Rheumatic Fever Prophylaxis: A Three-year Study

An effective programme of secondary prophylaxis against rheumatic fever has been established in Barbados over the last three years. Relatively unsophisticated patients collaborated well over prolonged periods. Adequate secondary prophylaxis was achieved with monthly injections of benzathine penicillin, with a resultant decrease in the complication rate.A total of 84 admissions over 32 months from a population of some 60,000 children under the age of 12 emphasizes the need for registration and prophylactic treatment of children with rheumatic fever. The low yield in the survey of schoolchildren between the ages of 5 and 11 and the large number of personnel required for the survey suggest that it might be extended to include older age groups. Automatic screening devices should be used when possible so that more may be screened.     

RHEUMATIC FEVER IN COLLEGE STUDENTS

The results of three independent surveys concerned with rheumatic fever and heart disease in students at the University of California were assembled and found to be in close agreement. A full 2 per cent of all students believed they had had rheumatic fever; and several times that proportion gave a history of one of the rheumatic manifestations. Only 0.25 per cent had demonstrable rheumatic heart disease and 0.1 per cent had congenital heart disease.Physiologic murmurs may occur in 3 per cent or more of students entering college.Penicillin prophylaxis is important in persons with rheumatic heart disease, but it is important not to put a label of rheumatic heart disease on persons who think they have had rheumatic fever but who have no demonstrable heart disease. Long term penicillin prophylaxis or other long term prophylactic procedures directed against rheumatic fever are not indicated unless the diagnostic criteria for rheumatic fever are clearly met or unless rheumatic heart involvement is definitely present.     

Ethnic differences in mortality from acute rheumatic fever and chronic rheumatic heart disease in New Mexico, 1958-1982.

To examine time trends and differences in mortality rates from acute rheumatic fever and chronic rheumatic heart disease in New Mexico''s Hispanic, American Indian, and non-Hispanic white populations, we analyzed vital records data for 1958 through 1982. Age-adjusted mortality rates for acute rheumatic fever were low and showed no consistent temporal trends among the three ethnic groups over the study period. Age-adjusted and age-specific mortality rates for chronic rheumatic heart disease in Hispanic and non-Hispanic whites decreased over the 25-year period, although rates were higher among Hispanics than among non-Hispanics during most of the time period. In American Indians, age-adjusted mortality rates for chronic rheumatic heart disease increased between 1968 and 1977 to twice the non-Indian mortality rates during the same period. Despite this increase in mortality from chronic rheumatic heart disease among New Mexico''s American Indians from 1968 to 1977, the New Mexico data generally reflect national trends of decreasing mortality from chronic rheumatic heart disease.     

Rheumatic heart disease: future prospects

Acute rheumatic fever develops after an inadequate immune response to throat streptococcal infection that induces the production of antibodies reacting against cardiac endothelial cells. Valve damage may lead to irreversible cardiac valve sequela (rheumatic heart disease) with further evolution towards severe valve dysfunction and heart failure. The disease has been almost eradicated in Western countries with the development of living conditions and prevention policies, including primary prevention (treatment of sore throats) and secondary prevention (long term administration of antibiotics). However, rheumatic heart disease remains a major health problem in developing countries. Recently, echocardiography identified children with mild features of the disease, thereby allowing early treatment.     

Socioeconomic and Environmental Risk Factors among Rheumatic Heart Disease Patients in Uganda

Background

Although low socioeconomic status, and environmental factors are known risk factors for rheumatic heart disease in other societies, risk factors for rheumatic heart disease remain less well described in Uganda.

Aims and Objective

The objective of this study was to investigate the role of socio-economic and environmental factors in the pathogenesis of rheumatic heart disease in Ugandan patients.

Methods

This was a case control study in which rheumatic heart disease cases and normal controls aged 5–60 years were recruited and investigated for socioeconomic and environmental risk factors such as income status, employment status, distance from the nearest health centre, number of people per house and space area per person.

Results

486 participants (243 cases and 243 controls) took part in the study. Average age was 32.37+/−14.6 years for cases and 35.75+/−12.6 years for controls. At univariate level, Cases tended to be more overcrowded than controls; 8.0+/−3.0 versus 6.0+/−3.0 persons per house. Controls were better spaced at 25.2 square feet versus 16.9 for cases. More controls than cases were employed; 45.3% versus 21.1%. Controls lived closer to health centers than the cases; 4.8+/−3.8 versus 3.3+/−12.9 kilometers. At multivariate level, the odds of rheumatic heart disease was 1.7 times higher for unemployment status (OR = 1.7, 95% CI = 1.05–8.19) and 1.3 times higher for overcrowding (OR = 1.35, 95% CI = 1.1–1.56). There was interaction between overcrowding and longer distance from the nearest health centre (OR = 1.20, 95% CI = 1.05–1.42).

