Preventive Interventions to Reduce the Burden of Rheumatic Heart Disease in Populations at Risk: A Systematic Review.

BACKGROUND: Rheumatic heart disease (RHD) is a devastating yet preventable condition that disproportionately affects low-middle-income countries and indigenous populations in some high-income countries. Various preventive interventions have been implemented across the globe, but evidence for the effectiveness of these measures in reducing the incidence or prevalence of acute rheumatic fever and RHD is scattered. This systematic review aims to assess the effectiveness of preventive interventions and identify the strategies used to reduce the burden of RHD. METHODS AND RESULTS: A comprehensive search was conducted to identify relevant studies on RHD prevention interventions including interventions for primordial, primary, and secondary prevention. Effectiveness measures for the interventions were gathered when available. The findings indicate that school-based primary prevention services targeting the early detection and treatment of Group A Streptococcus pharyngitis infection with penicillin have the potential to reduce the incidence of Group A Streptococcus pharyngitis and acute rheumatic fever. Community-based programs using various prevention strategies also reduced the burden of RHD. However, there is limited evidence from low-middle-income countries and a lack of rigorous evaluations reporting the true impact of the interventions. Narrative synthesis was performed, and the methodological quality appraisal was done using the Joanna Briggs Institute critical appraisal tools. CONCLUSIONS: This systematic review underscores the importance of various preventive interventions in reducing the incidence and burden of Group A Streptococcus pharyngitis, acute rheumatic fever, and RHD. Rigorous evaluations and comprehensive analyses of interventions are necessary for guiding effective strategies and informing public health policies to prevent and reduce the burden of these diseases in diverse populations. REGISTRATION: URL: https://www.crd.york.ac.uk/prospero/; Unique identifier: CRD42020170503.

Outcomes of rheumatic fever in Uganda: a prospective cohort study.

BACKGROUND: Rheumatic heart disease is the largest contributor to cardiac-related mortality in children worldwide. Outcomes in endemic settings after its antecedent illness, acute rheumatic fever, are not well understood. We aimed to describe 3-5 year mortality, acute rheumatic fever recurrence, changes in carditis, and correlates of mortality after acute rheumatic fever. METHODS: We conducted a prospective cohort study of Ugandan patients aged 4-23 years who were diagnosed with definite acute rheumatic fever using the modified 2015 Jones criteria from July 1, 2017, to March 31, 2020, enrolled at three rheumatic heart disease registry sites in Uganda (in Mbarara, Mulago, or Lira), and followed up for at least 1 year after diagnosis. Patients with congenital heart disease were excluded. Patients underwent annual review, most recently in August, 2022. We calculated rates of mortality and acute rheumatic fever recurrence, tabulated changes in carditis, performed Kaplan-Meier survival analyses, and used Cox regression models to identify correlates of mortality. FINDINGS: Data were collected between Sept 1 and Sept 30, 2022. Of 182 patients diagnosed with definite acute rheumatic fever, 156 patients were included in the analysis. Of these 156 patients (77 [49%] male and 79 (51%) female; data on ethnicity not collected), 25 (16%) died, 21 (13%) had a cardiac-related death, and 17 (11%) had recurrent acute rheumatic fever over a median of 4·3 (IQR 3·0-4·8) years. 16 (24%) of the 25 deaths occurred within 1 year. Among 131 (84%) of 156 survivors, one had carditis progression by echo. Moderate-to-severe carditis (hazard ratio 12·7 [95% CI 3·9-40·9]) and prolonged PR interval (hazard ratio 4·4 [95% CI 1·7-11·2]) at acute rheumatic fever diagnosis were associated with increased cardiac-related mortality. INTERPRETATION: These are the first contemporary data from sub-Saharan Africa on medium-term acute rheumatic fever outcomes. Mortality rates exceeded those reported elsewhere. Most decedents already had chronic carditis at initial acute rheumatic fever diagnosis, suggesting previous undiagnosed episodes that had already compounded into rheumatic heart disease. Our data highlight the large burden of undetected acute rheumatic fever in these settings and the need for improved awareness of and diagnostics for acute rheumatic fever to allow earlier detection. FUNDING: Strauss Award at Cincinnati Children's Hospital, American Heart Association, and Wellcome Trust.

