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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.
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 (NCT01550068). The study findings will be reported in peer-reviewed publications. Identifier
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.
PMCID: PMC3371575  PMID: 22685225
2.  Rheumatic Heart Disease in Kerala: A Vanishing Entity? An Echo Doppler Study in 5–15-Years-Old School Children 
Background. Early detection of subclinical rheumatic heart disease by use of echocardiography warrants timely implementation of secondary antibiotic prophylaxis and thereby prevents or retards its related complications. Objectives. The objective of this epidemiological study was to determine prevalence of RHD by echocardiography using World Heart Federation criteria in randomly selected school children of Trivandrum. Methods. This was a population-based cross-sectional screening study carried out in Trivandrum. A total of 2060 school children, 5–15 years, were randomly selected from five government and two private (aided) schools. All enrolled children were screened for RHD according to standard clinical and WHF criteria of echocardiography. Results. Echocardiographic examinations confirmed RHD in 5 children out of 146 clinically suspected cases. Thus, clinical prevalence was found to be 2.4 per 1000. According to WHF criteria of echocardiography, 12 children (12/2060) were diagnosed with RHD corresponding to echocardiographic prevalence of 5.83 cases per 1000. As per criteria, 6 children were diagnosed with definite RHD and 6 with borderline RHD. Conclusions. The results of the current study demonstrate that echocardiography is more sensitive and feasible in detecting clinically silent RHD. Our study, the largest school survey of south India till date, points towards declining prevalence of RHD (5.83/1000 cases) using WHF criteria in Kerala.
PMCID: PMC4584222  PMID: 26451146
3.  Prevalence and pattern of rheumatic heart disease in the Nigerian savannah: an echocardiographic study 
Cardiovascular Journal of Africa  2007;18(5):295-299.
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.
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.
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%).
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
4.  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
5.  Echocardiographic screening for rheumatic heart disease—some answers, but questions remain 
Translational Pediatrics  2015;4(3):206-209.
Despite being preventable, rheumatic heart disease (RHD) remains a significant global cause of cardiovascular disease. Echocardiographic screening for early detection of RHD has the potential to enable timely commencement of treatment (secondary prophylaxis) to halt progression to severe valvular disease. However, a number of issues remain to be addressed regarding its feasibility. The natural history of Definite RHD without a prior history of acute rheumatic fever (ARF) and Borderline RHD are both unclear. Even if they are variants of RHD it is not known whether secondary antibiotic prophylaxis will prevent disease progression as it does in “traditionally” diagnosed RHD. False positives can also have a detrimental impact on individuals and their families as well as place substantial burdens on health care systems. Recent research suggests that handheld echocardiography (HAND) may offer a cheaper and more convenient alternative to standard portable echocardiography (STAND) in RHD screening. However, while HAND is sensitive for the detection of Definite RHD, it is less sensitive for Borderline RHD and is relatively poor at detecting mitral stenosis (MS). Given its attendant limited specificity, potential cases detected with HAND would require re-examination by standard echocardiography. For now, echocardiographic screening for RHD should remain a subject of research rather than routine health care.
PMCID: PMC4729054  PMID: 26835376
Rheumatic heart disease (RHD); echocardiography; screening; prophylaxis
6.  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.
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.
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.
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
7.  An evaluation of secondary prophylaxis for rheumatic heart disease in rural Egypt 
Background: Although essentially disappeared from the industrialized world, rheumatic heart disease (RHD) is still prevalent in developing countries, with 300,000 new cases identified each year. In Aswan, Egypt, RHD affects about 2.3% of children with over 90% of the cases being subclinical. Secondary prophylaxis has proved to be an effective method of preventing the progression of RHD. However, its efficacy is limited by low patient adherence. A systematic, generalizable tool is necessary to outline, and ultimately address these barriers. Methods: A 43-item semi-structured questionnaire was developed based on the three domains outlined by Fishbein (capability, intention, and health care barriers). A preliminary evaluation of the barriers to RHD prophylaxis use in Aswan, Egypt was carried out as a pilot study using this tool. Participants were local school children diagnosed with RHD or flagged as high-risk (as per a set of echocardiographic criteria developed by the Aswan Heart Centre) through a previous screening program of randomly selected 3,062 school children in Aswan. Results: 29 patients were interviewed (65.5% adherent to RHD prophylaxis). Compared to non-adherent patients, adherent patients had better understanding of the disease (68.4% versus 20% in the non-adherent group, p = 0.021), and were more aware of the consequences of missing prophylaxis doses (79% versus 40% of non-adherent patients, p = 0.005). Furthermore, 90% of non-adherent patients consciously choose to miss injection appointments (as compared to 31.6% of adherent patients, p = 0.005). Clinic wait time was the most frequently reported deterrent for both groups. Conclusion: A standardized tool that systematically outlines barriers to prophylaxis is a necessary first step to improving adherence to penicillin. Although individually developed tools exist for specific populations, a generalizable tool that takes into account the demographic and cultural differences in the populations of interest will allow for more reliable data collection methodology. Application of this tool will be used to further explore barriers to prophylaxis adherence and inform the basis for the design of future KT interventions.
