Download Special Report

1082
Special Report
Prevention of Rheumatic Fever
A Statement for Health Professionals by the Committee on
Rheumatic Fever, Endocarditis, and Kawasaki Disease of the
Council on Cardiovascular Disease in the Young,
the American Heart Association
Downloaded from http://circ.ahajournals.org/ by guest on June 14, 2017
Adnan S. Dajani, MD, Chairman; Alan L. Bisno, MD; Kyung J. Chung, MD;
David T. Durack, MD, DPhil; Michael A. Gerber, MD; Edward L. Kaplan, MD;
H. Dean Millard, DDS, MS; Martin F. Randolph, MD; Stanford T. Shulman, MD;
Chatrchai Watanakunakorn, MD
revention of both initial and recurrent attacks
of acute rheumatic fever depends on control
of Group A j-hemolytic streptococcal upper
respiratory tract infections. These include tonsillopharyngitis (strep throat) and associated conditions
such as otitis, sinusitis, and mastoiditis. Prevention
of first attacks (primary prevention) is accomplished
by proper identification and adequate antibiotic treatment of these streptococcal infections. The individual who has suffered an attack of rheumatic fever is
inordinately susceptible to recurrences following subsequent Group A streptococcal upper respiratory
tract infections and needs continuous protection to
prevent recurrences (secondary prevention).
The current recommendations reflect the fact that
the incidence of rheumatic fever remains quite low in
most areas of the country. These recommendations
may not apply to certain areas of the United States
where sharp increases in incidence of rheumatic fever
have been noted recently, or regions of the world that
continue to have a high incidence of the disease.
Reappearance of acute rheumatic fever in a specific
geographic region should draw attention to therapeutic, preventive, and epidemological measures as well
as stimulate use of these recommendations.
P
Prevention of Initial Attacks
(Primary Prevention)
Group A streptococcal infections of the upper
respiratory tract are the precipitating cause of rheumatic fever. During epidemics, as many as 3% of
untreated acute streptococcal sore throats may be
followed by rheumatic fever; in endemic infections,
attacks of rheumatic fever may be fewer. AppropriThis report is an update of the 1984 statement, "Prevention of
Rheumatic Fever," published in Circulation (70:1118A-1121A).
Reprint requests should be addressed to the Office of Scientific
Affairs, American Heart Association, 7320 Greenville Ave,
Dallas, TX 75231.
ate antibiotic treatment of streptococcal upper respiratory tract infection prevents acute rheumatic
fever in most cases. Unfortunately, it is not uncommon for episodes of acute rheumatic fever to result
from inapparent streptococcal infections for which
patients do not seek medical care. These episodes,
therefore, are not preventable.
Diagnosis of Streptococcal Infections
Prevention of initial episodes of acute rheumatic
fever requires accurate recognition and proper antibiotic treatment of Group A streptococcal upper
respiratory tract infections. Streptococcal skin infections (impetigo or pyoderma) do not lead to acute
rheumatic fever and are not discussed here.
Symptoms common in individuals with streptococcal pharyngitis or tonsillitis include sore throat
(generally of sudden onset), headache, and fever of
varying degree (usually from 101°~-104° F). Abdominal
pain, nausea, and vomiting may occur, especially in
children. Clinical signs suggesting streptococcal infection include anterior cervical lymphadenitis (tender
lymph nodes), inflamed throat, tonsillopharyngeal exudate, excoriated nares (especially in infants), and a
scarlatiniform rash. However, most of these manifestations are nonspecific and may be associated with
respiratory tract infections from other causes. Signs
and symptoms usually not associated with streptococcal infection are simple coryza, hoarseness, cough,
conjunctivitis, anterior stomatitis, and diarrhea.
Throat Culture
Acute pharyngitis is more often caused by a virus
rather than Group A streptococci. It is often difficult to differentiate on clinical grounds alone among
infections caused by these etiologic agents. Group
A streptococci are not a common cause of pharyngitis in children less than three years of age, and
rheumatic fever is rare in this age group in the
AHA Scientific Council
Downloaded from http://circ.ahajournals.org/ by guest on June 14, 2017
United States. First attacks of rheumatic fever are
also rare in older adults.
