Studies on the Prevention of Rheumatic Fever: The Effect of Time of Initiation of Treatment of Streptococcal Infections on the Immune Response of the Host 1

Abstract

Previous studies have established the fact that penicillin treatment of acute streptococcal pharyngitis results in a marked suppression of antibody formation (1,2,3). This is in contrast to the failure of penicillin treatment to alter the immune response in patients with pneumococcal pneumonia (4). It has been suggested that in the latter case, sufficient pneumococcal antigen is formed during the early phases of pneumonia to provide a maximal antigenic challenge before penicillin therapy is instituted (4). The capacity of penicillin to suppress the production of streptococcal antibodies suggests that in streptococcal infections the antigenic challenge may be presented more gradually. Under such circumstances, it would be expected that the effectiveness of penicillin in this regard would be related to the time of institution of therapy. Since no definitive information on this point has hitherto been obtained, the present study was designed to test this hypothesis. DESCRIPTION OF STUDYAll patients fulfilling the following criteria were included in the study: the presence of exudative pharyngitis, history of onset of symptoms less than 31 hours before admission, and subsequent isolation of group A streptococci from the initial throat culture. Patients with a past history of rheumatic fever or chorea were excluded. A throat culture and a serum specimen were obtained on each patient at the time of admission and on the fourteenth, twenty-first and twenty-eighth days from the onset of symptoms.

Type-Specific Streptococcal Antibody1

“…This failure of penicillin to prevent completely the formation of antistreptolysin, in spite of the apparent eradication of the streptococcus and the complete inhibition of type-specific antibody, suggests that the major antigenic stimulus to the formation of antistreptolysin occurs early in the course of streptococcal infections, while the stimulus to the formation of type-specific antibody occurs over a much longer period. This observation is in agreement with data reported by Brock and Siegel (15). These authors found that treatment of streptococcal pharyngitis with penicillin within 31 hours after the onset of the disease was more effective in the suppression of antistreptolysin formation than therapy delayed for 3 or 5 days.…”

Streptococcal Pharyngitis Therapy: Comparison of Clindamycin Palmitate and Potassium Phenoxymethyl Penicillin

“…In this study, clindamycin and K penicillin V equally suppressed ASO responses. Also, in this and in several previous studies (2,4,21), antistreptococcal therapy incompletely prevented a significant ASO response despite complete eradication of group A streptococci and early institution of therapy. There is no relation between the development of ASO and type-specific streptococcal antibody.…”

Antibiotics for the primary prevention of acute rheumatic fever: a meta-analysis

“…The studies were all hospital-based, 8 out of 10 of which were conducted at U.S. military hospitals from 1950 to 1957 [16,18-24]. Only 3 of the studies used placebos for the control group [20,21,23]. The remainder used either no treatment or symptomatic treatment as controls.…”

“…Nine out of the ten studies reviewed date back to the 1950's when randomised trial methods were still evolving and good guidelines for conducting trials were not yet available [16-24]. Regarding randomisation and allocation concealment, two trials used shuffled cards and were considered to be truly randomised [20,21]. The remaining studies were categorized as 'quasi-randomised' as allocation was based on methods such as Air Force Serial number, and date of hospital admission.…”

“…As an "open" system of randomisation was used in all trials, allocation concealment was deemed inadequate in all cases. Three out of 10 studies were placebo-controlled [20,22,23], however, this did not ensure blinding of patients and providers as the placebo used was not identical in appearance to the experimental treatment. Four studies employed blinded assessors during follow-up for the diagnosis of rheumatic fever [16,18,19,22], 2 did not specify whether the assessor was blinded [24,25], and 1 used no blinding [17].…”