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1.  Protocol for a population-based study of rheumatic heart disease prevalence and cardiovascular outcomes among schoolchildren in Nepal 
BMJ Open  2012;2(3):e001320.
Introduction
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.
ClinicalTrials.gov Identifier
NCT01550068.
Article summary
Article focus
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.
Key messages
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.
doi:10.1136/bmjopen-2012-001320
PMCID: PMC3371575  PMID: 22685225
2.  Prevention and control of rheumatic fever and rheumatic heart disease: the Cuban experience (1986–1996–2002) 
Cardiovascular Journal of Africa  2008;19(3):135-140.
Summary
Background
Rheumatic fever (RF) and rheumatic heart disease (RHD) are still major medical and public health problems mainly in developing countries. Pilot studies conducted during the last five decades in developed and developing countries indicated that the prevention and control of RF/RHD is possible. During the 1970s and 1980s, epidemiological studies were carried out in selected areas of Cuba in order to determine the prevalence and characteristics of RF/RHD, and to test several long-term strategies for prevention of the diseases.
Methods
Between 1986 and 1996 we carried out a comprehensive 10-year prevention programme in the Cuban province of Pinar del Rio and evaluated its efficacy five years later. The project included primary and secondary prevention of RF/RHD, training of personnel, health education, dissemination of information, community involvement and epidemiological surveillance. Permanent local and provincial RF/RHD registers were established at all hospitals, policlinics and family physicians in the province. Educational activities and training workshops were organised at provincial, local and health facility level. Thousands of pamphlets and hundreds of posters were distributed, and special programmes were broadcast on the public media to advertise the project.
Results
There was a progressive decline in the occurrence and severity of acute RF and RHD, with a marked decrease in the prevalence of RHD in school children from 2.27 patients per 1 000 children in 1986 to 0.24 per 1 000 in 1996. A marked and progressive decline was also seen in the incidence and severity of acute RF in five- to 25-year-olds, from 18.6 patients per 100 000 in 1986 to 2.5 per 100 000 in 1996. There was an even more marked reduction in recurrent attacks of RF from 6.4 to 0.4 patients per 100 000, as well as in the number and severity of patients requiring hospitalisation and surgical care. Regular compliance with secondary prophylaxis increased progressively and the direct costs related to treatment of RF/RHD decreased with time. The implementation of the programme did not incur much additional cost for healthcare. Five years after the project ended, most of the measures initiated at the start of the programme were still in place and occurrence of RF/RHD was low.
PMCID: PMC3974561  PMID: 18568172
3.  Epidemiological survey of rheumatic heart disease among school children in the Shimla Hills of northern India: prevalence and risk factors. 
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.
PMCID: PMC1060206  PMID: 8762356
4.  Prevalence and pattern of rheumatic heart disease in the Nigerian savannah: an echocardiographic study 
Cardiovascular Journal of Africa  2007;18(5):295-299.
Summary
Background
Rheumatic heart disease (RHD) remains a major public health problem in developing countries. Whereas Africa has 10% of the world’s population, as many as half of the 2.4 million children affected by RHD globally live on the continent. RHD accounts for a major proportion of all cardiovascular disease in children and young adults in African countries. While acute rheumatic fever is on the decline even in the developing world, there are still a large number of chronic rheumatic heart disease cases, often complicated by chronic congestive heart failure and recurrent thrombo-embolic phenomena, both posing greater challenges for management. We report on the prevalence and pattern of valve involvement in RHD using echocardiography from our centre.
Methods
In this retrospective study, transthoracic echocardiography (TTE) data collected from two echocardiography laboratories in Kano over a period of 48 months (June 2002 to May 2006) were reviewed. Patients with a diagnosis of rheumatic heart disease were selected. Information obtained from the records included the age, gender, clinical diagnosis and echocardiographic diagnoses.