Conclusion

The major findings of this study were that there was a trend towards increased risk of rheumatic heart disease in association with overcrowding and unemployment. There was interaction between overcrowding and distance from the nearest health center, suggesting that the effect of overcrowding on the risk of acquiring rheumatic heart disease increases with every kilometer increase from the nearest health center.     

Rheumatic fever and rheumatic heart disease; incidence in California

The statistics quoted in this and other published reports appear to substantiate the impression that rheumatic fever in California, although still an important public health problem which varies widely from one locality to another, is of lower incidence and perhaps of more benign character than in most other parts of the United States. It also appears that in California aortic insufficiency may be of higher relative incidence and occurs more frequently as a clinically diagnosable sequel of rheumatic fever than does classical mitral stenosis. Congenital defects of the heart constitute a large proportion of the cases of organic heart disease in children and young adults in this state.     

Incidence of Heart Disease in Children in the City of Toronto

A special registry of children with heart disease in the City of Toronto was set up (a) to provide for follow-up of all children with heart disease in that community, (b) to remove the “cardiac” label from children with functional murmurs, (c) to acquaint parents with facilities available for the management of children with heart disease, and (d) to record useful data regarding heart disease in children.The 1961-62 Cardiac Registry showed that 542 of 156,775 pre-school and school children had evidence of heart disease; 464 were congenital and 68 rheumatic in origin: 121 children with congenital heart defects had been treated surgically. Congenital cardiac disease ranked fifth in frequency among the causes of death in children. There was a diminution of acute rheumatic fever and rheumatic heart disease in children in 1961-62 when compared with data for previous years. Seventy-eight per cent of children in this series with a history of rheumatic fever were receiving continuous prophylaxis.     

Acute Rheumatic Fever in Los Angeles County

There was a general downward trend in the reported incidence of acute rheumatic fever in Los Angeles County during the years 1954-1963. A survey of hospital records in five large hospitals in 1962 revealed 100 cases diagnosed, 39 of which were reported. Diagnoses in the charts reviewed conformed to the Modified Jones Criteria. Most of the patients were born in Los Angeles County.Mortality rates for acute rheumatic fever during the same period were greatly in excess of those expected from the reported morbidity. The mean crude mortality rate for the period concerned was higher than for New York City, although not as high as for Boston.Acute rheumatic fever appears to constitute a health problem in need of review in Los Angeles County.     

ABO Blood Groups in Patients with Congenital and Rheumatic Valvular Heart Disease

ABO blood groups were determined in 404 patients who had cardiac surgery for heart disease; 136 of these patients had rheumatic valvular heart disease and 268 had congenital heart disease. The incidence of each ABO blood group was compared to a control series of 2171 patients by means of the ϰ² test. There was no statistical difference in the incidence of ABO blood group when patients with congenital and rheumatic valvular heart disease were compared with the control group.     

A NOTE ON THE INCIDENCE OF RHEUMATIC FEVER IN LOS ANGELES

Nationwide campaigns to alert the public to the dangers of rheumatic heart disease carry the hazard that parents in some localities may become more alarmed than is warranted by the local rate of incidence of the disease; and the alarm of the parent may harm the child.In such circumstances physician and patient alike might be reassured if it could be ascertained that the incidence of rheumatic fever in a given community was relatively low.Application to the Los Angeles area of a statistical formula worked out from Coombs'' data on the incidence and death rate from the disease in England and from Ash''s data in Philadelphia, gave indication that the incidence of rheumatic fever in all age groups in Los Angeles is approximately 68 new cases a year—a relatively favorable figure in a population approaching two million.     

Genetic susceptibility to acute rheumatic fever: a systematic review and meta-analysis of twin studies

Background

Acute rheumatic fever is considered to be a heritable condition, but the magnitude of the genetic effect is unknown. The objective of this study was to conduct a systematic review and meta-analysis of twin studies of concordance of acute rheumatic fever in order to derive quantitative estimates of the size of the genetic effect.