Throat cultures are valuable in establishing diagnosis of streptococcal infection and management of
the patient with pharyngitis. Group A streptococci
are virtually always found on a throat culture obtained
during an active infection in an untreated patient.
Unfortunately, the culture does not reliably distinguish between acute streptococcal infections and
streptococcal carriers with concomitant viral infections. Nevertheless, the culture allows the physician
to withhold antibiotic therapy safely in the majority
of patients with sore throat, that is, those with
negative cultures for Group A streptococci.
Rapid antigen detection tests for diagnosis of
Group A streptococcal pharyngitis are now available commercially and can provide results in minutes compared with the 24-48 hours required to
obtain results of a throat culture. Most of these tests
have a high degree of specificity; therefore, treatment is indicated for the patient with acute pharyngitis who has a positive test result. Physicians
should be aware that most of these tests have less
than the desired degree of sensitivity, particularly in
instances where simultaneously obtained throat cultures show a sparse growth of Group A streptococci. Therefore, negative test results must be
confirmed with a throat culture. Sparse growth of
Group A streptococci does not necessarily reflect
the carrier state and may indicate acute infection.
Streptococcal Antibody Tests
Streptococcal antibody tests are of no immediate
value in diagnosis or management of acute streptococcal respiratory tract infections. However, antistreptolysin 0 (ASO), antideoxyribonuclease B (antiDNase B), and other streptococcal antibody tests
are useful in confirming a recent Group A streptococcal infection. The tests are, therefore, helpful in
patients who have possible nonsuppurative complications of streptococcal infections (acute rheumatic
fever or acute glomerulonephritis). A commercially
available agglutination test (such as the Streptozymes
test), which is based on antibody agglutination of
erythrocytes coated with a mixture of streptococcal
antigens, is simpler to perform than traditional
streptococcal antibody tests. However, the test
suffers from significant variation in the potency of
various lots, apparent lack of standardization, and
poorly characterized antigenic composition, and is
not recommended.
Recommended Treatment Schedules
Prevention of rheumatic fever requires eradication of Group A streptococci from the throat. Treatment should begin as soon as a definite diagnosis of
Group A streptococcal infection is made (see Table
1). Penicillin, even when started several days after
onset of acute illness, effectively prevents primary
attacks of rheumatic fever; however, early diagnosis and therapy may reduce the period of infectivity
Prevention of Rheumatic Fever
1083
TABLE 1. Primary Prevention of Rheumatic Fever (Treatment of
Streptococcal Tonsillopharyngitis)
Mode
Duration
Dose
Agent
intramuscular once
Benzathine
600,000 units for
patients <60 lb
penicillin G
1,200,000 units for
patients >60 lb
or
oral
10 days
Penicillin V
250 mg 3 times daily
(phenoxymethyl
penicillin)
For individuals allergic to penicillin:
Erythromycin
oral
10 days
estolate
20-40 mg/kg/day
2-4 times daily
(maximum 1 g/day)
or
oral
10 days
ethylsuccinate 40 mg/kg/day
2-4 times daily
(maximum 1 g/day)
The following agents are acceptable but usually not recommended: amoxicillin, dicloxacillin, oral cephalosporins, and clindamycin.
The following are not acceptable: sulfonamides, trimethoprim,
tetracyclines, and chloramphenicol.
as well as morbidity, allowing the patient to return
to normal activity sooner. Virtually all patients are
noncontagious 24 hours after initiation of therapy
and may return to normal activities at that time,
assuming that they complete the course of therapy.
Penicillin is the drug of choice except in patients
with allergic reactions.* Broad spectrum penicillins
such as ampicillin and amoxicillin offer no advantages over penicillin in treatment of streptococcal
pharyngitis. Penicillin may be administered intramuscularly or orally. Intramuscular administration
of a single dose of benzathine penicillin G ensures
adequate duration of treatment. If oral therapy is
used, a full 10 days of treatment is necessary. Oral
therapy requires patient compliance but may be
associated with fewer allergic reactions. The choice
between intramuscular and oral penicillin depends
on the physician's assessment of the patient's likely
compliance with an oral regimen and the risks of
rheumatic fever in a particular population.
