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OBJECTIVE: To summarize the latest developments in rheumatic fever and rheumatic heart disease (RHD) prevention, (early) diagnosis, and treatment.
RESULTS: The revised Jones criteria have demonstrated increased sensitivity and specificity for rheumatic fever diagnosis in high-risk populations. The management of rheumatic fever remains symptom-based, with no treatment options proven to alter the disease course or prevent chronic RHD. The revised World Heart Federation (WHF) guidelines for the echocardiographic diagnosis of RHD encourage task-shifting of RHD screening, extending reach in endemic regions. These guidelines also present an A-D classification of RHD and provide recommendations for the management of early disease. Integrated models for RHD screening within existing health structures are emerging and automated intelligence is showing potential to support RHD screening and diagnosis. Innovative strategies to foster adherence and equitable access to secondary prophylaxis, such as re-examination of the efficacy of oral penicillin, trials of longer acting penicillin formulations and implants are underway. There is renewed interest and investment in a well tolerated and effective GAS vaccine.
CONCLUSIONS: We are living in a time of possibility with global acceleration to address the prevailing burden of RHD. Together, we can ensure that RHD does not once again fall off the global health agenda, until equitable elimination has been achieved.

BACKGROUND: Acute rheumatic fever (ARF) and rheumatic heart disease (RHD) remain major public health issues. Although the primary and secondary prevention of RHD through appropriate management of bacterial pharyngitis and ARF are well-described in the literature, few studies address the knowledge, attitude, and practice (KAP) of developing countries. We aimed to evaluate the KAP of the frontline physicians in Egyptian university hospitals regarding pharyngitis and ARF.
METHODS: We employed a cross-sectional design between September 1st, 2022, and January 31st, 2023 using a self-administered questionnaire in 21 Egyptian universities. The questionnaire was developed based on previous studies and recent guidelines and included four domains: sociodemographic data, knowledge, attitude, and practice regarding pharyngitis and ARF. We utilized both online (Google Forms) and paper surveys. Frontline physicians, including interns, residents, and assistant lecturers, were conveniently invited to participate. Furthermore, with the help of participating phycisians in recruiting their colleagues, we utilized the snowball method. Data were analyzed using IBM SPSS version 27 software.
RESULTS: The final analysis included 629 participants, of whom 372 (59.1%) were males and 257 (40.9%) had direct contact with ARF patients. Most participants (61.5%) had a fair knowledge level while 69.5% had a fair level of practice regarding ARF and pharyngitis. Higher satisfactory knowledge levels were noted regarding pharyngitis (17.1% vs. 11.3%; p-value: 0.036) and ARF (26.8% vs. 18%; p-value: 0.008) among physicians dealing directly with ARF cases compared to physicians in departments not dealing directly with ARF cases. Physicians in Cairo region universities had significantly higher levels of satisfactory knowledge about ARF compared to Delta and Upper Egypt region universities (p = 0.014). Delta region universities showed significantly lower levels of practice compared to Cairo and Upper Egypt region universities (p = 0.027). The most frequently recognized barriers against health promotion were low socioeconomic status (90.3%) and lack of adequate public education (85.8%).
CONCLUSIONS: Despite the fair knowledge and practice levels towards bacterial pharyngitis and ARF among participants, many gaps were still identified that might contribute to RHD prevalence. Educational interventions should be implemented by updating the local guidelines in Egypt for diagnosis and management based on the most recent guidelines.

UNASSIGNED: Although infrequent, Sydenham\'s chorea (SC) may occur as a result of injury to the basal ganglia in children with acute rheumatic fever (ARF) secondary to group A Streptococcal infection. Certain hallmarks of SC, such as movement disorders, could be utilized as a predictive marker for carditis. The present study aimed to investigate neurologic and cardiologic symptoms in children with suspected SC after ARF.
UNASSIGNED: All children aged 5-16 who were admitted at Shahid Madani Pediatric Hospital (Tabriz, Iran), with an initial diagnosis of ARF and SC between 2009 and 2022 were included for echocardiographic assessment and prospective follow-up within 6 and 12 months after the start point. The pattern and severity of valvulopathy, as well as the prevalence of Jones criteria for rheumatic fever, were used to assess the effect. The collected data were analyzed using SPSS Statistics software (version 22.0) using Chi square and Fisher\'s exact tests. P<0.05 was considered statistically significant.
UNASSIGNED: The study enrolled 85 children, 36 girls and 49 boys, with a mean age of 9.7±2.7. On the first echocardiography, 42.4% of patients had mitral valve regurgitation (MR), with a predominance of female patients (P=0.04). Of those diagnosed with SC (12 girls and 6 boys), 66.7% showed cardiac involvement, with a higher prevalence of MR in both sexes (P=0.04). The pattern of cardiac involvement after 6 months was significantly different between the groups (P=0.04). However, no such difference was observed during the one-year follow-up (P=0.07). Female sex was found to have a significant relationship with SC localization (P=0.01).
UNASSIGNED: In addition to its neurological manifestations, SC can be associated with clinical or subclinical cardiac valve dysfunction that might last for more than a year. In addition to attempting early detection and appropriate management, a precise cardiac and neurologic assessment during admission and follow-up is recommended.A preprint version of this manuscript is available at DOI: 10.21203/rs.3.rs-772662/v1 (https://www.researchsquare.com/article/rs-772662/v1).

