Rheumatic heart disease (RHD) remains a major contributor to morbidity and mortality in developing countries. The reported prevalence rates of RHD are highly variable and mainly attributable to differences in the sensitivity of either clinical screening to detect advanced heart disease or echocardiographic evaluation where disease is diagnosed earlier across a continuous spectrum. The clinical significance of diagnosis of subclinical RHD by echocardiographic screening and early implementation of secondary prevention has not been clearly established.
Methods and analysis
The authors designed a cross-sectional survey to determine the prevalence of RHD in children from private and public schools between the age of 5 and 15 years in urban and rural areas of Eastern Nepal using both cardiac auscultation and echocardiographic evaluation. Children with RHD will be treated with secondary prevention and enrolled in a prospective cohort study. The authors will compare the prevalence rates by cardiac auscultation and echocardiography, determine risk factors associated with diagnosis and progression of RHD, investigate social and economic barriers for receiving adequate cardiac care and assess clinical outcomes with regular medical surveillance as a function of stage of disease at the time of diagnosis. Prospective clinical studies investigating the impact of secondary prevention for subclinical RHD on long-term clinical outcome will be of central relevance for future health resource utilisation in developing countries.
Ethics and dissemination
The study was considered ethically uncritical and was given an exempt status by the ethics committee at University of Bern, Switzerland. The study has been submitted to the National Nepal Health Research Council and was registered with http://www.ClinicalTrials.gov (NCT01550068). The study findings will be reported in peer-reviewed publications.
Study protocol of a population-based evaluation of the prevalence rate of RHD among schoolchildren in Eastern Nepal, with a subsequent prospective longitudinal cohort study assessing long-term clinical outcome of children undergoing secondary prevention for borderline and definite RHD according to the World Heart Federation criteria.
RHD remains a major contributor to morbidity and mortality in developing countries.
Echocardiographic screening allows diagnosis of RHD at an earlier stage across a continuous spectrum as compared with cardiac auscultation.
The clinical significance of diagnosis of subclinical RHD by echocardiographic screening and early implementation of secondary prevention has not been clearly established.
Strengths and limitations of this study
The protocol describes a comprehensive approach to implement echocardiographic screening in a high prevalence region as recommended by the WHO and outlines a robust analysis plan to investigate clinical outcome with secondary prevention for subclinical RHD.
Since access to education is a marker of socioeconomic status, restriction of screening to school going children is subjected to selection bias likely to underestimate the real disease burden related to RHD in Eastern Nepal.
Cultural sensitivity with education programmes and focus group discussions will anticipate the potential social stigma of a diagnosis with a heart condition during childhood and increase public awareness.
Little is known about the association of rheumatic heart disease (RHD) with incident heart failure (HF) among older adults.
Cardiovascular Health Study, a prospective cohort study.
Of the 4751 community-dwelling adults ≥65 years, free of prevalent HF at baseline, 140 had RHD, defined as self-reported physician-diagnosed RHD along with echocardiographic evidence of left-sided valvular disease. Propensity scores for RHD, estimated for each of the 4751 participants, were used to assemble a cohort of 720, in which 124 and 596 participants with and without RHD respectively were balanced on 62 baseline characteristics.
Incident HF developed in 33% and 22% of matched participants with and without RHD respectively during 13 years of follow-up (hazard ratio when RHD was compared to no-RHD, 1.60; 95% confidence interval, 1.13–2.28; P=0.008). Pre-match unadjusted, multivariable-adjusted and propensity-adjusted hazard ratios (95% confidence intervals) for RHD-associated incident heart failure were 2.04 (1.54–2.71; P<0.001), 1.32 (1.02–1.70; P=0.034) and 1.55 (1.14–2.11; P=0.005) respectively. RHD was not associated with all-cause mortality (HR, 1.09; 95% CI, 0.82–1.45; P=0.568).
RHD is an independent risk factor for incident HF among community-dwelling older adults free of HF, but has no association with mortality.
Heart failure; rheumatic heart disease; older adults
To determine the prevalence of rheumatic heart disease (RHD) and congenital heart disease (CHD) using clinical and echocardiographic criteria in rural and urban school children in Andhra Pradesh, South India.
Materials and methods
A total of 4213 school children between 5 and 16 years of age were screened. 1177 were from rural schools and 3036 from urban schools. Prevalence of RHD and CHD was estimated.
Clinically RHD was present in 3 (prevalence 0.7/1000). Using echocardiography RHD was detected in 32 (7.6/1000), 11 (7.3/1000) from rural and 21 (7/1000) from urban schools. (P = 0.000, O.R = 0.093 and C.I. = 0.023–0.317). Total prevalence of RHD is 8.3/1000.
