Submitted Successfully!
To reward your contribution, here is a gift for you: A free trial for our video production service.
Thank you for your contribution! You can also upload a video entry or images related to this topic.
Version Summary Created by Modification Content Size Created at Operation
1
Andrew Young Chang
 -- 7021 2022-05-16 09:27:27 |
2 Editing to meet requests of editors
Andrew Young Chang
 -2119 word(s) 4902 2022-05-17 20:11:51 | |
3 Reference format revised.
Lindsay Dong
 -23 word(s) 4879 2022-05-19 04:27:50 |

Video Upload Options

We provide professional Video Production Services to translate complex research into visually appealing presentations. Would you like to try it?
No, upload directly Yes

Confirm

Are you sure to Delete?
Yes No
Cite
If you have any further questions, please contact Encyclopedia Editorial Office.
Chang, A.; Rwebembera, J.; , .; Galdino, B.; Dutra, W. Scientific Advances in Rheumatic Fever/Rheumatic Heart Disease Control. Encyclopedia. Available online: https://encyclopedia.pub/entry/22957 (accessed on 26 December 2024).
Chang A, Rwebembera J,  , Galdino B, Dutra W. Scientific Advances in Rheumatic Fever/Rheumatic Heart Disease Control. Encyclopedia. Available at: https://encyclopedia.pub/entry/22957. Accessed December 26, 2024.
Chang, Andrew, Joselyn Rwebembera,  , Bruno Galdino, Walderez Dutra. "Scientific Advances in Rheumatic Fever/Rheumatic Heart Disease Control" Encyclopedia, https://encyclopedia.pub/entry/22957 (accessed December 26, 2024).
Chang, A., Rwebembera, J., , ., Galdino, B., & Dutra, W. (2022, May 16). Scientific Advances in Rheumatic Fever/Rheumatic Heart Disease Control. In Encyclopedia. https://encyclopedia.pub/entry/22957
Chang, Andrew, et al. "Scientific Advances in Rheumatic Fever/Rheumatic Heart Disease Control." Encyclopedia. Web. 16 May, 2022.
Scientific Advances in Rheumatic Fever/Rheumatic Heart Disease Control
Edit
This entry is adapted from the peer-reviewed paper 10.3390/pathogens11020179

Despite the fact that rheumatic fever (RF) and rheumatic heart disease (RHD) have largely been eradicated from high-income countries, the disease spectrum remains endemic in many low- and middle-income countries (LMICs), extacting a grim health and socioeconomic impact. Over 33 million people are believed to be living with RHD worldwide, claiming nearly a third of a million lives annually. Regrettably, the neglect of RHD as a global health priority was further exacerbated by competing infectious disease outbreaks, chief among them the human immunodeficiency virus (HIV) epidemic. Nevertheless, the prior two decades have seen a slowly resurgence of interest in RF/RHD control. Substantial recent advances in the field of RF/RHD continuum control, however, have been realized over this time period. Such primary advances include a better understanding the genetic predisposition to RHD, progress in Group A Streptococcus (GAS) vaccine development, and improved diagnostic strategies for GAS pharyngitis. Echocardiographic screening for RHD, in particular, has represented a major advance which has unearthed the prevailing high burden of RHD. Lastly, the recent demonstration of benefit of secondary antibiotic prophylaxis on halting progression of latent RHD has marked a major step forward in averting progression of end-stage valvular disease in LMIC settings.

rheumatic fever rheumatic heart disease RHD RF global health public health neglected tropical disease

1. Advances in Characterizing the Global Burden of Rheumatic Heart Disease

A number of factors over the past decade have dramatically improved our ability to estimate the prevailing burden of Rheumatic heart Disease (RHD), with estimates ranging from 15 million cases in 2005 [1] increasing to 40.5 million estimated cases in 2019 with refinement in epidemiologic methodology [2]. More granularly, however, individual nation-level studies have shown shifting prevalences even within LMICs. Echocardiographic surveys in some settings such as in India have revealed consistent decline in the burden of RHD before and after 2000, using similar screening methods among school children. This particular decline was associated with improvement in the indicators of socioeconomic state and health-care services. Three main advances have led to the knowledge gain of the global burden of RHD, including (a) screening echocardiography; (b) RHD registries and country-wide administrative health data; and (c) big data sources, namely the Global Burden of Disease repository.

1.1. Advances in Screening Echocardiography

RHD remains largely clinically silent until patients become symptomatic with the advanced form of disease. Echocardiographic (echo) screening [3], which has been one of the chief advancements in our understanding of the global burden of RHD, has resulted from school, community, and clinical echo screening to define the epidemiological burden of the disease. In particular, echo screening is responsible for the birth of the ‘latent RHD’ paradigm (namely the identification of subclinical echo-detected disease)—rallied as an opportunity for early intervention to prevent disease progression. Active case finding through echo screening has gained further traction in the past decade particularly following the publication of standardized diagnostic criteria by the World Heart Federation (WHF) in 2012 [4]. The value of echo screening in the control of RHD has been a subject of debate [5] in recent years [6]. Nevertheless, robust data from a landmark randomized-controlled trial strongly suggest that secondary antibiotic prophylaxis prevents the progression of latent RHD to moderate or severe stages of disease, thus supporting the clinical need for screening, even among asymptomatic individuals [7].
Key developments toward pragmatic echocardiographic screening capacity in LMICs have included: (a) development of handheld echo devices which are less expensive, generate smaller and shareable file sizes, and have a smaller profile without reliance on wired electricity [5]; (b) task-shifting of echo image acquisition from highly trained cardiologists and licensed sonographers to other healthcare workers such as nurses, allowing for expansion of screening capabilities; (c) supportive cloud-based telemedicine programs for remote echo image interpretation; and finally, (d) expanding technological advances [8][9], with several companies now offering artificial intelligence guidance technology built into hand-held devices, thus empowering novice operators to perform screening echoes even after only minimal training, and promising deep learning approaches for automated flagging of abnormalities in the near future [10]. There is also an ongoing effort to improve and simplify the WHF criteria for the diagnosis of latent RHD [11], with additional development of risk scores to predict outcomes in both borderline and definite latent RHD [11].

1.2. Establishment of RHD Registries and Big Data Resources

With the increasing interest in meeting the RHD challenge in endemic countries, a number of large disease-specific registries have been established in LMICs. These have illuminated the dire epidemiologic situation of clinical RHD in these settings [2][12][13]. The hospital-based sub-Saharan Africa Survey of Heart Failure (THESUS-HF) registry study showed that RHD was the second major cause of acute heart failure hospitalizations, with an inpatient mortality rate of 4.2% and a 180-day mortality rate of 17.8% [14]. The VALVAFRIC [15], REMEDY [16], and certain national [17][18] registry studies provide the most recent descriptions of chronic RHD complications in patients residing in low- and middle-income countries. In general, they have established that clinical RHD in LMICs is characterized by late presentation with substantial established complications [17][18]. The clinical course is thus punctuated by recurrent hospitalizations and unacceptably early mortality (mean age at death of 29.4 years), with most of these deaths occurring within the first three months following diagnosis.
On the global scale, contemporary surveys continue to reveal worldwide RHD disparities, with low-income countries bearing a disproportionate burden of the disease. RHD currently affects 40.5 million people across the globe and accounts for 306,000 deaths annually—representing 1.6% of all mortality from cardiovascular disease, the leading cause of death worldwide [2]. The increased prevalence of RHD detected in recent studies, when compared to historical surveys, is most likely related to improved case detection attributable to the increased availability of echocardiography, better survival of affected individuals, and the chronic nature of the disease [2]. Sub-Saharan Africa retains the highest prevalence of clinically-apparent RHD [19], and there is some evidence that the true burden of RHD in some African countries may be much higher than previous estimates [20]. Today, the highest age-standardized disability-adjusted life year (DALY) rates attributable to RHD are in the regions of Oceania (627.4 per 100,000) and South Asia (348.5 per 100,000). In Australia and New Zealand, the highest rates of RF and RHD are found among indigenous populations [21][22]. Unfortunately, epidemiological data on RHD prevalence is least robust from the most affected regions [23]. National, regional and global RHD registries continue to report female predominance, however no gender-based differences in complications such as heart failure, atrial fibrillation, stroke and pulmonary hypertension have been noted.