Intramuscular Benzathine Penicillin G
This formulation is preferred for patients who are
unlikely to complete a 10-day course of oral therapy, patients with a personal or family history of
rheumatic fever, and patients whose geographic or
socioeconomic environment is at substantial risk
for development of rheumatic fever. Injections that
contain procaine penicillin in addition to benzathine
penicillin G are less painful. If such mixtures are
*Published reports conflict as to whether penicillin, especially
ampicillin, interferes with effectiveness of oral contraceptives.
The physician should advise the patient of childbearing age of
possible drug interaction. The patient may choose to use a
supplementary method of contraception while taking these antibiotics.
1084
Special Report Circulation Vol 78, No 4, October 1988
used, they should contain benzathine penicillin G in
the following doses:
The recommended dosage of benzathine penicillin G is 600,000 units intramuscularly for patients
weighing 60 lb (27 kg) or less, and 1,200,000 units
for patients weighing more than 60 lb. The combination of 900,000 units of benzathine penicillin G
and 300,000 units of procaine penicillin G may be
satisfactory in many smaller patients, but this dosage is based on limited data. The efficacy of this
combination for heavier patients such as teenagers
or adults requires further study.
Downloaded from http://circ.ahajournals.org/ by guest on June 14, 2017
Oral Penicillin
The oral antibiotic of choice is penicillin V. Dosage for both children and adults is 250 mg, three
times daily for 10 days. It is important to emphasize
that patients should continue to take penicillin regularly for the entire 10-day period, even though they
will likely be asymptomatic after the first few days.
Other Antimicrobial Agents
Antibiotics other than penicillin should be prescribed only for patients who are allergic to penicillin. Erythromycin is indicated for such patients and
should be prescribed for 10 days. Erythromycin
estolate (20-40 mg/kg/day) in two to four divided
doses, or erythromycin ethyl succinate (40 mg/kg/day
in two to four divided doses) is effective in treating
streptococcal pharyngitis; however, efficacy of a
twice-daily regimen in adults requires further study.
The maximum dose of erythromycin is 1 g/day.
Although strains of Group A streptococci resistant to
erythromycin are prevalent in some areas of the
world, they are rare in the United States.
Oral cephalosporins, also given for 10 days, are
acceptable alternatives for the patient allergic to
penicillin. However, they should not be used in
patients with immediate hypersensitivity to penicillin, and are more expensive.
Certain antimicrobials are not recommended for
treatment of streptococcal upper respiratory tract
infections. Tetracyclines should not be used because
of the high prevalence of strains resistant to this
antibiotic. Sulfonamide drugs will not eradicate the
streptococcus and should not be used to treat streptococcal infection, although they are effective as
continuous prophylaxis for recurrent attacks of rheumatic fever (see below). Similarly, trimethoprimsulfamethoxazole should not be used to treat streptococcal pharyngitis.
Prevention of Recurrent Attacks of Rheumatic Fever
(Secondary Prevention)
General Considerations
A rheumatic patient who develops a streptococcal upper respiratory tract infection is at high
risk of developing a recurrent attack of acute rheumatic fever. An infection need not be symptomatic
to trigger a recurrence, which can strike even in
optimally treated symptomatic infections. For these
reasons, prevention of recurrent rheumatic fever
depends on continuous antimicrobial medication
rather than solely on recognition and treatment of
acute episodes of streptococcal pharyngitis. In general, continuous antimicrobial prophylaxis is recommended for patients with a well-documented history
of rheumatic fever (including cases manifested solely
by Sydenham's chorea) and those with definite
evidence of rheumatic heart disease. Such prophylaxis should be initiated as soon as acute rheumatic
fever or rheumatic heart disease is diagnosed. A full
therapeutic course of penicillin (as outlined under
Recommended Treatment Schedules) should first
be given to patients with acute rheumatic fever to
eradicate Group A streptococci that may or may not
be recovered on throat culture. Streptococcal infections occurring in family members of rheumatic
patients should be treated appropriately.
