Alvin Coburn, a young physician at Presbyterian Hospital in New York, published his classic monograph, "The factor of infection in the rheumatic state," in 1931.
Thirty years after the identification of streptococcus by Poynton and Paine, the exact etiology of rheumatic fever was still a topic of debate. Coburn was the first to identify hemolytic streptococcal throat infection as the etiologic basis for the development of rheumatic fever. Coburn performed extensive epidemiologic studies on rheumatic fever in New York area.
In the first part of the book, he described bacteriological studies that provided background for the hemolytic streptococcus hypothesis. In the first study, Coburn and his team followed 462 patients with bacteremia and positive blood culture involving various organisms. None of these patients developed any evidence of rheumatic fever.
Their second study was directed to determine the presence of microorganism in the blood of patients with rheumatic disease. The conclusion of this study was as follows: "...In over 500 patients with rheumatic disease, bacteriological studies made by a number of workers at the Presbyterian Hospital had failed to reveal the presence of organisms in the blood stream."
Their third study was designed to investigate the relationship between bacterial endocarditis and rheumatic fever and particularly the role of non-hemolytic streptococcus. The conclusion of this study was that non-hemolytic streptococcus could cause bacterial endocarditis in patients with rheumatic heart disease but did not precipitate rheumatic manifestations. This fact was also reported by Coombs.
The chapter five of this monograph is fundamental and is entitled, "Bacteriological observations on the upper respiratory flora in man and its relationship to the rheumatic state." In this section, Coburn performed four bacteriological studies and reported several important observations.
In all these well-designed clinical studies, Coburn observed a relationship between upper respiratory infection followed by a period of latency and the appearance of active rheumatic disease.
In some patients with throat infection followed by rheumatic fever, hemolytic streptococcus was isolated in the culture of the throat at the time of initial infection, but repeat cultures were negative at the time of rheumatic fever. In some patients who underwent tonsillectomy, the swab of the throat and tonsils were negative prior to surgery. The cultures from the excised tonsils were, however, positive with hemolytic streptococcus.
All these findings led Coburn to establish a relationship between hemolytic streptococcus throat infection and rheumatic fever. He also stated "...at least these four patient factors: susceptibility, age, environment, and infection " were necessary to the development of rheumatic fever.
In the conclusion of his book, Coburn remarked:
"The observations detailed in this study have led us to the final conclusions that the rheumatic process is a human reaction, which appears in susceptible individuals, and which represents a special type of tissue response to chemical substances arising from disease of the upper respiratory tract. That unrecognized infectious agents may be associated with these upper respiratory diseases is possible; nevertheless the findings in this study justify the conception that streptococcus hemolyticus is an important factor of infection in the rheumatic state."
A few months after the publication of Coburn's monograph, Williams Collis reported similar findings in an article entitled, "Acute rheumatism and hemolytic streptococci." The determination of this relation between a history of streptococcal throat infection and rheumatic fever has been the foundation for all subsequent research studies on pathogenesis, treatment and prevention of this disease.
Finally it is important to briefly mention the important work of Lancefield on serologic classification of hemolytic streptococci and Todd's studies on the significance of antihaemolysin titers in rheumatic fever. Todd was the first to provide the immunological confirmation of streptococcal infection in 1932.
Collis WRF. Acute rheumatism and hemolytic streptococci. Lancet 1934;1:1341-5
Lancefield RC. The antigenic complex of streptococcus haemolyticus . J Exp Med 1928;47:91,103, 460-480,481-493
Lancefield RC. A serological differentiation in human and other groups of hemolytic streptococci. J Exp Med 1933;57:571-595
Lancefield RC. Specific relationship of cell composition to biological activity of hemolytic streptococci. Harvey Lectures 1940-41;36:251-90
Todd EW. Antigenic streptococcal hemolysin. J Exp Med 1932; 55: 267-280
Todd EW. Antihaemolysin titres in haemolytic streptococcal infections and their significance in rheumatic fever. Br J exp pathol 1932;13:248-59
Todd EW. The differentiation of two distinct serological varieties of streptolysin, streptolysin O and streptolysin S. J Pathol Bacteriol1938;47: 423-445