Methods

We searched PubMed/MEDLINE, ISI Web of Science, EMBASE, and Google Scholar from their inception to 31 January 2011, and bibliographies of retrieved articles, for twin studies of the concordance for acute rheumatic fever or rheumatic heart disease in monozygotic versus dizygotic twins that used accepted diagnostic criteria for acute rheumatic fever and zygosity without age, gender or language restrictions. Twin similarity was measured by probandwise concordance rate and odds ratio (OR), and aggregate probandwise concordance risk was calculated by combining raw data from each study. ORs from separate studies were combined by random-effects meta-analysis to evaluate association between zygosity status and concordance. Heritability was estimated by fitting a variance components model to the data.

Results

435 twin pairs from six independent studies met the inclusion criteria. The pooled probandwise concordance risk for acute rheumatic fever was 44% in monozygotic twins and 12% in dizygotic twins, and the association between zygosity and concordance was strong (OR 6.39; 95% confidence interval, 3.39 to 12.06; P<0.001), with no significant study heterogeneity (P = 0.768). The estimated heritability across all the studies was 60%.

Conclusions

Acute rheumatic fever is an autoimmune disorder with a high heritability. The discovery of all genetic susceptibility loci through whole genome scanning may provide a clinically useful genetic risk prediction tool for acute rheumatic fever and its sequel, rheumatic heart disease.     

Rheumatic fever in native children in Manitoba.

From data reported to a central computer file, cases of rheumatic fever in persons under 17 years of age in Manitoba were reviewed. Although the overall incidence of the disease declined throughout the study period, Jan. 1, 1970 to July 1, 1979, the rates per 100 000 population were higher overall (36) and for non-natives (29) and much higher for natives (126) than average rates in urban centres around the world. Rates of death and readmission showed that the disease was also more severe in the native Manitoba children.     

EuroSCORE Models in a Cohort of Patients with Valvular Heart Disease and a High Prevalence of Rheumatic Fever Submitted to Surgical Procedures

ObjectivesEpidemiological differences can be found between Brazilian and European valvular heart disease patients. The prevalence of heart valve diseases due to rheumatic disease is significantly higher in the Brazilian compared with the European population. Therefore, they could have different risks during and after cardiac surgery. The aim of this study was to evaluate the applicability of the additive and logistic EuroSCORE and EuroSCORE II in a cohort of high-risk patients with valvular heart disease of predominantly rheumatic aetiology submitted to surgery.MethodsBetween 1 February and 30 December 2009, 540 consecutive patients scheduled for valvular heart surgery were included in this study. In this set of patients, we examined the performance of the additive, logistic, and EuroSCORE II models for predicting in-hospital mortality. Calibration of each model was assessed by comparing predicted and observed in-hospital mortality and by the goodness of fit of the Hosmer-Lemeshow chi-square test. Discrimination performance of the model was evaluated with the receiver operating characteristic (ROC) curve analysis.ResultsThe mean age was 56 ± 16 years, 50.6% were female, and the mortality rate was 16.0% (6.0% in elective surgery and 34.0% in emergency/urgency surgery). Mortality rates were estimated according to the additive and logistic EuroSCORE and EuroSCORE II at 6.1%, 8.7%, and 4.3%, respectively. The AUC was 0.76 (95% confidence interval [95% CI] 0.70–0.81) for the additive EuroSCORE, 0.76 (95% CI 0.70–0.81) for the logistic EuroSCORE and 0.81 (95% CI 0.76–0.86) for EuroSCORE II. Hosmer-Lemeshow goodness-of-fit statistics were P = 0.52, P = 0.07, and P = 0.12 for additive, logistic EuroSCORE, and EuroSCORE II.ConclusionsIn this cohort of Brazilian patients with valvular heart disease submitted to surgical procedure, the EuroSCORE models had a good discriminatory capacity; however, the calibration was compromised because of an underestimation of the mortality rate.     

A Cost-Effectiveness Analysis of a Program to Control Rheumatic Fever and Rheumatic Heart Disease in Pinar del Rio,Cuba

Background

Acute rheumatic fever (ARF) and rheumatic heart disease (RHD) persist in many low- and middle-income countries. To date, the cost-effectiveness of population-based, combined primary and secondary prevention strategies has not been assessed. In the Pinar del Rio province of Cuba, a comprehensive ARF/RHD control program was undertaken over 1986 – 1996. The present study analyzes the cost-effectiveness of this Cuban program.