Duration of Prophylaxis
Continuous antimicrobial prophylaxis provides
the most effective protection from rheumatic fever
recurrences. Risk of recurrence depends on several
factors. For example, risk decreases as the interval
since the most recent attack lengthens, while risk
increases with multiple previous attacks. In addition, the patient's risk of acquiring a streptococcal
upper respiratory tract infection must be considered. Adults with a high risk of exposure to streptococcal infections include parents of young children, teachers, physicians, nurses and allied health
personnel, military recruits, and others living in
crowded situations. Data also indicate a higher risk
of recurrences in economically disadvantaged populations. Physicians must consider each patient's
situation when determining appropriate duration of
prophylaxis.
Patients who have had rheumatic carditis are at a
relatively high risk for recurrences of carditis and
are likely to sustain serious cardiac involvement
with each recurrence. Therefore, patients who have
had rheumatic carditis should receive long-term
antibiotic prophylaxis well into adulthood and perhaps for life. Prophylaxis should continue even
after valve surgery, including prosthetic valve
replacement, because these patients remain at risk
of recurrence of rheumatic fever.
In contrast, patients who have not had rheumatic
carditis are at considerably less risk of cardiac
involvement with a recurrence. Therefore, a physician may wish to discontinue prophylaxis in these
patients after several years. In general, prophylaxis
should continue until the patient is in his or her
early 20s and five years have elapsed since the last
rheumatic attack. The decision to continue prophylaxis should be made after discussion with the
patient of potential risks and benefits and careful
consideration of the epidemiological risk factors
enumerated above.
AHA Scientific Council
TABLE 2. Secondary Prevention of Rheumatic Fever (Prevention
of Recurrent Attacks)
Agent
Dose
Mode
Benzathine
1,200,000 units
intramuscular every
penicillin G
four weeks*
or
Penicillin V
250 mg twice daily
oral
or
Sulfadiazine
0.5 g once daily for
oral
patients <60 lb
1.0 g once daily for
patients >60 lb
For individuals allergic to penicillin and sulfadiazine:
Erythromycin 250 mg twice daily
oral
*In high-risk situations, administration every three weeks is
advised.
Downloaded from http://circ.ahajournals.org/ by guest on June 14, 2017
Choice of Program for Prevention of Recurrent
Rheumatic Fever
Intramuscular Benzathine Penicillin G
An injection of 1,200,000 units of this long-acting
penicillin preparation every four weeks is the recommended method of secondary prevention. In countries where incidence of acute rheumatic fever is
particularly high, or in certain high-risk patients, use
of benzathine penicillin G every three weeks may be
warranted. Long-acting penicillin is of particular
value in patients with a high risk of rheumatic fever
recurrence, especially those with rheumatic heart
disease in whom recurrence is more dangerous. In
each patient, the advantages of benzathine penicillin
G must be weighed against inconvenience to the
patient and pain of injection, which may cause some
patients to discontinue prophylaxis.
Oral Agents
Successful oral prophylaxis depends primarily on
patient compliance. Patients need careful and
repeated instructions about the importance of continuing prophylaxis. Most failures of prophylaxis
occur in noncompliant patients. Even with optimal
compliance, risk of recurrence is still higher in
those on regular oral prophylaxis compared to those
receiving intramuscular benzathine penicillin G. Oral
agents are more appropriate for patients at lower
risk for rheumatic recurrence. Accordingly, some
physicians elect to switch patients to oral prophylaxis when they have reached late adolescence or
young adulthood and have remained free of rheumatic attacks for at least five years. In the doses
recommended below, sulfadiazine and oral penicillin are about equally effective.