A foodborne outbreak of Group A streptococcus: an under-recognised method of spread.

Foodborne transmission of Group A Streptococcus (GAS) is a rare cause of pharyngitis outbreaks. This report details a GAS outbreak in New Zealand that was associated with a foodborne route of transmission. This outbreak was relevant in the New Zealand context given the high incidence of rheumatic fever (RF).

Revising the value of Antistreptolysin O titre in childhood and its interpretation in the diagnostic approach of rheumatic diseases.

The burden of group A streptococcus (GAS) infection and its rheumatic sequelae remains dramatically high, especially in low-income countries. Recently, an increased number of Acute Rheumatic Fever (ARF) cases was documented in many regions of Italy. The diagnosis of rheumatic sequelae relies on clinical signs and on the evaluation of the Antistreptolysin O titre (ASO), whose variations are globally reported. To re-examine the standard reference value of ASO titre, by measuring either its upper limit of normal (ULN) in a population of healthy children (HC) or comparing these values with streptococcal antibodies registered in a cohort of patients affected by the rheumatic sequelae of GAS infection. We performed a multicenter retrospective study. We enrolled 125 HC, aged 2-17 years, and a total of 181 patients affected by ARF, acute streptococcal pharyngitis, post-streptococcal arthritis, Henoch-Schönlein purpura and erythema nodosum, divided into four groups. The levels of ASO and anti-deoxyribonuclease B (anti-DNase B) titres were analyzed and compared among the various groups. Moreover, the 80th percentile value was calculated and established as the ULN for ASO titre in HC group. The ULN for ASO titre in overall HC group was 515 IU/mL, resulting in higher than used in the routine investigation. The ASO titre was significantly higher in patients with rheumatic sequelae compared with HC group, with a peak in the age between 5 and 15 years.    Conclusion: Our study established a new ULN normal value of streptococcal serology in a childhood and adolescent population of Italy, suggesting the need to extend this revaluation to the critical areas, in order to avoid underestimating ARF diagnosis. The correct interpretation of ASO and anti-DNase B values in the context of rheumatic diseases has been discussed. What is Known: • The global burden of disease caused by group A streptococcus is not known and remains an important cause of morbidity and mortality. Acute rheumatic fever continues to be a serious worldwide public health problem and a recent recurrence of group A streptococcus infection cases is observed. • The streptococcal sequelae requires evidence of preceding streptococcal infection, commonly elevated streptococcal antibody titre, but the upper limit for these titres varies considerably based on age group, region, and origin. What is New: • This study provides population-specific values for streptococcal antibody titres in Italy. • Interpret the results of group A streptococcal antibody tests within the clinical context.

[Influence of underlying disease and immunosuppression on the immunocompetence in inflammatory rheumatic diseases]. / Einfluss von Grunderkrankung und Immunsuppression auf die Immunkompetenz bei entzündlich rheumatischen Erkrankungen.

Patients with inflammatory rheumatic diseases have a higher risk of infections in comparison to the general population. For this patient group, in addition to cardiovascular diseases, infections play an important role with respect to morbidity and mortality. Even if it is difficult to make concrete statements with respect to individual diseases, it can be assumed that there is a lower risk of infections in inflammatory joint diseases in comparison to connective tissue diseases and vasculitides. The increased risk of infections is determined by multiple factors, whereby the underlying factors are classified into three main categories: patient-related factors (age, comorbidities, lifestyle), disease-related factors (immunological dysfunction as part of the disease pathophysiology) and drug-related factors (type and dosage of the immunosuppression and/or immunomodulation). An improved understanding of the complexity of these associations enables the optimization of treatment and disease control taking the individual risk factors into account, with the aim of a significant reduction in the risk of infections.

Current Clinical Profile of Acute Rheumatic Fever and Recurrent Acute Rheumatic Fever in Pakistan.

