Secondary Prevention Of Rheumatic Fever Research Articles

Adherence to secondary prevention of rheumatic fever and rheumatic heart disease in young people: an 11‐year retrospective study

Objectives:To evaluate the secondary prevention of acute rheumatic fever (ARF) and rheumatic heart disease (RHD) in the Townsville region, Australia. Methods:Adherence to benzathine benzylpenicillin G (BPG) was determined for 196 children and young adults aged under 22 years between January 2009 and December 2019, and factors associated with BPG adherence were analysed. Secondary outcomes included attendance at specialist reviews and echocardiograms. Results:Adequate adherence (80%) to regular BPG injections was met by 51.1% of the cohort. Adequate BPG adherence more likely occurred for those that attended the Paediatric Outreach Clinic (OR4.15, 95%CI:2.13‐8.05) or a school delivery program (OR1.87, 95%CI:1.11‐3.45). People with moderate/severe RHD had greater BPG adherence (OR1.76,95%CI:1.00‐3.10). People in rural/remote areas were less likely to have adequate BPG adherence compared to urban counterparts (OR0.31, 95%CI:0.15‐0.65). Adherence to echocardiography was 66% and specialist review attendance was 12.5–50%. Conclusion:Half of the cohort in the Townsville region received adequate BPG prophylaxis to prevent ARF/RHD. Although rates were relatively higher than those reported in other Australian regions, health delivery goals should be close to 100%. Low attendance at specialist services was reported. Implication for public health:Delivery models with dedicated services, case management and family support could improve BPG adherence in individuals with ARF/RHD. Further resources in rural and remote areas are needed.

Study of the relation between serum levels of long-acting penicillin and the inflammatory markers: C-reactive protein and interleukin-6 in patients with chronic rheumatic heart disease

BackgroundThere is an evidence of a chronic inflammatory state in patients with chronic rheumatic valvular heart disease (RHD) as shown by high serum levels of high-sensitivity C-reactive protein (hs-CRP) and interleukin-6 (IL6). Despite the efficacy of long-acting penicillin (LAP) in secondary prevention of rheumatic fever, its effect on this inflammatory state is still unknown. So, we sought to study the effect of LAP on the inflammatory markers, CRP and IL-6, in patients with chronic rheumatic heart disease.ResultsEighty RHD patients coming to our hospital’s outpatient clinic for rheumatic fever secondary prophylaxis by regular administration of LAP were enrolled in the study. Patients were divided into 3 groups: group A, 70 patients with RHD already on prophylactic LAP, group B, 10 patients with RHD who have not yet started prophylactic LAP, and group C, control group of 10 healthy individuals not known to have RHD. Serum levels of LAP, IL-6, and CRP were measured for the three groups.Group A had significantly lower IL-6 levels than group B (25.22 ± 33.50 vs. 126.1 ± 33.76nng/ml, respectively, p < 0.0001). IL-6 levels were significantly lower in control subjects compared to patients in group B (3.600 ± 2.319, 25.22 ± 33.50 ng/ml, respectively, p < 0.0001). However, IL-6 levels in the control group were lower but non-significantly different compared to group A. CRP level was lower in group A than group B (8419 ± 4935 vs. 14400 ± 3375 mg/dl, respectively, p = 0.0002). CRP levels were significantly lower in control subjects compared to patients in group A and group B. IL-6 values were positively correlated with CRP values (r = 0.6387, p < 0.0001).CRP values were negatively correlated with LAP values (r = -0.5277, p < 0.0001). IL-6 values were negatively correlated with LAP values (r = − 0.4401, p < 0.0001). There was a highly significant difference between LAP level in compliant and non-compliant patients (1.045 ± 1.270 vs. 0.0785 ± 0.1057 ng/ml, respectively, p value < 0.0001).There was also a highly significant difference between CRP level in compliant and non-compliant patients (7640 ± 4558 vs. 13090 ± 4717 mg/dl, respectively, p = 0.005). Moreover, there was a significant difference between IL-6 levels in compliant and non-compliant patients (21.53 ± 32.70 vs. 47.40 ± 30.91 ng/ml, respectively, p value 0.03).ConclusionSerum LAP has a strong negative correlation with IL-6 and CRP levels. Regular administration of LAP strongly ameliorates the inflammatory state seen in patients with RHD.