2. Advances in Elucidating the Pathogenesis of RF/RHD

The general academic consensus remains that an immune-mediated pathologic process is the hallmark of RHD. Nevertheless, the exact mechanisms underlying this complex process have yet to be completely unveiled. Traditional dogma has held that GAS pharyngitis is responsible for triggering the immune reaction that leads to RHD pathology [24]. However, more recently, other superficial streptococcal infections, such as impetigo and pyoderma, have been found to be associated with RHD [25][26]. There is also emerging evidence potentially implicating group C and group G streptococcus in contributing to the pathogenesis of RHD [27][28][29][30][31].
The most widely accepted hypothesis in the pathogenesis of RF/RHD [32][33] is that molecular mimicry is responsible for the autoimmune phenomena of the disease, but more recent data suggests a more complex cascade of events, such as collagen-associated neo-antigens [34][35] epitope spreading [36], and T-cell receptor (TCR) degeneracy [37][38][39] may participate in the resultant pathology. Additionally, specific CD4+ T cells, as well as NK cells and CD4-CD8- T cells, might be important players in cardiac tissue destruction seen in RHD [40]. Recent efforts have been developed to take advantage of the intense GAS antigen-associated immune response for the creation of RF/RHD vaccines, but these have remained elusive largely due to lack of academic and financial investment [41]. Dissecting the immunopathogenic responses using state-of-the-art methods such as single cell RNA sequencing combined with TCR CDR3 region usage may open new insights to advance this field.
Furthermore, despite the widespread socioeconomic risk factors for RHD development present in LMICs, only a minority (roughly 3–6%) of GAS-endemic populations develop RF [24]. Furthermore, RHD is largely believed to have a complex genetic risk profile [42]. Historical RHD studies in twins have supported this postulation [43][44], and more recent modern genetic interrogation studies have she new light on RHD pathogenesis and predisposition.
Genetic associations in RHD have been explored through numerous candidate gene studies—for example, those reviewed by Martin et al. [45] and Muhamed et al. [46] elicited genetic associations in RHD through candidate gene studies. These have yielded conflicting and heterogeneous results, implicating a variety of genes with several listed study limitations [43][45][46] including those that have reported the association of human leukocyte antigen (HLA) molecules, encoded by genes on chromosome 6, and susceptibility to developing RF/RHD [43][47][48][49][50][51]. Within HLA genes, class II genes have been widely reported, with the majority linking HLA-DR7 [43][50] and HLA-DR4 [45][49][52] to the development of RHD.
There has also been interest in evaluating genetic polymorphisms coding for inflammatory mediators in RHD and their phenotypic expression. Polymorphisms in IL-2, IL-4, IL-6 and IL-10 genes have been associated with clinical disease, and the discriminative value of IL-4 to differentiate latent versus clinical RHD has been demonstrated [53]. Additionally, interleukins IL-4, IL-8 and IL-1RA seem to predict progression from latent to clinical RHD, while in individuals with advanced RHD, co-regulated expression of IL-6 and TNF-α are associated with severe valvular dysfunction, with higher IL-10 and IL-4 levels predicting adverse clinical outcomes [54].
The biggest advance in the field of RHD genetics has been genome-wide association studies (GWAS), of which four major studies have been published to date (Table 1) [47][55][56][57]. GWAS are considered more suitable studies for complex diseases in which large numbers of variants can be tested by comparing single-nucleotide polymorphism (SNP) distributions in patients with the disease against selected controls [58]. These GWAS studies have generated support for the presence of significant heritability in RHD, which is likely to be polygenic. The RhEumatiC Heart diseAse Genetics (RECHARGE) study is ongoing in Rwanda, using next-generation genetic sequencing on a sample of approximately 1000 participants (ClinicalTrials.gov Identifier: NCT02118818). It is expected to be completed in 2024. The importance of investing resources in the genetic association of RHD lies not just in the potential to substantially contribute towards understanding disease pathogenesis and etiology, but also the prospect of identifying novel or repurposed therapeutics and vaccine development [46].

3. Advances in Management of the RF/RHD Continuum

3.1. Progress Towards a Group A Streptococcus Vaccine

Efforts to create a vaccine to prevent GAS infections have been ongoing since 1923. However, the first vaccines were ineffective and highly reactogenic, raising concerns, though likely unfounded or overblown, about the potential for vaccines to increase ARF predisposition; this resulted in the US Food and Drug Administration (FDA) stopping GAS vaccine trials in the 1970s for over 30 years [59][60]. In the past two decades, studies on vaccine development have improved with advances in genomics, proteomics, and immunomics; still, most vaccines are in pre-clinical testing, and few have reached Phase I and II trials. Currently, there are no licensed vaccines of GAS available in any settings [60].
Vaccine candidates, however, include multivalent M protein-based vaccines, M protein vaccines containing conserved C-repeat epitopes, cell wall carbohydrate vaccines, and non-M protein multi-component vaccines. Table 1 provides a summary of vaccines that are in the development pipeline. Vaccines based on group A carbohydrate (GAC), a polysaccharide present in Streptococcus pyogenes cell wall, have not shown expressive results yet [60].
Table 1. Group A Streptococcus vaccines that are in the development pipeline. * Pioneered by University of Tennessee and Dalhousie, Canada; ** Pioneered by Queensland Institute of Medical Research, Australia; Pioneered by University of São Paulo, Brazil.
Type of Vaccine Stage of Development
StreptAvax: 26-valent vaccine Phase I and II trials demonstrated good safety, tolerance and immunogenicity [61][62]; however further studies stopped for commercial reasons
StreptAnova *: 4 recombinant proteins The 4 recombinant proteins represent 30 different M-types prevalent in North America and Europe Phase I trial: demonstrated good tolerance and immunogenicity in adults [63].
MJ8VAX **: based on C-terminus of the M protein Phase I trial: demonstrated that a single intramuscular dose of the vaccine was safe, well tolerated and immunogenic, but anti-J8 IgG concentration decreased after 180 days post immunization [64].
StreptInCor: peptide vaccine containing T and B cell epitopes of the M protein CRR Good results in models [65].
Multi-component vaccines [60] 3-Combo: SpyCEP, SpyAD, SLO; provides protection in models
5-Combo: ADI, TF, C5a peptidase, SpyCEP and SLO
5-CP: demonstrated protection against intranasal, skin and systemic challenges of GAS
Spy-7: showed significant reduction in the dissemination of types M1 and M3 GAS
Prevailing challenges in vaccine development are multifactorial, ranging from incomplete understanding of the basic science of GAS/RF/RHD to lack of commercial stakeholder interest. Specific challenges for GAS vaccine development include: (a) extensive genomic heterogenicity of Strep A and subsequent protein sequence variations, limiting the effectiveness of the vaccine over different populations [60]; (b) complexity of global GAS epidemiology; (c) incomplete understanding of ARF pathogenesis; (d) risk of serious autoimmune reactions to vaccines [59]; (e) dependence on controlled human infection models for vaccine development as GAS is strictly a human pathogen, thus precluding the use of animal models [66]; (f) lack of consensus on clinical endpoints for establishment of proof of concept, (g) limited market in high-income countries; and h) lack of commercial interest [60].
In order to overcome the myriad challenges in GAS vaccine development, in 2018 the World Health Assembly (WHA) launched a Global Resolution calling for improved control and prevention of GAS infections and RHD [67]. In 2019, the Strep A Vaccine Consortium (SAVAC) was formed to work along the World Health Organization (WHO) [60]. Furthermore, through the Coalition to Advance Vaccines Against Group A Streptococcus (CANVAS), the Australian and New Zealand governments have designated significant funding to support the development of a vaccine against GAS pharyngitis [68].

3.2. Advances in Primary Prevention

Diagnosis of Group A Strep Pharyngitis

Microbiological culture of a throat swab remains the gold standard for diagnosing GAS pharyngitis, despite the prohibitive cost of this modality at a population level, the long turn-around time precluding confirmed diagnosis in a single clinic visit, and lack of readily available culture-able laboratories in LMICs. Recognizing these limitations, alternative diagnostic tests which are less resource-intensive have been developed and continue to evolve.
Clinical decision rules can obviate the need for expensive bacteriological diagnostic tools since they do not require specialized equipment and are easy for providers to implement [69][70][71]. There has been a proliferation of Clinical Decision Rules (CDRs) for diagnosis of GAS pharyngitis in recent years [69][70][72][73][74][75][76][77]. Recent developments relevant to RHD endemic regions include: (a) validation studies of existing CDRs in RHD endemic regions [78] that have concluded that diagnostic performance varies considerably in different regions of the world, thus highlighting the importance of evaluating and validating CDRs in local settings before they are rolled out as the standard of care; and, (b) development of CDRs in RHD endemic regions such as the Cape Town Clinical Decision Rule [69] in South Africa. The Cape Town Clinical Decision Rule is likely a more relevant application to similar settings in sub-Saharan Africa. Tailoring decision rules to a specific population is a critical research area for population specific investment in LMICs.
Rapid Antigen Detection Tests (RADTs) have been in clinical use for four decades, with attractive features such as a quick turn-around time (<10 min), low cost, and ease of use. Recently, some external performance factors were learned, such as inadequate staff training, substantially reduce the accuracy of these tests [79]. There is also greater understanding of factors that potentially increase heterogeneity of testing results that have similar sensitivity and specificity [80] such as differences in throat culture sample collection [80][81], experience of the person performing the RADT, absence of a universally accepted blood agar plate culture method to serve as a reference standard [82], patient-level characteristics such as clinical presentation and inoculum size [83], and spectrum bias [84]. However, despite multiple advantages, RADTs remain vastly unavailable and are considered expensive for many low-resource settings. There is an overarching need to make existing RADTs available and affordable for use in such settings.
More recent progress in point-of-care tests for GAS pharyngitis include Nucleic Acid Amplification Tests (NAATs), which have much better sensitivity and specificity than RADTs [85]. For example, the sensitivity and specificity of the Illumigene assay are estimated to be in excess of 99% [85][86][87]. This high performance, coupled with speed of results, makes NAATs ideal candidates for point-of-care use in the clinical environment. Several NAATs have received approval over the past six years [88], but their high cost has precluded widespread use. Despite the prevailing cost, NAATs are being increasingly investigated as low-cost, integrated tools for use in low resource settings [89][90]. Research should strive towards the development of molecular diagnostic tests using a “pharyngitis panel” of targets.
Electrochemical detection methods, which use DNA, have been proposed as an affordable, effective method for diagnosing GAS; results are available in 30 minutes with 100% specificity, have been reported [91][92].
Machine learning and artificial intelligence techniques are also in development to aid in the diagnosis of strep throat through throat image processing [93] and automated examination of throat cultures to identify GAS [94]. Neural networks have also been suggested to assist in diagnosis, with reported correct diagnosis of pharyngitis in 95.4% of test cases in one study [95]. The Strepic® device, a qualitative point-of-care clinical prototype, has been designed specifically as a viable, low-cost, commercially realizable autofluorescence-based diagnostic test (ClinicalTrials.gov Identifier: NCT03777098).