Inclusion of echocardiography as diagnostic tool and polyarthralgia and monoarthritis as major criteria for high-risk populations in the Revised Jones Criteria 2015 is likely to surface substantial variability in clinical manifestations among various populations. This study aimed to compare clinical profile of patients presenting with first and recurrent episodes of acute rheumatic fever (ARF) using most recent criteria. 130 consecutive patients with ARF were included in the study from August 2019 to March 2022. World Heart Federation standardized echocardiographic criteria were used for cardiac evaluation. The socio-demographic variables, clinical details and relevant investigations were recorded. Median age was 13(6-26) years. Male to female ratio was 1.6:1. Majority was of low socioeconomic status (90%) and with > 5 family members in a house (83.8%). 27 patients (20.8%) were with ARF while 103 (79.2%) with recurrent ARF. Carditis was the most common presenting feature (n = 122, 93.8%), followed by polyarthralgia (n = 46, 35.4%), polyarthritis (n = 32, 24.6%), subcutaneous nodules (n = 10, 7.7%), monoarthritis (n = 10, 7.7%), and chorea (n = 5, 3.8%). Monoarthralgia was more common in ARF than recurrence (29.4% vs. 3.2%, p = 0.004). Carditis (97.1% vs. 81.5%, p = 0.01) and congestive cardiac failure (18.5% vs. 5.9%, p = 0.001) were more common in recurrent ARF than ARF. Diagnostic categorization of Jones criteria for different populations has highlighted important variability in clinical presentation of ARF. Monoarthralgia is common in first episode of ARF. Carditis is the most common feature in recurrent ARF. Polyarthralgia is seen with higher frequency that polyarthritis. Subcutaneous nodules seem to be more common in our population.

Research opportunities for the primary prevention and management of acute rheumatic fever and rheumatic heart disease: a National Heart, Lung, and Blood Institute workshop report.

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.

Research priorities for the primordial prevention of acute rheumatic fever and rheumatic heart disease by modifying the social determinants of health.

The social determinants of health (SDH), such as access to income, education, housing and healthcare, strongly shape the occurrence of acute rheumatic fever (ARF) and rheumatic heart disease (RHD) at the household, community and national levels. The SDH are systemic factors that privilege some more than others and result in poverty and inequitable access to resources to support health and well-being. Primordial prevention is the modification of SDH to improve health and reduce the risk of disease acquisition and the subsequent progression to RHD. Modifying these determinants using primordial prevention strategies can reduce the risk of exposure to Group A Streptococcus, a causative agent of throat and skin infections, thereby lowering the risk of initiating ARF and its subsequent progression to RHD.This report summarises the findings of the Primordial Prevention Working Group-SDH, which was convened in November 2021 by the National Heart, Lung, and Blood Institute to assess how SDH influence the risk of developing RHD. Working group members identified a series of knowledge gaps and proposed research priorities, while recognising that community engagement and partnerships with those with lived experience will be integral to the success of these activities. Specifically, members emphasised the need for: (1) global analysis of disease incidence, prevalence and SDH characteristics concurrently to inform policy and interventions, (2) global assessment of legacy primordial prevention programmes to help inform the co-design of interventions alongside affected communities, (3) research to develop, implement and evaluate scalable primordial prevention interventions in diverse settings and (4) research to improve access to and equity of services across the RHD continuum. Addressing SDH, through the implementation of primordial prevention strategies, could have broader implications, not only improving RHD-related health outcomes but also impacting other neglected diseases in low-resource settings.

Prevalence and Impact of HIV Infections in Patients with Rheumatic Heart Disease: A Systematic Review and Meta-Analysis.

Socioeconomic factors such as poor health and poor nutrition in low- and middle-income countries (LMICs) may favour inflammatory reactions, thus contributing to the recurrence of rheumatic fever (RF) and thereby modifying trends in rheumatic heart disease (RHD). Apart from epidemiological studies, studies of HIV infections in RHD patients are limited. This systematic review synthesises data on the prevalence and impact of HIV infections or AIDS on RHD from PubMed, Scopus, Web of Science databases up to April 2021. The outcomes were managed using PRISMA guidelines. Of a total of 15 studies found, 10 were eligible for meta-analyses. Meta-analysis found that 17% (95 % CI 8-33, I2 = 91%) of adults in cardiovascular disease (CVD) cohorts in Southern Africa are HIV positive. The proportion of RHD diagnosed among people living with HIV was 4% (95% CI 2-8, I2 = 79%) for adults but lower [2% (95% CI 1-4, I2 = 87%)] among perinatally infected children. Despite limited reporting, HIV-infected patients with RHD are prone to other infections that may enhance cardiac complications due to poor immunological control. PROSPERO registration number: CRD42021237046.

