THE NONSPECIFIC AGENTS 33 



in prophylactic or ordinary therapeutic inoculation. But it would mean 

 taking into account in cases which proved intractable to treatment with 

 the homologous vaccine the possibility of seeking for collateral immuniza- 

 tion by inoculating a microbe or mixture of microbes other than that with 

 which the patient is infected. The trial of this procedure might perhaps 

 recommend itself where from the outset there is very little immunizing 

 response to the homologous vaccine, and also where, as in long-standing 

 cases of tubercule or streptococcus infection, the power of direct immuniz- 

 ing response to the corresponding vaccines is becoming exhausted." 



This use of bacterial vaccines for "collateral immunization" as 

 Wright uses the term, or for nonspecific stimulation, is a modern con- 

 ception that dates practically from the work of Renaud and of Kraus. 

 The former used typhoid vaccine in the treatment of a number of non- 

 typhoidal diseases ; the latter treated typhoid patients with colon vac- 

 cine, and then proceeded to treat puerperal infection and other acute 

 infections with typhoid and colon vaccines with remarkable results. 

 Until this time the fear of overdosage had kept back investigation in 

 this particular field. The disastrous effects that had at times followed 

 the injection of tuberculin in tuberculosis had made a profound impres- 

 sion on medical men, and the emphasis placed on the negative phase of 

 the opsonic curve after vaccine injection had a similar effect. With 

 the introduction of the sensitized vaccines of the French school larger 

 doses came to be used, but here again a generalized reaction was 

 avoided. Occasionally one finds records of more heroic dosage and 

 cures following on general reactions; thus Szily cured a severe 

 ophthalmoblennorrhea with several large doses of gonococcus vaccine. 



Following the publication of Kraus's results a large number of 

 observers have used heterovaccinotherapy in the treatment of dis- 

 eases of various kinds. The reaction of these various bacterial vac- 

 cines varies of course; in general, however, the following bacteria 

 have given results. 



Typhoid Vaccine. The toxicity varies greatly with the age and 

 the strain. For convenience the vaccine is usually made up with 100 

 million organisms to the cubic centimeter, of this approximately 25 

 to 50 million may be given at the first dose if the particular vaccine 

 is not too toxic; great care must be observed. Typhoid vaccine is 

 followed by a prompt chill and temperature reaction, usually by a 

 leukocytosis. Headache is a common accompaniment. 



Colon Vaccine. Colon vaccine is usually followed by a severe 

 reaction, which may, however, be delayed for several hours after the 

 injection. Headache is usually severe after several hours. It has 

 been used more frequently by English observers. The dosage should 

 not exceed 25 million for the first intravenous injection; for later re- 

 actions this may be increased. 



Dysentery. Dysentery strains of all types when injected, both 



