504 THE TECHNIC OF COMPLEMENT-FIXATION REACTIONS 



Historic In 1906 Muller and Oppenheim 1 applied the complement-fixation test 

 to the diagnosis of gonorrheal arthritis, using a culture of the gonococcus as antigen. 

 To these observers, therefore, belongs the credit of being the first to record a comple- 

 ment-fixation test in a gonococcus infection. A little later in the same year Carl 

 Bruch 2 applied the reaction to three cases of gonorrhea, using the serum of immunized 

 rabbits, and reported favorable results. In 1907 Meakins 3 reported having secured 

 positive reactions in three cases of gonorrheal arthritis, which was the first report in 

 America published on this subject. Th. Vanned 4 studied the specificity of the reac- 

 tion with the serums of rabbits immunized with gonococcus protein and one of a 

 meningococcus, and reported that the meningococcus immune serum did not show 

 complement fixation with gonococcus antigen, and, vice versa, that gonococcus ambo- 

 ceptor was not bound by meningococcus antigen. Wollstein 5 (1907), in a study of 

 the biological relationship of the gonococcus and meningococcus, reported findings 

 differing from those of Vannod. The former observer found that bacteriolytic am- 

 boceptors in the serums of rabbits immunized with these cultures were closely related 

 and yielded fixation of complement with either antigen. Teaque and Torrey, 6 in 

 1907, issued a very important communication showing that the differences in results 

 of previous investigators were probably due in part to the use of single strains of the 

 organisms in the preparation of antigens and immune serums. They emphasized 

 the fact that the gonococcus belongs to a heterogeneous family, and that in attempt- 

 ing to formulate a diagnosis of gonorrheal infection by the complement-fixation 

 method, the extracts of several different strains should be used. Naz Vannod and 

 later Watabiki 7 found that the gonococcus and meningococcus antibodies were quite 

 specific for their homologous antigens in complement-fixation reactions. 



Particular attention was drawn to the gonococcus complement-fixation test by 

 the work of Schwartz and McNeal. 8 These investigators emphasized the necessity 

 of using polyvalent antigens, and their encouraging reports have stimulated renewed 

 interest in this subject. They found that if the infection is confined to the anterior 

 urethra, a positive reaction is not obtained; that a strong reaction is not to be ex- 

 pected before the fourth week of the infection, and then only in acute cases with com- 

 plications. They regard a positive reaction as indicating the presence or recent 

 activity in the body of a focus of living gonococci, although a negative reaction does 

 not exclude gonococcus infection. The test, therefore, has a more positive than a 

 negative value. With Flexner's antimeningococcus serum positive reactions re- 

 sulted with their gonococcus antigen; with serums from cases of cerebrospinal menin- 

 gitis (meningococcic) the results were negative. 



In the succeeding years numerous investigators, including Swinburne, Gradwohl, 

 O'Neil, Gardner and Clowes, Thomas and Ivy, Kolmer and Brown, have reported 

 favorably upon the practical value of the gonococcus complement-fixation test, 

 particularly as an aid in determining whether or not a patient is cured of the 

 infection. 



Technic. Since, because of the comparatively slight cellular in- 

 volvement, the quantity of antibody produced in a localized gonococcus 

 infection is probably small, the complement-fixation reactions are 

 generally weak, and consequently require the closest technical attention, 

 especially as regards the preparation of antigen and accurate adjust- 

 ment of the hemolytic system. 



Hemolytic System. As a rule, the antisheep hemolytic system is 

 employed; the various ingredients may be used in one-half the quantity 

 employed in the original Wassermann reaction, as given in the preceding 



1 Wien. klin. Wochenschr., 1906, 19, 894. 



2 Deutsch. med. Wochenschr., 1906, 70, 36. 



3 Johns Hopkins Medical Bull., 1907, 18, 255. 



4 Zeitschr. f. Bakter., 1907, 44, 10. 5 Jour. Exp. Med., 1907, 9, 588. 



6 Jour. Med. Research, 1907, 17, 223. 7 Jour. Infect. Diseases, 1910, 7, 159. 



8 Amer. Jour. Med. Sci., May, 1911; ibid., September, 1912; ibid., December, 

 1912. 