P3130Relation between serum levels of long acting penicillin and the inflammatory markers: High sensitivity C-reactive protein and interleukin-6 in patients with chronic rheumatic heart disease

Abstract Background There is evidence of a chronic inflammatory state in patients with chronic rheumatic valvular heart disease (RhD) as shown by high serum levels of high sensitivity C-reactive protein (CRP) and interleukin-6 (IL6). Despite the efficacy of long acting penicillin (LAP) in secondary prevention of rheumatic fever, its effect on this inflammatory state is still unknown Objective We sought to study the effect of (LAP) on the inflammatory markers, (CRP) and (IL-6), in patients with chronic rheumatic heart disease. Methods Eighty patients having (RhD) patients coming to our university hospitals outpatient clinic for rheumatic fever secondary prophylaxis by regular administration of (LAP) were enrolled in. the study. Patients were divided into to 3 groups: Group A; 70 patients with (RhD) already on prophylactic (LAP), Group B; 10 patients with (RhD) who have not yet started prophylactic (LAP), Group C; control group of 10 healthy individuals not known to have (RhD). Serum levels of (LAP), (IL6) and (CRP) were measured for the three groups. Results . Group A had significantly lower (IL6) levels than group B (25.22±33.50 vs. 126.1±33.76ng/ml, respectively, p&lt;0.0001). (IL6) levels were significantly lower in control subjects compared to patients in group B (3.600±2.319, 25.22±33.50 ng/ml respectively, p&lt;0.0001). However, IL6 levels in the control group were lower but non-significantly different compared to Group A . (CRP) level was lower in group A than group B (8419±4935 vs. 14400±3375mg/dl respectively, p=0.0002). (CRP) levels were significantly lower in control subjects compared to patients in group A and group B. (IL6) values were positively correlated with (CRP) values (r=0.6387, p&lt;0.0001). (CRP) level negatively correlated with Long acting penicillin level (r=−0.5277, p&lt;0.0001). (IL-6) level negatively correlated with (LAP) level (r=−0.4401, p&lt;0.0001). There was a highly significant difference between (LAP) level in compliant and non-compliant patients (1.045±1.270 vs. 0.0785±0.1057ng/ml, respectively, p value &lt;0.0001). There was also a highly significant difference between (CRP) level in compliant and non-compliant patients (7640±4558 vs. 13090±4717 mg/dl, respectively, p value 0.005).Moreover, there was a significant difference between (IL-6) levels in compliant and non-compliant patients (21.53±32.70 vs. 47.40±30.91 ng/ml, respectively, p value 0.03). Conclusion Serum (LAP) has a strong negative correlation with (IL-6) and (CRP) levels. Regular administration of (LAP) strongly ameliorates the inflammatory state seen in patients with (RhD).

How Many Doses Make a Difference? An Analysis of Secondary Prevention of Rheumatic Fever and Rheumatic Heart Disease.

BackgroundAcute rheumatic fever (ARF) and rheumatic heart disease cause substantial burdens worldwide. Long‐term antibiotic secondary prophylaxis is used to prevent disease progression, but evidence for benefits of different adherence levels is limited. Using data from northern Australia, we identified factors associated with adherence, and the association between adherence and ARF recurrence, progression to rheumatic heart disease, worsening or improvement of rheumatic heart disease, and mortality.Methods and ResultsFactors associated with adherence (percent of doses administered) were analyzed using logistic regression. Nested case–control and case–crossover designs were used to investigate associations with clinical outcomes; conditional logistic regression was used to estimate odds ratios (OR) with 95% CIs Adherence estimates (7728) were analyzed. Being female, younger, having more‐severe disease, and living remotely were associated with higher adherence. Alcohol misuse was associated with lower adherence. The risk of ARF recurrence did not decrease until ≈40% of doses had been administered. Receiving <80% was associated with a 4‐fold increase in the odds of ARF recurrence (case–control OR: 4.00 [95% CI: 1.7–9.29], case–crossover OR: 3.31 [95% CI: 1.09–10.07]) and appeared to be associated with increased all‐cause mortality (case–control OR: 1.90 [95% CI: 0.89–4.06]; case–crossover OR 1.91 [95% CI: 0.51–7.12]).ConclusionsWe show for the first time that increased adherence to penicillin prophylaxis is associated with reduced ARF recurrence, and a likely reduction in mortality, in our setting. These findings can motivate patients to receive doses since even relatively low adherence can be beneficial, and additional doses further reduce adverse clinical outcomes.