Results
A total of 1 499 echocardiographic examinations were done in the two centres over the four-year study period. One hundred and twenty-nine of the 1 312 patients (9.8%) with abnormal results had an echocardiographic diagnosis of RHD. There were 47 males and 82 females (ratio 1:1.7) and their ages ranged from five to 60 (mean 24.02 ± 12.75) years. Mitral regurgitation was the commonest echocardiographic diagnosis present in 49 patients (38.0%). Thirty-six (27.9%) patients had mixed mitral valve disease, 25 (19.5%) had mixed aortic and mitral valve disease, 10 (7.8%) had pure mitral stenosis and four (3.1) had pure aortic regurgitation. Complications of RHD observed included secondary pulmonary hypertension in 103 patients (72.1%), valvular cardiomyopathy in 41 (31.8%), and functional tricuspid regurgitation was seen in 39 (30.2%).
Conclusion
Our data show that RHD is still an important cause of cardiac morbidity and a large proportion of the patients already had complications at diagnosis. There is an urgent need to implement the ASAP programme of the Drakensberg declaration to avert this scourge.
PMCID: PMC3975544  PMID: 17957324
5.  Rheumatic heart disease in rural south India: A clinico-observational study 
Background
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.
Results
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.
Conclusions
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.
doi:10.1016/j.jcdr.2013.02.011
PMCID: PMC3758088  PMID: 24023467
Prevalence; RHD; South India
6.  Rheumatic Fever Follow-Up Study (RhFFUS) protocol: a cohort study investigating the significance of minor echocardiographic abnormalities in Aboriginal Australian and Torres Strait Islander children 
Background
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.
Methods/design
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.
Discussion
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.
doi:10.1186/1471-2261-12-111
PMCID: PMC3536578  PMID: 23186515
Rheumatic heart disease; Acute rheumatic fever; Screening; Aboriginal; Torres Strait Islander; Indigenous; Diagnosis; Prevention; Australia; Echocardiography
7.  Status of rheumatic heart disease in rural Pakistan 
Heart  2004;90(4):394-399.
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.
doi:10.1136/hrt.2003.025981
PMCID: PMC1768176  PMID: 15020513
rheumatic heart disease; Pakistan
8.  Risk Factors of Rheumatic Heart Disease in Bangladesh: A Case-Control Study 
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.
PMCID: PMC3702361  PMID: 23617207
Case-control study; Rheumatic fever; Rheumatic heart disease; Risk factors; Bangladesh
9.  Prevalence of rheumatic and congenital heart disease in school children of Andhra Pradesh, South India 
Objective
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.
Results
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).
Conclusion
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.
doi:10.1016/j.jcdr.2012.11.003
PMCID: PMC3758100  PMID: 24023464
Congenital heart disease (CHD); Echocardiography; Rheumatic heart disease (RHD)
10.  Prevalence of Rheumatic Heart Disease in Children and Young Adults in Nicaragua 
The American journal of cardiology  2010;105(12):1809-1814.
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.
doi:10.1016/j.amjcard.2010.01.364
PMCID: PMC2895982  PMID: 20538135
rheumatic heart disease; prevalence of disease; disease burden
11.  Congenital heart disease and rheumatic heart disease in Africa: recent advances and current priorities 
Heart  2013;99(21):1554-1561.
Africa has one of the highest prevalence of heart diseases in children and young adults, including congenital heart disease (CHD) and rheumatic heart disease (RHD). We present here an extensive review of recent data from the African continent highlighting key studies and information regarding progress in CHD and RHD since 2005. Main findings include evidence that the CHD burden is underestimated mainly due to the poor outcome of African children with CHD. The interest in primary prevention for RHD has been recently re-emphasised, and new data are available regarding echocardiographic screening for subclinical RHD and initiation of secondary prevention. There is an urgent need for comprehensive service frameworks to improve access and level of care and services for patients, educational programmes to reinforce the importance of prevention and early diagnosis and a relevant research agenda focusing on the African context.
doi:10.1136/heartjnl-2013-303896
PMCID: PMC3812860  PMID: 23680886
CONGENITAL HEART DISEASE
12.  Determinants of poor adherence to secondary antibiotic prophylaxis for rheumatic fever recurrence on Lifou, New Caledonia: a retrospective cohort study 
BMC Public Health  2013;13:131.