Treatment of Group A Strep Pharyngitis

Penicillin remains the first line recommendation for the treatment of GAS pharyngitis, with two Cochrane reviews supporting this recommendation [96][97]. Monthly intramuscular injections of benzathine benzyl penicillin (BPG) remain the gold standard for secondary antibiotic prophylaxis for the prevention of RHD [98][99]. Recent strategies to diminish pain [100] associated with BPG administration include the addition of lidocaine to BPG solution [101][102] and the use of pain distraction methods (buzzy R) [102][103][104][105]. There is also work underway in developing implantable and longer acting BPG delivery devices [106][107][108]. The WHO added BPG to the essential medicines list for member states as a way to increase access, however, disruptions in global and local BPG supply chains are not uncommon [109][110]. Regrettably, a recent report described geographically widespread reduced in-vitro susceptibility of Streptococcus pyogenes to beta-lactam antibiotics associated with mutations in the pbp2× gene [111], warranting enhanced surveillance and further epidemiological and molecular genetic study of this potential emergent antimicrobial threat.
Community and provider knowledge and awareness of the RHD-GAS relationship remain a pillar of primary prevention strategies. While previous awareness campaigns heavily utilized print and mass media [112][113][114], increasing availability of sophisticated personal technologies such as mobile devices and internet access (particularly in low-resource settings), have resulted in the employment of new electronic avenues of patient, public, and stakeholder education about RHD [115].
Additionally, it has been noted that streptococcal carriage rates often vary between communities and by season, especially in endemic countries [116][117]. It has thus been postulated that the GAS carrier state is not implicated in the pathogenesis of RF/RHD, and that transmission of GAS is almost limited exclusively to individuals with acute GAS infection [118][119]. Therefore, antibiotic treatment for eradication of GAS has been recommended only for individuals with acute GAS infection. However, this traditional benign dogma of the carrier state is being challenged and revisited, with additional investigation necessary to determine if this paradigm holds true in endemic regions of the globe.

3.3. Advances in Secondary Prevention

The Jones criteria for the diagnosis for ARF were first established in 1944 [120]. Since their inception, the criteria have undergone multiple revisions and updates, most recently in 2015 [121]. This most recent revision addressed two significant features: it (a) distinguished criteria between low-risk and moderate-to-high risk populations based on ARF incidence or RHD prevalence; and (b) recommended echocardiography of all suspected cases of ARF and incorporated subclinical carditis as evidenced by echocardiography as a major criteria. Differentiating criteria for low-risk and moderate-to-high risk populations aimed to increase sensitivity in endemic regions while retaining specificity in low-risk areas, thus making the criteria more globally relevant. However, ARF still remains a clinical diagnosis with no single confirmatory test, and there is ongoing work attempting to identify a unique immune signature that could be used to reliably diagnose ARF [122]. For example, in routine clinical practice it is often not feasible to obtain both acute and convalescent sera and therefore, the absolute quantitative measure of anti-streptolysin (ASO) titers is used more for diagnostic value [123]. However, there is wide geographic variability of the 80th percentile upper limit of normal (ULN) cutoffs for ASO titers [124][125]. It is therefore important to establish ULN ranges of ASO titers for various age groups in different geographic locations. Accordingly, there have been recent studies in some RHD endemic regions describing their population-specific streptococcal antibody titers [126].
This is particularly relevant, because, as previously mentioned, there is recent evidence for the benefit of secondary penicillin prophylaxis for prevention of progressive cardiac disease in latent RHD [7]. The recent GOAL trial demonstrated that among children and adolescents 5 to 17 years of age with latent RHD, secondary antibiotic prophylaxis reduced the risk of RHD progression at two years followup time [7]. This new evidence provides added justification for echocardiographic screening and active case detection of RHD as a key step in the control of RHD sequelae in susceptible populations.

3.4. Procedural and Medical Advances in Tertiary Care

Procedural Advances in RHD-Associated Valvular Disease
There is a growing body of evidence to support the use of PBMV for RHD-associated mitral stenosis, and the indications have considerably expanded in the past decade to include challenging and unfavorable MV involvement. Furthermore, additional prognostic parameters have been investigated—such as asymmetrical commissural fusion and atrioventricular compliance—and the Wilkins score has been updated with parameters derived from international RHD cohorts [127]. Meanwhile, percutaneous valve interventions continue to evolve worldwide, with transcatheter aortic valve implantation for the treatment of aortic stenosis (more below) being a prime example of such advances [128]. With its successful implementation, percutaneous valve intervention is gaining attention as a feasible treatment for both mitral and aortic valve disease, as well as an option for second valvular interventions after the failure of the primary valve surgery—common in RHD—with additional outcome information to be established in the upcoming decades [129][130].
TAVR is an established minimally invasive alternative to surgical aortic valve replacement (SAVR) in patients with severe aortic stenosis (AS) and calcific aortic valve disease [131][132]. In RHD with aortic involvement, SAVR is still the first choice of intervention due to the lower degree of valve calcification seen in rheumatic valves in most cases [132][133], younger age of patients, and limited scientific evidence of TAVR for RHD-associated AS [133]. Until recently, knowledge surrounding the application of TAVR for RHD patients was limited to case series and reports [132][134][135][136]. However, there is contemporary evidence for non-inferiority of TAVR to SAVR in rheumatic AS, safety of TAVR, and short and intermediate term outcomes of TAVR [132][135]. These novel data have changed the perspective of TAVR for RHD, suggesting it as a feasible approach for RHD patients with predominant aortic valve involvement. However, wider spectrum studies with larger subject numbers and long-term outcomes reports in RHD-specific patient populations are warranted in order to achieve generalization of such findings.

Advances in Medical Management of Clinical RHD

Given the limitation of surgical treatment options for many patients with symptomatic RHD in low-income regions, medical management remains a critical cornerstone of therapy for those awaiting or unable to obtain operative management of advanced valvular RHD. Unfortunately, medical therapy to date has yet to demonstrate slowed progression of the disease. As such, pharmacologic treatment has targeted symptom relief by addressing underlying left ventricular dysfunction and heart failure or by addressing the end-stage complications of RHD [137].
Atrial fibrillation (AF) is a major cause of morbidity and mortality in patients with RHD [16][137][138]. Anticoagulation is recommended to reduce the risk of cardioembolic events in patients with AF, often associated with advancing valvular pathologies [16][138][139]. Oral Vitamin K antagonists are the recommended drugs of choice for this purpose [137], but they are associated with challenges both for health care providers and patients in monitoring and maintaining their effectiveness [138][139]. New evidence may revolutionize anticoagulation in rheumatic atrial fibrillation, as novel oral anticoagulants (NOACs)—not yet formally recommended for AF in the presence of RHD—have proven to be non-inferior to warfarin in a Brazilian trial which allowed the inclusion of RHD patients with atrial fibrillation and bioprosthetic mitral valves [140]. The multicenter INVICTUS trial [141] examining warfarin versus rivaroxaban in rheumatic AF is nearing completion and may bring more definite conclusions in the near future. However, even if NOACs become a standard for anticoagulation in RHD, access and cost-effectiveness will require careful discussion for their use in LMICs, given the higher present market price of these drugs [142].
Another chief clinical concern among advanced RHD patients remains that of infective endocarditis in both prosthetic valves and diseased native heart valves. Given the lack of scientific evidence in reducing infective endocarditis (IE) burden in the absence of prosthetic valves or previous history of IE, antibiotic prophylaxis for dental procedures has been relegated to a limited role in recent professional society guidelines [143]. Currently, recommendations for such chemical prophylaxis is limited to high-risk patients—noticeably those following valve replacement or those with a previous IE episode—undergoing high-risk procedures with potential bacterial translocation [144]. Good dental hygiene and regular dental cleanings, however, still play an important role in IE prevention and should be emphasized [143].

4. RHD Policy Advances

4.1. Understanding of RHD-Associated Costs in Endemic Regions

RHD costing data from endemic countries and regions has historically been quite sparse. However, cost-effectiveness analyses comparing primary, secondary, and tertiary prevention of RHD in the African setting have recently been conducted [145]. Such findings have revealed that scaling up primary prevention would be a cost-saving approach, with a negative incremental cost-effectiveness ratio (ICER) of -$2539 USD per DALY averted, whilst putting efforts into secondary prevention programs would be cost-effective (USD $752 per DALY averted) [145]. The investments required for local surgical capacity development were high with limited impact (ICER of USD $23,827 per DALY averted for constructing a local surgical center) [145]. Several other analyses have separately explored optimal cost-effective strategies for primary prevention [146], secondary prevention [147][148][149][150], and a combination of both [150][151][152]. A recent modeling study for the prevention and management of RHD in the African Union concluded that, “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 [153]”. Most analyses make use of Markov models, and similar challenges relating to lack of precise transition probabilities on which to base the calculations have been reported [145][148][151].
Additionally, recent studies regarding the cost of illness have described the substantial economic impact of RHD at the household, health system, and national level in endemic countries such as Uganda [154], South Africa [155][156], India [157][158], and others [159].