Sulfadiazine. The dosage is 1.0 g once daily for
patients over 60 lb (27 kg) and 0.5 g once daily for
patients under 60 pounds. Reactions are infrequent
and usually minor. Blood counts may be advisable
two weeks after starting prophylaxis, as leukopenia
has been reported. Prophylaxis with sulfonamides is
contraindicated in late pregnancy because of transplacental passage and competition with bilirubin for
Prevention of Rheumatic Fever
1085
neonatal albumin-binding sites.* Data comparing sulfadiazine and other sulfonamides are not available.
Penicillin V. The dosage is 250 mg twice daily.
Penicillin V is the preferred form of oral penicillin
because it is relatively resistant to gastric acid.
Allergic reactions are similar to those with intramuscular penicillin. Anaphylaxis is rare in patients
receiving oral penicillin.
Note: Allergic reactions to penicillin are more
common in adults than children. They occur in only
a small percentage of patients, are more frequent
after injection, and include urticaria and angioneurotic edema. A serum sickness-like reaction characterized by fever and joint pains may be mistaken for
acute rheumatic fever. As with all penicillins, anaphylaxis, although rare, may occur. A careful history for
allergic reactions to penicillin should be obtained.
Other Drugs. For the exceptional patient who may
be allergic to both penicillin and sulfonamides, erythromycin may be used. An appropriate dose has not
been established, but 250 mg twice daily is suggested.
Bacterial Endocarditis Prophylaxis
Patients with evidence of rheumatic valvular heart
disease also require additional short-term antibiotic
prophylaxis before some surgical and dental procedures to prevent possible development of bacterial
endocarditis. Antibiotic regimens used to prevent
recurrences of acute rheumatic fever are inadequate
for prevention of bacterial endocarditis. These
patients should be protected by administration of
appropriate antibiotics in recommended doses.
Patients with prosthetic valves are at particularly
high risk. The current recommendations of the
American Heart Association concerning prevention
ofbacterial endocarditis should be followed. Patients
who have had rheumatic fever but do not have
evidence of rheumatic heart disease do not need
endocarditis prophylaxis.
Special Problems
There is uncertainty about the most appropriate
management of treatment failures, chronic carriers,
and contacts.
Treatment Failures
Failure to eradicate Group A streptococci from the
throat usually occurs more frequently after oral
antibiotic treatment than after administration of intramuscular benzathine penicillin G. Because risk of
acute rheumatic fever is low in most US populations,
and most patients who fail treatment are streptococcal carriers, post-treatment throat cultures are
now indicated only in patients who are at unusually
high risk for rheumatic fever, who remain symptom*Use of Sulfonamides for Rheumatic Fever Prophylaxis During Pregnancy. A statement by the Committee on Rheumatic
Fever and Bacterial Endocarditis of the Council on Cardiovascular Disease in the Young: Ayoub EM, Shulman ST. Dallas,
American Heart Association, 1981.
1086
Special Report Circulation Vol 78, No 4, October 1988
atic, or who develop recurring symptoms. Repeated
courses of antibiotic therapy are not indicated in
asymptomatic patients who continue to harbor Group
A streptococci after appropriate therapy, except in
rheumatic individuals, members of their families, or
other epidemiological circumstances.
Downloaded from http://circ.ahajournals.org/ by guest on June 14, 2017
Carriers
Chronic carriers usually do not need antibiotic
treatment. However, a difficult diagnostic problem
arises when carriers develop symptomatic upper
respiratory tract viral infections. It is frequently not
possible to determine whether Group A streptococci isolated from a carrier indicates current streptococcal infection or identifies that individual as a
chronic carrier. Thus, it is often reasonable to
administer a single course of therapy.
Streptococcal carriers appear to pose little threat
to themselves in developing sequelae of streptococcal infection, or in disseminating the organism to
those who live and work around them. Therefore,
streptococcal carriers usually do not need to be
identified or treated.
Asymptomatic Contacts
In most circumstances, identification and treatment of asymptomatic household contacts are not
indicated. However, in households with a rheumatic individual, or special epidemiological circumstances, it is advisable to obtain cultures and treat
those with positive cultures.