Background
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.
Methods
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.
Results
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).
Conclusions
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.
doi:10.1186/1471-2458-13-131
PMCID: PMC3626837  PMID: 23402561
Acute rheumatic fever; Rheumatic heart disease; Patient compliance; Antibiotic prophylaxis; Melanesia; New Caledonia
13.  Epidemiology of rheumatic heart disease in black shcoolchildren of Soweto, Johannesburg. 
British Medical Journal  1975;3(5981):474-478.
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.
PMCID: PMC1674319  PMID: 1156827
14.  Clinical Spectrum of Rheumatic Fever and Rheumatic Heart Disease: A 10 Year Experience in an Urban Area of South India 
Background:
Rheumatic fever (RF) is an important problem concerning developing countries like India. Rheumatic heart disease (RHD) is one of the most readily preventable chronic diseases.
Aim:
This study was done to find out the clinical profile, risk factors, compliance with treatment and outcome among RF/RHD cases so as to suggest better case management strategies.
Materials and Methods:
Clinical records of 51 RF and 71 RHD cases admitted in tertiary care hospitals in Mangalore between 2001 and 2010 were reviewed retrospectively.
Results:
Mean age of RF cases were 17.4 ± 12.1 years and RHD cases were 33.2 ± 18.6 years. More than half of RF and RHD cases were males. Commonest risk factors among RF cases were poor socioeconomic status (60.4%), history of upper respiratory tract infection before disease onset (58.8%) and undernutrition (35.3%). Commonest clinical manifestation among RF cases was fever 39 (76.5%) followed by polyarthritis 34 (66.7%). Commonest valvular lesions among RHD cases was mitral stenosis with mitral regurgitation found in 42.9% cases. Compliance of patients with prophylactic antibiotics was found to be 37 (30.3%). Mortality rate was significantly more among RHD cases (P = 0.0399).
Conclusions:
Improvement of socioeconomic and nutritional factors is an important task required for primary prophylaxis and of compliance for secondary prophylaxis of RF.
doi:10.4103/1947-2714.122307
PMCID: PMC3877438  PMID: 24404543
Clinical features; Compliance; Rheumatic fever; Rheumatic heart disease; Risk factors; Valvular lesions
15.  Rheumatic fever & rheumatic heart disease: The last 50 years 
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.
PMCID: PMC3724245  PMID: 23703332
Antistreptococcal vaccine; heart disease; myocarditis; rheumatic fever; rheumatic heart disease; streptococcal infections; subclinical carditis
16.  Rheumatic heart disease and risk of incident heart failure among community-dwelling older adults: a prospective cohort study 
Annals of Medicine  2011;44(3):253-261.
Background
Little is known about the association of rheumatic heart disease (RHD) with incident heart failure (HF) among older adults.
Design
Cardiovascular Health Study, a prospective cohort study.
Methods
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.
Results
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).
Conclusion
RHD is an independent risk factor for incident HF among community-dwelling older adults free of HF, but has no association with mortality.
doi:10.3109/07853890.2010.530685
PMCID: PMC3116996  PMID: 21254894
Heart failure; rheumatic heart disease; older adults
17.  N-Terminal proBNP Levels and Tissue Doppler Echocardiography in Acute Rheumatic Carditis 
ISRN Pediatrics  2013;2013:970394.
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.
doi:10.1155/2013/970394
PMCID: PMC3786526  PMID: 24109516
18.  Health education interventions to raise awareness of rheumatic fever: a systematic review protocol 
Systematic Reviews  2013;2:58.
Background
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.
Discussion
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.
doi:10.1186/2046-4053-2-58
PMCID: PMC3720575  PMID: 23866796
Acute rheumatic fever; Awareness; Health education; Pharyngitis; Rheumatic heart disease
19.  The new face of rheumatic heart disease in South West Nigeria 
Purpose
To determine the current prevalence of rheumatic heart disease (RHD), clinical features, types of valvular lesions, complications and mortality, at Ladoke Akintola University of Technology (LAUTECH) Teaching Hospital, Osogbo, South West Nigeria.
