EDITORIALS
ANNALS of Internal Medicine Volume 86
Number 4
April 1977 PUBLISHED monthly by the American College of Physicians under the direction of the Publications Committee of the Board of Regents; see advertising page 1-5 for listing of the Committee, the Editorial Staff, the Editorial Board, and the Business Staff. Editorial Policy ANNALS OF INTERNAL MEDICINE pub-
lishes original papers, topical reviews, editorials, book reviews, and medical news in the broad field of internal medicine and allied sciences. Detailed information on the kinds of papers that will be considered for publication, the proper form and style for manuscripts, and submission of manuscripts to the Editor are given in "INFORMATION FOR AUTHORS" on advertising page 1-6. Selected books will be reviewed monthly. Review copies should be sent to the Editor. The content of this journal is protected by copyright. Manuscripts are accepted for publication with the understanding that their contents, all or in part, have not been published elsewhere and will not be published elsewhere, except in abstract form or by the express consent of
the Editor. ANNALS
OF INTERNAL
MEDICINE accepts no responsibility for statements made by contributors. Subscriptions ANNALS
OF INTERNAL
MEDICINE
is
issued monthly; new volumes begin with the January and July issues each year. Subscription price per year, net postpaid: $25.00 in North and Central American countries, Puerto Rico, and Canal Zone; $28.00 in other countries; half price to medical students and to physicians within four years after graduation from medical school. Single copies of recent issues: $3.00 in North and Central American countries, Puerto Rico, and Canal Zone; $3.25 in other countries; price of supplements provided on request. Checks should be made payable to the American College of Physicians and remitted to the Circulation Manager. Communications to the Editor or the Circulation Manager should be sent to
Annals of Internal Medicine 4200 Pine St. Philadelphia, PA. 19104 USA Phone: 215/243-1200 494
Therapeutic Strategies for the Prevention of Rheumatic Fever A C U T E PHARYNGITIS is one of mankind's commonest maladies. Although it
can have many etiologic agents (Corynebacterium diphtheriae, Mycoplasma pneumoniae, Neisseria gonorrhoeae, and others), in most cases the differential diagnosis comes down to viral or streptococcal infection. Both are likely to be benign and self-limited, although the latter can be associated with suppurative sequelae, such as acute sinusitis, otitis media, or peritonsillar abscess. The therapeutic implications are straight-forward: viral pharyngitis requires only supportive care, while patients with group A streptococcal sore throat should ordinarily receive penicillin therapy. Antibiotic therapy of "strep throat" is advocated both to prevent suppurative and, more important, nonsuppurative sequelae. Prevention of acute rheumatic fever is the main issue; data on the preventability of acute glomerulonephritis by antibiotic therapy are much less persuasive. The major problem for the clinician in these recommendations is in deciding who does and who does not have "strep throat" ( 1 ) . Except in epidemics or in cases of scarlet fever, clinical findings alone do not distinguish viral from streptococcal sore throat with enough precision ( 1 , 2 ) . This fact has led to the current national recommendation of throat cultures to establish the diagnosis of streptococcal sore throat ( 3 ) . Throat cultures are an imperfect tool because they do not ordinarily differentiate between infection and asymptomatic pharyngeal carriage of group A streptococci. Nevertheless, they eliminate unnecessary antibiotic therapy for most patients with sore throat—those found to have negative cultures. Acceptance of these recommendations by the medical profession has never been unanimous. An academician reviewing these issues before a local medical society is sure to evoke vociferous argument and, on occasion, downright hostility! Many physicians continue to make therapeutic decisions on clinical grounds, and some administer antibiotics empirically to all patients complaining of sore throat. In this issue, Drs. Richard Tompkins, Daniel Burnes, and William Cable (4) have attempted to place this continuing town-gown controversy on a more rational basis. By applying mathematical models and sophisticated methods of computer-assisted decision analysis, they have tested the costeffectiveness of various strategies for management of sore throat. Their conclusions, based on painstaking analysis of published data, differ in some fundamental ways