Amoxicillin for the secondary prevention of rheumatic fever in children not allergic to penicillin

Amoxicillin for the secondary prevention of rheumatic fever in children not allergic to penicillin To the Editor: In October 2014, a communication from the Department of Health substituted azithromycin for erythromycin for penicillin-allergic patients. This was for certain conditions including acute rheumatic fever and prophylaxis of rheumatic fever. It has recently been suggested that owing to the challenges with the availability of oral penicillin, azithromycin should be used as a penicillin substitute for patients who are not allergic to penicillin. In our opinion it is inappropriate to substitute a macrolide for another form of penicillin (amoxicillin) in this situation. The primary reason is that despite many decades of use, there is no significant group A beta-haemolytic streptococcal (GABHS) resistance to penicillin. There are, however, increasing reports of GABHS resistance to macrolides, and azithromycin in particular.[1-4] A previously reported randomised trial[5] of 125 mg phenoxymethylpenicillin (pen VK) or amoxicillin given three times a day for 10 days to children with GABHS pharyngitis demonstrated that the recurrence of the original GABHS within 21 days after the end of therapy was higher with pen VK (20%) than with amoxicillin (13%). The geometric mean minimum inhibitory concentrations for amoxicillin and pen VK against 88 isolates of GABHS were 0.008 and 0.009 μg/mL, respectively. The mean concentrations of amoxicillin and pen VK in sera after 125 mg doses were 3.86 μg/ mL and 1.74 μg/ mL, respectively. In this study, therefore, amoxicillin was active against Gram-positive organisms at an inhibitory level similar to that of pen VK, but had higher blood levels. This study suggests that amoxicillin is probably at least as good as pen VK for the treatment of GABHS pharyngitis. We therefore recommend, as per the South African Essential Drugs List, benzathine penicillin 600 000 units for children <30 kg and 1.2 million units for children ≥30 kg by intramuscular injection every 28 days for the secondary prevention of rheumatic fever. If it is not advisable to use an intramuscular form of penicillin (for example with a patient on warfarin), then in the absence of pen VK and in the absence of penicillin allergy, children weighing <20 kg should be given amoxicillin 125 mg twice daily, and children weighing ≥20 kg given 250 mg twice daily. There is no defined azithromycin paediatric dosage for the secondary prevention of rheumatic fever in penicillin allergy. Azithromycin has however been dosed long term in clinical trials in children with cystic fibrosis.[6-8] There is no consensus on the dosage, but there is some support[6-9] for 250 mg once daily (<40 kg) or 500 mg once daily (≥40 kg) three times a week (Monday, Wednesday and Friday). We recommend that azithromycin is used for the secondary prevention of rheumatic fever only in children who are allergic to penicillin and is dosed 250 mg (<40 kg) or 500 mg (≥40 kg), once a day three times a week (Monday, Wednesday and Friday).

Amoxicillin for the secondary prevention of rheumatic fever in children not allergic to penicillin

To the Editor: In October 2014, a communication from the Department of Health substituted azithromycin for erythromycin for penicillin-allergic patients. This was for certain conditions including acute rheumatic fever and prophylaxis of rheumatic fever. It has recently been suggested that owing to the challenges with the availability of oral penicillin, azithromycin should be used as a penicillin substitute for patients who are not allergic to penicillin.

