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IntroductionPrimary prevention of rheumatic heart disease (RHD) is aimed at timely diagnosis and treatment of superficial Group A Streptococcal infections, most commonly Strep sore throat. However, uptake and delivery of primary prevention for RHD-endemic regions has room for improvement. Community co-design is an important aspect of intervention development to increase sustainability and reach.MethodsGroup-level assessment (GLA) sessions were used to understand the community’s priorities and insights around sore throat. Personas, or user archetypes, were then developed to capture the behaviours and characteristics of diverse future users of primary prevention in the district. Finally, these personas were used in community design workshops to identify barriers and facilitators to potential interventions, generate creative solutions to overcome identified barriers and prioritise implementation models based on impact and feasibility. The final list of implementation strategies was presented by workshop participants to the broader community for additional validation and feedback.ResultsThe GLA sessions identified five priority areas: (1) need for improved access to care, closer to home; (2) importance of mothers as caregivers; (3) strong influence of community leaders; (4) importance of community health workers and (5) role of traditional providers and practices. Five personas were created, including: hands-on caregiver, restricted caregiver, removed family decision-maker, helpful neighbour and influential leader. Design workshops identified the highest-rated interventions as: decentralisation of care delivery into the community (strategy 1), use of community health workers as key implementing partners (strategy 2) and streamlining sore throat services at public healthcare facilities (strategy 3). Participants proposed potential practical applications of these interventions.ConclusionsCommunity-based participatory research identified novel implementation strategies for an RHD primary prevention programme in Uganda. The value set and strategies developed in this study can now be used as guideposts to develop and test a package of implementation strategies for improving RHD primary prevention in Uganda.

Nearly a century after rheumatic fever (RF) and rheumatic heart disease (RHD) was eradicated from the developed world, the disease remains endemic in many low- and middle-income countries (LMICs), with grim health and socioeconomic impacts. The neglect of RHD which persisted for a semi-centennial was further driven by competing infectious diseases, particularly the human immunodeficiency virus (HIV) pandemic. However, over the last two-decades, slowly at first but with building momentum, there has been a resurgence of interest in RF/RHD. In this narrative review, we present the advances that have been made in the RF/RHD continuum over the past two decades since the re-awakening of interest, with a more concise focus on the last decade’s achievements. Such primary advances include understanding the genetic predisposition to RHD, group A Streptococcus (GAS) vaccine development, and improved diagnostic strategies for GAS pharyngitis. Echocardiographic screening for RHD has been a major advance which has unearthed the prevailing high burden of RHD and the recent demonstration of benefit of secondary antibiotic prophylaxis on halting progression of latent RHD is a major step forward. Multiple befitting advances in tertiary management of RHD have also been realized. Finally, we summarize the research gaps and provide illumination on profitable future directions towards global eradication of RHD.

IntroductionRheumatic heart disease (RHD) affects over 39 million people worldwide, the majority in low-income and middle-income countries. Secondary antibiotic prophylaxis (SAP), given every 3–4 weeks can improve outcomes, provided more than 80% of doses are received. Poor adherence is strongly correlated with the distance travelled to receive prophylaxis. Decentralising RHD care has the potential to bridge these gaps and at least maintain or potentially increase RHD prophylaxis uptake. A package of implementation strategies was developed with the aim of reducing barriers to optimum SAP uptake.Methods and analysisA hybrid implementation-effectiveness study type III was designed to evaluate the effectiveness of a package of implementation strategies including a digital, cloud-based application to support decentralised RHD care, integrated into the public healthcare system in Uganda. Our overarching hypothesis is that secondary prophylaxis adherence can be maintained or improved via a decentralisation strategy, compared with the centralised delivery strategy, by increasing retention in care. To evaluate this, eligible patients with RHD irrespective of their age enrolled at Lira and Gulu hospital registry sites will be consented for decentralised care at their nearest participating health centre. We estimated a sample size of 150–200 registrants. The primary outcome will be adherence to secondary prophylaxis while detailed implementation measures will be collected to understand barriers and facilitators to decentralisation, digital application tool adoption and ultimately its use and scale-up in the public healthcare system.Ethics and disseminationThis study was approved by the Institutional Review Board (IRB) at Cincinnati Children’s Hospital Medical Center (IRB 2021-0160) and Makerere University School of Medicine Research Ethics Committee (Mak-SOMREC-2021-61). Participation will be voluntary and informed consent or assent (>8 but <18) will be obtained prior to participation. At completion, study findings will be communicated to the public, key stakeholders and submitted for publication.