PMCID: PMC4633577  PMID: 26779516
8.  The natural history of latent rheumatic heart disease in a 5 year follow-up study: a prospective observational study 
Latent rheumatic heart disease (RHD) occurs in asymptomatic individuals with echocardiographic evidence of RHD and no history of acute rheumatic fever. The natural history of latent RHD is unclear but has important clinical and economic implications about whether these children should receive penicillin prophylaxis or not. We performed a 5-year prospective study of this question.
In August 2013 through September 2014, we conducted a follow-up study of latent RHD among school pupils using the World Heart Federation (WHF) echocardiographic criteria. Contingency tables were used to assess progression, persistence or regression of latent RHD.
Forty two borderline and 13 definite cases of RHD (n 55) were identified, 44 (80 %; mean age 13.8 ± 4.0 years; 29 (65.9 %) female) of whom were available for echocardiographic examination at a median follow-up of 60.8 months (interquartile range 51.3-63.5). Over the follow-up period, half the participants (n = 23; 52.3 %) improved to normal or better WHF category (regressors), a third (n = 14, 31.8 %) remained in the same category (persistors), while seven others (15.9 %) progressed from borderline to definite RHD (progressors). In total, 21 subjects (47.7 %) reverted to a normal status, nine (20.4 %) either improved from definite to borderline or remained in the borderline category, and 14 (31.8 %) either remained definite or progressed from borderline to a definite status. Two cases (20 %) progressed to symptomatic disease.
Latent RHD has a variable natural history that ranges from regression to normal in nearly half of cases, to persistence, progression or development of symptoms in the remainder of subjects.
PMCID: PMC4759741  PMID: 26892774
Latent rheumatic heart disease; Natural history; Outcome
9.  Prevalence of rheumatic fever and rheumatic heart disease in Bangladeshi children 
Indian Heart Journal  2015;67(1):45-49.
Recent prevalence data on rheumatic fever (RF) and rheumatic heart disease (RHD) are lacking in Bangladeshi population.
We have done this national level cross-sectional survey to determine the prevalence of RF and RHD in Bangladeshi children.
Samples were drawn from three out of seven divisions of Bangladesh from both urban and rural areas. Trained and experienced enumerators visited households to suspect cases of RF or RHD in 5–19 years children by asking structured questions on symptoms and signs of RF and RHD (n = 56,827). Then trained doctors again took history and examined them for RF/RHD. RF was defined according to the Modified Jones Criteria 1992. Doppler echocardiography was done to confirm the diagnosis in all suspected cases of RF/RHD.
A total of 36 RF cases (new and old) and 16 Doppler echocardiography confirmed RHD cases were identified. Prevalence of RF and RHD was 0.9 per 1000 (95% confidence interval: 0.7–1.2) while prevalence of RF was 0.6 per 1000 (95% CI: 0.4–0.9) and RHD 0.3 per 1000 (95% CI: 0.2–0.5).
Observed prevalence of RF and RHD indicates that RF/RHD is disappearing from Bangladesh. However, studies using new technology of portable echocardiographic screening are needed.
PMCID: PMC4382544  PMID: 25820050
Rheumatic fever; Rheumatic heart disease; Bangladesh; Children; Prevalence
10.  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 
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.
PMCID: PMC3536578  PMID: 23186515
Rheumatic heart disease; Acute rheumatic fever; Screening; Aboriginal; Torres Strait Islander; Indigenous; Diagnosis; Prevention; Australia; Echocardiography
11.  Rheumatic heart disease in rural south India: A clinico-observational study 
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.
