THERAPEUTIC IMMUNIZATION IN MAN 449 



From this table there appears a reduction of 58 per cent, in 

 mortality and a similar drop is evident from the German statistics 

 of Dieudonne, 1 from those of Welch, and many others. 



It should be considered, moreover, in reading such statistics that 

 they are made on gross mortality reports without elimination of the 

 many cases that have not come under observation until too severely 

 diseased to react to any form of treatment. The reason for the fail- 

 ure to obtain results with antitoxin when the cases have proceeded 

 beyond a certain stage of intoxication will become evident when we 

 consider the manner of absorption of the poison in a succeeding para- 

 graph. The mortality sinks to between 8 and 9 per cent., when such 

 cases are omitted, as is shown by the collective investigations of the 

 American Pediatric Society in 1896 figures which we take also 

 from Northrup's comprehensive study. This purely statistical evi- 

 dence, however good, is further reenforced by the unquestionable 

 and considerable diminution of emergency operations, 2 such as intu- 

 bation and tracheotomy, since introduction of the antitoxin. More- 

 over, there is the manifold clinical evidence of benefit, after the 

 serum treatment, familiar to every practicing physician. 



Although the injection of antitoxin is of benefit by whatever 

 route and in whatever quantity it may be given, nevertheless recent 

 experimental investigations have taught us much regarding the 

 proper use of this therapeutic agent. Especially interesting are the 

 investigations of Meyer, 3 who showed the extreme importance of an 

 early use of the antitoxin. Apparently, as we have mentioned in 

 another place, like tetanus antitoxin, the diphtheria poison may be 

 in part absorbed directly by the nerves. 4 



There is apparently a great difference in therapeutic efficiency, 

 according to the method in which the serum is administered, a differ- 

 ence probably depending upon speed of absorption. Berghaus 5 

 showed that intravenous injection is 500 times more potent therapeu- 

 tically than the subcutaneous, and 80 to 90 times more so than the 

 intraperitoneal injection. Schick, in discussing this problem from 

 the clinical point of view, for this reason lays special stress upon the 

 speed of administration. He says: "K"ot only days but hours are 

 of great importance." He bases this opinion largely upon the fact 

 that the toxin which has already united with the nerve substance can 

 probably no longer be influenced by the injection of the serum. 



According to the experiments of Meyer and Ranson diphtheritic 



1 Dieudonne. Arb. aus dem kais. Gesund., XIII, 1897. 



2 Siegert. "Jahrbuch f. Kinderheilkunde," Vol. 52, cited after Wernicke. 



3 Meyer. Berl kl Woch., 25, 26, 1909; Arch. f. exp. Path. u. Ther., Vol. 

 60, 1909, and Berl. kl. Woch., No. 45, 1911. 



4 For a thorough discussion of these conditions see Schick, Centralbl. f. 

 Bakt., Rev. Vol. 57, 1933, "Report of 7th Meeting of the Mikrobiol. Gesell.," 

 Berlin, 1913. 



5 Berghaus. Cited from Schick, loc. cit. 



