Tertiary prevention and treatment of rheumatic heart disease: a National Heart, Lung, and Blood Institute working group summary.

Although entirely preventable, rheumatic heart disease (RHD), a disease of poverty and social disadvantage resulting in high morbidity and mortality, remains an ever-present burden in low-income and middle-income countries (LMICs) and rural, remote, marginalised and disenfranchised populations within high-income countries. In late 2021, the National Heart, Lung, and Blood Institute convened a workshop to explore the current state of science, to identify basic science and clinical research priorities to support RHD eradication efforts worldwide. This was done through the inclusion of multidisciplinary global experts, including cardiovascular and non-cardiovascular specialists as well as health policy and health economics experts, many of whom also represented or closely worked with patient-family organisations and local governments. This report summarises findings from one of the four working groups, the Tertiary Prevention Working Group, that was charged with assessing the management of late complications of RHD, including surgical interventions for patients with RHD. Due to the high prevalence of RHD in LMICs, particular emphasis was made on gaining a better understanding of needs in the field from the perspectives of the patient, community, provider, health system and policy-maker. We outline priorities to support the development, and implementation of accessible, affordable and sustainable interventions in low-resource settings to manage RHD and related complications. These priorities and other interventions need to be adapted to and driven by local contexts and integrated into health systems to best meet the needs of local communities.

Sub-clinical rheumatic heart disease (RHD) detected by hand-held echocardiogram in children participating in a school-based RHD prevention program in Tanzania.

BACKGROUND: Rheumatic Heart Disease (RHD) continues to cause suffering and premature deaths in many sub-Saharan Africa (SSA) countries, where the disease is still endemic. RHD is largely preventable and determining its community burden is an important critical step in any RHD prevention program. METHODS: We conducted a cross-sectional study of 5-16 years old pupils from 11 primary schools participating in an RHD prevention program in 4 districts in Tanzania, between 2018 and 2019. At the school, all children were invited to participate after receiving consent from their parents/guardians. Participating children filled a questionnaire and were auscultated for cardiac murmurs. Echocardiographic screening was done by two experienced cardiologists, using a hand-held machine (V-Scan, GE®). All positive screening tests were stored for further examination by the same two cardiologists to reach to a consensus of definite, borderline or no RHD, using a modified World Heart Federation (WHF) criterion. RESULTS: Of the 6895 children invited, 4738 (68.7%) were screened and 4436 (64.3%) had complete data. The mean (SD) age was 10.04 (2.43) years, and 2422 (54.6%) were girls. Fifty three (1.2%) children were found to have a murmur. The proportion of children with trace or mild valvular regurgitation, sub-valvular/chordal thickening and valvular thickening/deformity were 8.3%, 1.3%, and 1.0%, respectively. Sub-clinical RHD was found in 95 children (59 definite and 36 borderline), giving a prevalence of 2.1%, [95% CI 1.7% - 2.6%]. Sub-clinical RHD was independently associated with female sex (aOR 1.83, 95% CI 1.18-2.85, p = 0.007), older age groups (aOR 1.73, 95% CI 1.10-2.72, p = 0.018 for age group 11-14 years; and aOR 3.02 95% CI 1.01-9.05, p = 0.048 for age group 15-16 years), as well as presence of a cardiac murmur, aOR 5.63 95% CI 2.31-13.69, p < 0.0001. None of the studied socio- or economic factors was associated with the presence of sub-clinical RHD in this study. CONCLUSION: The prevalence of sub-clinical RHD among primary school children in Tanzania is 2.1%, similar to previous reports in SSA. Efforts to prevent and control RHD in our communities are highly warranted.

Positive impact of training rural health workers in identification and prevention of acute rheumatic fever in eastern Uganda.

