In the first two papers findings were presented which point to a close relationship between the incidence of rheumatic fever and the distribution of Streptococcus hemolyticus. The fact was emphasized that in the rheumatic subject a recrudescence of the disease process is usually preceded by pharyngeal infection with hemolytic streptococci. These organisms conspicuous in the throat flora during the period of infection preliminary to an attack of acute rheumatism fell into six antigenic groups and produced toxins which in 70 per cent were neutralized by a monovalent streptococcus antiserum. In the present study, four series of observations have been presented, demonstrating the development of immune bodies to hemolytic streptococcus during the course of rheumatic fever. The agglutination and complement fixation reactions of sera from patients with acute rheumatism suggest recent infection with streptococcus. Precipitin tests indicate that at the time of appearance of the rheumatic attack, individuals develop, in their blood, precipitins to the protein fractions of hemolytic streptococcus. That these precipitins may not be entirely specific is recognized from their cross-reactions with antigens of chemically related organisms. The studies made in association with E. W. Todd of England have demonstrated that at the onset of an attack of acute rheumatism, there occurs in each instance a rise in the antistreptolysin titer of the patient's serum. This titer is much higher than that observed in normal subjects or in patients with bacterial infection other than hemolytic streptococcus. This presence of antistreptolysin with an N.D. of 0.005 cc. is considered strong evidence of recent infection by hemolytic streptococcus. In conclusion, the relationship between the incidence of hemolytic streptococcus and the geographical distribution of rheumatic fever, the relationship between the recrudescence in the rheumatic subject and infection of the throat with hemolytic streptococcus, the development of immune bodies for hemolytic streptococcus at the onset of the rheumatic attack and the apparently specific relationship of antistreptolysin formation to infection with hemolytic streptococcus,—together this combined evidence indicates that the infectious agent initiating the rheumatic process is Streptococcus hemolyticus.

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