from the current national recommendations. These authors present recommendations for both epidemic and endemic cases. "Epidemic" is used to denote explosive epidemics such as those occurring in military recruit camps. Their proposal—treatment of all nonallergic patients with penicillin—will arouse little controversy. That universal penicillin therapy might be needed in explosive epidemics of streptococcal pharyngitis and acute rheumatic fever in semiclosed populations is not new. Indeed, universal penicillin prophylaxis of all incoming recruits has been used for years in selected military camps where the problem of rheumatic fever was great ( 5 ) . For endemic cases, Tompkins and associates relate the most cost-effective strategy to the frequency of positive throat cultures among patients reporting
April 1977 • Annals of Internal Medicine • Volume 86 • Number 4
Downloaded from https://annals.org by Karolinska Institute user on 01/18/2019
to the physician with sore throat. When oral therapy is to be used and the frequency of positive throat cultures is more than 2 0 % , they advocate universal penicillin treatment without cultures (strategy B ) ; when the percent of positive cultures is between 5% and 2 0 % , throat culture and selective treatment of positives is most cost-effective (strategy A ) ; and when rates of less than 5% are observed, no treatment of any patient with pharyngitis is advocated (strategy C ) . Because streptococcal carrier rates in open populations of school children are generally in the 15% to 20% range ( 1 ) , one may presume that strategy C would rarely, if ever, be indicated. Indeed, in most large studies in urban areas (Chicago [6], Minneapolis [2], Memphis [7]), the frequency of positive cultures among sore throat patients is 30% or greater, thus mandating universal penicillin therapy according to the criteria of Tompkins and colleagues. It must be recognized, however, that the authors' estimates of cost-effectiveness of rheumatic fever prevention in civilian endemic cases rest on assumptions that cannot at present be verified. The first assumption is that one can apply a single rheumatic fever attack rate figure, derived from studies done in a northern urban environment, to the entire United States. The Chicago Children's Memorial Hospital data developed in the late 1950s by Siegel, Johnson, and Stollerman (6) are admittedly the best available estimates of the ratio of acute rheumatic fever cases to endemic streptococcal infections in an open population. Nevertheless, there are marked differences in the epidemiologic features of rheumatic fever related to time-period, geographic locale, socioeconomic setting, and, most likely, properties of prevalent streptococcal strains (7, 8). For instance, although the data differ, several authors have reported the incidence of rheumatic fever to be much lower in the southeastern United States than in the North (9, 10). Estimates developed in northern urban centers such as New York and Chicago may be entirely wrong for the South, both for the initial attack rate of rheumatic fever and the recurrence rate after streptococcal infection (11). Despite high rates of throat culture positivity, the risk of rheumatic fever in midsummer in Alabama, Tennessee, or Mississippi may be so vanishingly small (7) as to suggest the adoption of strategy C (no treatment) during the warmer months of the year! Indeed, one might be hard pressed to convince experienced pediatricians or generalists practicing in the affluent suburbs of America's cities in 1977 that universal penicillin treatment of all sore throats is indicated. Many of these physicians would never have seen even a single case of rheumatic fever over many years of busy practice. A second, crucial assumption is that universal penicillin treatment of all pharyngitis cases will prevent substantially more cases of rheumatic fever than will selective treatment of patients with positive cultures. This assumption rests upon the well-known fact that about 10% of patients harboring beta hemolytic streptococci in their throats will have false-negative cultures if only a single swab is done. The authors further assume that the risk of acquiring rheumatic fever is just as great in patients with "false-