Clinically CHD was present in 39 (9.2/1000) children, rural 9 (7.6/1000) and urban 30 (9.9/1000). Using echocardiography CHD was detected in 44 (10.4/1000) children, rural 11 (9.3/1000) and urban 33 (10.8/1000).
RHD was detected several fold using echocardiographic screening than by clinical examination alone. Longitudinal follow-up of children with echocardiographically diagnosed subclinical RHD is needed.
Congenital heart disease (CHD); Echocardiography; Rheumatic heart disease (RHD)
Objectives: To determine the community based prevalence of rheumatic heart disease (RHD) in the rural population of the district of Rahim Yaar Khan in Pakistan.
Subjects and methods: A representative sample of the rural population of Rahim Yaar Khan district was selected. RHD was screened for by physical examination and the diagnosis was confirmed with echocardiographic Doppler studies. Sociodemographic data on each screened person were collected.
Results: 54 cases of RHD were found among the 9430 people screened (prevalence of 5.7 in 1000, 95% confidence interval 4.2 to 7.2). Females were significantly more likely to be affected. There was no significant relation with other factors studied (education, crowding, and socioeconomic status). Less than 20% of those found to have RHD were aware of their diagnosis before participation in this study and only three affected people (8%) were taking rheumatic prophylaxis.
Conclusions: There is a high prevalence of RHD among the rural population of Pakistan. The prevalence has not declined over the past three decades. Nearly all people with RHD, including most of those who know their diagnosis, do not receive the benefit of potentially life saving secondary prevention measures.
rheumatic heart disease; Pakistan
In Australia, rheumatic heart disease (RHD) is almost exclusively restricted to Aboriginal Australian and Torres Strait Islander people with children being at highest risk. International criteria for echocardiographic diagnosis of RHD have been developed but the significance of minor heart valve abnormalities which do not reach these criteria remains unclear. The Rheumatic Fever Follow-Up Study (RhFFUS) aims to clarify this question in children and adolescents at high risk of RHD.
RhFFUS is a cohort study of Aboriginal and/or Torres Strait Islander children and adolescents aged 8–17 years residing in 32 remote Australian communities. Cases are people with non-specific heart valve abnormalities detected on prior screening echocardiography. Controls (two per case) are age, gender, community and ethnicity-matched to cases and had a prior normal screening echocardiogram. Participants will have echocardiography about 3 years after initial screening echocardiogram and enhanced surveillance for any history suggestive of acute rheumatic fever (ARF). It will then be determined if cases are at higher risk of (1) ARF or (2) developing progressive echocardiography-detected valve changes consistent with RHD.
The occurrence and timing of episodes of ARF will be assessed retrospectively for 5 years from the time of the RhFFUS echocardiogram. Episodes of ARF will be identified through regional surveillance and notification databases, carer/subject interviews, primary healthcare history reviews, and hospital separation diagnoses.
Progression of valvular abnormalities will be assessed prospectively using transthoracic echocardiography and standardized operating and reporting procedures. Progression of valve lesions will be determined by specialist cardiologist readers who will assess the initial screening and subsequent RhFFUS screening echocardiogram for each participant. The readers will be blinded to the initial assessment and temporal order of the two echocardiograms.
RhFFUS will determine if subtle changes on echocardiography represent the earliest changes of RHD or mere variations of normal heart anatomy. In turn it will inform criteria to be used in determining whether secondary antibiotic prophylaxis should be utilized in individuals with no clear history of ARF and minor abnormalities on echocardiography. RhFFUS will also inform the ongoing debate regarding the potential role of screening echocardiography for the detection of RHD in this setting.
Rheumatic heart disease; Acute rheumatic fever; Screening; Aboriginal; Torres Strait Islander; Indigenous; Diagnosis; Prevention; Australia; Echocardiography
Rheumatic heart disease (RHD) is still a public health issue in many countries in the world, and particularly in Southeast Asia. India, for example, contributes 25%–50% of the global burden of RHD. Clinic-based and epidemiological studies on RHD in India have used different methodologies and clinical criteria to estimate RHD burden in India. The present study employs strict clinical criteria, including echocardiography, to estimate RHD prevalence and associated clinical complications in a large unique rural population in southern India covered through a governmental health insurance scheme.
Materials and methods
Total 44,164 eligible patients were screened from 238 primary care health centers in rural southern India between October 2007 and March 2012 using strict clinical criteria and objective ascertainment. A total of 403 patients aged 15 years or above were finally analyzed based on both the inclusion and exclusion criteria. Detailed information on both demographic and clinical characteristics was obtained through personal interviews and clinical examinations. Descriptive analyses were performed, including age standardization.