Methods
We conducted a retrospective, descriptive study of all the cases of RHD seen in the medical outpatient clinics and wards of LAUTECH for 9 years, from January 2003 to December 2011. Statistical analysis of data obtained was done using SPSS 16.
Results
The total number of attendees of all the medical outpatient clinics during the 9-year period was 67,378, with a subset of 9423 attending the cardiology clinic. There were 11 cases of RHD, which translates to a prevalence of 0.16/1000 and 1.2/1000 for medical outpatient clinics and the cardiology clinic respectively. The mean age of the patients was 25.64 ± 9.65 years, age range 14–40 years and male to female ratio of 1:1.2. The most common valve affected was mitral (90.9%), followed by the aortic (36.4%), and the tricuspid (18.2%). Mitral and aortic lesions coexisted in 18.2% of the patients, and late presentation was common in all RHD cases. Heart failure was the most common complication (90.9%). Other complications were secondary pulmonary hypertension (36.4%), infective endocarditis (27.3%), atrial fibrillation (27.3%), cardioembolic cerebrovascular disease (18.2%), and atrial flutter (9.1%). Mortality was 9.1%, while only one patient (9.1%) had definitive surgery. Financial constraints precluded others from having definitive surgery.
Conclusion
The prevalence of RHD has declined considerably as a result of improvements in the primary health care delivery system, with widespread use of appropriate antibiotic therapy for sore throats resulting in the prevention of rheumatic fever and RHD. However, late presentation is still very common, hence we advocate a more aggressive drive to make the Drakensberg declaration on the control of rheumatic fever and rheumatic heart disease functional in our practice area.
doi:10.2147/IJGM.S44289
PMCID: PMC3666550  PMID: 23723716
rheumatic fever; group A β-hemolytic streptococcal pharyngitis; valvular lesions; heart failure
20.  Epidemiological trends of RF/RHD in school children of Shimla in north India 
The Indian Journal of Medical Research  2013;137(6):1121-1127.
Background & objectives:
There are no active surveillance studies reported from South East Asian Region to document the impact of change in socio-economic state on the prevalence of rheumatic fever/rheumatic heart disease (RF/RHD) in children. Therefore, we conducted a study to determine the epidemiological trends of RF/RHD in school children of Shimla city and adjoining suburbs in north India and its association with change in socio-economic status.
Methods:
Active surveillance studies were conducted in 2007-2008 in urban and rural areas of Shimla, and 15145 school children, aged 5-15 yr were included and identical screening methodology as used in earlier similar survey conducted in 1992-1993 was used. The study samples were selected from schools of Shimla city and adjoining rural areas by multistage stratified cluster sampling method in both survey studies. After a relevant history and clinical examination by trained doctor, echocardiographic evaluation of suspected cases was done. An updated Jones (1992) criterion was used to diagnose cases of acute rheumatic fever (ARF) and identical 2D-morphological and Doppler criteria were used to diagnose RHD in both the survey studies. The socio-economic and healthcare transitions of study area were assessed during the study interval period.
Results:
Time trends of prevalence of RF/RHD revealed about five-fold decline from 2.98/1000 (95% C.I. 2.24-3.72/1000) in 1992-1993 to 0.59/1000 (95% C.I. 0.22-0.96/1000) in 2007-2008. (P<0.0001). While the prevalence of ARF and RHD with recurrence of activity was 0.176/1000 and 0.53/1000, respectively in 1992-1993, no case of RF was recorded in 2007-2008 study. Prevalence of RF/RHD was about two- fold higher in rural school children than urban school children in both the survey studies (4.42/1000 vs. 2.12/1000) and (0.88/1000 vs. 0.41/1000), respectively. The indices of socio-economic development revealed substantial improvement during this interim period.