ObjectiveTo determine the ability to accurately diagnose acute rheumatic fever (ARF) given the resources available at three levels of the Ugandan healthcare system.MethodsUsing data obtained from a large epidemiological database on ARF conducted in three districts of Uganda, we selected variables that might positively or negatively predict rheumatic fever based on diagnostic capacity at three levels/tiers of the Ugandan healthcare system. Variables were put into three statistical models that were built sequentially. Multiple logistic regression was used to estimate ORs and 95% CI of predictors of ARF. Performance of the models was determined using Akaike information criterion, adjusted R2, concordance C statistic, Brier score and adequacy index.ResultsA model with clinical predictor variables available at a lower-level health centre (tier 1) predicted ARF with an optimism corrected area under the curve (AUC) (c-statistic) of 0.69. Adding tests available at the district level (tier 2, ECG, complete blood count and malaria testing) increased the AUC to 0.76. A model that additionally included diagnostic tests available at the national referral hospital (tier 3, echocardiography, anti-streptolysin O titres, erythrocyte sedimentation rate/C-reactive protein) had the best performance with an AUC of 0.91.ConclusionsReducing the burden of rheumatic heart disease in low and middle-income countries requires overcoming challenges of ARF diagnosis. Ensuring that possible cases can be evaluated using electrocardiography and relatively simple blood tests will improve diagnostic accuracy somewhat, but access to echocardiography and tests to confirm recent streptococcal infection will have the greatest impact.

IntroductionOver 46 million people are living with rheumatic heart disease (RHD) globally, resulting in 380 000 premature deaths each year. Effective RHD prevention strategies are known but their implementation in low-resource settings has lagged. This study evaluated the feasibility and effectiveness of integrating secondary antibiotic prophylaxis into primary health centres to improve access and adherence to RHD care.MethodsWe conducted a hybrid type III study using a mixed-method, pre–post design to evaluate a package of implementation strategies centred on decentralised RHD care and use of an electronic medical record in Gulu and Lira, Uganda. We combined clinical and programmatic data with provider and patient interviews to assess effectiveness, adoption and acceptability. The mean difference in the annualised percentage of days adherent to benzathine penicillin G (BPG) monthly injections predecentralisation and postdecentralisation was calculated using linear mixed effect regression. Thematic analysis was used to analyse qualitative data.ResultsWe decentralised 151 patients (median age 17.9 years, 64% female) from district hospitals to eight primary health centres. The percentage of days adherent to BPG was 77.2% predecentralisation and 80.5% postdecentralisation (mean difference 3.25, (95% CI −0.72 to 6.86), p=0.081), which was statistically non-inferior at the −10% non-inferiority margin. Interview data identified knowledge, confidence and intrinsic motivation as major determinants of provider adoption. Patients expressed mixed feelings towards pain control and provider services, but convenience and financial savings resulted in a high level of acceptability. The electronic registry presented challenges in a naive environment but showed a strong potential as an oversight tool at the district level.DiscussionThis study is the first to demonstrate that decentralised RHD care is effective in sub-Saharan Africa. Lessons learnt provide a platform for future integration of RHD services countrywide, with implications for increasing access to and scale-up of secondary prevention measures for RHD care in Uganda.

Primary prevention of acute rheumatic fever (ARF) and rheumatic heart disease (RHD) encompasses the timely diagnosis and adequate treatment of the superficial group A Streptococcus (GAS) infections pharyngitis and impetigo. GAS is the only known inciting agent in the pathophysiology of the disease. However, sufficient evidence indicates that the uptake and delivery of primary prevention approaches in RHD-endemic regions are significantly suboptimal. This report presents expert deliberations on priority research and implementation opportunities for primary prevention of ARF/RHD that were developed as part of a workshop convened by the US National Heart, Lung, and Blood Institute in November 2021. The opportunities identified by the Primary Prevention Working Group encompass epidemiological, laboratory, clinical, implementation and dissemination research domains and are anchored on five pillars including: (A) to gain a better understanding of superficial GAS infection epidemiology to guide programmes and policies; (B) to improve diagnosis of superficial GAS infections in RHD endemic settings; (C) to develop scalable and sustainable models for delivery of primary prevention; (D) to understand potential downstream effects of the scale-up of primary prevention and (E) to develop and conduct economic evaluations of primary prevention strategies in RHD endemic settings. In view of the multisectoral stakeholders in primary prevention strategies, we emphasise the need for community co-design and government engagement, especially in the implementation and dissemination research arena. We present these opportunities as a reference point for research organisations and sponsors who aim to contribute to the increasing momentum towards the global control and prevention of RHD.

Background. Routine testing of microalbuminuria and retinopathy is not done among patients with high blood pressure in resource-limited settings. We determined the prevalence of microalbuminuria and retinopathy and their risk factors among hypertensive patients at a large hospital in western Uganda. Methods. We consecutively recruited nondiabetic patients with hypertension at the outpatients’ clinic over a period of 3 months. Spot urine samples were tested for urine albumin. Direct fundoscopy was done to assess retinal vasculature and optic disc for signs of hypertensive retinopathy. Logistic regression was done with retinopathy and microalbuminuria as primary outcomes. Results. We enrolled 334 patients and, of these, 208 (62.3%) were females, with median age of 55 years (range: 25–90). The prevalence of microalbuminuria was 59.3% (95% CI: 50.1–72.2) and that of retinopathy was 66.8% (95% CI: 58.6–76.5). The independent correlates of retinopathy and microalbuminuria were systolic blood pressure (SBP) > 140 mmHg (OR = 2.76, 95% CI: 1.29–5.93) and treatment with beta-blockers (OR = 2.16, 95% CI: 1.05–4.44). Use of ACEIs was unrelated to the study outcomes. Conclusion. The prevalence of retinopathy and microalbuminuria is high. Clinicians should aim for better control of blood pressure and routinely perform fundoscopy and urine albumin, especially for patients with poorly controlled blood pressure.