negative" throat cultures as in those with positive cultures. "False-negative" cultures, however, occur primarily among subjects with small numbers of organisms in their pharynx (2). Such persons may well be streptococcal carriers rather than represent cases of symptomatic streptococcal pharyngitis. Several reports suggest that patients with more strongly positive throat cultures are more likely to have overt clinical disease (12, 13) and significant immunologic rises (14), both features positively correlated with the risk of rheumatic fever. The issue is crucial, because if one assumes equivalent rheumatic fever attack rates for strategies A and B, the cost-effectiveness of strategy A (culturetreat) for oral penicillin therapy in the endemic situation is slightly better than that of strategy B (treat-all). There are other disturbing aspects of the proposed strategies. In addition to the increase in penicillin reactions that would inevitably accompany the twofold to threefold or greater increase in penicillin administrations associated with strategy B, there are potential ecologic changes as well. The recent emergence of strains of Hemophilus influenzae and N. gonorrhoeae markedly resistant to penicillin and ampicillin underscores the need for physicians to become medical ecologists who consider the effects of each antibiotic administration not only on their patient but on the overall human microflora as well. Finally, a major problem with the proposed strategy is that its use requires detailed knowledge of the frequency of positive throat cultures among patients with pharyngitis in the population being served. The cost of periodic culture surveys to ascertain this information has not been included in estimates of the cost-effectiveness of the "treatall" strategy. Indeed, for the individual physician this requirement may represent a sort of "Catch 22": one need not culture to treat but must culture to ascertain positive culture prevalences to justify universal treatment. Armed with the culture results, most physicians would surely use them as guides to management. To obviate this problem, Dr. Tompkins and associates suggest that the culture positivity rate may be predicted from the patients' clinical findings. At this point, they depart radically from the concept of precise therapeutic strategies based on well-defined and easily quantifiable bacteriologic variables. Instead, they would have individual physicians making "treat" or "no-treat" decisions on the basis of clinical findings. The limitations of this approach, commented on many times in the literature (1, 2, 15, 16), have given rise to the present culture recommendations! Dr. Tompkins and colleagues are to be congratulated for giving us an elegant model of decision-analysis. Their study also poignantly illustrates, however, the limits for such an analysis when the needed basic data are either incomplete or unavailable. When such analyses lead to recommendations for startling changes in conventional therapy, it is time to pause and reflect. As stated by the authors themselves, their proposed strategies would have to be carefully validated in prospective field trials before being advocated for general use. Until we have data from such trials, physicians should recall that the throat culture has proved itself over many years to be a simple, reliable tool for discerning who should and who should Editorials
Downloaded from https://annals.org by Karolinska Institute user on 01/18/2019
495
not receive antibiotic therapy for "strep throat." More effective approaches to rheumatic fever prevention will require extensions of present knowledge. For example, interest has recently been reawakened in the concept that different group A streptococcal types may differ widely in rheumatogenic potential (7, 8 ) . More than 30 years ago, Kuttner and Krumweide (17) reported that a virulent epidemic of type 4 streptococcal pharyngitis in a rheumatic fever sanatorium failed completely to reactivate the disease. More recently, Potter and co-workers (18) have shown that the strains of streptococci causing rheumatic fever in Trinidad differed from those simultaneously causing glomerulonephritis in the same population. Widdowson and associates (19) have presented evidence suggesting that a readily measured biologic property, lipoproteinase ("opacity factor") elaboration, may be associated with diminished immunogenicity and rheumatogenicity of group A streptococci. If precise markers of rheumatogenicity can be identified and readily assayed, then we may be able to concentrate our most intensive therapy on truly dangerous streptococcal infections. Moreover, the prospect of a protective streptococcal M-protein vaccine is drawing nearer to reality. Limited trials of one such vaccine have recently been initiated ( 2 0 ) . Current breakthroughs by Beachey and colleagues (21) in purifying the type-specific moiety of M-protein from closely linked non-type-specific proteins may open the way to a vaccine preparation that is immunogenic, well tolerated, and free of any possible rheumatogenic contaminants. Equally intriguing are the prospects for interfering with the earliest phases of streptococcal infection, now that we know that lipoteichoic acid is the substance responsibile for adherence of group A streptococci to oral mucosal cells and that such adherence can be blocked in vitro by various manipulations ( 2 2 ) . These new approaches to the management of streptococcal pharyngitis are adding uncommon excitement to the study