Allergic reaction to long – term Benzathine penicillin injection for secondary prevention of acute rheumatic fever and recommendations for skin testing

Background Rheumatic Fever (RF) causes 25-40% of all cardio vascular disease in developing countries. Long term benzathine penicillin injection is being used for secondary prophylaxis of RF / RHD. Although allergic reaction to penicillin is rare skin testing is performed routinely before each and every penicillin injection delivery in most of the hospitals in Nepal. Objectives Objectives of this study was to evaluate safety of long term benzathine penicillin injection and establish recommendations for penicillin skin testing. Methods Data from the registers of National RF/RHD prevention and control programme from 32 hospitals of Nepal were collected and analyzed in a retrospective study. Results 65 patients (1.4%) among 77300 injections of benzathine penicillin given to 4712 patients, had allergic reactions. 5 had anaphylaxis, an incidence of 0.1% (0.7/10000 injections), 60 had minor allergy, an incidence of 1.3%. Conclusions Life-threatening allergic reactions are very rare in patients on long-term intramuscular benzathine penicillin for secondary prevention of RF. With these rare complications, regular skin test before each and every benzathine penicillin injection delivery has no significant role. Nevertheless Skin testing is recommended before 1st injection and patients having different batch number and or brand name. DOI: http://dx.doi.org/10.3126/njh.v8i1.8331 Nepalese Heart Journal Vol.8(1) 2011 pp.16-18

Is Long Acting Penicillin Still Effective for Secondary Prevention of Rheumatic Fever?

Is Long Acting Penicillin Still Effective for Secondary Prevention of Rheumatic Fever?

Rheumatic Heart Disease: Progress and Challenges in India

Rheumatic heart disease, a neglected disease, continues to be a burden in India and other developing countries. It is a result of an autoimmune sequalae in response to group A beta hemolytic streptococcus (GAS) infection of the pharynx. Acute rheumatic fever (RF), a multisystem inflammatory disease, is followed by rheumatic heart disease (RHD) and has manifestations of joints, skin and central nervous system involvement. A review of epidemiological studies indicates unchanged GAS pharyngitis and carrier rates in India. The apparent decline in RHD rates in India as indicated by the epidemiological studies has to be taken with caution as methodological differences exist among studies. Use of echocardiography increases case detection rates of RHD in population surveys. However, the significance of echo based diagnosis of carditis needs further evaluation to establish the significance. Research in this area through prospective follow up studies will have to be undertaken by the developing countries as the interest of developed countries in the disease has waned due the declined burden in their populations. Prevention of RHD is possible through treatment of GAS pharyngitis (primary prophylaxis) and continued antibiotic treatment for number of years in patients with history of RF to prevent recurrences (secondary prophylaxis). The cost effectiveness and practicality of secondary prophylaxis is well documented. The challenge to any secondary prophylaxis program for prevention of RF in India will be the availability of benzathine penicillin G and dissipation of fears of allergic reactions to penicillin among practitioners, general public and policy makers. The authors review here the progress and challenges in epidemiology, diagnosis and primary and secondary prevention of RF and RHD.

Once weekly azithromycin in secondary prevention of rheumatic fever

Rheumatic fever and rheumatic heart disease (RHD) are still important problems in developing countries. Secondary prophylaxis which is the most cost-effective method in preventing recurrences of rheumatic fever is fraught with problems of drug compliance. The utility of 500 mg once weekly azithromycin (AZT), an orally effective long-acting antibiotic was evaluated against oral penicillin (phenoxy methyl penicillin 250 mg twice daily) in this study. Forty-eight consecutive patients (44% males, mean age 29.4 years) with established RHD were randomised into two groups-26 patients received AZT and 22 received oral penicillin. Patients were evaluated at randomisation, at 1 month, 3 months, and 6 months, clinically, serologically and by throat swab culture. End points were absence of streptococcal colonisation, infection or fever at the end of 6 months. During the study, 4 patients (15.4%) in the AZT group developed sore throat and fever, had positive throat culture and positive serology indicating streptococcal infection. None satisfied the criteria for rheumatic fever reactivation. None in the oral penicillin group developed streptococcal infection. In conclusion, weekly 500 mg of AZT is not effective in the prevention of streptococcal throat infection compared to oral penicillin therapy in adult patients with established RHD.