BACKGROUND: Diagnosis of acute rheumatic fever (ARF) is mainly clinical. Delayed or missed diagnosis and failure to administer appropriate and timely treatment of ARF leads to rheumatic heart disease (RHD), which could necessitate expensive treatments such as open-heart surgery. Implementation of preventative guidelines depends on availability of trained healthcare workers. As part of the routine support supervision, the Uganda Heart Institute sent out a team to rural eastern Uganda to evaluate health workers' knowledge level regarding management of ARF. METHODS: Health workers from selected health facilities in Tororo district, eastern Uganda, were assessed for their knowledge on the clinical features and role of benzathine penicillin G (BPG) in the treatment and prevention of ARF recurrence. Using the RHD Action Needs assessment tool, we generated and administered a pre-test, then conducted training and re-administered a post-test. Eight months later, health workers were again assessed for knowledge retention and change in practices. Statistical analysis was done using Stata version 15. RESULTS: During the initial phase, 34 of the 109 (31%) health workers passed the pre-test, indicating familiarity with clinical features of ARF. The level of knowledge of BPG use in ARF was very poor in all the health units [25/109 (22.6%)] but improved after training to 80%, as shown by the chi-squared test ( χ2 = 0.000). However, retention of this knowledge waned after eight months and was not significantly different compared to pre-training (χ2 ≥ 0.2). CONCLUSIONS: A critical knowledge gap is evident among health workers, both in awareness and treatment of ARF, and calls for repetitive training as a priority strategy in prevention.

Rheumatic heart disease in The Gambia: clinical and valvular aspects at presentation and evolution under penicillin prophylaxis.

BACKGROUND: Rheumatic heart disease (RHD) remains the leading cause of cardiac-related deaths and disability in children and young adults worldwide. In The Gambia, the RHD burden is thought to be high although no data are available and no control programme is yet implemented. We conducted a pilot study to generate baseline data on the clinical and valvular characteristics of RHD patients at first presentation, adherence to penicillin prophylaxis and the evolution of lesions over time. METHODS: All patients registered with acute rheumatic fever (ARF) or RHD at two Gambian referral hospitals were invited for a clinical review that included echocardiography. In addition, patients were interviewed about potential risk factors, disease history, and treatment adherence. All clinical and echocardiography information at first presentation and during follow-up was retrieved from medical records. RESULTS: Among 255 registered RHD patients, 35 had died, 127 were examined, and 111 confirmed RHD patients were enrolled, 64% of them females. The case fatality rate in 2017 was estimated at 19.6%. At first presentation, median age was 13 years (IQR [9; 18]), 57% patients had late stage heart failure, and 84.1% a pathological heart murmur. Although 53.2% of them reported history of recurrent sore throat, only 32.2% of them had sought medical treatment. A history suggestive of ARF was reported by 48.7% patients out of whom only 15.8% were adequately treated. Two third of the patients (65.5%) to whom it was prescribed were fully adherent to penicillin prophylaxis. Progressive worsening and repeated hospitalisation was experienced by 46.8% of the patients. 17 patients had cardiac surgery, but they represented only 18.1% of the 94 patients estimated eligible for cardiac surgery. CONCLUSION: This study highlights for the first time in The Gambia the devastating consequences of RHD on the health of adolescents and young adults. Our findings suggest a high burden of disease that remains largely undetected and without appropriate secondary prophylaxis. There is a need for the urgent implementation of an effective national RHD control programto decrease the unacceptably high mortality rate, improve case detection and management, and increase community awareness of this disease.

Diagnosing rheumatic heart disease: where are we now and what are the challenges?

INTRODUCTION: Rheumatic heart disease (RHD), a sequela of acute rheumatic fever (ARF), affects 40.5 million people worldwide. The burden of disease disproportionately falls on low- and middle-income countries (LMIC) and sub-populations within high-income countries (HIC). Advances have been made in earlier detection of RHD, though several barriers to ideal management persist. AREAS COVERED: This article reviews the current burden of RHD, highlighting the disparate impact of disease. It also reviews the clinical and echocardiographic presentation of RHD, as some may present in late stages of disease with associated complications. Finally, we review the advances which have been made in echocardiographic screening to detect latent RHD, highlighting the challenges which remain regarding secondary prophylaxis management and uncertainty of best practices for treatment of latent RHD. EXPERT OPINION: Advances in technology and validation of portable echocardiography have made screening and identifying latent RHD feasible in the most burdened regions. However, uncertainty remains around best management of those with latent RHD and best methods to ensure ideal secondary prophylaxis for RHD. Research regarding latent RHD management, as well as continued work on innovative solutions (such as group A streptococcal vaccine), are promising as efforts to improve outcomes of this preventable disease persist.

Using community-led development to build health communication about rheumatic heart disease in Aboriginal children: a developmental evaluation.