Methods and Findings

We developed a decision tree model based on the natural history of ARF/RHD, comparing the costs and effectiveness of the 10-year Cuban program to a “do nothing” approach. Our population of interest was the cohort of children aged 5 – 24 years resident in Pinar del Rio in 1986. We assessed costs and health outcomes over a lifetime horizon, and we took the healthcare system perspective on costs but did not apply a discount rate. We used epidemiologic, clinical, and direct medical cost inputs that were previously collected for publications on the Cuban program. We estimated health gains as disability-adjusted life years (DALYs) averted using standard approaches developed for the Global Burden of Disease studies. Cost-effectiveness acceptability thresholds were defined by one and three times per capita gross domestic product per DALY averted. We also conducted an uncertainty analysis using Monte Carlo simulations and several scenario analyses exploring the impact of alternative assumptions about the program’s effects and costs. We found that, compared to doing nothing, the Cuban program averted 5051 DALYs (1844 per 100,000 school-aged children) and saved $7,848,590 (2010 USD) despite a total program cost of $202,890 over 10 years. In the scenario analyses, the program remained cost saving when a lower level of effectiveness and a reduction in averted years of life lost were assumed. In a worst-case scenario including 20-fold higher costs, the program still had a 100% of being cost-effective and an 85% chance of being cost saving.

Conclusions

A 10-year program to control ARF/RHD in Pinar del Rio, Cuba dramatically reduced morbidity and premature mortality in children and young adults and was cost saving. The results of our analysis were robust to higher program costs and more conservative assumptions about the program’s effectiveness. It is possible that the program’s effectiveness resulted from synergies between primary and secondary prevention strategies. The findings of this study have implications for non-communicable disease policymaking in other resource-limited settings.     

Synthesis and Immunological Evaluation of M Protein Targeted Tetra-Valent and Tri-Valent Group A Streptococcal Vaccine Candidates Based on the Lipid-Core Peptide System

Group A streptococcus (GAS) is responsible for causing many clinical complications including the relatively benign streptococcal pharyngitis and impetigo. However, if left untreated, these conditions may lead to more severe diseases such as rheumatic fever (RF) and rheumatic heart disease (RHD). These diseases exhibit high morbidity and mortality, particularly in developing countries and in indigenous populations of affluent countries. As RF and RHD only ever occur following GAS infection, a vaccine offers promise for their prevention. As such, we have investigated the use of the lipid-core peptide (LCP) system for the development of multi-valent prophylactic GAS vaccines. The current study has investigated the capacity of this system to adjuvant up to four different GAS peptide epitopes. Presented are the synthesis and immunological assessment of tetra-valent and tri-valent GAS LCP systems. We demonstrated their capacity to elicit systemic IgG antibody responses in B10.BR mice to all GAS peptide epitopes. The data also showed that the LCP systems were self-adjuvanting. These findings are particularly encouraging for the development of multi-valent LCP-based GAS vaccines.     

Distribution of cells bearing B-cell alloantigen(s) in North Indian rheumatic fever/rheumatic heart disease patients

Numerous investigators have developed monoclonal antibodies against B-cell alloantigen(s) of rheumatic fever. However, the developed monoclonals do not have the same significance in all the populations. We have developed a battery of monoclonals against B-cell alloantigens of North Indian rheumatic fever patients. In the present study, we have used these monoclonals to examine the frequency of rheumatic antigens in 30 patients with recurrence of rheumatic activity (RRA), 30 of rheumatic heart disease (RHD) patients and 50 controls using alkaline phosphatase anti-alkaline phosphatase (APAAP) technique. These patients were examined at the time of registry and after three months follow up. RRA patients showed higher percentage of lymphocyte positive as compare to RHD and controls. Interestingly, On follow-up RRA patients showed significant decline in positive lymphocyte as compare to first visit whereas no such change was observed in RHD patients. There were 90–93% of RRA and RHD patients positive with these monoclonals. A significant age variation of rheumatic cells was also noticed in all groups of rheumatic patients. We conclude that monoclonals raised from the same ethnic population are highly specific and cost effective to use them to develop an easy field test system such as APAAP, to identify the individual at risk, to develop rheumatic fever. It is also suggested that the alloantigen marker may persist through out life and gets activated after recurrence of the disease.     

