92 VACCINE AND SERUM THERAPY. 



ally no immediate reaction, the symptoms appearing six to twelve 

 days after injection. When the interval between injections is 

 six days or less, the disease is not produced. Serum disease 

 follows re-injections more frequently than it does in the first in- 

 jection and is usually produced by smaller amounts of serum. 



The "immediate reaction" occuring when re-injection is made 

 within an interval of twelve to forty days, manifests itself in one 

 to six hours after injection and usually reaches its maximum 

 within twenty-four hours after injection. The "second reaction" 

 is not seen after the first injection of serum but occurs most fre- 

 quently when, the interval between injections is between forty 

 days and six months. The incubation period for the second 

 reaction is somewhat shorter than it is for serum disease produced 

 by first injections. The symptoms of serum disease produced by 

 re-injection are usually more acute and general but of shorter 

 duration. In many cases there is vomiting. 



When serum disease was first recognized it was supposed to 

 be caused by toxin in the immune serum. However, as early as 

 1894, Heubner expressed doubt as to the importance of specific 

 immune sera in the production of the disease. Later the mani- 

 festations of serum disease were produced by the injection of nor- 

 mal serum. In 1906 Rosenau and Anderson of the Hygienic 

 Laboratory of the Public Health and Marine Hospital Service 

 of the United States, published a work in which experiments were 

 reported on "sudden death" of guinea pigs following serum in- 

 jections. These investigators found that re-injections of normal 

 horse serum into guinea pigs are very poisonous if the interval 

 between injections is more than ten days. The length of time for 

 which this hypersusceptibility persists has not been definitely 

 determined but lasts at least as long as two years and two days. 

 On the other hand when the interval between injections is less 

 than ten days, normal horse serum will produce no such effect. 



The nature and causes of the reaction have been matters of 

 considerable investigation and contention. The reaction was at 

 first regarded as one resulting from the injection of toxin or poison. 

 The long period of incubation, however, is explained with diffi- 

 culty by such a conception of the phenomenon. While it is true 

 that to produce disease by certain toxins, a period of incubation 

 is necessary, this period is seldom as long as eight to twelve days. 



