J. Kingston Fowler drew attention to the association of throat infection with acute rheumatism in 1880 and described a latent period between the two events.
As early as 1887, Mantle suggested the bacteriologic origin of rheumatic fever. In the conclusion of his work, he stated that "he was convinced that rheumatism was produced by the agency of a bacterium which in most cases entered the system through the lymphoid structure of the tonsil".
Frederick John Poynton and Alexander Paine did extensive investigations on the etiology of rheumatic fever. They started their research in 1899 and produced several articles. In 1913, they published their book, "Researches on rheumatism", which included all their previous works. This textbook can be divided into three sections. The first section is mostly on the dilatation of the heart and myocardial changes in rheumatic fever. Most of these publications were done in collaboration with Drs Lees and Still. The second section, which is the most interesting, is about the investigational research on the etiology of rheumatic fever and the discovery of "Diplococcus rheumaticus." The third section covers various topics including acute rheumatism in children with heart disease, nervous manifestations of acute rheumatism, rheumatic iritis, and rheumatic fever and infective endocarditis, etc.
The paper number eight in this book is entitled, "The etiology of rheumatic fever," and was first published in Lancet in 1900. In this paper, Poynton and paine reviewed the entire literature on the microbic origin of rheumatic fever. In none of these works hemolytic streptococcus appeared as the causative agent of rheumatic fever. Furthermore in most these publications, rheumatic heart disease was believed to be caused by direct infection of myocardial or valvular structures. Contamination of the culture media and secondary postmortem localization of organisms are the likely explanations for these positive results.
Following their investigations, Poynton and Paine isolated a diplococcus that they thought to be the cause of rheumatic fever. They also wrote "a diplococcus which grew in liquid media in streptococcal chains" and reported in their book that this strain was different from streptococcus pyogenes. According to these authors, this agent was isolated from acute rheumatic lesions, although they mentioned several times in their manuscript that it was difficult to isolate this organism in valve structures. The same infectious agent was also identified in the diseased tonsils of the rheumatic patients.
In this study, they also inoculated rabbits with this agent isolated from patients with rheumatic disease and they were able to produce similar lesions in animal model. In fact, they were able to create arthritis and complex lesions of pericarditis and endocarditis in these animals. Furthermore, they were able to isloate the "diplococcus rheumaticus" in their heart and joint fluids. These findings led Poynton and Paine to believe that rheumatic fever was a form of bacterial infection.
In the introduction of their book Poynton and Paine wrote: "We relied and still rely on the belief that the nearest approach that can be reached in the establishment of the causal agency of any micro-organism to a disease is the isolation of it from the acute lesions in man and the reproduction of these with it in animals...the results obtained in living animals under these circumstances bring us we believe nearer the truth than do any tests of a micrococcus outside the living body conducted in the laboratory." As it was shown later, the animal model was not ideal to study rheumatic fever, as the inoculation of large amounts of microorganism was at the origin of direct infection of joints, and cardiac structures. Poynton and Paine's animal model was an experimental model of bacterial endocarditis, not rheumatic fever.
Although Poynton and Paine identified streptococcus as the agent responsible of rheumatic fever, they still viewed this disease as an infectious process and were not able to describe its exact pathologic mechanism. The determination of the etiology of rheumatic fever remained a topic of controversy for several decades. Extensive research studies were performed before it was determined that rheumatic fever results from an inflammatory process secondary to a hemolytic streptococcus throat infection rather than from a direct infectious process.
Fowler JK. On the association of affections of the throat with acute rheumatism. Lancet 1880;2:933-34
Mantel A. Etiology of rheumatism considered from a bacterial point of view. Br med J 1887;1:1381