Interpretation & conclusions:
The prevalence of RF/RHD has declined by five-fold over last 15 yr and appears to be largely contributed by improvement in socio-economic status and healthcare delivery systems. However, the role of change in the rheumatogenic characteristics of the streptococcal stains in the study area over a period of time in decline of RF/RHD cannot be ruled out. Policy interventions to improve living standards, existing healthcare facilities and awareness can go a long way in reducing the morbidity and mortality burden of RF/RHD in developing countries.
PMCID: PMC3734717  PMID: 23852293
Environmental factors; GABHS; heart disease; India; prevalence; rheumatic fever; time trends
21.  Doppler Echocardiography Imaging in Detecting Multi-Valvular Lesions: A Clinical Evaluation in Children with Acute Rheumatic Fever 
PLoS ONE  2013;8(9):e74114.
Rationale
Doppler echocardiography has been demonstrated to be accurate in diagnosing valvular lesions in rheumatic heart disease (RHD) when compared to clinical evaluation alone.
Objective
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.
Conclusion
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.
doi:10.1371/journal.pone.0074114
PMCID: PMC3775808  PMID: 24069273
22.  Incidence, prevalence and outcomes of rheumatic heart disease in South Africa: a systematic review protocol 
BMJ Open  2014;4(6):e004844.
Background
Rheumatic heart disease (RHD) is the principal cause of acquired heart disease affecting people living largely in poverty and deprived conditions. Sub-Saharan Africa was long thought to be the hotspot of the disease but recent reports suggest that this is no longer the case. South Africa is the leading economic force within this region yet contends with continued extreme income disparities. It is of interest to ascertain whether the strides that have been made in healthcare since the democratic transition in South Africa have translated into decreased RHD burden. We therefore propose to review the current best estimates of incidence of newly diagnosed RHD and prevalence of existing RHD within the past two decades. We also propose to characterise the fatal and non-fatal outcomes of RHD and identify any trends in this period.
Methods and design
We plan to search electronic databases and reference lists of relevant articles published from April 1994 to April 2014. Studies will be included if they estimated one of the following epidemiological measures: incidence, prevalence, remission rate, relative risk of mortality or cause-specific mortality. For studies deemed eligible for inclusion, we will assess overall study quality, reliability and risk of bias using design-specific criteria. We will extract data using a standardised form and perform descriptive and quantitative analysis to assess RHD prevalence, mortality and morbidity. This review protocol is registered in the PROSPERO International Prospective Register of systematic reviews, registration number CRD42014007072.
Dissemination
Our planned review will provide healthcare providers, public health officials and policymakers with pooled contemporary data regarding RHD, in particular regarding the effect the new political dispensation has had on the burden of this preventable disease within South Africa. In addition, these important country-specific data could influence policy decisions regarding prevention, management and control of RHD.
doi:10.1136/bmjopen-2014-004844
PMCID: PMC4067809  PMID: 24916089
Epidemiology; Public Health
23.  Tumor necrosis factor-alpha 308G>A polymorphism and risk of rheumatic heart disease: a meta-analysis 
Scientific Reports  2014;4:4731.
Rheumatic heart disease (RHD) remains a serious cardiovascular disorder across the world. Tumor necrosis factor alpha (TNF-α) codifies a potent immunomodulator and pro-inflammatory cytokine that mediates diverse pathological processes. A promoter 308G>A polymorphism in TNF-α has been implicated in RHD risk. However, the results remain controversial. Therefore, to evaluate more precise estimations of the relationship, a meta-analysis was performed. A total of 7 studies including 735 RHD cases and 926 controls were involved in this meta-analysis. Overall, our results revealed that there was a significant association with RHD risk in three genetic models (homozygous model: OR = 3.06, 95%CI = 1.22–10.60, P = 0.020; dominant model, OR = 2.03, 95%CI = 1.01–4.07, P = 0.048; and recessive model, OR = 4.26, 95%CI = 2.41–7.55, P < 0.001). Further ethnic population analysis found a significantly increased risk of RHD among Asians and Europeans. Interestingly, similar results were found among hospital-based studies. Begg's funnel plot and Egger's test did not reveal any publication bias. Taken together, this meta-analysis demonstrates that the TNF-α 308G>A polymorphism is associated with RHD susceptibility, and it contributes to the increased risk of RHD. However, additional well-designed studies with larger samples are warranted to confirm these findings.