Group A ß-hemolytic Streptococcus (S. pyogenes), also known as GAS, is a Gram-positive bacterium. It can be easily identified in the microbiology laboratory by its ability to hemolyse blood in culture media. This bacterium is highly virulent due to its production of enzymes and toxins, and its ability to cause immunologically mediated diseases such as rheumatic fever and post-streptococcal glomerulonephritis. GAS is the primary cause of bacterial pharyngotonsillitis, although it is typically a benign and non-invasive disease. However, it also has the potential to cause severe skin and soft tissue infections, necrotising fasciitis, bacteraemia and endocarditis, pneumonia and empyema, and streptococcal toxic shock syndrome, without any age or predisposition limits. The term invasive GAS disease (iGAS) is used to refer to this group of conditions. In more developed countries, iGAS disease has declined thanks to improved hygiene and the availability of antibiotics. For example, rheumatic fever has practically disappeared in countries such as Spain. However, recent data suggests a potential increase in some iGAS diseases, although the accuracy of this data is not consistent. Because of this, the COVID and Emerging Pathogens Committee of the Illustrious Official College of Physicians of Madrid (ICOMEM) has posed several questions about invasive GAS infection, especially its current situation in Spain. The committee has enlisted the help of several experts in the field to answer these questions. The following lines contain the answers that we have collaboratively produced, aiming to assist not only the members of ICOMEM but also anyone interested in this topic.

OBJECTIVE: To describe the clinical profile of acute rheumatic fever (ARF) presentations to paediatric cardiology tertiary services in Western Australia (WA).
METHODS: A retrospective clinical audit of individuals with confirmed ARF referred to the only paediatric tertiary cardiac service in WA (1 January 1987 to 31 December 2020). Comparisons between inpatient, outpatient, remote and non-remote groups were assessed.
RESULTS: Four hundred seventy-one episodes of ARF in 457 individuals (235 male; median age = 8 years) met clinical criteria. The majority were Aboriginal and Torres Strait Islander children (91.2%), with 62.1% living in remote areas. The number of ARF and rheumatic heart disease (RHD) diagnoses per year increased from 1987 to 2017 with notable peaks in 2013 and 2017. The average annual incidence of tertiary-referred ARF in WA of 4-15-year-olds from 1987 to 2020 was 4.96 per 100 000. ARF features included carditis (59.9%), chorea (31%), polyarthritis (30%) and polyarthralgia (24.2%). RHD was evident in 61.8% of cases and predominantly manifested as mitral regurgitation (55.7%). Thirty-four children (7.4%) with severe RHD underwent valvular surgery. 12% had at least one recurrent ARF episode. Remote individuals had more than double the rate of recurrence compared to non-remote individuals (P = 0.0058). Compared to non-remote episodes, remote presentations had less polyarthritis (P = 0.0022) but greater proportions of raised ESR (P = 0.01), ASOT titres (P = 0.0073), erythema marginatum (P = 0.0218) and severe RHD (P = 0.0133).
CONCLUSIONS: The high proportion of Aboriginal and Torres Strait Islander Australians affected by ARF/RHD in WA reflects the significant burden of disease within this population. Children from remote communities were more likely to present with concurrent severe RHD. Our study reinforces the persisting need to improve primary and secondary ARF initiatives in rural and remote communities.

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Rheumatic heart disease (RHD) remains a public health issue in low- and middle-income countries (LMICs). However, there are few large studies enrolling individuals from multiple endemic countries.
To assess the risk and predictors of major patient-important clinical outcomes in patients with clinical RHD.
Multicenter, hospital-based, prospective observational study including 138 sites in 24 RHD-endemic LMICs.
The primary outcome was all-cause mortality. Secondary outcomes were cause-specific mortality, heart failure (HF) hospitalization, stroke, recurrent rheumatic fever, and infective endocarditis. This study analyzed event rates by World Bank country income groups and determined the predictors of mortality using multivariable Cox models.
Between August 2016 and May 2022, a total of 13 696 patients were enrolled. The mean age was 43.2 years and 72% were women. Data on vital status were available for 12 967 participants (94.7%) at the end of follow-up. Over a median duration of 3.2 years (41 478 patient-years), 1943 patients died (15% overall; 4.7% per patient-year). Most deaths were due to vascular causes (1312 [67.5%]), mainly HF or sudden cardiac death. The number of patients undergoing valve surgery (604 [4.4%]) and HF hospitalization (2% per year) was low. Strokes were infrequent (0.6% per year) and recurrent rheumatic fever was rare. Markers of severe valve disease, such as congestive HF (HR, 1.58 [95% CI, 1.50-1.87]; P < .001), pulmonary hypertension (HR, 1.52 [95% CI, 1.37-1.69]; P < .001), and atrial fibrillation (HR, 1.30 [95% CI, 1.15-1.46]; P < .001) were associated with increased mortality. Treatment with surgery (HR, 0.23 [95% CI, 0.12-0.44]; P < .001) or valvuloplasty (HR, 0.24 [95% CI, 0.06-0.95]; P = .042) were associated with lower mortality. Higher country income level was associated with lower mortality after adjustment for patient-level factors.
Mortality in RHD is high and is correlated with the severity of valve disease. Valve surgery and valvuloplasty were associated with substantially lower mortality. Study findings suggest a greater need to improve access to surgical and interventional care, in addition to the current approaches focused on antibiotic prophylaxis and anticoagulation.

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