4.2. Global Efforts, Advocacy, and Stakeholder Engagement in the Fight against RHD

The growing research and healthcare/awareness projects in RHD worldwide, combined with a considerable increase in research interest over the past two decades, has raised multisectoral attention regarding this neglected disease. This has resulted in international coordination of efforts which have been multifaceted, with ambitious aims (Table 2).
Table 2. Summarized aims of global efforts in the fight against RHD, and key charges from the 2018 WHA resolution to member states. Abbreviations: RHD, rheumatic heart disease; WHO, World Health Organization; WHF, World Heart Federation; WHA, World Health Assembly.
Summarized Aims of Global Efforts in the Fight against RHD
• Developing a collaborative agenda to address the key health impacts of RHD worldwide (premature morbidity and mortality, maternal deaths)
• Improving access to basic healthcare, from prophylaxis to more advanced therapies
• Sensitizing stakeholders and the political sector on the importance of RHD and the need for reducing its burden, especially in the hardest hit regions
• Developing position statements, guidelines, and calls-to-action focused on RHD
• Including RHD as a priority in the world agenda, establishing action plans and goals led by international organizations such as the WHO, WHF, and key cardiovascular societies
Key Charges from the 2018 WHA Resolution to Member States [160][161][162]
• Accelerate multisectoral efforts to improve socioeconomic determinants of RHD
• Estimate the burden of disease and implement multisectoral RHD programs
• Improve access to primary health care, including RHD prevention and control
• Ensure access to cost-effective essential laboratory technologies and medicines for RHD
• Strengthen national and international cooperation to address RHD.
As an example of practical outcomes of this international coordination, in 2011 the United Nations set key targets to reach by 2025, including a reduction in the risk of premature noncommunicable disease death–markedly cardiovascular disease–by 25% by 2025; with RHD notably included in this agenda [163]. Consequently, multiple authoritative individuals [164][165], societies, task forces, unions and federations, at regional, continental and international levels have published position statements [163][166][167][168][169], serving as a basis for guiding research and healthcare initiatives, helping define “next steps” and priorities for the global scientific agenda. The WHF has played a particularly pivotal role in such initiatives, with its first broad position statement on RHD released in 2013 reinforcing key aims and actions in a similar direction of preceding African statements [169]. More recently, there was a re-dedication of the American Heart Association (AHA) on the RHD agenda [170] with resumption of its intensive work on the development of guidelines and statements [121][137], research funding through its councils, and a working group dedicated to RF and RHD control.
These aforementioned position publications and statements from different organizations and regions, combined with the intensive collaborative multisectoral efforts worldwide, were recognized by the 2018 World Health Assembly Global Resolution to end RHD [160][161][162]. The key charges that this resolution brought to member states are listed in Table 2. In light of this unprecedented collaborative resolution, health systems should move towards enacting its actionable recommendations, increasing investment in primary care and general health infrastructure, sanitation and housing, medical supply and building capacity for RHD prevention and management.