The age-standardized RHD prevalence rate was 9.7/1000 populations—more common in younger age groups (<44 years) and relatively high among females. Pulmonary hypertension was the most common clinical complication followed by CHF, tricuspid regurgitation, as well as infective endocarditis. More than two-thirds had no past history of RHD or penicillin prophylaxis.
RHD rates are still high in rural India among populations covered through governmental health insurance scheme. Both primary and secondary preventive measures, including widespread coverage of penicillin prophylaxis, must be considered mainstay tools to both prevent and reduce RHD burden in endemic populations, including rural India.
Prevalence; RHD; South India
Rheumatic heart disease (RHD) results in morbidity and mortality that is disproportionate among people in developing countries compared to those living in economically developed countries. The global burden of disease is uncertain because most previous studies to determine the prevalence of RHD in children relied on clinical screening criteria that lacked the sensitivity to detect most cases. The present study was performed to determine the prevalence of RHD in children and young adults in León, Nicaragua, an area previously thought to have a high prevalence of RHD. This was an observational study of 3150 children, ages 5–15, and 489 adults, ages 20–35, randomly selected from urban and rural areas of León. Cardiopulmonary exams and echo-Doppler studies were performed on all subjects. Echo-Doppler diagnosis of RHD was based on pre-defined consensus criteria that were developed by a WHO/NIH working group. The overall prevalence of RHD in children was 48/1000 (95% C.I. = 35/1000–60/1000. The prevalence in urban children was 34/1000 and in rural children it was 80/1000. Using more stringent echo-Doppler criteria designed to diagnose definite RHD in adults, the prevalence was 22/1000 (95% C.I.=8/1000–37/1000). In conclusion, the prevalence of RHD among children and adults in this economically disadvantaged population far exceeds previously predicted rates. The findings underscore the potential health and economic burden of acute rheumatic fever and RHD and support the need for more effective measures of prevention, which may include safe, effective and affordable vaccines to prevent the streptococcal infections that trigger the disease.
rheumatic heart disease; prevalence of disease; disease burden
The occurrence of acute rheumatic fever (ARF) and rheumatic heart disease (RHD) among Navajos was ascertained for the period from 1962 through 1977 by means of hospital discharge diagnoses and patients' charts. The annualized attack rate for ARF was 12.4 per 100,000 population, with no clear evidence of an overall secular trend. The proportion of recurrences (19.6 percent) and clinical features were similar to those reported elsewhere, but no seasonal variation in attack rates was noted. Between 1962-71 and 1972-77, the age of RHD patients increased, suggesting few newly diagnosed cases and the aging of known patients. A streptococcal disease control program was instituted in many Navajo elementary schools before 1975. In the program, throat cultures were performed routinely for some asymptomatic children and for all symptomatic children. During the subsequent 3 years, ARF rates declined from 13.5 to 8.2 per 100,000 in areas covered by the program, while in the noncovered areas the rates showed little change-9.5 to 10.1 per 100,000.
STUDY OBJECTIVE: To determine the prevalence of rheumatic heart disease (RHD) and study the relationship of this disease to factors such as age, sex, housing, and socioeconomic status in Shimla town and the adjoining rural area. DESIGN: A cross sectional survey, carried out by a specially trained examiner in cardiology. SETTING: The study involved high risk school children (5-16 years of age) from Shimla town and the adjoining rural area of Kasumpti-Suni Block in the period 1992-93. SUBJECTS: A total of 15,080 children on the school register (8120 boys and 6960 girls) were examined generally and specifically for evidence of RHD. MAIN RESULTS: Of the 15,080 children screened, the prevalence of rheumatic fever (RF)/RHD was 2.98 per thousand with no significant difference between the age groups of 5-10 and 11-16 years or in either sex (p > 0.05). The prevalence was significantly greater in rural schools (4.8/1000) than in urban schools (1.98/1000) (p < 0.05). There was overcrowding and poor housing in most cases. There were fewer cases of RHD with severe valvular lesions in the younger age group than in the older children. The mitral valve was the valve most commonly affected by RF/RHD. CONCLUSIONS: RHD continues to be a serious health problem. Regular surveys are needed to identify cases early and to ensure secondary prophylaxis with penicillin is given thereby preventing recurrence of RF and progression of the severity of the valvular lesion. Echocardiography is necessary to identify cases of RF/RHD. Strategies for preventing RHD should involve primary prevention to avert the first attack of carditis and strengthening of secondary prophylaxis through improved education and motivation of patients, parents, and physicians.