ciation Committee Report. Prevention of rheumatic fever. Circulation 55:Sl-4, 1977 4. TOMPKINS RK, BURNES DC, CABLE WE: An analysis of the
cost-effectiveness of pharyngitis management and acute rheumatic fever. Ann Intern Med 86:481-492, 1977 5. FRANK PF, STOLLERMAN GH, MILLER LF: Protection of a mili-
tary population from rheumatic fever. Routine administration of benzathine penicillin G to healthy individuals. JAMA 193: 775-783, 1965 6. SIEGEL AC, JOHNSON EE, STOLLERMAN GH: Controlled studies
of streptococcal pharyngitis in a pediatric population. I. Factors related to the attack rate of rheumatic fever. N Engl J Med 265:559-566, 1961 7. BISNO AL, PEARCE IA, WALL HP, et al: Contrasting epidemiol-
ogy of acute rheumatic fever and acute glomerulonephritis. Nature of the antecedent streptococcal infection. N Engl J Med 283:561-565, 1970 8. STOLLERMAN GH: Rheumatogenic and nephritogenic streptococci. Circulation 43:915-921, 1971 9. SCHWENTKER FF: The epidemiology of rheumatic fever, in Rheumatic Fever, edited by THOMAS L. Minneapolis, University of Minnesota Press, 1952, pp. 17-27 10. SASLAW MS, STREITFELD MM: Group A beta hemolytic streptococci in relation to rheumatic fever. Study of school children in Miami, Fla. AM A J Dis Child 92:550-557, 1956 11. BISNO AL, PEARCE I A, STOLLERMAN GH: Streptococcal infec-
tions in rheumatic subjects without recurrences (abstract). Clin Res 23:415A, 1975 12. BELL SM, SMITH DD: Quantitative throat-swab culture in the diagnosis of streptococcal pharyngitis in children. Lancet 2: 61-63, 1976 13. BREESE BB, DISNEY FA, TAPLEY WB, et al:
of a common disease. (ALAN L. BISNO, M.D., F.A.C.P.;
Chief, Division of Infectious Diseases, Department of Medicine, University of Tennessee; Memphis, Tennessee)
Beta-hemolytic
streptococcal infection. The clinical and epidemiologic importance of the number of organisms found in cultures. Am J Dis Child 119:18-26, 1970 14. MILLER JM, STANCER SL, MASSELL BF: A controlled study of
beta hemolytic streptococcal infection in rheumatic families. I. Streptococcal disease among healthy siblings. Am J Med 25: 825-844, 1958 15. GLEZEN WP, CLYDE WA JR, SENIOR RJ, et al: Group A strep-
tococci, mycoplasmas, and viruses associated with acute pharyngitis. JAMA 202:455-460, 1967 16. ALPERT JL, PICKERING MR, WARREN RJ: Failure to isolate
streptococci from children under the age of 3 years with exudative tonsillitis. Pediatrics 38:663-666, 1966 17. KUTTNER AG, KRUMWEIDE E: Observations on the effect of
streptococcal upper respiratory infections on rheumatic children: a three-year study. J Clin Invest 20:273-287, 1941 18. POTTER EV, SVARTMAN M, POON-KING T, et al: Streptococcal
infections antecedent to acute glomerulonephritis and acute rheumatic fever in Trinidad (abstract). Clin Res 23:533A, 1975 19. WIDDOWSON JP, MAXTED WR, NOTLEY CM, et al: The antibody
responses in man to infection with different serotypes of groupA streptococci. / Med Microbiol 7:483-496, 1974 20. POLLY SM, WALDMAN RH, HIGH P, et al: Protective studies
References 1. WANNAMAKER LW: Perplexity and precision in the diagnosis of streptococcal pharyngitis. Am J Dis Child 124:352-358, 1972 2. KAPLAN LW, TOP FH JR, DUDDING BA, et al: Diagnosis of
streptococcal pharyngitis: differentiation of active infection from the carrier state in the symptomatic child. / Infect Dis 123: 490-501, 1971 3. KAPLAN EL, BISNO A, DERRICK W, et al: American Heart Asso-
496
April 1977 • Annals of Internal Medicine • Volume 86 • Number 4
Downloaded from https://annals.org by Karolinska Institute user on 01/18/2019
with a group A streptococcal M protein vaccine. II. Challenge of volunteers after local immunization in the upper respiratory tract. J Infect Dis 131:217-224, 1975 21. BEACHEY EH, CHIANG EY, SEYER JM, et al: Separation of the
type-specific M-protein from toxic cross-reactive antigens of group A streptococci (abstract). Clin Res, in press, 1977 22. BEACHEY EH, OFEK I: Epithelial cell binding of group A streptococci by lipoteichoic acid on fimbriae denuded of M protein. J Exp Med 143:759-771, 1976