Secondary Prophylaxis Among First Nations People With Acute Rheumatic Fever in Australia: An Integrative Review.

INTRODUCTION: The prevalence of acute rheumatic fever (ARF) and rheumatic heart disease (RHD) among Australia's First Nations populations are some of the highest in the world, accounting for 95% of the 2,244 ARF notifications between 2015 and 2019 in Australia. A key issue in treating ARF is long-term secondary prophylaxis, yet only one in five patients received treatment in 2019. This review identifies barriers to secondary prophylaxis of ARF in Australia's First Nations people. METHODS: An integrative review was undertaken utilizing PubMed, CINAHL, ProQuest, and Wiley Online. Joanna Briggs Institute critical appraisal tools were used, followed by thematic analysis. RESULTS: The key themes uncovered included: issues with database and recall systems, patient/family characteristics, service delivery location and site, pain of injection, education (including language barriers), and patient-clinician relationship. CONCLUSIONS: A national RHD register, change in operation model, improved pain management, improved education, and need for consistent personnel is suggested.

Sydenham chorea in the top end of Australia's Northern Territory: A 20-year retrospective case series.

AIM: Sydenham chorea is an immune-mediated neuropsychiatric condition, and a major criterion for diagnosis of acute rheumatic fever (ARF). Children in remote Northern Australia experience disproportionately high rates of ARF, yet studies looking at the epidemiology, clinical presentation and management of Sydenham chorea are limited in this population. METHODS: We conducted a retrospective case series from January 2002 to April 2022 of all paediatric patients aged ≤18 years admitted to Royal Darwin Hospital with Sydenham chorea. Cases were identified using the hospital's clinical coding system (ICD10). Medical records were reviewed and data on demographics, clinical presentation, investigation results, treatment and outcome were extracted, deidentified and analysed. RESULTS: One hundred ten presentations of Sydenham chorea occurred between 2002 and 2022, 109 (99%) of these were in First Nations children, with 85% residing in very remote locations. Most commonly, chorea presented as a generalised movement disorder affecting all four limbs (49%). Neuropsychiatric symptoms were reported in 33 (30%), and there was evidence of rheumatic heart disease on echocardiogram in 86 (78%) at presentation. All patients received benzathine penicillin, but there was significant variation in management of chorea, ranging from supportive management, to symptomatic management with anticonvulsants, to immunomodulatory medications including corticosteroids. CONCLUSION: This case series highlights the significant burden of Sydenham chorea among First Nations children living in Northern Australia and demonstrates wide variation in treatment approaches. High-quality clinical trials are required to determine the best treatment for this disabling condition.

The evidence that rheumatic heart disease control programs in Australia are making an impact.

OBJECTIVE: Rheumatic heart disease (RHD) comprises heart-valve damage caused by acute rheumatic fever (ARF). The Australian Government Rheumatic Fever Strategy funds RHD Control Programs to support detection and management of ARF and RHD. We assessed epidemiological changes during the years of RHD Control Program operation. METHODS: Linked RHD register, hospital and death data from four Australian jurisdictions were used to measure ARF/RHD outcomes between 2010 and 2017, including: 2-year progression to severe RHD/death; ARF recurrence; secondary prophylaxis delivery and earlier disease detection. RESULTS: Delivery of secondary prophylaxis improved from 53% median proportion of days covered (95%CI: 46-61%, 2010) to 70% (95%CI: 71-68%, 2017). Secondary prophylaxis adherence protected against progression to severe RHD/death (hazard ratio 0.2, 95% CI 0.1-0.8). Other measures of program effectiveness (ARF recurrences, progression to severe RHD/death) remained stable. ARF case numbers and concurrent ARF/RHD diagnoses increased. CONCLUSIONS: RHD Control Programs have contributed to major success in the management of ARF/RHD through increased delivery of secondary prevention yet ARF case numbers, not impacted by secondary prophylaxis and sensitive to increased awareness/surveillance, increased. IMPLICATIONS FOR PUBLIC HEALTH: RHD Control Programs have a major role in delivering cost-effective RHD prevention. Sustained investment is needed but with greatly strengthened primordial and primary prevention.