References

  1. Carapetis, J.R.; Steer, A.C.; Mulholland, E.K.; Weber, M. The global burden of group A streptococcal diseases. Lancet Infect. Dis. 2005, 5, 685–694.
  2. Roth, G.A.; Mensah, G.A.; Johnson, C.O.; Addolorato, G.; Ammirati, E.; Baddour, L.M.; Barengo, N.C.; Beaton, A.Z.; Benjamin, E.J.; Benziger, C.P.; et al. Global Burden of Cardiovascular Diseases and Risk Factors, 1990–2019: Update From the GBD 2019 Study. J. Am. Coll. Cardiol. 2020, 76, 2982–3021.
  3. Marijon, E.; Ou, P.; Celermajer, D.S.; Ferreira, B.; Mocumbi, A.; Jani, D.; Paquet, C.; Jacob, S.; Sidi, D.; Jouven, X. Prevalence of Rheumatic Heart Disease Detected by Echocardiographic Screening. N. Engl. J. Med. 2007, 357, 470–476.
  4. Reményi, B.; Wilson, N.; Steer, A.; Ferreira, B.; Kado, J.; Kumar, K.; Lawrenson, J.; Maguire, G.; Marijon, E.; Mirabel, M.; et al. World Heart Federation criteria for echocardiographic diagnosis of rheumatic heart disease—an evidence-based guideline. Nat. Rev. Cardiol. 2012, 9, 297–309.
  5. Hunter, L.D.; Monaghan, M.; Lloyd, G.; Pecoraro, A.J.K.; Doubell, A.F.; Herbst, P.G. Screening for rheumatic heart disease: Is a paradigm shift required? Echo Res. Pract. 2017, 4, R43–R52.
  6. Recommendation No. R (94) 11 on Screening as Tool of Preventive Medicine. 10 October 1994. Available online: http://hrlibrary.umn.edu/instree/coerecr94-11.html (accessed on 15 October 2021).
  7. Beaton, A.Z.; Okello, E.; Rwebembera, J.; Grobler, A.; Engelman, D.; Carapetis, J.; Canales, L.; Dewyer, A.; Lwabi, P.; Mirabel, M. A Randomized Controlled Trial of Secondary Antibiotic Prophylaxis for Latent Rheumatic Heart Disease. Circulation 2021, 144, A12503.
  8. Ali, F.; Hasan, B.; Ahmad, H.; Hoodbhoy, Z.; Bhuriwala, Z.; Hanif, M.; Ansari, S.U.; Chowdhury, D. Detection of subclinical rheumatic heart disease in children using a deep learning algorithm on digital stethoscope: A study protocol. BMJ Open 2021, 11, e044070.
  9. Beaton, A.; Nascimento, B.R.; Diamantino, A.C.; Pereira, G.T.; Lopes, E.L.; Miri, C.O.; Bruno, K.K.; Chequer, G.; Ferreira, C.G.; Lafeta, L.C.; et al. Efficacy of a Standardized Computer-Based Training Curriculum to Teach Echocardiographic Identification of Rheumatic Heart Disease to Nonexpert Users. Am. J. Cardiol. 2016, 117, 1783–1789.
  10. Nascimento, B.R.; Martins, J.F.B.; Nascimento, E.R.; Pappa, G.L.; Sable, C.A.; Beaton, A.Z.; Gomes, P.R.; Nunes, M.C.; Oliveira, K.K.; Franco, J.; et al. Deep learning for automatic identification of rheumatic heart disease in echocardiographic screening images: Data from the atmosphere-provar study. J. Am. Coll. Cardiol. 2020, 75, 3577.
  11. Nunes, M.C.P.; Sable, C.; Nascimento, B.R.; de Lima, E.M.; da Silva, J.L.P.; Diamantino, A.C.; Oliveira, K.K.; Okello, E.; Aliku, T.; Lwabi, P.; et al. Simplified Echocardiography Screening Criteria for Diagnosing and Predicting Progression of Latent Rheumatic Heart Disease. Circ. Cardiovasc. Imaging 2019, 12, e007928.
  12. Watkins, D.A.; Johnson, C.O.; Colquhoun, S.; Karthikeyan, G.; Beaton, A.; Bukhman, G.; Forouzanfar, M.H.; Longenecker, C.T.; Mayosi, B.M.; Mensah, G.A.; et al. Global, Regional, and National Burden of Rheumatic Heart Disease, 1990–2015. New Engl. J. Med. 2017, 377, 713–722.
  13. Gündüz, S.; Kalçık, M.; Gürsoy, M.O.; Güner, A.; Özkan, M. Diagnosis, treatment and management of prosthetic valve thrombosis: The key considerations. Expert Rev. Med Devices 2020, 17, 209–221.
  14. Damasceno, A.; Mayosi, B.M.; Sani, M.; Ogah, O.S.; Mondo, C.; Ojji, D.; Dzudie, A.; Kouam, C.K.; Suliman, A.; Schrueder, N. The causes, treatment, and outcome of acute heart failure in 1006 Africans from 9 countries: Results of the sub-Saharan Africa survey of heart failure. Arch. Intern. Med. 2012, 172, 1386–1394.
  15. Kingué, S.; Ba, S.A.; Balde, D.; Diarra, M.B.; Anzouan-Kacou, J.-B.; Anisubia, B.; Damorou, J.-M.; Ndobo, P.; Menanga, A.; Kane, A.; et al. The VALVAFRIC study: A registry of rheumatic heart disease in Western and Central Africa. Arch. Cardiovasc. Dis. 2016, 109, 321–329.
  16. Zuhlke, L.; Engel, M.; Karthikeyan, G.; Rangarajan, S.; Mackie, P.; Cupido, B.; Mauff, K.; Islam, S.; Joachim, A.; Daniels, R.; et al. Characteristics, complications, and gaps in evidence-based interventions in rheumatic heart disease: The Global Rheumatic Heart Disease Registry (the REMEDY study). Eur. Hear. J. 2015, 36, 1115–1122.
  17. Fabi, M.; Calicchia, M.; Palleri, D.; Ndikubwimana, I.; Conard, C.; Kamanzi, E.R.; Balducci, A.; Frabboni, I.; Dondi, A.; Gargiulo, G.; et al. Pediatric rheumatic carditis in Italy and Rwanda: The same disease, different socio-economic settings. Int. J. Cardiol. 2021, 338, 154–160.
  18. Okello, E.; Wanzhu, Z.; Musoke, C.; Kakande, B.; Mondo, C.K.; Freers, J.; Twalib, A.; Lwabi, P.; Wilson, N.B.; Odoi-Adome, R. Cardiovascular complications in newly diagnosed rheumatic heart disease patients at Mulago Hospital, Uganda: Cardiovascular topics. Cardiovasc. J. Afr. 2013, 24, 82.
  19. Essop, M.R.; Nkomo, V.T. Rheumatic and nonrheumatic valvular heart disease: Epidemiology, management, and prevention in Africa. Circulation 2005, 112, 3584–3591.
  20. Scheel, A.; Ssinabulya, I.; Aliku, T.; Bradley-Hewitt, T.; Clauss, A.; Clauss, S.; Crawford, L.; Dewyer, A.; Donofrio, M.T.; Jacobs, M.; et al. Community study to uncover the full spectrum of rheumatic heart disease in Uganda. Heart 2018, 105, 60–66.
  21. Baker, M.G.; Gurney, J.; Oliver, J.; Moreland, N.J.; A Williamson, D.; Pierse, N.; Wilson, N.; Merriman, T.R.; Percival, T.; Murray, C.; et al. Risk Factors for Acute Rheumatic Fever: Literature Review and Protocol for a Case-Control Study in New Zealand. Int. J. Environ. Res. Public Health 2019, 16, 4515.
  22. Katzenellenbogen, J.M.; Bond-Smith, D.; Seth, R.J.; Dempsey, K.; Cannon, J.; Stacey, I.; Wade, V.; de Klerk, N.; Greenland, M.; Sanfilippo, F.M.; et al. Contemporary Incidence and Prevalence of Rheumatic Fever and Rheumatic Heart Disease in Australia Using Linked Data: The Case for Policy Change. J. Am. Heart Assoc. 2020, 9, e016851.
  23. Rwebembera, J.; Beaton, A.Z.; de Loizaga, S.R.; Rocha, R.T.; Doreen, N.; Ssinabulya, I.; Okello, E.; Fraga, C.L.; Galdino, B.F.; Nunes, M.C.P. The Global Impact of Rheumatic Heart Disease. Curr. Cardiol. Rep. 2021, 23, 1–10.
  24. Carapetis, J.R.; Beaton, A.; Cunningham, M.W.; Guilherme, L.; Karthikeyan, G.; Mayosi, B.M.; Sable, C.; Steer, A.; Wilson, N.; Wyber, R. Acute rheumatic fever and rheumatic heart disease. Nat. Rev. Dis. Primers 2016, 2, 1–24.
  25. Pandey, M.; Langshaw, E.; Hartas, J.; Lam, A.; Batzloff, M.R.; Good, M.F. A Synthetic M Protein Peptide Synergizes with a CXC Chemokine Protease To Induce Vaccine-Mediated Protection against Virulent Streptococcal Pyoderma and Bacteremia. J. Immunol. 2015, 194, 5915–5925.
  26. Parks, T.; Smeesters, P.R.; Steer, A.C. Streptococcal skin infection and rheumatic heart disease. Curr. Opin. Infect. Dis. 2012, 25, 145–153.
  27. Sikder, S.; Williams, N.L.; Sorenson, A.; Alim, A.; E Vidgen, M.; Moreland, N.; Rush, C.M.; Simpson, R.S.; Govan, B.L.; Norton, R.; et al. Group G Streptococcus Induces an Autoimmune Carditis Mediated by Interleukin 17A and Interferon γ in the Lewis Rat Model of Rheumatic Heart Disease. J. Infect. Dis. 2017, 218, 324–335.
  28. O’Sullivan, L.; Moreland, N.; Webb, R.H.; Upton, A.; Wilson, N.J. Acute Rheumatic Fever After Group A Streptococcus Pyoderma and Group G Streptococcus Pharyngitis. Pediatr. Infect. Dis. J. 2017, 36, 692–694.
  29. Sikder, S. Determination of the Role of Group G Streptococcus in the Pathogenesis of Rheumatic Heart Disease Using a Rat Model. Ph.D. Thesis, James Cook University, Douglas, Australia, 2018.
  30. Essop, M.R.; Peters, F. Contemporary Issues in Rheumatic Fever and Chronic Rheumatic Heart Disease. Circulation 2014, 130, 2181–2188.
  31. Dooley, L.M.; Ahmad, T.B.; Pandey, M.; Good, M.F.; Kotiw, M. Rheumatic heart disease: A review of the current status of global research activity. Autoimmun. Rev. 2020, 20, 102740.
  32. Tashima, Y.; Stanley, P. Antibodies that detect O-linked β-DN-acetylglucosamine on the extracellular domain of cell surface glycoproteins. J. Biol. Chem. 2014, 289, 11132–11142.
  33. Gorton, D.; Sikder, S.; Williams, N.L.; Chilton, L.; Rush, C.M.; Govan, B.L.; Cunningham, M.W.; Ketheesan, N. Repeat exposure to group A streptococcal M protein exacerbates cardiac damage in a rat model of rheumatic heart disease. Autoimmunity 2016, 49, 563–570.
  34. Dinkla, K.; Rohde, M.; Jansen, W.T.; Kaplan, E.L.; Chhatwal, G.S.; Talay, S.R. Rheumatic fever–associated Streptococcus pyogenes isolates aggregate collagen. J. Clin. Investig. 2003, 111, 1905–1912.
  35. Dinkla, K.; Talay, S.R.; Mörgelin, M.; Graham, R.M.; Rohde, M.; Nitsche-Schmitz, D.P.; Chhatwal, G.S. Crucial role of the CB3-region of collagen IV in PARF-induced acute rheumatic fever. PLoS ONE 2009, 4, e4666.
  36. Guilherme, L.; Köhler, K.F.; Kalil, J. Rheumatic heart disease: Mediation by complex immune events. Adv. Clin. Chem. 2011, 53, 31–50.