BackgroundScreening programmes using echocardiography offer opportunity for intervention through identification and treatment of early (latent) rheumatic heart disease (RHD). We aimed to compare two methods for classifying progression or regression of latent RHD: serial review method and blinded, side-by-side review.MethodsA four-member expert panel reviewed 799 enrolment (in 2018) and completion (in 2020) echocardiograms from the GOAL Trial of latent RHD in Uganda to make consensus determination of normal, borderline RHD or definite RHD. Serial interpretations (enrolment and completion echocardiograms read at two different time points, 2 years apart, not beside one another) were compared with blinded side-by-side comparisons (enrolment and completion echocardiograms displayed beside one another in random order on same screen) to determine outcomes according to prespecified definitions of disease progression (worsening), regression (improving) or no change. We calculated inter-rater agreement using Cohen’s kappa.ResultsThere were 799 pairs of echocardiogram assessments included. A higher number, 54 vs 38 (6.8% vs 4.5%), were deemed as progression by serial interpretation compared with side-by-side comparison. There was good inter-rater agreement between the serial interpretation and side-by-side comparison methods (kappa 0.89). Disagreement was most often a result of the difference in classification between borderline RHD and mild definite RHD. Most discrepancies between interpretation methods (46 of 47, 98%) resulted from differences in valvular morphological evaluation, with valves judged to be morphologically similar between enrolment and final echocardiograms when compared side by side but classified differently on serial interpretation.ConclusionsThere was good agreement between the methods of serial and side-by-side interpretation of echocardiograms for change over time, using the World Heart Federation criteria. Side-by-side interpretation has higher specificity for change, with fewer differences in the interpretation of valvular morphology, as compared with serial interpretation.

Background Although rheumatic heart disease remains the leading cause of valve heart disease (VHD) in developing countries, other forms of valve disease have been over shadowed and not regarded as a public health problem. However, several facts suggest that the role of non-rheumatic VHD as a significant cardiovascular disease should be reconsidered. We aimed to assess the prevalence and characteristics of different forms of primary left sided valve diseases from a series of 15,009 echocardiographic studies. Methods This was a retrospective review of echocardiographic reports for studies performed between January 2012 and December 2013 (24 months) at Uganda Heart Institute. All patients with primary left-sided valve disease were classified into one of five major diagnostic categories and in each diagnostic category; patients were sub-classified into stages A-D of primary valve disease as defined by the American College of Cardiology. Results Three thousand five hundred eighty-two echocardiography reports qualified for final data analysis. The “sclerotic valve changes with normal valve function”, a Stage A sub-class of “degenerative valve disease” overwhelmingly overshadowed all the other diagnostic categories in this stage. “Rheumatic Heart Disease”, “Degenerative Valve Disease”, “Bicuspid Aortic Valve”, “Mitral Valve Prolapse” and “Endomyocardial Fibrosis” diagnostic categories accounted for 53.0%, 41.8%, 2.2%, 1.4% and 1.7% respectively in stages B-D of primary VHD. Rheumatic heart disease disproportionately affected the young, productive age groups. It was the major risk factor for infective endocarditis; and was the indication for valve surgery in 44 of 50 patients who had undergone valve replacement procedures. Conclusions We acknowledge that rheumatic heart disease remains a leading cause of progressive and severe primary left-sided valve disease among young adults in Uganda. But we bring to light the contemporary footprints of other forms of primary valve disease that require coordinated multidisciplinary approach to research, education and clinical management to ensure improved patient outcomes.

Acute rheumatic fever (ARF) is an autoimmune disorder resulting from Group A Streptococcus (GAS) pharyngitis or impetigo in children and adolescents, which may evolve to rheumatic heart disease (RHD) with persistent cardiac valve damage. RHD causes substantial mortality and morbidity globally, predominantly among socioeconomically disadvantaged populations, with an interplay of social determinants of health and genetic factors determining overall risk. ARF diagnosis is based on a constellation of clinical and laboratory features as defined by the 2015 Jones Criteria, although advances in molecular point-of-care testing and the ongoing search for ARF biomarkers offer the potential to revolutionise diagnostics. There are persistent gaps in ARF pathophysiology with little progress in therapeutics over the last several years. The greater focus towards primordial, primary, and secondary prevention such as advances in GAS vaccine development, innovations in digital health technology, improved antibiotic formulations for secondary prevention, and decentralised programmatic implementation to improve health-care delivery offer feasible solutions towards reducing future ARF burden globally.