720 PASSIVE IMMUNIZATION SERUM THERAPY 



especially when the nature of the disease is understood and the serum is 

 administered accordingly. 



Preparation and Standardization of Tetanus Antitoxin. This technic has 

 been described in Chapter XIV. Briefly, it consists in immunizing the horse 

 with gradually increasing doses of tetanus toxin over a period of several months, 

 until the blood of the animal contains the antitoxin in sufficient quantities for thera- 

 peutic use. The animal is then bled under aseptic precautions, and the serum, with 

 the addition of a small amount of preservative, constitutes the antitoxin of commerce. 

 Several manufacturers concentrate the antitoxin in the same manner as diphtheria 

 antitoxin is concentrated. In view of the very large doses required in the treatment 

 of tetanus this is quite desirable. 



The American unit is defined as the amount of antitoxin required just to neu- 

 tralize 1000 fatal doses of tetanus toxin for a 350-gram guinea-pig. The United 

 States Government has adopted this unit, and supplies the different producers with 

 standardized toxin for testing the antitoxin. 



Action of Tetanus Toxin. It may be well to recall briefly the main 

 features concerning the pathogenesis of tetanus, as successful treatment 

 depends upon a thorough understanding of these principles. 



1. Tetanus is a local infection accompanied and characterized by a 

 general toxemia. The bacilli and spores never gain access to the blood, 

 and are never distributed through the tissues and internal organs, but 

 reside at the local site of infection, where they produce a powerful toxin, 

 which, when absorbed, is responsible for the main lesions and symptoms 

 of the infection. Therefore while the blood of the tetanus patient is 

 sterile, it usually contains the toxin. Neisser has produced tetanus in 

 mice by giving them subcutaneous injections of the blood of a tetanus 

 patient. 



2. Tetanus toxin has a strong affinity for nerve tissue, and this con- 

 stitutes the most important feature in the pathogenesis of the disease. 

 The toxin is rapidly absorbed from the local site of infection into the 

 blood and lymph-streams, where it is distributed to other muscles and 

 reaches the central nervous system indirectly through absorption by 

 the end-plates of motor nerves. As expected, absoiption is most likely 

 to occur along the motor nerves supplying the parts injured, and for this 

 reason the muscles and nerves should be infiltrated with antitoxin as 

 soon as possible after an injury has been received. 



According to Meyer and Ransom, Marie and Morax, absorption 

 occurs along the axis-cylinders of motor nerves, the intramuscular end- 

 ings of which the toxin penetrates. The experiments of Field, Cerno- 

 vodeanu, and Henni indicate, however, that the toxins are absorbed by 

 way of the lymphatics of the nerves, and not by way of the axis-cylinders; 

 the latter view is now most generally accepted. 