PMCID: PMC3758088  PMID: 24023467
Prevalence; RHD; South India
12.  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
13.  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.
PMCID: PMC1768176  PMID: 15020513
rheumatic heart disease; Pakistan
14.  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.
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.
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
15.  Prevalence of rheumatic and congenital heart disease in school children of Andhra Pradesh, South India 
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.
PMCID: PMC3758100  PMID: 24023464
Congenital heart disease (CHD); Echocardiography; Rheumatic heart disease (RHD)
16.  Screening for Rheumatic Heart Disease among Peruvian Children: A Two-Stage Sampling Observational Study 
PLoS ONE  2015;10(7):e0133004.
The objective of the study was to evaluate the implications of different classifications of rheumatic heart disease on estimated prevalence, and to systematically assess the importance of incidental findings from echocardiographic screening among schoolchildren in Peru.
We performed a cluster randomized observational survey using portable echocardiography among schoolchildren aged 5 to 16 years from randomly selected public and private schools in Arequipa, Peru. Rheumatic heart disease was defined according to the modified World Health Organization (WHO) criteria and the World Heart Federation (WHF) criteria.
Among 1395 eligible students from 40 classes and 20 schools, 1023 (73%) participated in the present survey. The median age of the children was 11 years (interquartile range [IQR] 8–13 years) and 50% were girls. Prevalence of possible, probable and definite rheumatic heart disease according to the modified WHO criteria amounted to 19.7/1000 children and ranged from 10.2/1000 among children 5 to 8 years of age to 39.8/1000 among children 13 to 16 years of age; the prevalence of borderline/definite rheumatic heart disease according to the WHF criteria was 3.9/1000 children. 21 children (2.1%) were found to have congenital heart disease, 8 of which were referred for percutaneous or surgical intervention.
Prevalence of RHD in Peru was considerably lower compared to endemic regions in sub-Saharan Africa, southeast Asia, and Oceania; and paralleled by a comparable number of undetected congenital heart disease. Strategies to address collateral findings from echocardiographic screening are necessary in the setup of active surveillance programs for RHD.
Trial Registration identifier: NCT02353663
PMCID: PMC4514892  PMID: 26208006
17.  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.
PMCID: PMC2895982  PMID: 20538135
rheumatic heart disease; prevalence of disease; disease burden
18.  Heart Lesion After the First Attack of the Rheumatic Fever 22 Years Experience in Single Centre 
Medical Archives  2015;69(1):49-53.
Acute rheumatic fever and its sequels, rheumatic heart diseases, remain major unsolved preventable health problems in Kosovo population, particularly among the disadvantages indigenous Albanian and Egyptians people. In Kosovo, despite of performing secondary prophylaxis with benzathine penicillin, acute rheumatic fever hospitalization rates have remained essentially unchanged for the last 20 years. The role of echocardiography in the diagnosis of acute rheumatic carditis was established over the last 20 years.
In this study we aimed to determine the prevalence of rheumatic heart disease in children from Kosovo population with first attack of acute rheumatic fever. Also, we presented that echocardiography examination detects a greater prevalence of rheumatic heart disease than other diagnostic procedures. We aimed to compare the sensitivity and specificity of cardiac auscultation, ECG record, lab analysis to echocardiography and to determine the feasibility of specific age in this setting.
To optimize accurate diagnosis of rheumatic fever and rheumatic heart disease, we utilized two group models. In the first group of 388 children, hospitalized and treated before 1999, diagnosis of rheumatic fever was decided basing on the clinical and laboratory findings whereas in second group (221 children treated from1999 to 2010) clinical and lab diagnosis were amplified also on the detection by echocardiography.
In second group, using echocardiography as a method of diagnosis and assessment children with rheumatic fever, we found high rates of undetected rheumatic heart disease in this high-risk group population. Echocardiographic examination of children with rheumatic fever for rheumatic heart disease may over diagnose rheumatic heart disease unless congenital mitral valve anomalies and physiological regurgitation are excluded.