  37. Ellis, N.M.J.; Li, Y.; Hildebrand, W.; Fischetti, V.A.; Cunningham, M.W. T Cell Mimicry and Epitope Specificity of Cross-Reactive T Cell Clones from Rheumatic Heart Disease. J. Immunol. 2005, 175, 5448–5456.
  38. Guilherme, L.; Köhler, K.; Postol, E.; Kalil, J. Genes, autoimmunity and pathogenesis of rheumatic heart disease. Ann. Pediatr. Cardiol. 2011, 4, 13–21.
  39. Guilherme, L.; Kalil, J. Rheumatic Fever and Rheumatic Heart Disease: Cellular Mechanisms Leading Autoimmune Reactivity and Disease. J. Clin. Immunol. 2010, 30, 17–23.
  40. Toor, D.; Sharma, N. T cell subsets: An integral component in pathogenesis of rheumatic heart disease. Immunol. Res. 2017, 66, 18–30.
  41. Excler, J.-L.; Kim, J.H. Accelerating the development of a group A Streptococcus vaccine: An urgent public health need. Clin. Exp. Vaccine Res. 2016, 5, 101–107.
  42. Abdallah, A.M.; Abu-Madi, M. The genetic control of the rheumatic heart: Closing the genotype-phenotype gap. Front. Med. 2021, 8, 611036.
  43. Bryant, P.A.; Robins-Browne, R.; Carapetis, J.R.; Curtis, N. Some of the people, some of the time: Susceptibility to acute rheumatic fever. Circulation 2009, 119, 742–753.
  44. Engel, M.E.; Stander, R.; Vogel, J.; Adeyemo, A.A.; Mayosi, B.M. Genetic Susceptibility to Acute Rheumatic Fever: A Systematic Review and Meta-Analysis of Twin Studies. PLoS ONE 2011, 6, e25326.
  45. Martin, W.J.; Steer, A.C.; Smeesters, P.; Keeble, J.; Inouye, M.; Carapetis, J.; Wicks, I.P. Post-infectious group A streptococcal autoimmune syndromes and the heart. Autoimmun. Rev. 2015, 14, 710–725.
  46. Muhamed, B.; Parks, T.; Sliwa, K. Genetics of rheumatic fever and rheumatic heart disease. Nat. Rev. Cardiol. 2020, 17, 145–154.
  47. Auckland, K.; Mittal, B.; Cairns, B.J.; Garg, N.; Kumar, S.; Mentzer, A.J.; Kado, J.; Perman, M.L.; Steer, A.C.; Hill, A.V.S.; et al. The Human Leukocyte Antigen Locus and Rheumatic Heart Disease Susceptibility in South Asians and Europeans. Sci. Rep. 2020, 10, 1–9.
  48. El-Hagrassy, N.; El-Chennawi, F.; Zaki, M.E.-S.; Fawzy, H.; Zaki, A.; Joseph, N. HLA Class I and Class II HLA DRB Profiles in Egyptian Children with Rheumatic Valvular Disease. Pediatr. Cardiol. 2010, 31, 650–656.
  49. Ayoub, E.M.; Barrett, D.J.; MacLaren, N.K.; Krischer, J.P. Association of class II human histocompatibility leukocyte antigens with rheumatic fever. J. Clin. Investig. 1986, 77, 2019–2026.
  50. Guilherme, L.; Weidebach, W.; Kiss, M.H.; Snitcowsky, R.; Kalil, J. Association of human leukocyte class II antigens with rheumatic fever or rheumatic heart disease in a Brazilian population. . Circulation 1991, 83, 1995–1998.
  51. Okello, E.; Beaton, A.; Mondo, C.K.; Kruszka, P.; Kiwanuka, N.; Odoi-Adome, R.; Freers, J. Rheumatic heart disease in Uganda: The association between MHC class II HLA DR alleles and disease: A case control study. BMC Cardiovasc. Disord. 2014, 14, 1–5.
  52. Nana, M.L.A.; Anderson, J.L.; Carlquist, J.F.; Nanas, J.N. HLA-DR typing and lymphocyte subset evaluation in rheumatic heart disease: A search for immune response factors. Am. Hear. J. 1986, 112, 992–997.
  53. Akkaya, E.; Berkowitsch, A.; Rieth, A.; Erkapic, D.; Hamm, C.W.; Neumann, T.; Kuniss, M. Clinical outcome and left atrial function after left atrial roof ablation using the cryoballoon technique in patients with symptomatic persistent atrial fibrillation. Int. J. Cardiol. 2019, 292, 112–118.
  54. Tormin, J.P.; Nascimento, B.R.; Sable, C.A.; da Silva, J.L.P.; Brandao-De-Resende, C.; Rocha, L.P.C.; Pinto, C.H.; Neves, E.G.A.; Macedo, F.V.; Fraga, C.L.; et al. Cytokine gene functional polymorphisms and phenotypic expression as predictors of evolution from latent to clinical rheumatic heart disease. Cytokine 2021, 138, 155370.
  55. Parks, T.; Network, P.I.R.H.D.G.; Mirabel, M.M.; Kado, J.; Auckland, K.; Nowak, J.; Rautanen, A.; Mentzer, A.J.; Marijon, E.; Jouven, X.; et al. Association between a common immunoglobulin heavy chain allele and rheumatic heart disease risk in Oceania. Nat. Commun. 2017, 8, 1–10.
  56. Gray, L.-A.; D’Antoine, H.A.; Tong, S.Y.C.; McKinnon, M.; Bessarab, D.; Brown, N.; Reményi, B.; Steer, A.; Syn, G.; Blackwell, J.M.; et al. Genome-Wide Analysis of Genetic Risk Factors for Rheumatic Heart Disease in Aboriginal Australians Provides Support for Pathogenic Molecular Mimicry. J. Infect. Dis. 2017, 216, 1460–1470.
  57. Machipisa, T.; Chong, M.; Muhamed, B.; Chishala, C.; Shaboodien, G.; Pandie, S.; de Vries, J.; Laing, N.; Joachim, A.; Daniels, R. Association of Novel Locus With Rheumatic Heart Disease in Black African Individuals: Findings From the RHDGen Study. JAMA Cardiol. 2021, 6, 1000–1011.
  58. Visscher, P.M.; Wray, N.R.; Zhang, Q.; Sklar, P.; McCarthy, M.I.; Brown, M.A.; Yang, J. 10 years of GWAS discovery: Biology, function, and translation. Am. J. Hum. Genet. 2017, 101, 5–22.
  59. Azuar, A.; Jin, W.; Mukaida, S.; Hussein, W.M.; Toth, I.; Skwarczynski, M. Recent Advances in the Development of Peptide Vaccines and Their Delivery Systems Against Group A Streptococcus. Vaccines 2019, 7, 58.
  60. Dale, J.B.; Walker, M.J. Update on group A streptococcal vaccine development. Curr. Opin. Infect. Dis. 2020, 33, 244–250.
  61. McNeil, S.A.; Halperin, S.A.; Langley, J.; Smith, B.; Baxendale, D.M.; Warren, A.; Sharratt, G.P.; Reddish, M.A.; Fries, L.F.; Vink, P.; et al. A double-blind, randomized phase II trial of the safety and immunogenicity of 26-valent group A streptococcus vaccine in healthy adults. Int. Congr. Ser. 2006, 1289, 303–306.
  62. McNeil, S.A.; Halperin, S.A.; Langley, J.M.; Smith, B.; Warren, A.; Sharratt, G.P.; Baxendale, D.M.; Reddish, M.A.; Hu, M.C.; Stroop, S.D.; et al. Safety and immunogenicity of 26-valent group a streptococcus vaccine in healthy adult volunteers. Clin. Infect. Dis. Off. Publ. Infect. Dis. Soc. Am. 2005, 41, 1114–1122.
  63. Pastural, É.; McNeil, S.A.; MacKinnon-Cameron, D.; Ye, L.; Langley, J.M.; Stewart, R.; Martin, L.H.; Hurley, G.J.; Salehi, S.; Penfound, T.A.; et al. Safety and immunogenicity of a 30-valent M protein-based group a streptococcal vaccine in healthy adult volunteers: A randomized, controlled phase I study. Vaccine 2020, 38, 1384–1392.
  64. Sekuloski, S.; Batzloff, M.R.; Griffin, P.; Parsonage, W.; Elliott, S.; Hartas, J.; O’Rourke, P.; Marquart, L.; Pandey, M.; Rubin, F.A.; et al. Evaluation of safety and immunogenicity of a group A streptococcus vaccine candidate (MJ8VAX) in a randomized clinical trial. PLOS ONE 2018, 13, e0198658.
  65. De Sá-Rocha, L.C.; Demarchi, L.; Postol, E.; Sampaio, R.O.; de Alencar, R.E.; Kalil, J.; Guilherme, L. StreptInCor, a Group A Streptococcal Adsorbed Vaccine: Evaluation of Repeated Intramuscular Dose Toxicity Testing in Rats. Front. Cardiovasc. Med. 2021, 8, 643317.
  66. Osowicki, J.; Azzopardi, K.I.; Baker, C.; Waddington, C.S.; Pandey, M.; Schuster, T.; Grobler, A.; Cheng, A.C.; Pollard, A.J.; McCarthy, J.; et al. Controlled human infection for vaccination against Streptococcus pyogenes (CHIVAS): Establishing a group A Streptococcus pharyngitis human infection study. Vaccine 2019, 37, 3485–3494.
  67. Vekemans, J.; Gouvea-Reis, F.; Kim, J.H.; Excler, J.L.; Smeesters, P.R.; O’Brien, K.L.; Van Beneden, C.A.; Steer, A.C.; Carapetis, J.R.; Kaslow, D.C. The Path to Group A Streptococcus Vaccines: World Health Organization Research and Development Technology Roadmap and Preferred Product Characteristics. Clin. Infect. Dis. Off. Publ. Infect. Dis. Soc. Am. 2019, 69, 877–883.
  68. Wright, C.M.; Langworthy, K.; Manning, L. The Australian burden of invasive group A streptococcal disease: A narrative review. Intern. Med. J. 2021, 51, 835–844.
  69. Engel, M.E.; Cohen, K.; Gounden, R.; Kengne, A.P.; Barth, D.; Whitelaw, A.C.; Francis, V.; Badri, M.; Stewart, A.; Dale, J.; et al. The Cape Town Clinical Decision Rule for Streptococcal Pharyngitis in Children. Pediatr. Infect. Dis. J. 2017, 36, 250–255.
  70. Joachim, L.; Smeesters, P.R.; Campos, D., Jr. Pragmatic Scoring System for Pharyngitis in Low-Resource Settings. Pediatrics 2010, 126, e608–e614.
  71. Irlam, J.; Mayosi, B.M.; Engel, M.; Gaziano, T.A. Primary prevention of acute rheumatic fever and rheumatic heart disease with penicillin in South African children with pharyngitis: A cost-effectiveness analysis. Circ. Cardiovasc. Qual. Outcomes 2013, 6, 343–351.
  72. McIsaac, W.J.; White, D.; Tannenbaum, D.; E Low, D. A clinical score to reduce unnecessary antibiotic use in patients with sore throat. Can. Med Assoc. J. 1998, 158, 75–83.
  73. Janovsky, K. The Management of Acute Respiratory Infections in Children: Practical Guidelines for Outpatient Care; World Health Organization: Geneva, Switzerland, 1995.
  74. Dougherty, S.; Carapetis, J.; Zuhlke, L.; Wilson, N. Primary Prevention of Acute Rheumatic Fever and Rheumatic Heart Disease. In Acute Rheumatic Fever and Rheumatic Heart Disease; Elsevier: Amsterdam, The Netherlands, 2020; p. 195.
