BACILLUS DIPHTHERIA 579 



little skill that even in outlying districts the physician can easily carry 

 out the steps himself with a simple equipment. 



In order to understand the practical principles of diphtheria anti- 

 toxin treatment, it is necessary for the physician to remember chiefly 

 two basic facts. One is the observation by Schick and others that even 

 though diphtheria toxin does not enter so rapidly into combination 

 with the tissues of the nervous system, as does tetanus toxin, it, never- 

 theless, is bound to some extent and that the antitoxin probably does 

 not reach poison that is already combined with tissue elements. It is 

 probable that the injury once done is irretrievable, at least to a great 

 extent, and that the antitoxin is chiefly effective against the circulating 

 poison before such cellular attachment has been established. Experi- 

 ments of Park and his co-workers have shown that if rabbits are given 

 10 lethal doses of diphtheria toxin, they can be saved by relatively 

 small doses of antitoxin if this is given just before or with the poison. 

 As the time between injection of the poison and the injection of the 

 antitoxin grows longer, rapidly increasing doses of antitoxin are neces- 

 sary and if an hour or more has elapsed, no amount of antitoxin will save. 

 The second basic point is the one brought out by the measurements of 

 Henderson Smith and others which show that antitoxin subcutaneously 

 injected, is but slowly absorbed and reaches its maximum concentration 

 in the blood not much before seventy-three hours after injection. 



The deductions to be made from these considerations are, first, that 

 early diagnosis must be made, that it is essential to get the antitoxin 

 in as early as possible, and that when the injection is made, it is better 

 to give a sufficient amount at the first dose than to dribble it along in 

 insufficient amounts with intervals of many hours between doses. 

 These observations impose upon the physician great responsibilities of 

 judgment, since in cases seen late in the disease, with very severe symp- 

 toms of intoxication, it may be necessary to resort to intramuscular or 

 intravenous injections of the antitoxin. 



The dosage of antitoxin must vary according to severity of the case, 

 the stage at which it is seen, and the age of the patient. In severe cases, 

 10,000 to 20,000 units should be injected. 



If intravenous injection is resorted to, precautions against the 

 occurrence of anaphylaxis must of course be taken, but in view of the 

 relatively slight danger of death from horse serum injections in man, the 

 risk of anaphylaxis in cases in which intravenous test is actually indi- 

 cated, is probably much less than the risk of delaying the introduction 

 of antitoxin into the blood. If skin tests can be done beforehand, 