OBJECTIVE: A high prevalence of acute rheumatic fever (ARF) and rheumatic heart disease (RHD) among Aboriginal children in northern Australia is coupled with low understanding among families. This has negative impacts on children's health, limits opportunities for prevention and suggests that better health communication is needed. METHODS: During an RHD echocardiography screening project, Aboriginal teachers in a remote community school created lessons to teach children about RHD in their home languages, drawing on principles of community-led development. Access to community-level RHD data, previously unknown to teachers and families, was a catalyst for this innovative work. Careful, iterative discussions among speakers of four Aboriginal languages ensured a culturally coherent narrative and accompanying teaching resources. RESULTS: The evaluation demonstrated the importance of collective work, local Indigenous Knowledge and metaphors. As a result of the lessons, some children showed new responses and attitudes to skin infections and their RHD treatment. Language teachers used natural social networks to disseminate new information. A community interagency collaboration working to prevent RHD commenced. Conclusions and implications for public health: Action to address high rates of RHD must include effective health communication strategies that value Indigenous Knowledge, language and culture, collaborative leadership and respect for Indigenous data sovereignty.

An investment case for the prevention and management of rheumatic heart disease in the African Union 2021-30: a modelling study.

BACKGROUND: Despite declines in deaths from rheumatic heart disease (RHD) in Africa over the past 30 years, it remains a major cause of cardiovascular morbidity and mortality on the continent. We present an investment case for interventions to prevent and manage RHD in the African Union (AU). METHODS: We created a cohort state-transition model to estimate key outcomes in the disease process, including cases of pharyngitis from group A streptococcus, episodes of acute rheumatic fever (ARF), cases of RHD, heart failure, and deaths. With this model, we estimated the impact of scaling up interventions using estimates of effect sizes from published studies. We estimated the cost to scale up coverage of interventions and summarised the benefits by monetising health gains estimated in the model using a full income approach. Costs and benefits were compared using the benefit-cost ratio and the net benefits with discounted costs and benefits. FINDINGS: Operationally achievable levels of scale-up of interventions along the disease spectrum, including primary prevention, secondary prevention, platforms for management of heart failure, and heart valve surgery could avert 74 000 (UI 50 000-104 000) deaths from RHD and ARF from 2021 to 2030 in the AU, reaching a 30·7% (21·6-39·0) reduction in the age-standardised death rate from RHD in 2030, compared with no increase in coverage of interventions. The estimated benefit-cost ratio for plausible scale-up of secondary prevention and secondary and tertiary care interventions was 4·7 (2·9-6·3) with a net benefit of $2·8 billion (1·6-3·9; 2019 US$) through 2030. The estimated benefit-cost ratio for primary prevention scale-up was low to 2030 (0·2, <0·1-0·4), increasing with delayed benefits accrued to 2090. The benefit-cost dynamics of primary prevention were sensitive to the costs of different delivery approaches, uncertain epidemiological parameters regarding group A streptococcal pharyngitis and ARF, assumptions about long-term demographic and economic trends, and discounting. INTERPRETATION: Increased coverage of interventions to control and manage RHD could accelerate progress towards eradication in AU member states. Gaps in local epidemiological data and particular components of the disease process create uncertainty around the level of benefits. In the short term, costs of secondary prevention and secondary and tertiary care for RHD are lower than for primary prevention, and benefits accrue earlier. FUNDING: World Heart Federation, Leona M and Harry B Helmsley Charitable Trust, and American Heart Association.

Effectiveness of Systematic Echocardiographic Screening for Rheumatic Heart Disease in Nepalese Schoolchildren: A Cluster Randomized Clinical Trial.