  75. Le Marechal, F.; Martinot, A.; Duhamel, A.; Pruvost, I.; Dubos, F. Streptococcal pharyngitis in children: A meta-analysis of clinical decision rules and their clinical variables. BMJ Open 2013, 3, e001482.
  76. Shaikh, N.; Swaminathan, N.; Hooper, E.G. Accuracy and Precision of the Signs and Symptoms of Streptococcal Pharyngitis in Children: A Systematic Review. J. Pediatr. 2012, 160, 487–493.e3.
  77. Cohen, J.F.; Cohen, R.; Levy, C.; Thollot, F.; Benani, M.; Bidet, P.; Chalumeau, M. Selective testing strategies for diagnosing group A streptococcal infection in children with pharyngitis: A systematic review and prospective multicentre external validation study. Can. Med. Assoc. J. 2015, 187, 23–32.
  78. Walker, C.L.F.; Rimoin, A.W.; Hamza, H.; Steinhoff, M.C. Comparison of clinical prediction rules for management of pharyngitis in settings with limited resources. J. Pediatr. 2006, 149, 64–71.
  79. Toepfner, N.; Henneke, P.; Berner, R.; Hufnagel, M. Impact of technical training on rapid antigen detection tests (RADT) in group A streptococcal tonsillopharyngitis. Eur. J. Clin. Microbiol. Infect. Dis. 2013, 32, 609–611.
  80. Stewart, E.H.; Davis, B.; Clemans-Taylor, B.L.; Littenberg, B.; Estrada, C.A.; Centor, R.M. Rapid Antigen Group A Streptococcus Test to Diagnose Pharyngitis: A Systematic Review and Meta-Analysis. PLoS ONE 2014, 9, e111727.
  81. Adler, L.; Parizade, M.; Koren, G.; Yehoshua, I. Oral cavity swabbing for diagnosis of group a Streptococcus: A prospective study. BMC Fam. Pr. 2020, 21, 1–6.
  82. Gerber, M.A.; Shulman, S.T. Rapid diagnosis of pharyngitis caused by group A streptococci. Clin. Microbiol. Rev. 2004, 17, 571–580.
  83. Cohen, J.F.; Bertille, N.; Cohen, R.; Chalumeau, M. Rapid antigen detection test for group A streptococcus in children with pharyngitis. Cochrane Database Syst. Rev. 2016, 2016, CD010502.
  84. Plainvert, C.; Duquesne, I.; Touak, G.; Dmytruk, N.; Poyart, C. In vitro evaluation and comparison of 5 rapid antigen detection tests for the diagnosis of beta-hemolytic group A streptococcal pharyngitis. Diagn. Microbiol. Infect. Dis. 2015, 83, 105–111.
  85. Thompson, T.Z.; McMullen, A.R. Group A streptococcus testing in pediatrics: The move to point-of-care molecular testing. J. Clin. Microbiol. 2020, 58, e01494-19.
  86. Anderson, N.W.; Buchan, B.W.; Mayne, D.; Mortensen, J.E.; Mackey, T.-L.A.; Ledeboer, N.A. Multicenter clinical evaluation of the illumi gene group A Streptococcus DNA amplification assay for detection of group A Streptococcus from pharyngeal swabs. J. Clin. Microbiol. 2013, 51, 1474–1477.
  87. Henson, A.M.; Carter, D.; Todd, K.; Shulman, S.T.; Zheng, X. Detection of Streptococcus pyogenes by Use of Illumigene Group A Streptococcus Assay. J. Clin. Microbiol. 2013, 51, 4207–4209.
  88. Luo, R.; Sickler, J.; Vahidnia, F.; Lee, Y.-C.; Frogner, B.; Thompson, M. Diagnosis and Management of Group a Streptococcal Pharyngitis in the United States, 2011–2015. BMC Infect. Dis. 2019, 19, 1–9.
  89. Cantera, J.L.; White, H.; Diaz, M.H.; Beall, S.G.; Winchell, J.M.; Lillis, L.; Kalnoky, M.; Gallarda, J.; Boyle, D.S. Assessment of eight nucleic acid amplification technologies for potential use to detect infectious agents in low-resource settings. PLoS ONE 2019, 14, e0215756.
  90. Lu, H.-W.; Roskos, K.; Hickerson, A.I.; Carey, T.; Niemz, A. System for portable nucleic acid testing in low resource settings. In Microfluidics, BioMEMS, and Medical Microsystems XI; International Society for Optics and Photonics: Bellingham, WA, USA, 2013; Volume 8615, p. 0I–86150I-12.
  91. Singh, S.; Kaushal, A.; Khare, S.; Kumar, P.; Kumar, A. Gold–mercaptopropionic acid–polyethylenimine composite based DNA sensor for early detection of rheumatic heart disease. Anal. 2014, 139, 3600–3606.
  92. Malinowska, N.; Białobrzeska, W.; Łęga, T.; Pałka, K.; Dziąbowska, K.; Żołędowska, S.; Czaczyk, E.; Pala, K.; Nidzworski, D. Antibody Modified Gold Electrode as an Impedimetric Biosensor for the Detection of Streptococcus pyogenes. Sensors 2020, 20, 5324.
  93. Askarian, B.; Yoo, S.-C.; Chong, J.W. Novel Image Processing Method for Detecting Strep Throat (Streptococcal Pharyngitis) Using Smartphone. Sensors 2019, 19, 3307.
  94. Van, T.T.; Mata, K.; Bard, J.D. Automated Detection of Streptococcus pyogenes Pharyngitis by Use of Colorex Strep A CHROMagar and WASPLab Artificial Intelligence Chromogenic Detection Module Software. J. Clin. Microbiol. 2019, 57.
  95. Farhan, S.; Alshraideh, M.; Mahafza, T. A medical decision support system for ent disease diagnosis using artificial neural networks. Int. J. Artif. Intell. Mechatron. 2015, 4, 45–54.
  96. Spinks, A.; Glasziou, P.P.; Del Mar, C.B. Antibiotics for sore throat. Cochrane Database Syst. Rev. 2013, 11.
  97. Driel, M.L.; De Sutter, A.I.; Thorning, S.; Christiaens, T. Different antibiotic treatments for group A streptococcal pharyngitis. Cochrane Database Syst. Rev. 2021, 3.
  98. De Dassel, J.L.; de Klerk, N.; Carapetis, J.R.; Ralph, A.P. How Many Doses Make a Difference? An Analysis of Secondary Prevention of Rheumatic Fever and Rheumatic Heart Disease. J. Am. Heart Assoc. 2018, 7, e010223.
  99. Manyemba, J.; Mayosi, B.M. Penicillin for secondary prevention of rheumatic fever. Cochrane Database Syst Rev. 2002, 2002, Cd002227.
  100. Musoke, C.; Mondo, C.K.; Okello, E.; Zhang, W.Z.; Kakande, B.; Nyakoojo, W.; Freers, J. Benzathine penicillin adherence for secondary prophylaxis among patients affected with rheumatic heart disease attending Mulago Hospital: Cardiovascular topics. Cardiovasc. J. Afr. 2013, 24, 124–129.
  101. Bennett, J.; Rentta, N.; Leung, W.; Anderson, A.; Oliver, J.; Wyber, R.; Harwod, M.; Webb, R.; Malcom, J.; Baker, M.G. Structured review of primary interventions to reduce group A streptococcal infections, acute rheumatic fever and rheumatic heart disease. J. Paediatr. Child Health 2021, 57, 797–802.
  102. Russell, K.; Nicholson, R.; Naidu, R. Reducing the pain of intramuscular benzathine penicillin injections in the rheumatic fever population of C ounties M anukau D istrict H ealth B oard. J. Paediatr. Child Health 2014, 50, 112–117.
  103. Huck, D.M.; Nalubwama, H.; Longenecker, C.T.; Frank, S.H.; Okello, E.; Webel, A.R. A Qualitative Examination of Secondary Prophylaxis in Rheumatic Heart Disease: Factors Influencing Adherence to Secondary Prophylaxis in Uganda. Glob. Heart 2015, 10, 63–69.e1.
  104. Morsy, M.-M.F.; Mohamed, M.A.; Abosedira, M.M.; Al-Harbi, K.M.; Abdelaziz, N.A.; Khosh Hal, S.Q.; Boraey, N.F.; Aly, S.H.; Hassan, I.A.; Sharaf, A.E. Lidocaine as a Diluent for Benzathine Penicillin G Reduces Injection Pain in Patients with Rheumatic Fever: A Prospective, Randomized Double-Blinded Crossover Study. Aust. J. Basic Appl. Sci. 2012, 6, 236–240.
  105. Ndagire, E.; Kawakatsu, Y.; Nalubwama, H.; Atala, J.; Sarnacki, R.; Pulle, J.; Kyarimpa, R.; Mwima, R.; Kansiime, R.; Okello, E.; et al. Examining the Ugandan health system’s readiness to deliver rheumatic heart disease-related services. PLoS Negl. Trop. Dis. 2021, 15, e0009164.
  106. Carapetis, J.R.; Zühlke, L.J. Global research priorities in rheumatic fever and rheumatic heart disease. Ann. Pediatr Cardiol. 2011, 4, 4–12.
  107. Maguire, G.P.; Carapetis, J.; Walsh, W.F.; Brown, A.D.H. The future of acute rheumatic fever and rheumatic heart disease in Australia. Med J. Aust. 2012, 197, 133–134.
  108. Holanda e Silva, K.; Xavier-Junior, F.; Farias, I.; Caldas Neto, J.; Silva, A.; Nakashima-Junior, T.; Araujo, I.; Oliveira, A.; Medeiros, A.; Tabosa do Egito, E. A new insight about pharmaceutical dosage forms for benzathine penicillin G. J. Basic Appl. Pharm. Sci. 2006, 27, 21–26.
  109. Wyber, R.; Taubert, K.; Marko, S.; Kaplan, E.L. Benzathine penicillin G for the management of RHD: Concerns about quality and access, and opportunities for intervention and improvement. Glob. Heart 2013, 8, 227–234.
  110. Taubert, K.; Marko, S.B. Access to essential medicines: Illuminating disparities in the global supply of benzathine penicillin G in the context of rheumatic fever/rheumatic heart disease prevention. J. Am. College Cardiol. 2013, 61, E2004.
  111. Musser, J.M.; Beres, S.B.; Zhu, L.; Olsen, R.J.; Vuopio, J.; Hyyryläinen, H.-L.; Gröndahl-Yli-Hannuksela, K.; Kristinsson, K.G.; Darenberg, J.; Henriques-Normark, B.; et al. Reduced In Vitro Susceptibility of Streptococcus pyogenes to β-Lactam Antibiotics Associated with Mutations in the pbp2x Gene Is Geographically Widespread. J. Clin. Microbiol. 2020, 58.
  112. Nordet, P. WHO programme for the prevention of rheumatic fever/rheumatic heart disease in 16 developing countries: Report from phase I (1986–90). Bull. World Health Organ. 1992, 70, 213–219.
  113. Nordet, P.; Lopez, R.; Duenas, A.; Sarmiento, L. Prevention and control of rheumatic fever and rheumatic heart disease: The Cuban experience (1986–1996–2002): Cardiovascular topic. Cardiovasc. J. Afr. 2008, 19, 135–140.