To estimate the incidence of RhD immunisation after implementation of first trimester non-invasive fetal RHD screening to select only RhD negative women carrying RHD positive fetuses for routine antenatal anti-D prophylaxis (RAADP).
Materials and Methods
We present a population-based prospective observational cohort study with historic controls including all maternity care centres and delivery hospitals in the Stockholm region, Sweden. All RhD negative pregnant women were screened for fetal RHD genotype in the first trimester of pregnancy. Anti-D immunoglobulin (250–300 µg) was administered intramuscularly in gestational week 28–30 to participants with RHD positive fetuses. Main outcome measure was the incidence of RhD immunisation developing during or after pregnancy.
During the study period 9380 RhD negative women gave birth in Stockholm. Non-invasive fetal RHD genotyping using cell-free fetal DNA in maternal plasma was performed in 8374 pregnancies of which 5104 (61%) were RHD positive and 3270 (39%) RHD negative. In 4590 pregnancies with an RHD positive test the women received antenatal anti-D prophylaxis. The incidence of RhD immunisation in the study cohort was 0.26 percent (24/9380) (95% CI 0.15–0.36%) compared to 0.46 percent (86/18546) (95% CI 0.37 to 0.56%) in the reference cohort. The risk ratio (RR) for sensitisation was 0.55 (95% CI 0.35 to 0.87) and the risk reduction was statistically significant (p = 0.009). The absolute risk difference was 0.20 percent, corresponding to a number needed to treat (NNT) of 500.
Using first trimester non-invasive antenatal screening for fetal RHD to target routine antenatal anti-D prophylaxis selectively to RhD negative women with RHD positive fetuses significantly reduces the incidence of new RhD immunisation. The risk reduction is comparable to that reported in studies evaluating the outcome of non selective RAADP to all RhD negative women. The cost-effectiveness of this targeted approach remains to be studied.
Rheumatic fever (RF) is a sequel of group A streptococcal throat infection and occurs in untreated susceptible children. Rheumatic heart disease (RHD), the major sequel of RF, occurs in 30%–45% of RF patients. RF is still considered endemic in some regions of Brazil and is responsible for approximately 90% of early childhood valvular surgery in the country. In this study, we present a 15-year clinical follow-up of 25 children who underwent surgical valvular repair. Histopathological and immunological features of heart tissue lesions of RHD patients were also evaluated. The patients presented severe forms of RHD with congestive symptoms at a very young age. Many of them had surgery at the acute phase of RF. Histological analysis showed the presence of dense valvular inflammatory infiltrates and Aschoff nodules in the myocardium of 21% of acute RHD patients. Infiltrating T-cells were mainly CD4+ in heart tissue biopsies of patients with rheumatic activity. In addition, CD4+ and CD8+ infiltrating T-cell clones recognized streptococcal M peptides and cardiac tissue proteins. These findings may open the possibilities of new ways of immunotherapy. In addition, we demonstrated that the surgical procedure during acute phase of the disease improved the quality of life of young RHD patients.
rheumatic heart disease; Streptococcus pyogenes; heart failure; inflammatory infiltrate; T lymphocytes; molecular mimicry
Not all cases of rheumatic fever (RF) end up as rheumatic heart disease (RHD). The fact raises the possibility of existence of a subgroup with characteristics that prevent RF patients from developing the RHD. The present study aimed at exploring the risk factors among patients with RHD. The study assessed the risk of RHD among people both with and without RF. In total, 103 consecutive RHD patients were recruited as cases who reported to the National Centre for Control of Rheumatic Fever and Heart Disease, Dhaka, Bangladesh. Of 309 controls, 103 were RF patients selected from the same centre, and the remaining 206 controls were selected from Shaheed Suhrawardy Medical College Hospital, who got admitted for other non-cardiac ailments. RHD was confirmed by auscultation and colour Doppler echocardiography. RF was diagnosed based on the modified Jones criteria. An unadjusted odds ratio was generated for each variable, with 95% confidence interval (CI), and only significant factors were considered candidate for multivariate analysis. Three separate binary logistic regression models were generated to assess the risk factors of RF, risk factors of RHD compared to non-rheumatic control patients, and risk factors of RHD compared to control with RF. RF and RHD shared almost a similar set of risk factors in the population. In general, age over 19 years was found to be protective of RF; however, age of the majority (62.1%) of the RHD cases was over 19 years. Women [odds ratio (OR)=2.2, 95% CI 1.1-4.3], urban resident (OR=3.1, 95% CI 1.2–8.4), dwellers in brick-built house (OR=3.6, 95% CI 1.6-8.1), having >2 siblings (OR=3.1, 95% CI 1.5- 6.3), offspring of working mothers (OR=7.6, 95% CI 2.0-24.2), illiterate mother (OR=2.6, 95% CI 1.2-5.8), and those who did not brush after taking meals (OR=2.5, 95% CI 1.0-6.3) were more likely to develop RF. However, more than 5 members in a family showed a reduced risk of RF. RHD shared almost a similar set of factors in general. More than three people sharing a room also showed an increased risk of RHD (OR=1.9, 95% CI 1.0-3.4), in addition to the risk factors of RF. Multivariate model also assessed the factors that may perpetuate RHD among RF patients. Overcrowding (OR=2.4, 95% CI 1.2-4.7) and illiteracy (OR=2.4, 95% CI 1.1-5.2) posed the risk of RHD in the RF patients. The study did not find new factors that might pose an increased risk, rather looked for the documented risk factors and how these operate in the population of Bangladesh.