Importance: Echocardiographic screening allows for early detection of subclinical stages of rheumatic heart disease among children in endemic regions. Objective: To investigate the effectiveness of systematic echocardiographic screening in combination with secondary antibiotic prophylaxis on the prevalence of rheumatic heart disease. Design, Setting, and Participants: This cluster randomized clinical trial included students 9 to 16 years of age attending public and private schools in urban and rural areas of the Sunsari district in Nepal that had been randomly selected on November 17, 2012. Echocardiographic follow-up was performed between January 7, 2016, and January 3, 2019. Interventions: In the experimental group, children underwent systematic echocardiographic screening followed by secondary antibiotic prophylaxis in case they had echocardiographic evidence of latent rheumatic heart disease. In the control group, children underwent no echocardiographic screening. Main Outcomes and Measures: Prevalence of the composite of definite or borderline rheumatic heart disease according to the World Heart Federation criteria in experimental and control schools as assessed 4 years after intervention. Results: A total of 35 schools were randomized to the experimental group (n = 19) or the control group (n = 16). After a median of 4.3 years (interquartile range [IQR], 4.0-4.5 years), 17 of 19 schools in the experimental group (2648 children; median age at follow-up, 12.1 years; IQR, 10.3-12.5 years; 1308 [49.4%] male) and 15 of 16 schools in the control group (1325 children; median age at follow-up, 10.6 years; IQR, 10.0-12.5 years; 682 [51.5%] male) underwent echocardiographic follow-up. The prevalence of definite or borderline rheumatic heart disease was 10.8 per 1000 children (95% CI, 4.7-24.7) in the control group and 3.8 per 1000 children (95% CI, 1.5-9.8) in the experimental group (odds ratio, 0.34; 95% CI, 0.11-1.07; P = .06). The prevalence in the experimental group at baseline had been 12.9 per 1000 children (95% CI, 9.2-18.1). In the experimental group, the odds ratio of definite or borderline rheumatic heart disease at follow-up vs baseline was 0.29 (95% CI, 0.13-0.65; P = .008). Conclusions and Relevance: School-based echocardiographic screening in combination with secondary antibiotic prophylaxis in children with evidence of latent rheumatic heart disease may be an effective strategy to reduce the prevalence of definite or borderline rheumatic heart disease in endemic regions. Trial Registration: ClinicalTrials.gov Identifier: NCT01550068.

Echocardiographic Screening Detects a Significant Burden of Rheumatic Heart Disease in Australian Torres Strait Islander Children and Missed Opportunities for its Prevention.

Rheumatic heart disease (RHD) is almost entirely preventable, but its incidence in indigenous Australians remains one of the highest in the world. A community-based echocardiogram screening program of 862 Torres Strait Islander children identified 25 (2.9%) new cases of RHD. Among these 25 children, 5/7 (71%) prior acute rheumatic fever presentations had not been recognized. There was a history of microbiologically confirmed group A Streptococcus infection in 17/25 (68%) children with RHD compared with 9/25 (36%) controls (odds ratio [OR] [95% CI]: 3.78 [1.17-12.19], P = 0.03). This was more likely to be a skin swab (16/25 [64%] cases versus 6/25 [24%] controls) than a throat swab (1/25 [4%] cases versus 3/25 [12%] controls) (OR [95% CI]: 5.33 [1.51-18.90] [P = 0.01]), supporting a role for skin infection in RHD pathogenesis. Household crowding and unemployment were common in the cohort, emphasizing the need for prioritizing strategies that address the social determinants of health.

Contemporary Diagnosis and Management of Rheumatic Heart Disease: Implications for Closing the Gap: A Scientific Statement From the American Heart Association.

The global burden of rheumatic heart disease continues to be significant although it is largely limited to poor and marginalized populations. In most endemic regions, affected patients present with heart failure. This statement will seek to examine the current state-of-the-art recommendations and to identify gaps in diagnosis and treatment globally that can inform strategies for reducing disease burden. Echocardiography screening based on World Heart Federation echocardiographic criteria holds promise to identify patients earlier, when prophylaxis is more likely to be effective; however, several important questions need to be answered before this can translate into public policy. Population-based registries effectively enable optimal care and secondary penicillin prophylaxis within available resources. Benzathine penicillin injections remain the cornerstone of secondary prevention. Challenges with penicillin procurement and concern with adverse reactions in patients with advanced disease remain important issues. Heart failure management, prevention, early diagnosis and treatment of endocarditis, oral anticoagulation for atrial fibrillation, and prosthetic valves are vital therapeutic adjuncts. Management of health of women with unoperated and operated rheumatic heart disease before, during, and after pregnancy is a significant challenge that requires a multidisciplinary team effort. Patients with isolated mitral stenosis often benefit from percutaneous balloon mitral valvuloplasty. Timely heart valve surgery can mitigate the progression to heart failure, disability, and death. Valve repair is preferable over replacement for rheumatic mitral regurgitation but is not available to the vast majority of patients in endemic regions. This body of work forms a foundation on which a companion document on advocacy for rheumatic heart disease has been developed. Ultimately, the combination of expanded treatment options, research, and advocacy built on existing knowledge and science provides the best opportunity to address the burden of rheumatic heart disease.