PMCID: PMC4384842  PMID: 25870479
rheumatic fever; rheumatic heart disease; chorea minor; echocardiography
19.  A Cost-Effectiveness Analysis of a Program to Control Rheumatic Fever and Rheumatic Heart Disease in Pinar del Rio, Cuba 
PLoS ONE  2015;10(3):e0121363.
Acute rheumatic fever (ARF) and rheumatic heart disease (RHD) persist in many low- and middle-income countries. To date, the cost-effectiveness of population-based, combined primary and secondary prevention strategies has not been assessed. In the Pinar del Rio province of Cuba, a comprehensive ARF/RHD control program was undertaken over 1986 – 1996. The present study analyzes the cost-effectiveness of this Cuban program.
Methods and Findings
We developed a decision tree model based on the natural history of ARF/RHD, comparing the costs and effectiveness of the 10-year Cuban program to a “do nothing” approach. Our population of interest was the cohort of children aged 5 – 24 years resident in Pinar del Rio in 1986. We assessed costs and health outcomes over a lifetime horizon, and we took the healthcare system perspective on costs but did not apply a discount rate. We used epidemiologic, clinical, and direct medical cost inputs that were previously collected for publications on the Cuban program. We estimated health gains as disability-adjusted life years (DALYs) averted using standard approaches developed for the Global Burden of Disease studies. Cost-effectiveness acceptability thresholds were defined by one and three times per capita gross domestic product per DALY averted. We also conducted an uncertainty analysis using Monte Carlo simulations and several scenario analyses exploring the impact of alternative assumptions about the program’s effects and costs. We found that, compared to doing nothing, the Cuban program averted 5051 DALYs (1844 per 100,000 school-aged children) and saved $7,848,590 (2010 USD) despite a total program cost of $202,890 over 10 years. In the scenario analyses, the program remained cost saving when a lower level of effectiveness and a reduction in averted years of life lost were assumed. In a worst-case scenario including 20-fold higher costs, the program still had a 100% of being cost-effective and an 85% chance of being cost saving.
A 10-year program to control ARF/RHD in Pinar del Rio, Cuba dramatically reduced morbidity and premature mortality in children and young adults and was cost saving. The results of our analysis were robust to higher program costs and more conservative assumptions about the program’s effectiveness. It is possible that the program’s effectiveness resulted from synergies between primary and secondary prevention strategies. The findings of this study have implications for non-communicable disease policymaking in other resource-limited settings.
PMCID: PMC4358951  PMID: 25768008
20.  A new look at acquired heart diseases in a contemporary sub-Saharan African pediatric population: the case of Yaoundé, Cameroon 
Acquired heart diseases (AHD) in children cause significant morbidity and mortality especially in low resource settings. There is limited description of acquired childhood heart diseases in Cameroon, making it difficult to estimate its current contribution to childhood morbidity and mortality. Echocardiography is the main diagnostic modality in low resource settings and has a key role in the characterization and management of these disorders. We aimed to determine the prevalence and spectrum of AHD in children in Yaoundé-Cameroon, in an era of echocardiography. These data are needed for health service and policy formulation.
Echocardiography records from August 2003 to December 2013 were reviewed. Echocardiography records of children ≤18 years with an echocardiographic diagnosis of a definite AHD were identified and relevant data extracted from their records.
One hundred and fifty eight children (13.4%) ≤18 years had an AHD. The mean [± standard deviations (SD)] age was 11.9 (±4.4) years .The most common affected age group was 15-18 years (36.1%). Heart failure (20.3%), suspicion of rheumatic heart disease (RHD) (12.0%) and the presence of a heart murmur (8.9%) were the most common indications for echocardiography. RHD (41.1%), pericardial disease (25.3%), dilated cardiomyopathy (DCM) (15.8%) and endomyocardial fibrosis (EMF) (13.9%) were the most common AHD. Cor pulmonale was rare (1.3%). Fifty-seven (87.7%) children with RHD had mitral regurgitation alone or in combination with other heart valve lesions and 63.3% of the lesions were severe.
RHD remains the most common AHD in children in this setting and is frequently severe. Multicenter collaborative studies will help to better describe the pattern of AHD and there should be a renewed focus on the prevention of RHD.
PMCID: PMC4666696  PMID: 26672632
Acquired heart disease (AHD); children; sub-Saharan Africa; Cameroon
21.  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.
