Rheumatic Fever in Children and Adolescents: A Long-term Epidemiologic Study of Subsequent Prophylaxis, Streptococcal Infections, and Clinical Sequelae: III. Comparative Effectiveness of Three Prophylaxis Regimens in Preventing Streptococcal Infections and Rheumatic Recurrences

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Abstract
The 431 known rheumatic patients were divided by a statistically controlled method of random selection into 3 comparable groups, each assigned to a different prophylactic agent. There were 1,681 patient-years of observation: 560 on benzathine penicillin, 545 on oral penicillin, and 576 on sulfadiazine. A total of 285 streptococcal infections, including the carrier state, occurred over the period of the study: 34 in the benzathine penicillin G group, 113 in the group on oral penicillin, and 138 in the sulfadiazine group. The streptococcal infection rates/100 patient-years for each of the drugs was 6.1 for benzathine penicillin G, 20.7 for oral penicillin, and 24.0 for sulfadiazine. There were 48 recurrences of acute rheumatic fever, 2 in the group on benzathine penicillin G, 30 in the group on oral penicillin, and 16 in the sulfadiazine group. The recurrence rates/100 patient-years were: benzathine penicillin G, 0.4; oral penicillin, 5.5; and sulfadiazine, 2.8. Forty-seven of the 48 rheumatic recurrences were demonstrated to be associated with preceding streptococcal infection. Adequate sera for testing were not available in the 48th. Each of the 47 rheumatogenic infections was characterized by rise in titer of one or more of the streptococcal antibodies measured in this study. The degree of fidelity with which patients adhered to their prophylaxis programs was found to bear a relationship to streptococcal infection and recurrence rates for both oral prophylaxis groups. Age of patients also bore a definite relationship to infection and recurrence rates for the 2 oral drug groups, the rates decreasing as age of patients increased. In the parenteral prophylaxis group, fidelity of maintenance was assured by the activities of the clinic staff. In this group, the rates of infection remained low regardless of age of patients.