How accurate is the diagnosis of rheumatic fever in Egypt? Data from the national rheumatic heart disease prevention and control program (2006-2018).

Rheumatic heart disease (RHD) as a chronic sequela of repeated episodes of acute rheumatic fever (ARF), remains a cause of cardiac morbidity in Egypt although it is given full attention through a national RHD prevention and control program. The present report reviews our experience with subjects presenting with ARF or its sequelae in a single RHD centre and describes the disease pattern over the last decade. A cross-sectional study was conducted in El-Mahalla RHD centre between 2006 and 2018. A total of 17014 individual were enrolled and evaluated. Diagnosis ARF was based on the 2015 revised Jones criteria and RHD was ruled in by echocardiography. The majority of the screened subjects were female (63.2%), in the age group 5-15 years (64.6%), rural residents (61.2%), had primary education (43.0%), and of low socioeconomic standard (50.2%). The total percentage of cases presenting with ARF sequelae was 29.3% [carditis/RHD (10.8%), rheumatic arthritis (Rh.A) (14.9%), and Sydenham's chorea (0.05%)]. Noticeably, 72% were free of any cardiac insult, of which 37.7% were victims of misdiagnoses made elsewhere by untrained practitioners who prescribed for them long term injectable long-acting penicillin [Benzathine Penicillin G (BPG)] without need. About 54% of the study cohort reported the occurrence of recurrent attacks of tonsillitis of which 65.2% underwent tonsillectomy. Among those who experienced tonsillectomy and/or received BPG in the past, 14.5% and 22.3% respectively had eventually developed RHD. Screening of family members of some RHD cases who needed cardiac surgery revealed 20.7% with undiagnosed ARF sequalae [RHD (56.0%) and Rh.A (52.2%)]. Upon the follow-up of RHD cases, 1.2% had improved, 98.4% were stable and 0.4% had their heart condition deteriorated. Misdiagnosis of ARF or its sequelae and poor compliance with BPG use may affect efforts being exerted to curtail the disease. Updating national guidelines, capacity building, and reliance on appropriate investigations should be emphasized. Since the genetic basis of RHD is literally confirmed, a family history of RHD warrants screening of all family members for early detection of the disease.

Prevalence of group A Streptococcal infection in Africa to inform GAS vaccines for rheumatic heart disease: A systematic review and meta-analysis.

BACKGROUND: The prevalence of group A streptococcal (GAS) disease is estimated at >18.1 million cases with an incidence of >1.78 million cases per year. While a significant cause of mortality and morbidity on the global scale, the burden of GAS disease in Africa is unknown. We conducted a systematic review on the prevalence of GAS disease among children and adults in Africa and the frequency and distribution of emm types among isolates. METHODS: We performed a comprehensive literature search in a number of databases, using an African search filter. Two reviewers independently selected articles meeting pre-specified criteria and extracted relevant data as per a data extraction form. We applied the random-effects meta-analysis model to aggregate GAS prevalence estimates with 95% CI for GAS prevalence, incorporating the Freeman-Tukey transformation to account for between-study variability. RESULTS: Twenty-five studies were included. Invasive GAS disease prevalence ranged from 0.6% to 10.8% in samples from normally-sterile sites including blood, CSF and soft tissue. A single study reported a prevalence of 74% in skin infections. Prevalence of emm types varied with up to 88 different strains reported, corresponding to a vaccine coverage of 28% to 65%. The pooled prevalence of GAS in persons presenting with pharyngitis was 21% (95% CI, 17% to 26%). CONCLUSIONS: The prevalence of GAS remains high among symptomatic individuals residing in Africa. Data on molecular strain characterisation of GAS in Africa is largely non-existent, thus the need for further studies is warranted to inform current prevention efforts including vaccine development.

Clinic factors associated with better delivery of secondary prophylaxis in acute rheumatic fever management.