doi:10.1038/srep04731
PMCID: PMC3994435  PMID: 24751687
24.  Global research priorities in rheumatic fever and rheumatic heart disease 
We now stand at a critical juncture for rheumatic fever (RF) and rheumatic heart disease (RHD) control. In recent years, we have seen a surge of interest in these diseases in regions of the world where RF/RHD mostly occur. This brings real opportunities to make dramatic progress in the next few years, but also real risks if we miss these opportunities. Most public health and clinical approaches in RF/RHD arose directly from programmes of research. Many unanswered questions remain, including those around how to implement what we know will work, so research will continue to be essential in our efforts to bring a global solution to this disease. Here we outline our proposed research priorities in RF/RHD for the coming decade, grouped under the following four challenges: Translating what we know already into practical RHD control; How to identify people with RHD earlier, so that preventive measures have a higher chance of success; Better understanding of disease pathogenesis, with a view to improved diagnosis and treatment of ARF and RHD; and Finding an effective approach to primary prevention. We propose a mixture of basic, applied, and implementation science. With concerted efforts, strong links to clinical and public health infrastructure, and advocacy and funding support from the international community, there are good prospects for controlling these RF and RHD over the next decade.
doi:10.4103/0974-2069.79616
PMCID: PMC3104531  PMID: 21677798
Rheumatic fever; rheumatic heart disease; prevention
25.  Improvement in rheumatic fever and rheumatic heart disease management and prevention using a health centre-based continuous quality improvement approach 
Background
Rheumatic heart disease (RHD) remains a major health concern for Aboriginal Australians. A key component of RHD control is prevention of recurrent acute rheumatic fever (ARF) using long-term secondary prophylaxis with intramuscular benzathine penicillin (BPG). This is the most important and cost-effective step in RHD control. However, there are significant challenges to effective implementation of secondary prophylaxis programs. This project aimed to increase understanding and improve quality of RHD care through development and implementation of a continuous quality improvement (CQI) strategy.
Methods
We used a CQI strategy to promote implementation of national best-practice ARF/RHD management guidelines at primary health care level in Indigenous communities of the Northern Territory (NT), Australia, 2008–2010. Participatory action research methods were employed to identify system barriers to delivery of high quality care. This entailed facilitated discussion with primary care staff aided by a system assessment tool (SAT). Participants were encouraged to develop and implement strategies to overcome identified barriers, including better record-keeping, triage systems and strategies for patient follow-up. To assess performance, clinical records were audited at baseline, then annually for two years. Key performance indicators included proportion of people receiving adequate secondary prophylaxis (≥80% of scheduled 4-weekly penicillin injections) and quality of documentation.
Results
Six health centres participated, servicing approximately 154 people with ARF/RHD. Improvements occurred in indicators of service delivery including proportion of people receiving ≥40% of their scheduled BPG (increasing from 81/116 [70%] at baseline to 84/103 [82%] in year three, p = 0.04), proportion of people reviewed by a doctor within the past two years (112/154 [73%] and 134/156 [86%], p = 0.003), and proportion of people who received influenza vaccination (57/154 [37%] to 86/156 [55%], p = 0.001). However, the proportion receiving ≥80% of scheduled BPG did not change. Documentation in medical files improved: ARF episode documentation increased from 31/55 (56%) to 50/62 (81%) (p = 0.004), and RHD risk category documentation from 87/154 (56%) to 103/145 (76%) (p < 0.001). Large differences in performance were noted between health centres, reflected to some extent in SAT scores.
Conclusions
A CQI process using a systems approach and participatory action research methodology can significantly improve delivery of ARF/RHD care.
doi:10.1186/1472-6963-13-525
PMCID: PMC3878366  PMID: 24350582
Continuous quality improvement; Rheumatic fever; Rheumatic heart disease; Secondary prophylaxis

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