A pilot study to develop assessment tools for Group A Streptococcus surveillance studies.

Introduction: Group A Streptococcus (GAS) causes pharyngitis (sore throat) and impetigo (skin sores) GAS pharyngitis triggers rheumatic fever (RF) with epidemiological evidence supporting that GAS impetigo may also trigger RF in Australian Aboriginal children. Understanding the concurrent burden of these superficial GAS infections is critical to RF prevention. This pilot study aimed to trial tools for concurrent surveillance of sore throats and skins sore for contemporary studies of RF pathogenesis including development of a sore throat checklist for Aboriginal families and pharynx photography. Methods: Yarning circle conversations and semi-structured interviews were performed with Aboriginal caregivers and used to develop the language and composition of a sore throat checklist. The sore throat story checklist was combined with established methods of GAS pharyngitis and impetigo surveillance (examination, bacteriological culture, rapid antigen detection and serological tests) and new technologies (photography) and used for a pilot cross-sectional surveillance study of Aboriginal children attending their health clinic for a routine appointment. Feasibility, acceptability, and study costs were compiled. Results: Ten Aboriginal caregivers participated in the sore-throat yarning circles; a checklist was derived from predominant symptoms and their common descriptors. Over two days, 21 Aboriginal children were approached for the pilot surveillance study, of whom 17 were recruited; median age was 9 years [IQR 5.5-13.5], 65% were female. One child declined throat swabbing and three declined finger pricks; all other surveillance elements were completed by each child indicating high acceptability of surveillance assessments. Mean time for screening assessment was 19 minutes per child. Transport of clinical specimens enabled gold standard microbiological and serological testing for GAS. Retrospective examination of sore throat photography concorded with assessments performed on the day. Conclusion: Yarning circle conversations were effective in deriving culturally appropriate sore throat questionnaires for GAS pharyngitis surveillance. New and established tools were feasible, practical and acceptable to participants and enable surveillance to determine the burden of superficial GAS infections in communities at high risk of RF. Surveillance of GAS pharyngitis and impetgio in remote Australia informs primary RF prevention with potential global translation.

Addressing rheumatic fever inequities in Aotearoa New Zealand: a scoping review of prevention interventions.

Introduction Rheumatic fever is a preventable illness caused by untreated Group A Streptococcus (GAS) infection. Despite reductions in most high-income countries, rheumatic fever rates remain a concern in Aotearoa New Zealand. Pacific and Maori people are inequitably affected, with risk of initial hospitalisation due to rheumatic fever 12- and 24-fold more likely, respectively, compared to non-Maori and non-Pacific people. Aim This scoping review aims to explore the range of interventions and initiatives in New Zealand seeking to prevent GAS and rheumatic fever, with a particular focus on Pacific and Maori. Methods Databases Scopus, Medline, EMBASE and CINAHL, along with grey literature sources, were searched to broadly identify interventions in New Zealand. Data were screened for eligibility and the final articles were charted into a stocktake table. Results Fifty-eight studies were included, reporting 57 interventions. These targeted school-based throat swabbing, awareness and education, housing, secondary prophylaxis, improving primary care guidelines and diagnosis of sore throats and skin infections. Some interventions reported short-term outcomes of improvements in awareness, a reduction in rheumatic fever risk and fewer hospitalisations. Evaluation outcomes were, however, lacking for many initiatives. Pacific and Maori people primarily served only in an advisory or delivery capacity, rather than as partners in co-design or leadership from the beginning. Discussion Although positive outcomes were reported for some interventions identified in this review, rheumatic fever rates have not shown any long-term reduction over time. Co-designing interventions with affected communities could ensure that strategies are better targeted and do not contribute to further stigma.

Evaluating efficiency and equity of prevention and control strategies for rheumatic fever and rheumatic heart disease in India: an extended cost-effectiveness analysis.