PMCID: PMC3812860  PMID: 23680886
22.  Rheumatic heart disease screening by “point-of-care” echocardiography: an acceptable alternative in resource limited settings? 
Translational Pediatrics  2015;4(3):210-213.
Rheumatic heart disease (RHD) is estimated to affect over 20 million people worldwide, the vast majority being in developing countries. Screening for RHD has been recommended by World Health Organization (WHO) since 2004. Conventionally, auscultation has been used for diagnosing RHD. Auscultation has its limitations and may not detect mild cases. With the evolution of portable echocardiographic systems, mass screening for subclinical RHD has become possible. Portable echo has the advantage of rapid access and hence screening in schools or communities is possible. Its cost is lower than that of standard echo equipment. A large number of studies have reported echocardiographic screening for RHD over the last decade or so. A 3-10 fold increase in prevalence of RHD has been detected by using portable echo when compared with conventional method of auscultation. More recently, a small, compact, easy to carry in a pocket, hand held system has been introduced which is much cheaper than the conventional portable system. A few previous reports have shown the feasibility of using hand held echo system for diagnosis of various cardiac diseases. A recently published article has shown that the hand held system can be used to screen for RHD. It is more sensitive than the conventional auscultation for RHD. Authors of this report have concluded that screening with the hand held device may be a more cost effective strategy for screening for RHD in resource limited settings, since it is much cheaper than the portable echocardiography equipment.
PMCID: PMC4729056  PMID: 26835377
Rheumatic heart disease (RHD); echocardiography; screening
23.  Improving delivery of secondary prophylaxis for rheumatic heart disease in remote Indigenous communities: study protocol for a stepped-wedge randomised trial 
Trials  2016;17:51.
Rheumatic heart disease (RHD), caused by acute rheumatic fever (ARF), is a major health problem in Australian Aboriginal communities. Progress in controlling RHD requires improvements in the delivery of secondary prophylaxis, which comprises regular, long-term injections of penicillin for people with ARF/RHD.
This trial aims to improve uptake of secondary prophylaxis among Aboriginal people with ARF/RHD to reduce progression or worsening of RHD. This is a stepped-wedge, randomised trial in consenting communities in Australia’s Northern Territory. Pairs of randomly-chosen clinics from among those consenting enter the study at 3-monthly steps. The intervention to which clinics are randomised comprises a multi-faceted systems-based package, in which clinics are supported to develop and implement strategies to improve penicillin delivery, aligned with elements of the Chronic Care Model. Continuous quality improvement processes will be used, including 3-monthly feedback to clinic staff of adherence rates of their ARF/RHD clients.
The primary outcome is the proportion of people with ARF/RHD receiving ≥80 % of scheduled penicillin injections over a minimum 12-month period. The sample size of 300 ARF/RHD clients across five community clusters will power the study to detect a 20 % increase in the proportion of individuals achieving this target, from a worrying low baseline of 20 %, to 40 %. Secondary outcomes pertaining to other measures of adherence will be assessed. Within the randomised trial design, a mixed-methods evaluation will be embedded to evaluate the efficiency, effectiveness, impact and relevance, sustainability, process and fidelity, and performance of the intervention. The evaluation will establish any causal link between outcomes and the intervention. The planned study duration is from 2013 to 2016.
Continuous quality improvement has a strong track record in Australia’s Northern Territory, and its use has resulted in modest benefits in a pilot, non-randomised ARF/RHD study. If successful, this new intervention using the Chronic Care Model as a scaffold and evaluated using a well-developed theory-based framework, will provide a practical and transferable approach to ARF/RHD control.
Trial registration
Australian New Zealand Clinical Trials Registry: ACTRN12613000223730. Date registered: 25 February 2013
Electronic supplementary material
The online version of this article (doi:10.1186/s13063-016-1166-y) contains supplementary material, which is available to authorized users.
PMCID: PMC4729116  PMID: 26818484
Acute rheumatic fever; Rheumatic heart disease; Continuous quality improvement; Health-systems research; Stepped-wedge design
24.  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.
PMCID: PMC3786526  PMID: 24109516
25.  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.
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.
PMCID: PMC3626837  PMID: 23402561
Acute rheumatic fever; Rheumatic heart disease; Patient compliance; Antibiotic prophylaxis; Melanesia; New Caledonia

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