The Cochrane Library and the Treatment of Sore Throat in Children and Adolescents: An Overview of Reviews

AbstractBackgroundSore throat is a common respiratory tract symptom responsible for 6% of children's visits to pediatricians or family physicians. Even though sore throat is usually self‐limiting, antibiotics are often prescribed in hopes of decreasing symptom length and the risk of developing sequelae. However, antibiotic over‐prescription could lead to adverse events in individuals and bacterial resistance in the community, so the efficacy and safety of antibiotics must first be established, and alternative treatment options should also be investigated.ObjectivesThis overview of reviews aims to synthesize evidence from the Cochrane Database of Systematic Reviews (CDSR) on the efficacy and safety of different antibiotic treatment strategies (standard antibiotics, delayed antibiotics, short‐duration antibiotics and different types of antibiotics) to improve symptoms of sore throat in children and adolescents. The efficacy and safety of two other treatments, steroids and Chinese herbal medicine, are also investigated.MethodsIssue 1, 2011 of the CDSR was searched for all reviews examining the treatment of sore throat and disorders which commonly have sore throat as part of their clinical presentation. We also searched for reviews examining the prevention of important sequelae of sore throat. All systematic reviews examining pharmacologic or non‐pharmacologic treatments in children were identified, and data were extracted, compiled into tables and synthesized using quantitative and qualitative methods.Main resultsData pertaining to sore throat in children and adolescents were extracted from seven Cochrane reviews. Antibiotics provided only modest benefit over placebo for symptoms of sore throat and fever. Immediate versus delayed prescription of antibiotics resulted in a 58% decrease in severity of pain due to sore throat on day three (RR: 0.42; 95% CI: 0.33, 0.54), and a significant, moderate decrease in fever on day three (SMD: − 0.53; 95% CI: − 0.74, − 0.31). Most studies of macrolides, cephalosporins and carbacephem showed no significant benefit over oral penicillin for resolution of symptoms, but in two trials a short course of a cephalosporin compared to oral penicillin led to modest decreases in both sore throat (half a day; MD: − 0.50; 95% CI: − 0.78, − 0.22) and fever (seven hours; MD: − 0.30; 95% CI: − 0.45, − 0.14). Steroids compared to placebo decreased symptoms of sore throat in children with infectious mononucleosis at 12 hours (RR: 0.54; 95% CI: 0.30, 0.99) but not at any other measured time points. A higher rate of vomiting was associated with delayed antibiotics (RR: 0.07; 95% CI: 0.03, 0.20); vomiting, diarrhea and abdominal pain were associated with short‐duration antibiotics (RR: 1.74; 95% CI: 1.31, 2.32); and overall adverse effects were associated with macrolides (RR: 2.19; 95% CI: 1.04, 4.61). Trials involving Chinese herbal medications for sore throat were of low quality and no good evidence for the use of these agents was available.Antibiotics compared to placebo were associated with lower rates of acute rheumatic fever, but the difference was not statistically significant when only pediatric data were included (RR: 0.20: 95% CI: 0.01, 4.18). One review examining the secondary prevention of rheumatic fever found that intramuscular versus oral penicillin reduced the recurrence of rheumatic fever by 92% (RR: 0.08; 95% CI: 0.04, 0.18) and significantly reduced the number of participants who developed streptococcal throat infections (RR: 0.22; 95% CI: 0.17, 0.27; I2: 81%).Authors' ConclusionsEvidence from the CDSR suggests that antibiotics provide only modest improvements in symptoms of sore throat in children and adolescents. If antibiotics are prescribed, macrolides are less ideal compared to other agents, and there is some evidence that a short course of a newer cephalosporin may be slightly better than a standard course of penicillin. Any potential benefit of antibiotic treatment must be weighed against the cost of treatment and the possibility of adverse effects. Children with a past history of rheumatic fever or those living in a region with a high prevalence of this condition are more likely to benefit from antibiotics than those without these risk factors. Oral corticosteroids can decrease sore throat symptoms within the first day and may be helpful for children with severe symptoms of infectious mononucleosis. There is no compelling evidence that any Chinese herbal medicine has beneficial effects for the relief of sore throat symptoms or prevention of sequelae. Copyright © 2011 The Cochrane Collaboration. Published by John Wiley &amp; Sons, Ltd. The Cochrane Collaboration

Prevention of Rheumatic Fever and Diagnosis and Treatment of Acute Streptococcal Pharyngitis

