Rheumatic fever and rheumatic heart disease are the delayed consequence of an untreated group A beta-haemolytic Streptococcal infection of the upper respiratory tract. The disease can cause serious, debilitating damage to the heart and involve other tissues. Those people who have already suffered a rheumatic fever attack are extremely susceptible to a recurrence if they are again infected with group A streptococci.

Group A streptococcal infections are universally endemic. There is no available vaccine for group A infections, and preventive measures remain dependent upon accurate clinical diagnosis and appropriate antibiotic treatment. Although epidemics in nurseries and infection in younger children are reported, the majority of Streptococcal infections occur in school-age children between 5 and 15 years of age. Adult infections are most frequently observed in establishments, military bases or residential facilities.

Group A streptococcal upper respiratory tract infection is spread by droplets, thus accounting for its high transmission rate where crowding is frequent. Most outbreaks are associated with this kind of transmission, but food-borne transmission has also been reported. In contrast to other infectious agents, there are approximately 100 recognized serotypes of group A streptococci. Therefore, although infection with a given serotype is thought to confer long lasting type-specific immunity, the abundance of serotypes makes the threat of new infections a continuous worldwide public health problem.

Diagnosis, treatment and management

Young children, school-age children, and adults may present with significantly different clinical manifestations. An accurate clinical diagnosis of group A streptococcal upper respiratory tract infection can be very difficult and laboratory confirmation of the infection should be sought whenever possible. The classical signs and symptoms - high fever, severe pain on swallowing often accompanied by abdominal pain, nausea and vomiting - may not always be present, especially in endemic situations. Likewise, in young children under three years of age the presentation of streptococcal upper respiratory tract infection varies.

As difficult as it may be to clinically establish a diagnosis of acute streptococcal tonsillitis or pharyngitis, the signs and symptoms of this bacterial infection typically are quite different from those associated with viral upper respiratory tract infections. Culture using throat swabs continues to be the most useful method for determining the presence of group A streptococci in the upper respiratory tract although prior administration of antibiotics may result in a false-negative test-result.

Rapid antigen detection tests are available which allow the detection from the throat swab. Although antibody tests such as antistreptolysin O (ASO) and anti-deoxyribonuclease- B (anti-DNase B) are very useful in confirming diagnosis of rheumatic fever or acute glomerulonephritis, they are not indicated for the diagnosis of patients with acute group A streptococcal pharyngitis.

1. Primary prevention of rheumatic fever

In general, once the condition has been diagnosed, antibiotic therapy is indicated.

Penicillins

Penicillin remains the treatment of choice for group A streptococcal upper respiratory tract infections, since it is the only antibiotic that has been evaluated in controlled studies. A single injection of intramuscular benzathine benzylpenicillin is the most effective treatment in eradicating group A streptococci, probably due to its long duration of action. It can also be used for mass prophylaxis.

Oral phenoxymethylpenicillin administration for streptococcal pharyngitis must be continued for 10 days. Other orally administered penicillins include ampicillin, amoxicillin and the semisynthetic penicillins.

Macrolides

For penicillin-allergic patients, treatment with oral erythromycin for 10 days is often used. Newer macrolides are reported to be associated with fewer adverse effects but are generally more expensive. Short-course therapy with these newer macrolides is effective, but more definitive data are required before use in primary prevention is recommended.

Cefalosporins

First and second generation cefalosporins have been used to treat group A streptococcal infections. As a rule, cefalosporins are more expensive than penicillin. Short-course therapy (less than 10 days) with some cefalosporins is also under evaluation.

Resistance

No clinical isolate of group A streptococci has shown resistance to penicillin but resistance to macrolide antibiotics (e.g. erythromycin) is increasing in some countries. None the less, group A streptococcal resistance to the macrolides remains at less than five percent. Clinical use of macrolides should be made in relation to local resistance rates. Resistance to sulfonamides and tetracyclines is known to occur.

Recommended antibiotics

Table 1 shows commonly recommended antibiotics for the treatment of acute streptococcal pharyngitis for primary prevention of rheumatic fever. Sulfonamides or tetracyclines are not acceptable therapy for group A streptococcal pharyngitis.

Table 1: Treatment of Group A streptococcal pharyngitis (primary prevention of rheumatic fever)

If individuals remain symptomatic following a complete course of antibiotic therapy in which compliance was assured, a second course may be indicated. In these relatively rare instances, laboratory confirmation of the organism is advisable.

2. Secondary prophylaxis of rheumatic fever

For all individuals who have had an initial attack of rheumatic fever, whether or not they have rheumatic heart disease, continuous administration of an antibiotic is mandatory to prevent acquisition and infection of the upper respiratory tract by group A streptococci. Secondary prophylaxis reduces the risk of recurrent attacks with their attendant morbidity and mortality.

Antibiotic regimens for secondary prophylaxis differ. The regular intramuscular injection of benzathine benzylpenicillin is the most effective available treatment. Although usually given every four weeks, recent data indicate that 1 200 000 units of benzylbenzathine penicillin given every three weeks may be more effective in preventing recurrences of rheumatic fever, especially in high-risk patients. Commonly recommended antibiotics are set out in Table 2.

Table 2: Prevention of recurrence of rheumatic fever (secondary prophylaxis)

* Contraindicated in late pregnancy

Several technical factors related to the benzathine benzylpenicillin injection can affect its bioavailability. It is recommended that health workers are trained in the technique of giving injections. The injection should be made deep into the muscle as recommended. Superficial injections lead to the benzathine benzylpenicillin remaining in the subcutaneous tissue, resulting in decreased absorption and lower serum levels. Care should be taken that the entire content of the vial is injected.

For patients who are not able to receive injections of benzathine benzylpenicillin, a less effective method is oral phenoxymethylpenicillin daily. The potential problems with oral prophylaxis are adherence and rheumatic fever recurrence rates, which have been shown to be higher with this regimen than with intramuscular benzathine benzylpenicillin.

For patients known to be allergic to penicillin, an oral sulfonamide is recommended for secondary prophylaxis. However, it is not effective for treating established group A streptococcal infection. For individuals who cannot take either penicillin or sulfadiazine, erythromycin in a dose of 250 mg twice daily may be used, although resistance to erythromycin has been reported.

Duration of secondary prophylaxis

There are several variables that affect the likelihood of recurrences of rheumatic fever, including the time since the most recent attack, the age of the patient and the risk posed by the environment. The duration of secondary prophylaxis should be adapted to the individual patient but some general principles can be stated. Patients without carditis in a previous attack should continue prophylaxis for a minimum of five years after the last attack, and at least until age 18 and often longer if risk factors are high. Patients with cardiac involvement in the initial attack should continue prophylaxis at least until the age of 25 years, and longer if environmental conditions or other risk factors are present.

The general principles for secondary prophylaxis are:

For patients with chronic valvular rheumatic heart disease, secondary prophylaxis for prolonged periods, even for life, has sometimes been recommended. Antibiotic prophylaxis for secondary rheumatic fever should be continued through pregnancy. However, sulfonamides present a risk to the fetus and an alternative antibiotic (penicillin or erythromycin) should be substituted.