ANNALS of Internal Medicine Volume 86
Number 4
April 1977 PUBLISHED monthly by the American College of Physicians under the direction of the Publications Committee of the Board of Regents; see advertising page 1-5 for listing of the Committee, the Editorial Staff, the Editorial Board, and the Business Staff. Editorial Policy ANNALS OF INTERNAL MEDICINE pub-
lishes original papers, topical reviews, editorials, book reviews, and medical news in the broad field of internal medicine and allied sciences. Detailed information on the kinds of papers that will be considered for publication, the proper form and style for manuscripts, and submission of manuscripts to the Editor are given in "INFORMATION FOR AUTHORS" on advertising page 1-6. Selected books will be reviewed monthly. Review copies should be sent to the Editor. The content of this journal is protected by copyright. Manuscripts are accepted for publication with the understanding that their contents, all or in part, have not been published elsewhere and will not be published elsewhere, except in abstract form or by the express consent of
the Editor. ANNALS
OF INTERNAL
MEDICINE accepts no responsibility for statements made by contributors. Subscriptions ANNALS
OF INTERNAL
MEDICINE
is
issued monthly; new volumes begin with the January and July issues each year. Subscription price per year, net postpaid: $25.00 in North and Central American countries, Puerto Rico, and Canal Zone; $28.00 in other countries; half price to medical students and to physicians within four years after graduation from medical school. Single copies of recent issues: $3.00 in North and Central American countries, Puerto Rico, and Canal Zone; $3.25 in other countries; price of supplements provided on request. Checks should be made payable to the American College of Physicians and remitted to the Circulation Manager. Communications to the Editor or the Circulation Manager should be sent to
Annals of Internal Medicine 4200 Pine St. Philadelphia, PA. 19104 USA Phone: 215/243-1200 494
Therapeutic Strategies for the Prevention of Rheumatic Fever A C U T E PHARYNGITIS is one of mankind's commonest maladies. Although it
can have many etiologic agents (Corynebacterium diphtheriae, Mycoplasma pneumoniae, Neisseria gonorrhoeae, and others), in most cases the differential diagnosis comes down to viral or streptococcal infection. Both are likely to be benign and self-limited, although the latter can be associated with suppurative sequelae, such as acute sinusitis, otitis media, or peritonsillar abscess. The therapeutic implications are straight-forward: viral pharyngitis requires only supportive care, while patients with group A streptococcal sore throat should ordinarily receive penicillin therapy. Antibiotic therapy of "strep throat" is advocated both to prevent suppurative and, more important, nonsuppurative sequelae. Prevention of acute rheumatic fever is the main issue; data on the preventability of acute glomerulonephritis by antibiotic therapy are much less persuasive. The major problem for the clinician in these recommendations is in deciding who does and who does not have "strep throat" ( 1 ) . Except in epidemics or in cases of scarlet fever, clinical findings alone do not distinguish viral from streptococcal sore throat with enough precision ( 1 , 2 ) . This fact has led to the current national recommendation of throat cultures to establish the diagnosis of streptococcal sore throat ( 3 ) . Throat cultures are an imperfect tool because they do not ordinarily differentiate between infection and asymptomatic pharyngeal carriage of group A streptococci. Nevertheless, they eliminate unnecessary antibiotic therapy for most patients with sore throat—those found to have negative cultures. Acceptance of these recommendations by the medical profession has never been unanimous. An academician reviewing these issues before a local medical society is sure to evoke vociferous argument and, on occasion, downright hostility! Many physicians continue to make therapeutic decisions on clinical grounds, and some administer antibiotics empirically to all patients complaining of sore throat. In this issue, Drs. Richard Tompkins, Daniel Burnes, and William Cable (4) have attempted to place this continuing town-gown controversy on a more rational basis. By applying mathematical models and sophisticated methods of computer-assisted decision analysis, they have tested the costeffectiveness of various strategies for management of sore throat. Their conclusions, based on painstaking analysis of published data, differ in some fundamental ways from