Primary prevention of acute rheumatic fever is accomplished by proper identification and adequate antibiotic treatment of group A β-hemolytic streptococcal (GAS) tonsillopharyngitis. Diagnosis of GAS pharyngitis is best accomplished by combining clinical judgment with diagnostic test results, the criterion standard of which is the throat culture. Penicillin (either oral penicillin V or injectable benzathine penicillin) is the treatment of choice, because it is cost-effective, has a narrow spectrum of activity, and has long-standing proven efficacy, and GAS resistant to penicillin have not been documented. For penicillin-allergic individuals, acceptable alternatives include a narrow-spectrum oral cephalosporin, oral clindamycin, or various oral macrolides or azalides. The individual who has had an attack of rheumatic fever is at very high risk of developing recurrences after subsequent GAS pharyngitis and needs continuous antimicrobial prophylaxis to prevent such recurrences (secondary prevention). The recommended duration of prophylaxis depends on the number of previous attacks, the time elapsed since the last attack, the risk of exposure to GAS infections, the age of the patient, and the presence or absence of cardiac involvement. Penicillin is again the agent of choice for secondary prophylaxis, but sulfadiazine or a macrolide or azalide are acceptable alternatives in penicillin-allergic individuals. This report updates the 1995 statement by the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee. It includes new recommendations for the diagnosis and treatment of GAS pharyngitis, as well as for the secondary prevention of rheumatic fever, and classifies the strength of the recommendations and level of evidence supporting them.

Protocols for antibiotic use in primary and secondary prevention of rheumatic fever.

The prevention of the first attack of RF requires antibiotic treatment of suspected or proven streptococcal throat infection or tonsillitis in children between the ages of 3 and 15 years. In communities where RF is endemic, all cases of sore throat in children 3 15 years of age should be regarded as a streptococcal infection and be treated as such unless any one of the following clinical characteristics, which indicate that the sore throat should not be diagnosed as a ‘strep’ throat, is present: ulceration, hoarseness, watery nasal secretion, and/or conjunctivitis. Children not diagnosed with streptococcal pharyngitis should be treated symptomatically. If laboratory services are available, diagnosis of ‘strep’ sore throat should be confirmed microbiologically, but this confirmation should not delay the initiation of treatment. The recommended treatment of ‘strep’ throat is set out in Table I.

Intramuscular penicillin is more effective than oral penicillin in secondary prevention of rheumatic fever--a systematic review.

People with a history of rheumatic fever (RF) are at high risk of recurrent attacks and of developing rheumatic heart disease following a streptococcal throat infection. Giving penicillin to these people can prevent recurrent attacks of RF and subsequent rheumatic heart disease. However, there is no agreement on the most effective method of giving penicillin. To assess the effects of different penicillin regimens and formulations for preventing streptococcal infection and RF recurrence. We searched the Controlled Trials Register (Cochrane Library Issue 2, 2001), Medline (January 1966-July 2000), Embase (January 1985-July 2000), reference lists of articles, and contacted experts in the field. Randomised and quasi-randomised studies comparing: (i) oral with intramuscular penicillin; and (ii) 2- or 3-weekly with 4-weekly intramuscular penicillin in patients with previous RF. Two reviewers independently assessed trial quality and extracted data. Six studies were included (1,707 patients). Data were not pooled because of clinical and methodological heterogeneity of the trials. Four trials (1,098 patients) compared intramuscular with oral penicillin and all showed that intramuscular penicillin was more effective in reducing RF recurrence and streptococcal throat infections than oral penicillin. One trial (360 patients) compared 2-weekly with 4-weekly intramuscular penicillin. Penicillin given every 2 weeks was better at reducing RF recurrence (relative risk (RR) 0.52, 95% confidence interval (CI): 0.33-0.83) and streptococcal throat infections (RR 0.60, 95% CI: 0.42-0.85). One trial (249 patients) showed that 3-weekly intramuscular penicillin injections reduced streptococcal throat infections (RR 0.67, 95% CI: 0.48-0.92) compared with 4-weekly intramuscular penicillin. Intramuscular penicillin seemed to be more effective than oral penicillin in preventing RF recurrence and streptococcal throat infections. Two-weekly or 3-weekly injections appeared to be more effective than 4-weekly injections. However, the evidence is based on poor-quality trials and the use of outdated formulations of oral penicillin.

Rheumatic Fever and Long-term Sequelae in Children.