BACKGROUND AND OBJECTIVES: Acute rheumatic fever (ARF) is a complication of infection with group A streptococcus. ARF is treated with a long-term regimen of antibiotic secondary prophylaxis. Recent data have shown that only 36% of clients receive >80% of their regimen. The aim of this study was to determine clinic-level factors independently associated with the performance of primary healthcare clinics in delivering secondary prophylaxis to patients with ARF. METHOD: Cross-sectional de-identified data from clinics agreeing to data retention through the Audit and Best Practice for Chronic Disease National Research Partnership were accessed to calculate secondary prophylaxis performance scores and clinic-level factors associated with secondary prophylaxis performance using regression analysis. RESULTS: Thirty-six clinics and 496 client records met eligibility criteria for analysis. Clinic secondary prophylaxis performance was significantly associated with 'systematic processes of follow-up'. Every one unit increase in 'systematic approach to follow-up' increased the median level of secondary prophylaxis performance by 30% (95% confidence interval: 2, 66). Clinic accreditation status, location or workforce were not associated with secondary prophylaxis performance. DISCUSSION: General practitioners as clinical leaders are well placed to support managers to critically review follow-up and electronic reminder systems for secondary prophylaxis delivery at clinic level.

Rheumatic Fever: A Disease without Color / Febre Reumática: Uma Doença sem Cor

Abstract Background: Brazil has approximately 30.000 cases of Acute Rheumatic Fever (ARF) annually. A third of cardiovascular surgeries performed in the country are due to the sequelae of rheumatic heart disease (RHD), which is an important public health problem. Objectives: to analyze the historical series of mortality rates and disease costs, projecting future trends to offer new data that may justify the need to implement a public health program for RF. Methods: we performed a cross-sectional study with a time series analysis based on data from the Hospital Information System of Brazil from 1998 to 2016. Simple linear regression models and Holt's Exponential Smoothing Method were used to model the behavior of the series and to do forecasts. The results of the tests with a value of p < 0.05 were considered statistically significant. Results: each year, the number of deaths due to RHD increased by an average of 16.94 units and the mortality rate from ARF increased by 215%. There was a 264% increase in hospitalization expenses for RHD and RHD mortality rates increased 42.5% (p-value < 0.05). The estimated mortality rates for ARF and RHD were, respectively, 2.68 and 8.53 for 2019. The estimated cost for RHD in 2019 was US$ 26.715.897,70. Conclusions: according to the Brazilian reality, the 1-year RHD expenses would be sufficient for secondary prophylaxis (considering a Benzatin Penicillin G dose every 3 weeks) in 22.574 people for 10 years. This study corroborates the need for public health policies aimed at RHD.

Resumo Fundamento: O Brasil tem aproximadamente 30.000 casos de febre reumática aguda (FRA) por ano. Um terço das cirurgias cardiovasculares realizadas no país se deve às sequelas da doença reumática cardíaca (DRC), a qual é um importante problema de saúde pública. Objetivos: Analisar as séries históricas de taxas de mortalidade e custos das doenças, projetando tendências futuras para oferecer novos dados que possam justificar a necessidade de implementação de um programa de saúde pública para FR. Métodos: Foi realizado um estudo transversal com análise de séries temporais a partir de dados do Sistema de Informações Hospitalares do Brasil, de 1998 a 2016. Modelos de regressão linear simples e o método de suavização exponencial de Holt foram utilizados para modelar o comportamento das séries e fazer previsões. Os resultados dos testes com um valor de p <0,05 foram considerados estatisticamente significantes. Resultados: A cada ano, o número de mortes por DRC aumentou em média 16,94 unidades, e a taxa de mortalidade por FRA aumentou em 215%. Houve um aumento de 264% nas despesas de hospitalização por DRC, e as taxas de mortalidade por DRC aumentaram 42,5% (p-valor < 0,05). As taxas de mortalidade estimadas para FRA e DRC foram, respectivamente, 2,68 e 8,53 para 2019. O custo estimado para a DRC em 2019 foi de US$ 26.715.897,70. Conclusões: De acordo com a realidade brasileira, o gasto relativo a 1 ano de DRC seria suficiente para a profilaxia secundária (considerando uma dose de penicilina G benzatina a cada 3 semanas) em 22.574 pessoas por 10 anos. Este estudo corrobora a necessidade de políticas públicas de saúde direcionadas à DRC.

Rheumatic fever and rheumatic heart disease: Facts and research progress in Africa.

In recent years, the devastating effect of rheumatic fever (RF) and rheumatic heart disease (RHD) in Africa has been acknowledged by Institutions such as the Pan-African Society of Cardiology, the African Union Commission, and the World Health Organization. Key priorities set to eradicate RF and RHD include diagnosing and managing RF and RHD, building registries, improving adequate supplies of benzathine penicillin, reproductive health services, and cardiac surgery, developing multi-sectoral RHD awareness programmes, understanding RHD pathogenesis and fostering international partnership for resource mobilization. There were volumes of peer reviewed publications focusing on the key priorities to fight RHD in different parts to Africa; both individually as well as through international collaborations. This article analyzed findings and reports from 1961 to 2018 on efforts to eradicate RF and RHD in Africa.