the current national recommendations. These authors present recommendations for both epidemic and endemic cases. "Epidemic" is used to denote explosive epidemics such as those occurring in military recruit camps. Their proposal—treatment of all nonallergic patients with penicillin—will arouse little controversy. That universal penicillin therapy might be needed in explosive epidemics of streptococcal pharyngitis and acute rheumatic fever in semiclosed populations is not new. Indeed, universal penicillin prophylaxis of all incoming recruits has been used for years in selected military camps where the problem of rheumatic fever was great ( 5 ) . For endemic cases, Tompkins and associates relate the most cost-effective strategy to the frequency of positive throat cultures among patients reporting
April 1977 • Annals of Internal Medicine • Volume 86 • Number 4
Downloaded from https://annals.org by Karolinska Institute user on 01/18/2019
to the physician with sore throat. When oral therapy is to be used and the frequency of positive throat cultures is more than 2 0 % , they advocate universal penicillin treatment without cultures (strategy B ) ; when the percent of positive cultures is between 5% and 2 0 % , throat culture and selective treatment of positives is most cost-effective (strategy A ) ; and when rates of less than 5% are observed, no treatment of any patient with pharyngitis is advocated (strategy C ) . Because streptococcal carrier rates in open populations of school children are generally in the 15% to 20% range ( 1 ) , one may presume that strategy C would rarely, if ever, be indicated. Indeed, in most large studies in urban areas (Chicago [6], Minneapolis [2], Memphis [7]), the frequency of positive cultures among sore throat patients is 30% or greater, thus mandating universal penicillin therapy according to the criteria of Tompkins and colleagues. It must be recognized, however, that the authors' estimates of cost-effectiveness of rheumatic fever prevention in civilian endemic cases rest on assumptions that cannot at present be verified. The first assumption is that one can apply a single rheumatic fever attack rate figure, derived from studies done in a northern urban environment, to the entire United States. The Chicago Children's Memorial Hospital data developed in the late 1950s by Siegel, Johnson, and Stollerman (6) are admittedly the best available estimates of the ratio of acute rheumatic fever cases to endemic streptococcal infections in an open population. Nevertheless, there are marked differences in the epidemiologic features of rheumatic fever related to time-period, geographic locale, socioeconomic setting, and, most likely, properties of prevalent streptococcal strains (7, 8). For instance, although the data differ, several authors have reported the incidence of rheumatic fever to be much lower in the southeastern United States than in the North (9, 10). Estimates developed in northern urban centers such as New York and Chicago may be entirely wrong for the South, both for the initial attack rate of rheumatic fever and the recurrence rate after streptococcal infection (11). Despite high rates of throat culture positivity, the risk of rheumatic fever in midsummer in Alabama, Tennessee, or Mississippi may be so vanishingly small (7) as to suggest the adoption of strategy C (no treatment) during the warmer months of the year! Indeed, one might be hard pressed to convince experienced pediatricians or generalists practicing in the affluent suburbs of America's cities in 1977 that universal penicillin treatment of all sore throats is indicated. Many of these physicians would never have seen even a single case of rheumatic fever over many years of busy practice. A second, crucial assumption is that universal penicillin treatment of all pharyngitis cases will prevent substantially more cases of rheumatic fever than will selective treatment of patients with positive cultures. This assumption rests upon the well-known fact that about 10% of patients harboring beta hemolytic streptococci in their throats will have false-negative cultures if only a single swab is done. The authors further assume that the risk of acquiring rheumatic fever is just as great in patients with "false-