Case-control study; Rheumatic fever; Rheumatic heart disease; Risk factors; Bangladesh
Incidence of acute rheumatic fever (ARF) and prevalence of rheumatic heart disease (RHD) in the Pacific region, including New Caledonia, are amongst the highest in the world. The main priority of long-term management of ARF or RHD is to ensure secondary prophylaxis is adhered to. The objectives of this study were to evaluate rates of adherence in people receiving antibiotic prophylaxis by intramuscular injections of penicillin in Lifou and to determine the factors associated with a poor adherence in this population.
We conducted a retrospective cohort study and we included 70 patients receiving injections of antibiotic prophylaxis to prevent ARF recurrence on the island of Lifou. Patients were classified as “good-adherent” when the rate of adherence was ≥80% of the expected injections and as “poor-adherent” when it was <80%. Statistical analysis to identify factors associated with adherence was performed using a multivariate logistic regression model.
Our study showed that 46% of patients from Lifou receiving antibiotic prophylaxis for ARF or RHD had a rate of adherence <80% and were therefore at high risk of recurrence of ARF. Three independent factors were protective against poor adherence: a household with more than five people (odds ratio, 0.25; 95% confidence interval [CI], 0.08 to 0.75), a previous medical history of symptomatic ARF (odds ratio, 0.20; 95% CI, 0.04 to 0.98) and an adequate healthcare coverage (odds ratio, 0.21; 95% CI 0.06 to 0.72).
To improve adherence to secondary prophylaxis in Lifou, we therefore propose the following recommendations arising from the results of this study: i) identifying patients receiving antibiotic prophylaxis without medical history of ARF to strengthen their therapeutic education and ii) improving the medical coverage in patients with ARF or RHD. We also recommend that the nurse designated for the ARF prevention program in Lifou coordinate an active recall system based on an updated local register. But the key point to improve adherence among Melanesian patients is probably to give appropriate information regarding the disease and the treatment, taking into account the Melanesian perceptions of the disease.
Acute rheumatic fever; Rheumatic heart disease; Patient compliance; Antibiotic prophylaxis; Melanesia; New Caledonia
Background. Rheumatic heart disease (RHD) is a leading cause of heart failure in children and young adults worldwide. B-type natriuretic peptide (BNP) is a useful marker of critical pediatric heart disease, and its N-terminal peptide, NT-proBNP, is elevated in congenital and acquired heart disease in children. Aim. To measure NT-proBNP levels as a marker of carditis in children with acute rheumatic carditis, as compared to children with quiescent RHD and healthy controls. Methods. 16 children with acute rheumatic carditis, 33 children with quiescent RHD, and a cohort of 30 healthy children were studied. Transthoracic echocardiography was performed to assess valve and cardiac function. Tissue Doppler echocardiography was performed for E/E′ (ratio between mitral inflow E wave and lateral mitral annulus E′ wave) and systolic strain. Results. NT-proBNP levels were significantly higher in children with acute rheumatic carditis and dropped with its resolution. Strain and E/E′ values were comparable among the three groups. Conclusion. NT-proBNP is significantly elevated in children with acute rheumatic carditis in the acute stage compared to children with quiescent RHD and healthy subjects, in the presence of comparable echocardiographic indices of LV systolic and diastolic function.
