SERUM TREATMENT OF LOCALIZED PNEUMOCOCCUS MENINGITIS 811 



possess some antitoxic value, it is desirable that the animals be immunized also with 

 autolysates. The whole process may be conducted after the method described for 

 the production of antimeningococcus serum. 



In the Rockefeller Institute different horses are immunized with strains belong- 

 ing to Groups 1 and 2. It would appear possible to produce a potent polyvalent 

 serum, and this is very much to be desired, especially if further studies continue to 

 show that 65 per cent, of infections are caused by organisms belonging to these two 

 groups. 



Kolle, by immunizing horses with cultures secured from pneumonia patients, 

 produces an antipneumococcic serum. These cultures are grown in broth for forty- 

 eight hours, heated to 60 C., and 5 c.c. injected intravenously into a horse. The 

 dose is increased each week until 120 c.c. are given at one time. Then 5 c.c. of living 

 culture is injected, and the doses increased in a similar manner until 120 c.c. are given 

 at one time. About six months are consumed in the process of immunization, and 

 two weeks after the last injection has been given the serum is tested. 



Concentration of Antipneumococcus Serum. In view of the large doses of 

 serum required in the treatment of lobar pneumonia and the possible injurious 

 effects of the large amount of horse-serum protein injected, Gay and Chickering 1 and 

 Chickering 2 have endeavored to concentrate the immune serum by adding rela- 

 tively small amounts of the extract of pneumococcus and recovering the resulting 

 precipitate. These precipitates have been found to contain practically all the pro- 

 tective antibodies of the original serum and relatively small amounts of protein as 

 compared with the original serum. 



Standardization of Antipneumococcus Serum. As previously mentioned, there 

 is at present no accurate method for standardizing an antibacterial serum. It 

 is possible, however, to obtain some measure of its protective and curative power by 

 employing various tests. 



1. Protective Value. The lethal dose of a living pneumococcus culture for mice 

 is determined, and from 10 to 100 times this amount of culture is mixed with decreas- 

 ing doses of immune serum and the mixtures injected subcutaneously or intraperitone- 

 ally into a series of mice in order to determine the dose of serum that will protect. 

 Dochez has found that when these mixtures are injected at once and in the same place, 

 the serum will obey the law of multiple proportions up to a certain limit. 



Merck's antipneumococcus serum is so standardized that 0.01 c.c. injected 

 subcutaneously protects a mouse inoculated intraperitoneally twenty-four hours 

 later with from 10 to 100 times the lethal dose of a living virulent culture. This is 

 known as a normal serum, 1 c.c. containing an immunity unit (I. U.). The serum is 

 marketed in vials containing from 20 to 40 c.c. Kolle regards as satisfactory a serum 

 that, in doses of 0.001 c.c. and less, will protect mice. 



2. Bacteriotropic Value. Neufeld lays considerable stress upon this point. The 

 technic of this titration has been described elsewhere. 



3. Complement- fixation and Agglutination Tests. While these tests are fre- 

 quently sharply cut, and while they serve as a measure for record in the laboratory, 

 they do not necessarily indicate the therapeutic value of the serum. 



Action of Antipneumococcus Serum. The curative and protective 

 value of this serum depend mainly upon bacteriolysins, bacteriotropins, 

 and antitoxins. The first are readily demonstrated in protection ex- 

 periments and also in pneumonic patients when pneumococci in the 

 blood-stream are destroyed. Bacteriotropins may likewise be demon- 

 strated experimentally and in the blood of patients if the corresponding 



1 Jour. Exper. Med., 1915, xxi, 389. 2 Jour. Exper. Med., 1915, xxii, 248. 