negative" throat cultures as in those with positive cultures. "False-negative" cultures, however, occur primarily among subjects with small numbers of organisms in their pharynx (2). Such persons may well be streptococcal carriers rather than represent cases of symptomatic streptococcal pharyngitis. Several reports suggest that patients with more strongly positive throat cultures are more likely to have overt clinical disease (12, 13) and significant immunologic rises (14), both features positively correlated with the risk of rheumatic fever. The issue is crucial, because if one assumes equivalent rheumatic fever attack rates for strategies A and B, the cost-effectiveness of strategy A (culturetreat) for oral penicillin therapy in the endemic situation is slightly better than that of strategy B (treat-all). There are other disturbing aspects of the proposed strategies. In addition to the increase in penicillin reactions that would inevitably accompany the twofold to threefold or greater increase in penicillin administrations associated with strategy B, there are potential ecologic changes as well. The recent emergence of strains of Hemophilus influenzae and N. gonorrhoeae markedly resistant to penicillin and ampicillin underscores the need for physicians to become medical ecologists who consider the effects of each antibiotic administration not only on their patient but on the overall human microflora as well. Finally, a major problem with the proposed strategy is that its use requires detailed knowledge of the frequency of positive throat cultures among patients with pharyngitis in the population being served. The cost of periodic culture surveys to ascertain this information has not been included in estimates of the cost-effectiveness of the "treatall" strategy. Indeed, for the individual physician this requirement may represent a sort of "Catch 22": one need not culture to treat but must culture to ascertain positive culture prevalences to justify universal treatment. Armed with the culture results, most physicians would surely use them as guides to management. To obviate this problem, Dr. Tompkins and associates suggest that the culture positivity rate may be predicted from the patients' clinical findings. At this point, they depart radically from the concept of precise therapeutic strategies based on well-defined and easily quantifiable bacteriologic variables. Instead, they would have individual physicians making "treat" or "no-treat" decisions on the basis of clinical findings. The limitations of this approach, commented on many times in the literature (1, 2, 15, 16), have given rise to the present culture recommendations! Dr. Tompkins and colleagues are to be congratulated for giving us an elegant model of decision-analysis. Their study also poignantly illustrates, however, the limits for such an analysis when the needed basic data are either incomplete or unavailable. When such analyses lead to recommendations for startling changes in conventional therapy, it is time to pause and reflect. As stated by the authors themselves, their proposed strategies would have to be carefully validated in prospective field trials before being advocated for general use. Until we have data from such trials, physicians should recall that the throat culture has proved itself over many years to be a simple, reliable tool for discerning who should and who should Editorials
Downloaded from https://annals.org by Karolinska Institute user on 01/18/2019
495
not receive antibiotic therapy for "strep throat." More effective approaches to rheumatic fever prevention will require extensions of present knowledge. For example, interest has recently been reawakened in the concept that different group A streptococcal types may differ widely in rheumatogenic potential (7, 8 ) . More than 30 years ago, Kuttner and Krumweide (17) reported that a virulent epidemic of type 4 streptococcal pharyngitis in a rheumatic fever sanatorium failed completely to reactivate the disease. More recently, Potter and co-workers (18) have shown that the strains of streptococci causing rheumatic fever in Trinidad differed from those simultaneously causing glomerulonephritis in the same population. Widdowson and associates (19) have presented evidence suggesting that a readily measured biologic property, lipoproteinase ("opacity factor") elaboration, may be associated with diminished immunogenicity and rheumatogenicity of group A streptococci. If precise markers of rheumatogenicity can be identified and readily assayed, then we may be able to concentrate our most intensive therapy on truly dangerous streptococcal infections. Moreover, the prospect of a protective streptococcal M-protein vaccine is drawing nearer to reality. Limited trials of one such vaccine have recently been initiated ( 2 0 ) . Current breakthroughs by Beachey and colleagues (21) in purifying the type-specific moiety of M-protein from closely linked non-type-specific proteins may open the way to a vaccine preparation that is immunogenic, well tolerated, and free of any possible rheumatogenic contaminants. Equally intriguing are the prospects for interfering with the earliest phases of streptococcal infection, now that we know that lipoteichoic acid is the substance responsibile for adherence of group A streptococci to oral mucosal cells and that such adherence can be blocked in vitro by various manipulations ( 2 2 ) . These new approaches to the management of streptococcal pharyngitis are adding uncommon excitement to the study