BACKGROUND: There is a dearth of evidence on the cost-effectiveness of a combination of population-based primary, secondary, and tertiary prevention and control strategies for rheumatic fever and rheumatic heart disease. The present analysis evaluated the cost-effectiveness and distributional effect of primary, secondary, and tertiary interventions and their combinations for the prevention and control of rheumatic fever and rheumatic heart disease in India. METHODS: A Markov model was constructed to estimate the lifetime costs and consequences among a hypothetical cohort of 5-year-old healthy children. Both health system costs and out-of-pocket expenditure (OOPE) were included. OOPE and health-related quality-of-life were assessed by interviewing 702 patients enrolled in a population-based rheumatic fever and rheumatic heart disease registry in India. Health consequences were measured in terms of life-years and quality-adjusted life-years (QALY) gained. Furthermore, an extended cost-effectiveness analysis was undertaken to assess the costs and outcomes across different wealth quartiles. All future costs and consequences were discounted at an annual rate of 3%. FINDINGS: A combination of secondary and tertiary prevention strategies, which had an incremental cost of ₹23 051 (US$30) per QALY gained, was the most cost-effective strategy for the prevention and control of rheumatic fever and rheumatic heart disease in India. The number of rheumatic heart disease cases prevented among the population belonging to the poorest quartile (four cases per 1000) was four times higher than the richest quartile (one per 1000). Similarly, the reduction in OOPE after the intervention was higher among the poorest income group (29·8%) than among the richest income group (27·0%). INTERPRETATION: The combined secondary and tertiary prevention and control strategy is the most cost-effective option for the management of rheumatic fever and rheumatic heart disease in India, and the benefits of public spending are likely to be accrued much more by those in the lowest income groups. The quantification of non-health gains provides strong evidence for informing policy decisions by efficient resource allocation on rheumatic fever and rheumatic heart disease prevention and control in India. FUNDING: Department of Health Research, Ministry of Health and Family Welfare, New Delhi.

Rheumatic Heart Disease: JACC Focus Seminar 2/4.

It is a sad reality that although eminently preventable, and despite possessing such knowledge for >70 years, rheumatic heart disease (RHD) remains the most common cause of cardiovascular morbidity and early mortality in young people worldwide. A disease of the poor, RHD is one of the most neglected diseases. Several challenges are unique to the acute rheumatic fever/RHD continuum and contribute to its persistence, including its sequestration among the poorest, its protracted natural history, the erratic availability of penicillin, and the lack of a concerted effort in endemic regions. However, there is cause for optimism following a resurgence in scientific interest over the last 15 years. This review presents the latest advancements in epidemiology, diagnosis, and management. It also discusses pressing research questions on disease pathophysiology, the barriers to implementation of effective management strategies, and pragmatic policy solutions required for translation of current knowledge into meaningful action.

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.

Research opportunities for the primordial prevention of rheumatic fever and rheumatic heart disease-streptococcal vaccine development: a national heart, lung and blood institute workshop report.

Streptococcus pyogenes, also known as group A streptococcus (StrepA), is a bacterium that causes a range of human diseases, including pharyngitis, impetigo, invasive infections, and post-infection immune sequelae such as rheumatic fever and rheumatic heart disease. StrepA infections cause some of the highest burden of disease and death in mostly young populations in low-resource settings. Despite decades of effort, there is still no licensed StrepA vaccine, which if developed, could be a cost-effective way to reduce the incidence of disease. Several challenges, including technical and regulatory hurdles, safety concerns and a lack of investment have hindered StrepA vaccine development. Barriers to developing a StrepA vaccine must be overcome in the future by prioritising key areas of research including greater understanding of StrepA immunobiology and autoimmunity risk, better animal models that mimic human disease, expanding the StrepA vaccine pipeline and supporting vaccine clinical trials. The development of a StrepA vaccine is a complex and challenging process that requires significant resources and investment. Given the global burden of StrepA infections and the potential for a vaccine to save lives and livelihoods, StrepA vaccine development is an area of research that deserves considerable support. This report summarises the findings of the Primordial Prevention Working Group-VAX, which was convened in November 2021 by the National Heart, Lung, and Blood Institute. The focus of this report is to identify research gaps within the current StrepA vaccine landscape and find opportunities and develop priorities to promote the rapid and successful advancement of StrepA vaccines.