Selected References
Books
Shulman ST (ed): Pharyngitis: Management in an Era of Declining Rheumatic Fever. Philadelphia, Praeger Pubs, 1984
Breese BB, Hall C: Beta Hemolytic Streptococcal Diseases.
Boston, Houghton Mifflin, 1980
Stollerman GH: Rheumatic Fever and Streptococcal Infection.
New York, Grune & Stratton Inc, 1975
Markowitz M, Gordis L: Rheumatic Fever, ed 2. Philadelphia,
WB Saunders Co, 1972
Book Chapters and Articles
Krause RM: Streptococcal diseases, in Wyngaarden JB, Smith
LH (eds): Cecil's Textbook of Medicine, ed 18. Philadelphia,
WB Saunders Co, 1988, pp 1572-1580
Bisno AL: Rheumatic fever, in Wyngaarden JB, Smith LH (eds):
Cecil's Textbook of Medicine, ed 18. Philadelphia, WB Saunders Co, 1988, pp 1580-1586
Markowitz M: Rheumatic fever, in Behrman RE, Vaughn VC III
(eds): Nelson Textbook of Pediatrics, ed 13. Philadelphia, WB
Saunders Co, 1987, pp 539-543
Wannamaker LW, Kaplan EL: Acute rheumatic fever, in Adams
FH, Emmanouilides GC (eds): Moss' Heart Disease in Infants,
Children, and Adolescents, ed 3. Baltimore, Williams and
Wilkins Co, 1983, pp 534-552
Veasy GL, Wiedmeier SE, Orsmond GS, Ruttenburg HD, Boucek MM, Roth SJ, Tait VF, Thompson JA, Daly JA, Kaplan
EL, Hill HR: Resurgence of acute rheumatic fever in the
intermountain area of the United States. N EngI J Med
1987 ;3 16:421-427
American Heart Association Publications
Prevention of bacterial endocarditis. A statement for health
professionals by the Committee on Rheumatic Fever and
Infective Endocarditis of the Council on Cardiovascular Disease in the Young: Shulman ST, Amren DP, Bisno AL, Dajani
AS, Durack DT, Gerber MA, Kaplan EL, Millard HD, Sanders WE, Schwartz RH, Watanakunakorn C. Special report.
Circulation 1984;70:1123A-1 127A
Ad hoc committee to revise the Jones Criteria (modified) of the
Council on Rheumatic Fever and Congenital Heart Disease of
the American Heart Association: Jones criteria (revised) for
guidance in the diagnosis of rheumatic fever. Circulation
1984;69:203A-208A
Wannamaker LW: A method for culturing beta hemolytic streptococci from the throat. Circulation 1965;32:1054-1058
Prevention of rheumatic fever. A statement for health professionals by the Committee on
Rheumatic Fever, Endocarditis, and Kawasaki Disease of the Council on Cardiovascular
Disease in the Young, the American Heart Association.
A S Danjani, A L Bisno, K J Chung, D T Durack, M A Gerber, E L Kaplan, H D Millard, M F
Randolph, S T Shulman and C Watanakunakorn
Downloaded from http://circ.ahajournals.org/ by guest on June 14, 2017
Circulation. 1988;78:1082-1086
doi: 10.1161/01.CIR.78.4.1082
Circulation is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231
Copyright © 1988 American Heart Association, Inc. All rights reserved.
Print ISSN: 0009-7322. Online ISSN: 1524-4539
The online version of this article, along with updated information and services, is located on
the World Wide Web at:
http://circ.ahajournals.org/content/78/4/1082.citation
Permissions: Requests for permissions to reproduce figures, tables, or portions of articles originally
published in Circulation can be obtained via RightsLink, a service of the Copyright Clearance Center, not the
Editorial Office. Once the online version of the published article for which permission is being requested is
located, click Request Permissions in the middle column of the Web page under Services. Further
information about this process is available in the Permissions and Rights Question and Answer document.
Reprints: Information about reprints can be found online at:
http://www.lww.com/reprints
Subscriptions: Information about subscribing to Circulation is online at:
http://circ.ahajournals.org//subscriptions/