A survey to determine the prevalence of rheumatic heart disease (R.H.D.) in Black children was conducted in the creeches and primary schools of the South Western Townships of Johannesburg (Soweto). A total of 12 050 Black children were examined by 10 cardiologists in May to October 1972. The overal prevalence rate of R.H.D. was 6.9 per 1000, with a peak rate of 19.2 per 1000 in children of the seventh school grade. The maximal age incidence was 15-18 years and there was a female preponderance of 1 6:1. A rise in prevalence occurred with increasing family size. Most children (92%) were asymptomatic, and in 82.5% R.H.D. was diagnosed for the first time during the school survey. The commonest valve lesion was mitral regurgitation, which was present in 93% and occurred as an isolated lesion in 47.5%. Lancefield's group A beta-haemolytic streptococcus was isolated from the throats of 52 per 1000 Soweto children. The auscultatory features of a non-ejection systolic click and late systolic murmur were prevalent (13.9 per 1000) and had several epidemiological factors in common with R.H.D. A comprehensive preventative campaign is urgently needed in South Africa, directed at both primary and secondary prophylaxis of R.H.D. The socioeconomic status of the community must be improved if optimal prevention is to be achieved.
Rheumatic fever (RF) and rheumatic heart disease (RHD) continue to be a major health hazard in most developing countries as well as sporadically in developed economies. Despite reservations about the utility, echocardiographic and Doppler (E&D) studies have identified a massive burden of RHD suggesting the inadequacy of the Jones’ criteria updated by the American Heart Association in 1992. Subclinical carditis has been recognized by E&D in patients with acute RF without clinical carditis as well as by follow up of RHD patients presenting as isolated chorea or those without clinical evidence of carditis. Over the years, the medical management of RF has not changed. Paediatric and juvenile mitral stenosis (MS), upto the age of 12 and 20 yr respectively, severe enough to require operative treatement was documented. These negate the belief that patients of RHD become symptomatic ≥20 years after RF as well as the fact that congestive cardiac failure in childhood indicates active carditis and RF. Non-surgical balloon mitral valvotomy for MS has been initiated. Mitral and/or aortic valve replacement during active RF in patients not responding to medical treatment has been found to be life saving as well as confirming that congestive heart failure in acute RF is due to an acute haemodynamic overload. Pathogenesis as well as susceptibility to RF continue to be elusive. Prevention of RF morbidity depends on secondary prophylaxis which cannot reduce the burden of diseases. Primary prophylaxis is not feasible in the absence of a suitable vaccine. Attempts to design an antistreptococcal vaccine utilizing the M-protein has not succeeded in the last 40 years. Besides pathogenesis many other questions remain unanswered.
Antistreptococcal vaccine; heart disease; myocarditis; rheumatic fever; rheumatic heart disease; streptococcal infections; subclinical carditis
Our aim was to evaluate whether adenotonsillar hypertrophy (ATH) is associated with rheumatic heart disease (RHD) in children. Fifty-three patients with ATH and 50 healthy children as a control group were enrolled in the study. Medical history and clinical findings were investigated, and echocardiographies were done by researchers who were unaware of the diagnosis. The two groups were compared. Valvular findings suggesting RHD were encountered in four patients (7.5%) in the ATH group and in two children (4%) in the control group. This difference was not statistically significant (p = 0.098); however, we found physiological mitral regurgitation to be significantly more frequent in the ATH group than in the control group (p = 0.023). ATH did not increase the risk of valvulitis related to RHD regardless of adenoid size and frequency of the infection. To preclude the misdiagnosis of mitral regurgitation that results from RHD, diagnostic criteria for pathological mitral regurgitation should be carefully applied.
Rheumatic fever (RF) is an autoimmune disease which affects more than 20 million children in developing countries. It is triggered by Streptococcus pyogenes throat infection in untreated susceptible individuals. Carditis, the most serious manifestation of the disease, leads to severe and permanent valvular lesions, causing chronic rheumatic heart disease (RHD). We have been studying the mechanisms leading to pathological autoimmunity in RF/RHD for the last 15 years. Our studies allowed us a better understanding of the cellular and molecular pathogenesis of RHD, paving the way for the development of a safe vaccine for a post-infection autoimmune disease. We have focused on the search for protective T and B cell epitopes by testing 620 human blood samples against overlapping peptides spanning 99 residues of the C-terminal portion of the M protein, differing by one amino acid residue. We identified T and B cell epitopes with 22 and 25 amino acid residues, respectively. Although these epitopes were from different regions of the C-terminal portion of the M protein, they showed an identical core of 16 amino acid residues. Antibodies against the B cell epitope inhibited bacterial invasion/adhesion in vitro. Our results strongly indicated that the selected T and B cell epitopes could potentially be protective against S. pyogenes.