Gene Specific Impedimetric Bacterial DNA Sensor for Rheumatic Heart Disease

An impedimetric mga gene specific DNA sensor was developed by immobilization of single stranded DNA probe onto the screen printed modified gold-dendrimer nanohybrid composite electrode for early and rapid detection of S. pyogenes in human throat swab samples causing rheumatic heart disease. Electrochemical impedance response was measured after hybridization with bacterial single stranded genomic DNA (ssG-DNA) with probe. The sensor was found highly specific to S. pyogenes and can detect as low as 0.01 ng ssDNA in 6 µL sample only in 30 min. The nanohybrid sensor was also tested with non-specific pathogens and characterized by FTIR. An early detection of the pathogen S. pyogenes in human can save damage of mitral and aortic heart valves (rheumatic heart disease) by proper medical care.     

Rheumatic fever in Southern California; problems related to diagnosis

Rheumatic fever occurs in native of Southern California and is a cause of death. The incidence of streptococcosis in Los Angeles is approximately equal to that in three other major cities in the United States where rheumatic fever is known to occur commonly. Manifestations of rheumatic fever may range from mild to severe. It is suggested that a greater percentage of patients in Southern California have symptoms of rheumatic fever that are more mild. Differentiation between prolonged, uncomplicated streptococcosis and rheumatic fever is a major problem. The judicious use of a battery of tests, acute phase reactants, on the same blood sample will frequently help to establish the diagnosis in borderline situations so common to Southern California.     

硝普钠治疗风湿性心脏病并发心衰患者的临床效果研究

目的:探讨硝普钠治疗风湿性心脏病并发心衰患者的临床效果及安全性。方法:选取内蒙古医科大学第三附属医院2016-2019年收治的80例风湿性心脏病并发心衰患者,将其随机分为研究组和对照组,每组40例。对照组采取常规治疗,研究组在此基础上应用硝普钠治疗,对比两组治疗前后心脏血流动力学参数、舒张压、收缩压、心率、呼吸的变化、临床效果及不良反应的发生情况。结果:两组治疗后左心室收缩末期内径(Left ventricular end-systolic diameter,LVESD)、左房内径(left atrial diameter,LAD)、左心室舒张末期内径(left ventricular end-diastolic diameter,LVEDD)均较治疗前明显降低,左室射血分数值(left ventricular ejection fraction,LVEF)均明显高于治疗后(P0.05),且研究组上述指标的改善程度均明显优于对照组(P0.05)。研究组治疗后舒张压、收缩压、心率、呼吸低于对照组(P0.05);研究组的治疗有效率心脏高于对照组(P0.05);两组不良反应的发生率比较差异无统计学意义(P0.05)。结论:硝普钠治疗风湿性心脏病并发心衰患者应可有效改善患者心功能,提高临床治疗效果,具安全性较好。     

Mimicry in recognition of cardiac myosin peptides by heart-intralesional T cell clones from rheumatic heart disease

Molecular mimicry between Streptococcus pyogenes Ags and human proteins has been considered as a mechanism leading to autoimmune reactions in rheumatic fever and rheumatic heart disease (RHD). Cardiac myosin has been shown as a putative autoantigen recognized by autoantibodies of rheumatic fever patients. We assessed the human heart-intralesional T cell response against human light meromyosin (LMM) and streptococcal M5 peptides and mitral-valve-derived proteins by proliferation assay. Cytokines induced by LMM peptides were also evaluated. The frequency of intralesional T cell clones that recognized LMM peptides was 63.2%. Thirty-four percent of T cell clones presented cross-reactivity with different patterns: 1) myosin and valve-derived proteins; 2) myosin and streptococcal M5 peptides; and 3) myosin, valve-derived proteins and M5 peptides. In addition, several LMM peptides were recognized simultaneously showing a multiple reactivity pattern of heart-infiltrating T cells. Inflammatory cytokines (IFN-gamma and TNF-alpha) were predominantly produced by heart-infiltrating T cells upon stimulation with LMM peptides. The alignment of LMM and streptococcal M5 peptides showed frequent homology among conserved amino acid substitutions. This is the first study showing the cellular response by human heart-infiltrating T cells against cardiac myosin epitopes in RHD patients. The high percentage of reactivity against cardiac myosin strengthens its role as one of the major autoantigens involved in rheumatic heart lesions. T cell reactivity toward myosin epitopes in RHD patients may also trigger the broad recognition of valvular proteins with structural or functional similarities.