Rheumatic heart disease in the modern era: recent developments and current challenges.

Rheumatic heart disease (RHD) remains a major cause of preventable death and disability in children and young adults. Despite significant advances in medical technology and increased understanding of disease mechanisms, RHD continues to be a serious public health problem throughout the world, especially in low- and middle-income countries. Echocardiographic screening has played a key role in improving the accuracy of diagnosing RHD and has highlighted the disease burden. Most affected patients present with severe valve disease and limited access to life-saving cardiac surgery or percutaneous valve intervention, contributing to increased mortality and other complications. Although understanding of disease pathogenesis has advanced in recent years, key questions remain to be addressed. Preventing or providing early treatment for streptococcal infections is the most important step in reducing the burden of this disease.

Rheumatic heart disease in the modern era: recent developments and current challenges

Abstract Rheumatic heart disease (RHD) remains a major cause of preventable death and disability in children and young adults. Despite significant advances in medical technology and increased understanding of disease mechanisms, RHD continues to be a serious public health problem throughout the world, especially in low- and middle-income countries. Echocardiographic screening has played a key role in improving the accuracy of diagnosing RHD and has highlighted the disease burden. Most affected patients present with severe valve disease and limited access to life-saving cardiac surgery or percutaneous valve intervention, contributing to increased mortality and other complications. Although understanding of disease pathogenesis has advanced in recent years, key questions remain to be addressed. Preventing or providing early treatment for streptococcal infections is the most important step in reducing the burden of this disease.

Rheumatic Heart Disease in the Twenty-First Century.

Rheumatic heart disease (RHD) is a chronic valvular disease resulting after severe or repetitive episodes of acute rheumatic fever (ARF), an autoimmune response to group A Streptococcus infection. RHD has been almost eliminated with improved social and health infrastructure in affluent countries while it remains a neglected disease with major cause of morbidity and mortality in many low- and middle-income countries, and resource-limited regions of high-income countries. Despite our evolving understanding of the pathogenesis of RHD, there have not been any significant advances to prevent or halt progression of disease in recent history. Long-term penicillin-based treatment and surgery remain the backbone of a RHD control program in the absence of an effective vaccine. The advent of echocardiographic screening algorithms has improved the accuracy of diagnosing RHD and has shed light on the enormous burden of disease. Encouragingly, this has led to a rekindled commitment from researchers in the most affected countries to advocate and take bold actions to end this disease of social inequality.

Predicted Coverage and Immuno-Safety of a Recombinant C-Repeat Region Based Streptococcus pyogenes Vaccine Candidate.

The C-terminal region of the M-protein of Streptococcus pyogenes is a major target for vaccine development. The major feature is the C-repeat region, consisting of 35-42 amino acid repeat units that display high but not perfect identity. SV1 is a S. pyogenes vaccine candidate that incorporates five 14mer amino acid sequences (called J14i variants) from differing C-repeat units in a single recombinant construct. Here we show that the J14i variants chosen for inclusion in SV1 are the most common variants in a dataset of 176 unique M-proteins. Murine antibodies raised against SV1 were shown to bind to each of the J14i variants present in SV1, as well as variants not present in the vaccine. Antibodies raised to the individual J14i variants were also shown to bind to multiple but different combinations of J14i variants, supporting the underlying rationale for the design of SV1. A Lewis Rat Model of valvulitis was then used to assess the capacity of SV1 to induce deleterious immune response associated with rheumatic heart disease. In this model, both SV1 and the M5 positive control protein were immunogenic. Neither of these antibodies were cross-reactive with cardiac myosin or collagen. Splenic T cells from SV1/CFA and SV1/alum immunized rats did not proliferate in response to cardiac myosin or collagen. Subsequent histological examination of heart tissue showed that 4 of 5 mice from the M5/CFA group had valvulitis and inflammatory cell infiltration into valvular tissue, whereas mice immunised with SV1/CFA, SV1/alum showed no sign of valvulitis. These results suggest that SV1 is a safe vaccine candidate that will elicit antibodies that recognise the vast majority of circulating GAS M-types.