ciation Committee Report. Prevention of rheumatic fever. Circulation 55:Sl-4, 1977 4. TOMPKINS RK, BURNES DC, CABLE WE: An analysis of the
cost-effectiveness of pharyngitis management and acute rheumatic fever. Ann Intern Med 86:481-492, 1977 5. FRANK PF, STOLLERMAN GH, MILLER LF: Protection of a mili-
tary population from rheumatic fever. Routine administration of benzathine penicillin G to healthy individuals. JAMA 193: 775-783, 1965 6. SIEGEL AC, JOHNSON EE, STOLLERMAN GH: Controlled studies
of streptococcal pharyngitis in a pediatric population. I. Factors related to the attack rate of rheumatic fever. N Engl J Med 265:559-566, 1961 7. BISNO AL, PEARCE IA, WALL HP, et al: Contrasting epidemiol-
ogy of acute rheumatic fever and acute glomerulonephritis. Nature of the antecedent streptococcal infection. N Engl J Med 283:561-565, 1970 8. STOLLERMAN GH: Rheumatogenic and nephritogenic streptococci. Circulation 43:915-921, 1971 9. SCHWENTKER FF: The epidemiology of rheumatic fever, in Rheumatic Fever, edited by THOMAS L. Minneapolis, University of Minnesota Press, 1952, pp. 17-27 10. SASLAW MS, STREITFELD MM: Group A beta hemolytic streptococci in relation to rheumatic fever. Study of school children in Miami, Fla. AM A J Dis Child 92:550-557, 1956 11. BISNO AL, PEARCE I A, STOLLERMAN GH: Streptococcal infec-
tions in rheumatic subjects without recurrences (abstract). Clin Res 23:415A, 1975 12. BELL SM, SMITH DD: Quantitative throat-swab culture in the diagnosis of streptococcal pharyngitis in children. Lancet 2: 61-63, 1976 13. BREESE BB, DISNEY FA, TAPLEY WB, et al:
of a common disease. (ALAN L. BISNO, M.D., F.A.C.P.;
Chief, Division of Infectious Diseases, Department of Medicine, University of Tennessee; Memphis, Tennessee)
Beta-hemolytic
streptococcal infection. The clinical and epidemiologic importance of the number of organisms found in cultures. Am J Dis Child 119:18-26, 1970 14. MILLER JM, STANCER SL, MASSELL BF: A controlled study of
beta hemolytic streptococcal infection in rheumatic families. I. Streptococcal disease among healthy siblings. Am J Med 25: 825-844, 1958 15. GLEZEN WP, CLYDE WA JR, SENIOR RJ, et al: Group A strep-
tococci, mycoplasmas, and viruses associated with acute pharyngitis. JAMA 202:455-460, 1967 16. ALPERT JL, PICKERING MR, WARREN RJ: Failure to isolate
streptococci from children under the age of 3 years with exudative tonsillitis. Pediatrics 38:663-666, 1966 17. KUTTNER AG, KRUMWEIDE E: Observations on the effect of
streptococcal upper respiratory infections on rheumatic children: a three-year study. J Clin Invest 20:273-287, 1941 18. POTTER EV, SVARTMAN M, POON-KING T, et al: Streptococcal
infections antecedent to acute glomerulonephritis and acute rheumatic fever in Trinidad (abstract). Clin Res 23:533A, 1975 19. WIDDOWSON JP, MAXTED WR, NOTLEY CM, et al: The antibody
responses in man to infection with different serotypes of groupA streptococci. / Med Microbiol 7:483-496, 1974 20. POLLY SM, WALDMAN RH, HIGH P, et al: Protective studies
References 1. WANNAMAKER LW: Perplexity and precision in the diagnosis of streptococcal pharyngitis. Am J Dis Child 124:352-358, 1972 2. KAPLAN LW, TOP FH JR, DUDDING BA, et al: Diagnosis of
streptococcal pharyngitis: differentiation of active infection from the carrier state in the symptomatic child. / Infect Dis 123: 490-501, 1971 3. KAPLAN EL, BISNO A, DERRICK W, et al: American Heart Asso-
496
April 1977 • Annals of Internal Medicine • Volume 86 • Number 4
Downloaded from https://annals.org by Karolinska Institute user on 01/18/2019
with a group A streptococcal M protein vaccine. II. Challenge of volunteers after local immunization in the upper respiratory tract. J Infect Dis 131:217-224, 1975 21. BEACHEY EH, CHIANG EY, SEYER JM, et al: Separation of the
type-specific M-protein from toxic cross-reactive antigens of group A streptococci (abstract). Clin Res, in press, 1977 22. BEACHEY EH, OFEK I: Epithelial cell binding of group A streptococci by lipoteichoic acid on fimbriae denuded of M protein. J Exp Med 143:759-771, 1976