Rheumatic fever and rheumatic heart disease continue unabated, affecting young individuals in most of the developing nations. Focal outbreaks of smaller magnitude have also been reported since the mid-1980s from industrialized western nations, where this disease had almost disappeared. The introduction of penicillin in the mid-1940s has markedly changed the natural history of rheumatic fever, although the incidence of rheumatic fever declined in developed nations even before that, mainly due to better living conditions. Treatment of rheumatic fever chiefly involves the use of antibiotics (penicillin) and anti-inflammatory drugs, like salicylates or corticosteroids, to eradicate Streptococci. Patients with severe carditis, congestive heart failure, or pericarditis are best treated with corticosteroids because these are more potent anti-inflammatory agents than salicylates. Salicylates may be sufficient for cases with mild or no carditis. The treatment must be continued for 12 weeks. Several studies have shown that valvular regurgitation, and not myocarditis, is the cause of congestive heart failure in active rheumatic carditis. Therefore, surgery with mitral valve replacement or repair is indicated in cases with intractable hemodynamics due to mitral regurgitation. The development of chronic valvular lesion after an episode of rheumatic fever is dependent upon the presence or absence of carditis in the previous attack and compliance with secondary prophylaxis. Recurrences due to inadequate penicillin prophylaxis are responsible for hemodynamically significant chronic valvular lesions requiring surgery. Primary prevention of rheumatic fever is fraught with difficulties and may not be feasible in most of the countries where the disease is rampant. Secondary prevention, ie, preventing recurrence of rheumatic fever, is the appropriate strategy with proven efficacy. A repository form of penicillin, benzathine penicillin G, given as an intramuscular injection at 3 weekly intervals in the dose of 1,200,000 U, remains the treatment of choice for secondary prevention of rheumatic fever. Alternative antibiotics may be used in those allergic to penicillin. An effective and safe vaccine against rheumatic fever is not yet available.

Penicillin for secondary prevention of rheumatic fever.

People with a history of rheumatic fever are at high risk of recurrent attacks of rheumatic fever and developing rheumatic heart disease following a streptococcal throat infection. Giving penicillin to these people can prevent recurrent attacks of rheumatic fever and subsequent rheumatic heart disease. However, there is no agreement on the most effective method of giving penicillin. To assess the effects of penicillin compared to placebo and the effects of different penicillin regimens and formulations for preventing streptococcal infection and rheumatic fever recurrence. We searched the Controlled Trials Register (Cochrane Library Issue 2, 2001), MEDLINE (1997 to July 2000), EMBASE (1998 to July 2000), reference lists of articles and we contacted experts in the field. Randomised and quasi-randomised studies comparing (i) penicillin with control, (ii) oral with intramuscular penicillin (iii) 2- or 3-weekly with 4-weekly intramuscular penicillin in patients with previous rheumatic fever. Two reviewers independently assessed trial quality and extracted data. Nine studies were included (n=3008). Data were not pooled because of heterogeneity. Overall, the methodological quality of included studies was poor. Three trials (n= 1301) compared penicillin with control. Only one of three studies showed that penicillin reduced rheumatic fever recurrence (RR 0.45, 95% CI 0.22 to 0.92) and streptococcal throat infection (RR 0.84, 95% CI 0.72 to 0.97). Four trials (n=1098) compared intramuscular with oral penicillin and all showed that intramuscular penicillin reduced rheumatic fever recurrence and streptococcal throat infections compared to oral penicillin. One trial (n= 360) compared 2-weekly with 4-weekly intramuscular penicillin. Penicillin given every two-weeks was better at reducing rheumatic fever recurrence (RR 0.52, 95% CI 0.33 to 0.83) and streptococcal throat infections (RR 0.60, 95% CI 0.42 to 0.85). One trial (n= 249) showed 3-weekly intramuscular penicillin injections reduced streptococcal throat infections (RR 0.67, 95% CI 0.48 to 0.92) compared to 4-weekly intramuscular penicillin. Intramuscular penicillin seemed to be more effective than oral penicillin in preventing rheumatic fever recurrence and streptococcal throat infections. Two-weekly or 3-weekly injections appeared to be more effective than 4-weekly injections. However, the evidence is based on poor quality of trials.

