by the injection of autolysate of diphtheria bacilli or some- 

 times by the injection of broth media. The most satisfactory method 

 for detection of the pseudoreaction is to make a control injection of 

 1/50 M.L.D. of a toxin which has been heated at 80 C. for five 

 minutes. This heating destroys the toxin, but leaves uninjured the 

 substances which produce the pseudoreaction. 



Active Immunization with Neutralized Diphtheria Toxin. It was 

 suggested some years ago by Theobald Smith that more lasting prophy- 

 lactic immunity in diphtheria might be produced if individuals were 

 stimulated to produce their own antitoxin by injection of toxin-anti- 

 toxin mixture. This method has recently been applied by Behring and 

 by Park and Zingher. 2 It has been found that individuals who have 

 no natural antitoxin, as shown by a positive Shick reaction, may be 

 rendered Shick-negative by injection of diphtheria toxin partially neu- 

 tralized by antitoxin. For this purpose Park and Zingher recommend 

 three injections at intervals of six or seven days, consisting of 1 c.c. 

 of toxin-antitoxin mixture plus 1,000,000,000 killed diphtheria bacilli. 

 The mixture is made up to contain 85 to 90 per cent of an L. + dose 

 of toxin, per unit of antitoxin. The toxin used contains about four 

 L. + doses per c.c. Individuals treated in this way develop antitoxin 

 slowly, and in many instances their Shick reaction does not become 

 negative for from six to eight months after immunization. A few indi- 

 viduals apparently do not respond to such immunization by the devel- 

 opment of antitoxin and remain Shick-positive. 



1 Park and Zingher, Am. Jour. Pub. Health, 1916, vi, p. 431. 



2 Park and Zingher, Jour. Am. Med. Ass., 1915, Ixv, p. 2216. 



