338 



INFECTION AND RESISTANCE 



'0 II 



13/4/5 



PROLONGATION OF THE NEGATIVE PHASE DUE TO 

 Too VIGOROUS TREATMENT WITH TYPHOID 

 VACCINE. 



(After A. E. Wright, Brit. Med. Journ., May 

 9, 1903. Also from "Studies on Im- 

 munity," p. 179.) 



cidal power of the sera of patients treated with typhoid vaccines 

 made by Wright 10 himself. Similar, again, are the various ag- 

 glutinin curves constructed by Jorgensen and Madsen n and others. 

 Apart from the purely theoretical value of such measurements, 

 they demonstrate features which are therapeutically of the greatest 

 importance. They show that in all processes of active immunization 

 the injection of antigen is followed almost immediately by a rapid 

 decline of specific antibodies in the blood serum. This "negative" 

 phase, as it is called, is probably due to a neutralization of existing 



antibodies and lasts for 

 varying periods, which 

 must, of course, depend 

 upon complex relations be- 

 tween the degree of resist- 

 ance (or amount of anti- 

 body constituents of the 

 serum), the quantity of 

 antigen injected, and the 

 general recuperative pow- 

 ers of the subject. There- 

 fore, without some control 

 like that furnished by the 

 measurement of opsonins 



or other antibodies it is impossible to determine whether the negative 

 phase has ended or is still in progress unless the clinical condition is 

 of such a nature or location that degrees of improvement or exacerba- 

 tion are well marked and easily observed. Even then clinical 

 observation alone is at best not an absolutely reliable guide. 



The practical importance of the question lies in the harm which 

 may accrue to the patient if a second injection is practiced before 

 the cessation of the negative phase. Wright himself accentuates 

 this danger by expressing the opinion that, in typhoid inoculations, 

 an excessive dose administered to a patient in the physiological con- 

 dition of the negative phase may be followed by a prolongation of 

 this phase into a period of several months. 



In the case of successive inoculations, as in vaccine treatment, a 

 too rapid repetition i. e., a repetition of injection during such a 

 period of depression leads to what Wright speaks of as a "summa- 

 tion of the negative phase," which obviously may seriously aggra- 

 vate the condition of the case. ' 



It is to such a cumulation of the negative phase that Wright 

 attributes the failures attendant upon the use of tuberculin during 

 the early days after its introduction, since injections at this time 



10 Wright. Practitioner, Vol. 72, 1904, p. 118. 



11 Jorgensen and Madsen. Festschrift. Serum Institut. Kopenhagen, 

 1902. 