Bacteria-Triggered reactive arthritis: implications for antibacterial treatment.

Reactive arthritis (ReA) is definitely caused by an infection. Several observations suggest that the triggering microbe may persist in the tissues of the patient for a prolonged time. The obvious conclusion is to consider antibacterial treatment. In two instances antibacterial agents are of definite value: in the primary and secondary prevention of rheumatic fever and for early eradication of Borrelia burgdorferi in order to prevent development of the arthritis associated with Lyme disease. Altogether, clinical and experimental data exist to indicate that if antibacterial treatment of ReA can be started very early during the pathogenetic process, the disease can be prevented or the prognosis improved. In fully developed ReA, the value of antibacterial agents is less certain. All available evidence indicates that short term antibacterial treatment has no effect on the prognosis and final outcome of ReA, and the results with long term administration of antibacterials are also overall poor. In some instances sulfasalazine appears useful, rather as a result of its antirheumatic effect or influence on an underlying inflammatory bowel disease than its action as an antibacterial agent. Tetracyclines have also been found to have an effect on ReA, but again, this is probably due to their anti-inflammatory action rather than any antibacterial effect.

Long-term outcome of patients with rheumatic fever receiving benzathine penicillin G prophylaxis every three weeks versus every four weeks

Objective: To compare the efficacy of injections of 1.2 million units of benzathine penicillin G given every 3 weeks versus every 4 weeks for secondary prevention of rheumatic fever, based on the long-term outcome of patients receiving such prophylaxis. Methods: A total of 249 consecutive patients with rheumatic fever, randomly assigned to either a 3-week or a 4-week regimen, were examined every 3 to 6 months, and followed for 794 and 775 patient-years, respectively. Results: Compliance with each regimen was comparable: 83 (66.9%) of 124 patients in the 3-week group versus 92 (73.6%) of 125 patients in the 4-week group stayed in the program (p >0.05). Streptococcal infections occurred less frequently in those receiving the 3-week regimen: 7.5 versus 12.6 per 100 patient-years (p <0.01). Prophylaxis failed in 2 patients receiving the 3-week regimen and in 10 receiving the 4-week regimen (0.25 and 1.29 per 100 patient-years respectively; p = 0.015). Serum penicillin levels were adequate (≥0.02 μg/ml) in 100 (56%) of 179 samples obtained 21 days after penicillin injection in the 3-week regimen, and in 51 (33%) of 155 samples obtained 28 days after injection in the 4-week regimen (p <0.01). Of 71 patients with mitral regurgitation in the 3-week regimen, 47 (66%) no longer had the murmur; of 87 patients in the 4-week regimen, 40 (46%) no longer had the murmur (p <0.05). Conclusions: This 12-year controlled study indicates that the outcome of patients with rheumatic fever is better with a 3-week than with a 4-week penicillin prophylaxis regimen. Greater emphasis and more widespread use of the 3-week regimen should be recommended. (J PEDIATR 1994;125:812-6)

Clinician compliance and the prevention of bacterial endocarditis

Analysis of our data indicates confusion about, and lack of compliance with, the AHA recommendations. Clinician level of knowledge varies with issues of risk management and by specialty group membership. Patient groups that are particularly problematic include children and all patients with congenital heart disease, those receiving a continuing antibiotic regimen for secondary prevention of rheumatic fever, those with a penicillin allergy, and those with prosthetic heart valves. Another area of clinician uncertainty concerns dental procedures which may or may not be associated with the possible causation of bacterial endocarditis. The biodynamic principles involved in endocarditis are central to the structure of the AHA recommendations. These principles, as well as those which provide theoretical support for the loading dose, timing, sequence, and duration recommended by the AHA, have been presented with the hope that clinician compliance with these recommendations will be increased.

Disease Control Programs in the United States

Programs administered by health departments and heart associations for control of streptococcal and poststreptococcal disease differ greatly from state to state. The year 1974 was used as a representative year when studying the variety of state policies and programs regarding surveillance of streptococcal disease, primary and secondary prevention of rheumatic fever, and prevention of poststreptococcal glomerulonephritis. A uniform national policy for streptococcal control is desirable but should be based on evidence not now available concerning the impact of various elements of control programs on morbidity and mortality.