SERUM TREATMENT OF DIPHTHERIA 703 



disease, practically no mortality occurs. Parents and guardians should 

 be taught this fact, and cautioned to seek medical advice promptly when- 

 ever a child complains of sore throat. While the use of diphtheria anti- 

 toxin is still decried and opposed by a few members of the medical pro- 

 fession, and this is not to be wondered at when it is remembered that 

 cowpox vaccination still has its opponents, it is at least to be hoped 

 that no physician will deprive a patient suffering from diphtheria of the 

 benefits to be derived from the antitoxin treatment. In the absence of 

 special contraindications the refusal or neglect to use antitoxin in the treat- 

 ment of diphtheria would, in the opinion of most physicians, constitute an 

 act of criminal negligence and malpractice. 



Preparation of Diphtheria Antitoxin. The methods of preparing and stand- 

 ardizing diphtheria antitoxin are given in Chapter XIV. Briefly, these con- 

 sist in the preparation of a strong toxin by cultivating a virulent strain of the bacillus 

 in a suitable broth for ten days or two weeks; the culture is then passed through a 

 porcelain filter, which retains the bacilli, the filtrate being a strong solution of toxin. 

 This is standardized by the physiologic test of determining its action upon guinea- 

 pigs, the minimal lethal dose (M. L. D.) or toxin unit being the amount of toxin that 

 will cause the death of a 250-gram guinea-pig in four days. 



Strong and healthy horses that have been proved by the tuberculin and mallein 

 tests to be free from tubercle or glanders, are then continuously immunized by a 

 series of injections of the toxin. The first doses are guarded by the simultaneous 

 injection of antitoxin, but after from four to six months the animals are able to tolerate 

 enormous quantities of pure toxin. The horses are then bled aseptically from a jugu- 

 lar vein, and the separated blood-serum, preserved with a small percentage of an 

 antiseptic, becomes the antitoxin of commerce. 



Many manufacturing concerns market a concentrated diphtheria antitoxin 

 prepared by precipitating the globulin fraction of the raw serum with ammonium 

 sulphate, and redissolving it in a minimal quantity of salt solution. The globulins 

 carry with them most of the antitoxin, and in this manner a serum may be concen- 

 trated so that a large number of units are contained in a small bulk of fluid, obviously 

 a most desirable feature in the treatment of diphtheria. Further than this, it has been 

 observed that these concentrated antitoxins are much less likely to produce serum 

 sickness, a train of symptoms due to substances present alike in normal and in 

 antitoxic horse serum, and independent of the antitoxin. 



The antitoxic unit is the smallest amount of serum that will just neutralize 100 

 times the minimal lethal dose of toxin for a 250-gram guinea-pig. The adoption of 

 such a standard enables us to attain some accuracy in dosage. Before its introduction 

 antitoxin was given in so many cubic centimeters, just as antimeningococcus and 

 antistreptococcus serums are given today, but since some horses produce more 

 potent serums than others, the results were quite irregular. At the present time an 

 antitoxic serum is marketed according to the number of units it contains, irrespective 

 of the actual amount of serum, the constant endeavor being to produce as potent a 

 product as possible. 



Since antitoxin gradually deteriorates with time, physicians should carefully 

 observe the date printed upon each package of antitoxin, which is the time limit 

 calculated by the manufacturers beyond which they do not guarantee that the full 

 antitoxic strength is maintained. 