STUDY OBJECTIVE--The aim was to determine the prevalence of rheumatic fever and rheumatic heart disease and to initiate a programme of secondary prophylaxis in Sahafa Town, Sudan. DESIGN--The study was a prospective case finding survey, carried out by a specially trained team headed by a cardiologist. SETTING--The study involved high risk school children (5-15 years of age) from Sahafa Town in the period 1986-1989. SUBJECTS--A total of 13,332 children on the school registers (7892 boys and 5430 girls) were examined generally and specifically for evidence of rheumatic fever or rheumatic heart disease. MAIN RESULTS--Out of the 13,322 children screened 351 were suspected cases and 146 were confirmed cases of rheumatic fever or rheumatic heart disease. The prevalence rates for all ages were 10/1000 for boys and 14/1000 for girls. The overall prevalence rate of the whole programme area was 11/1000, prevalence of rheumatic fever was 8/1000, and prevalence of rheumatic heart disease was 3/1000. The prevalence rate was significantly increased among the inner town inhabitants (15/1000) compared to the outer town inhabitants 4/1000 (p < 0.001). Monthly prophylactic benzathine penicillin in a dose of 1,200,000 IU was given to both suspected and confirmed cases. Penicillin coverage rate was 72%. CONCLUSIONS--Rheumatic fever continues to be a serious health problem. With economic pressures causing impending change in socioeconomic conditions in most Third World countries in the immediate future, rheumatic fever will continue to have a high prevalence rate and rheumatic fever and rheumatic heart disease prevention programmes will remain a central goal.
Rheumatic fever (RF) is an autoimmune disease triggered by Streptococcus pyogenes infection frequently observed in infants from developing countries. Rheumatic heart disease (RHD), the major sequel of RF, leads to chronic inflammation of the myocardium and valvular tissue. T cells are the main population infiltrating cardiac lesions; however, the chemokines that orchestrate their recruitment are not clearly defined. Here, we investigated the expression of chemokines and chemokine receptors in cardiac tissue biopsies obtained from chronic RHD patients. Our results showed that CCL3/MIP1α gene expression was upregulated in myocardium while CCL1/I-309 and CXCL9/Mig were highly expressed in valvular tissue. Auto-reactive T cells that infiltrate valvular lesions presented a memory phenotype (CD4+CD45RO+) and migrate mainly toward CXCL9/Mig gradient. Collectively, our results show that a diverse milieu of chemokines is expressed in myocardium and valvular tissue lesions and emphasize the role of CXCL9/Mig in mediating T cell recruitment to the site of inflammation in the heart.
rheumatic fever; rheumatic heart disease; chemokines; CXCL9 (Mig); valvular lesions
Objectives: To investigate the progress of rheumatic fever (RF) and the predictors of severe chronic valvar disease.
Design: Patients prospectively followed up since their first attack of acute RF (ARF).
Setting: Universidade Federal de Minas Gerais, Brazil.
Patients: 258 children and adolescents who met the revised Jones criteria for RF. The follow up period ranged from 2–15 years.
Main outcome measures: The presence and severity of mitral or aortic valvar disease were determined by both clinical and Doppler echocardiographic examinations. The variables associated with severe chronic valvar disease were initially identified by the Kaplan-Meier method and, later, by multivariate analysis.
Results: Doppler echocardiography of 258 patients studied showed that 186 (72.1%) developed chronic valvar disease and 41 (15.9%) progressed to severe chronic mitral or aortic lesions. Of 146 patients who developed carditis, 49 (33.6%) had a normal clinical examination in the chronic phase but only nine (6.2%) had normal Doppler echocardiographic findings—that is, 40 (27.4%) patients progressed to chronic subclinical valvar disease. Moderate or severe carditis, recurrences of ARF, and mother’s low educational level were risk factors in predicting severe chronic valvar diseases.
Conclusion: The increased risk of progressing to severe chronic valvar disease was associated with moderate or severe carditis, recurrences of ARF, and mother’s low educational level. Hence, in a country such as Brazil, the options available for disease control are mainly primary and secondary prophylaxis.
Doppler echocardiography; rheumatic fever; rheumatic heart disease
Background and Aim:
Rheumatic fever is still a common cause of acquired heart disease in children and young adult in many developing countries. The aim was to investigate the role of myocardial involvement in the hemodynamic changes in patients with acute rheumatic fever using cardiac troponin assay and echocardiography. Design: A prospective cohort study was designed.
Patients and Methods:
Thirty-four children with acute rheumatic fever, 20 with carditis, and 14 without carditis. Level of cardiac troponin T (cTnT) and echocardiographic measurement of left ventricular function were the main outcome measure.
The level of cardiac troponin in children with carditis was 0.051 ± 0.01 ng/dL, and it was 0.039 ± 0.02 ng/dL in those without carditis. The difference is not significant. In addition, there was no significant difference between the children with carditis and those without carditis regarding left ventricular ejection and shortening fractions.
There are no significant echocardiographic measurements abnormalities or cTnT levels elevation suggesting clinically relevant hemodynamic abnormalities due to myocardial involvement during acute rheumatic fever.
Acute rheumatic fever; cardiac troponin assay; echocardiography; myocardial involvement
There is a significant global health burden associated with acute rheumatic fever (ARF) and rheumatic heart disease (RHD), especially in developing countries. ARF and RHD most often strike children and young adults living in impoverished settings, where unhygienic conditions and lack of awareness and knowledge of streptococcal infection progression are common. Secondary prophylactic measures have been recommended in the past, but primary prevention measures have been gaining more attention from researchers frustrated by the perpetual prevalence of ARF and RHD in developing countries. Health education aims to empower people to take responsibility for their own well-being by gaining control over the underlying factors that influence health. We therefore conducted a review of the current best evidence for the use of health education interventions to increase awareness and knowledge of streptococcal pharyngitis and ARF.
Methods and design
This article describes the protocol for a systematic review of the effectiveness of health education interventions aimed at increasing awareness and knowledge of the symptoms, causes and consequences of streptococcal pharyngitis, rheumatic fever and/or rheumatic heart disease. Studies will be selected in which the effect of an intervention is compared with either a pre-intervention or a control, targeting all possible audience types. Primary and secondary outcomes of interest are pre-specified. Randomized controlled trials, quasi-randomized trials, controlled before–after studies and controlled clinical trials will be considered. We will search several bibliographic databases (for example, PubMed, EMBASE, World Health Organization Library databases, Google Scholar) and search sources for gray literature. We will meta-analyze included studies. We will conduct subgroup analyses according to intervention subtypes: printed versus audiovisual and mass media versus training workshops.
This review will provide evidence for the effectiveness of educational components in health promotion interventions in raising public awareness in regard to the symptoms, causes and consequences of streptococcal pharyngitis, ARF and/or RHD. Our results may provide guidance in the development of future intervention studies and programs.
Acute rheumatic fever; Awareness; Health education; Pharyngitis; Rheumatic heart disease
Introduction: Rheumatic heart disease (RHD) occurs in 30-45% of the patients with rheumatic fever (RF) and it leads to chronic valvular lesions. The human leukocyte antigen (HLA) might confer a susceptibility to RHD. The aim of the present study was to determine the prevalent HLA class II DR/DQ allelic types which were associated with rheumatic heart disease (RHD) in a small group of south Indian patients and to compare them with those in the control subjects.
Methods: A total of 23 patients who were diagnosed with RHD and 6 control samples were included in this study. A low resolution HLA Class II DR/DQ typing was performed on the blood samples by the PCR-SSP method.
Results and Conclusion: The DRB3*01:01:02:01 allele showed a positive association with RHD, whereas the DQB1 loci alleles did not show any significant association.
HLA Class II DR/DQ typing; Rheumatic Heart Disease; South India
Doppler echocardiography has been demonstrated to be accurate in diagnosing valvular lesions in rheumatic heart disease (RHD) when compared to clinical evaluation alone.
To perform Doppler echocardiography in children clinically diagnosed by the Jones criteria to have acute rheumatic fever (ARF), and to then compare the effectiveness of echo in detecting single/multi-valvular lesions with that of the initial clinical evaluation.
Methods and Results
We enrolled 93 children who were previously diagnosed with ARF by clinical examination. Presence of valvular lesions were enlisted, first by clinical auscultation, and then by performing Doppler echocardiography. We found that Doppler echocardiography was a sensitive technique, capable of detecting valvular lesions that were missed by clinical auscultation alone. Echocardiography of patients with carditis revealed mitral regurgitation to be the most common lesion present (53 patients, 56.98%), followed by aortic regurgitation in 21 patients (22.6%). The difference between clinical and echocardiographic diagnosis in ARF children with carditis was statistically significant for mitral regurgitation, aortic regurgitation and tricuspid regurgitation. Clinical auscultation alone revealed 4 cases of mitral stenosis, 39 mitral regurgitation, 14 aortic regurgitation, 9 tricuspid regurgitation; in contrast, echo revealed 5 cases of mitral stenosis, 53 mitral regurgitation, 21 aortic regurgitation, 18 tricuspid regurgitation.
Doppler echocardiography is a more sensitive technique for detecting valvular lesions. In the setting of ARF, echo enables a 46.9% higher detection level of carditis, as compared to the clinical examination alone. Echo was very significant in detecting regurgitation lesions, especially for cases of tricuspid regurgitation in the setting of multivalvular involvement. The results of our study are in accordance with previous clinical studies, all of which clearly demonstrate the advantages of Doppler echocardiography, paving the way for its probable inclusion as one of the Jones major criteria for diagnosing ARF.