  114. Arguedas, A.; Mohs, E. Prevention of rheumatic fever in Costa Rica. J. Pediatr. 1992, 121, 569–572.
  115. Matheka, D.M.; Murgor, M.; Kibochi, E.; Nigel, S.; Nderitu, J.; Selnow, G. O028 Role of Technology In Creating Rheumatic Heart Disease Awareness Among School-Going Children In Kenya. Glob. Heart 2014, 9, e7–e8.
  116. Engel, M.; Muhamed, B.; Whitelaw, A.C.; Musvosvi, M.; Mayosi, B.; Dale, J.B. Group A Streptococcal emm Type Prevalence Among Symptomatic Children in Cape Town and Potential Vaccine Coverage. Pediatr. Infect. Dis. J. 2014, 33, 208–210.
  117. DeWyer, A.; Scheel, A.; Webel, A.R.; Longenecker, C.T.; Kamarembo, J.; Aliku, T.; Engel, M.E.; Bowen, A.; Bwanga, F.; Hovis, I.; et al. Prevalence of group A β-hemolytic streptococcal throat carriage and prospective pilot surveillance of streptococcal sore throat in Ugandan school children. Int. J. Infect. Dis. 2020, 93, 245–251.
  118. Hill, H.R. Group A Streptococcal Carrier versus Acute Infection: The Continuing Dilemma. Clin. Infect. Dis. 2010, 50, 491–492.
  119. Shulman, S.T.; Bisno, A.L.; Clegg, H.W.; Gerber, M.A.; Kaplan, E.L.; Lee, G.; Martin, J.M.; Van Beneden, C. Clinical practice guideline for the diagnosis and management of group A streptococcal pharyngitis: 2012 update by the Infectious Diseases Society of America. Clin. Infect. Dis. 2012, 55, e86–e102.
  120. Jones, T.D. The Diagnosis of Rheumatic Fever. J. Am. Med. Assoc. 1944, 126, 481–484.
  121. Gewitz, M.H.; Baltimore, R.S.; Tani, L.Y.; Sable, C.A.; Shulman, S.T.; Carapetis, J.; Remenyi, B.; Taubert, K.A.; Bolger, A.F.; Beerman, L. Revision of the Jones Criteria for the diagnosis of acute rheumatic fever in the era of Doppler echocardiography: A scientific statement from the American Heart Association. Circulation 2015, 131, 1806–1818.
  122. Ralph, A.P.; Webb, R.; Moreland, N.J.; McGregor, R.; Bosco, A.; Broadhurst, D.; Lassmann, T.; Barnett, T.C.; Benothman, R.; Yan, J.; et al. Searching for a technology-driven acute rheumatic fever test: The START study protocol. BMJ Open 2021, 11, e053720.
  123. Wannamaker, L.W.; Ayoub, E.M. Antibody titers in acute rheumatic fever. Circulation 1960, 21, 598–614.
  124. Shet, A.; Kaplan, E.L. Clinical use and interpretation of group A streptococcal antibody tests: A practical approach for the pediatrician or primary care physician. Pediatric Infect. Dis. J. 2002, 21, 420–426.
  125. Kotby, A.A.; Habeeb, N.M.; Ezz El Arab, S. Antistreptolysin O titer in health and disease: Levels and significance. Pediatric Rep. 2012, 4, 25–29.
  126. Okello, E.; Murali, M.; Rwebembera, J.; Atala, J.; Bowen, A.; Harik, N.; Kaudha, G.; Kitooleko, S.; Longenecker, C.; Ndagire, E.; et al. Cross-sectional study of population-specific streptococcal antibody titres in Uganda. Arch. Dis. Child. 2020, 105, 825–829.
  127. Nunes, M.C.; Tan, T.C.; Elmariah, S.; do Lago, R.; Margey, R.; Cruz-Gonzalez, I.; Zheng, H.; Handschumacher, M.D.; Inglessis, I.; Palacios, I.F.; et al. The echo score revisited: Impact of incorporating commissural morphology and leaflet displacement to the prediction of outcome for patients undergoing percutaneous mitral valvuloplasty. Circulation 2014, 129, 886–895.
  128. Howard, C.; Jullian, L.; Joshi, M.; Noshirwani, A.; Bashir, M.; Harky, A. TAVI and the future of aortic valve replacement. J. Card. Surg. 2019, 34, 1577–1590.
  129. Fawzy, M.E.; Fadel, B.; Al-Sergani, H.; Al Amri, M.; Hassan, W.; Abdulbaki, K.; Shoukri, M.; Canver, C. Long-Term Results (Up to 16.5 Years) of Mitral Balloon Valvuloplasty in a Series of 518 Patients and Predictors of Long-Term Outcome. J. Interv. Cardiol. 2007, 20, 66–72.
  130. Russell, E.A.; Tran, L.; A Baker, R.; Bennetts, J.S.; Brown, A.; Reid, C.M.; Tam, R.; Walsh, W.F.; Maguire, G.P. A review of valve surgery for rheumatic heart disease in Australia. BMC Cardiovasc. Disord. 2014, 14, 134.
  131. Rotman, O.M.; Bianchi, M.; Ghosh, R.P.; Kovarovic, B.; Bluestein, D. Principles of TAVR valve design, modelling, and testing. Expert Rev. Med Devices 2018, 15, 771–791.
  132. Zilla, P.; Williams, D.F.; Bezuidenhout, D. TAVR for Patients With Rheumatic Heart Disease: Opening the Door for the Many? J. Am. Coll Cardiol. 2021, 77, 1714–1716.
  133. Popma, J.J.; Deeb, G.M.; Yakubov, S.J.; Mumtaz, M.; Gada, H.; O’Hair, D.; Bajwa, T.; Heiser, J.C.; Merhi, W.; Kleiman, N.S.; et al. Transcatheter Aortic-Valve Replacement with a Self-Expanding Valve in Low-Risk Patients. N. Engl. J. Med. 2019, 380, 1706–1715.
  134. Ntsekhe, M.; Scherman, J. TAVI for rheumatic aortic stenosis–The next frontier? Int J. Cardiol. 2019, 280, 51–52.
  135. Mentias, A.; Saad, M.; Desai, M.Y.; Krishnaswamy, A.; Menon, V.; Horwitz, P.A.; Kapadia, S.; Sarrazin, M.V. Transcatheter Versus Surgical Aortic Valve Replacement in Patients With Rheumatic Aortic Stenosis. J. Am. Coll. Cardiol. 2021, 77, 1703–1713.
  136. Brennan, P.; Santos, A.; Johnston, N.; Owens, C.; Jeganathan, R.; Manoharan, G.; Spence, M. Extending the role of TAVR to rheumatic aortic stenosis: Our 10 year experience in Belfast. J. Am. Coll. Cardiol. 2019, 73, 1242.
  137. Kumar, R.K.; Antunes, M.J.; Beaton, A.; Mirabel, M.; Nkomo, V.T.; Okello, E.; Regmi, P.R.; Reményi, B.; Sliwa-Hähnle, K.; Zühlke, L.J.; et al. Contemporary Diagnosis and Management of Rheumatic Heart Disease: Implications for Closing the Gap: A Scientific Statement From the American Heart Association. Circulation 2020, 142, e337–e357.
  138. Russell, E.A.; Walsh, W.F.; Costello, B.; McLellan, A.J.A.; Brown, A.; Reid, C.M.; Tran, L.; Maguire, G.P. Medical Management of Rheumatic Heart Disease: A Systematic Review of the Evidence. Cardiol. Rev. 2018, 26, 187–195.
  139. January, C.T.; Wann, L.S.; Calkins, H.; Chen, L.Y.; Cigarroa, J.E.; Cleveland, J.C., Jr.; Ellinor, P.T.; Ezekowitz, M.D.; Field, M.E.; Furie, K.L.; et al. 2019 AHA/ACC/HRS Focused Update of the 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society in Collaboration With the Society of Thoracic Surgeons. Circulation 2019, 140, e125–e151.
  140. Guimarães, H.P.; Lopes, R.D.; Silva, P.G.D.B.E.; Liporace, I.L.; Sampaio, R.O.; Tarasoutchi, F.; Hoffmann-Filho, C.R.; Patriota, R.D.L.S.; Leiria, T.L.; Lamprea, D.; et al. Rivaroxaban in Patients with Atrial Fibrillation and a Bioprosthetic Mitral Valve. N. Engl. J. Med. 2020, 383, 2117–2126.
  141. Karthikeyan, G.; Connolly, S.J.; Ntsekhe, M.; Benz, A.; Rangarajan, S.; Lewis, G.; Yun, Y.; Sharma, S.K.; Maklady, F.; Elghamrawy, A.E.; et al. The INVICTUS rheumatic heart disease research program: Rationale, design and baseline characteristics of a randomized trial of rivaroxaban compared to vitamin K antagonists in rheumatic valvular disease and atrial fibrillation. Am. Heart J. 2020, 225, 69–77.
  142. Ene, G.; Garcia-Raso, A.; Gonzalez-Dominguez Weber, A.; Hidalgo-Vega, A.; Llamas, P. Cost of vitamin K antagonist anticoagulant treatment in patients with metallic prosthetic valve in mitral position. SAGE Open Med. 2016, 4.
  143. Baddour, L.M.; Wilson, W.R.; Bayer, A.S.; Fowler, V.G., Jr.; Tleyjeh, I.M.; Rybak, M.J.; Barsic, B.; Lockhart, P.B.; Gewitz, M.H.; Levison, M.E.; et al. Infective Endocarditis in Adults: Diagnosis, Antimicrobial Therapy, and Management of Complications: A Scientific Statement for Healthcare Professionals From the American Heart Association. Circulation 2015, 132, 1435–1486.
  144. Habib, G.; Lancellotti, P.; Antunes, M.J.; Bongiorni, M.G.; Casalta, J.P.; Del Zotti, F.; Dulgheru, R.; El Khoury, G.; Erba, P.A.; Iung, B.; et al. 2015 ESC Guidelines for the management of infective endocarditis: The Task Force for the Management of Infective Endocarditis of the European Society of Cardiology (ESC). Endorsed by: European Association for Cardio-Thoracic Surgery (EACTS), the European Association of Nuclear Medicine (EANM). Eur. Heart J. 2015, 36, 3075–3128.
  145. Watkins, D.; Lubinga, S.J.; Mayosi, B.; Babigumira, J.B. A Cost-Effectiveness Tool to Guide the Prioritization of Interventions for Rheumatic Fever and Rheumatic Heart Disease Control in African Nations. PLoS Negl. Trop. Dis. 2016, 10, e0004860.
  146. Irlam, J.H.; Mayosi, B.M.; Engel, M.E.; Gaziano, T.A. A cost-effective strategy for primary prevention of acute rheumatic fever and rheumatic heart disease in children with pharyngitis. South Afr. Med J. 2013, 103, 894.
  147. Watkins, D.A.; Mvundura, M.; Nordet, P.; Mayosi, B.M. A Cost-Effectiveness Analysis of a Program to Control Rheumatic Fever and Rheumatic Heart Disease in Pinar del Rio, Cuba. PLoS ONE 2015, 10, e0121363.
  148. Manji, R.A.; Witt, J.; Tappia, P.S.; Jung, Y.; Menkis, A.H.; Ramjiawan, B. Cost–effectiveness analysis of rheumatic heart disease prevention strategies. Expert Rev. Pharm. Outcomes Res. 2013, 13, 715–724.
  149. Roberts, K.; Cannon, J.; Atkinson, D.; Brown, A.; Maguire, G.; Remenyi, B.; Wheaton, G.; Geelhoed, E.; Carapetis, J.R. Echocardiographic Screening for Rheumatic Heart Disease in Indigenous Australian Children: A Cost–Utility Analysis. J. Am. Heart Assoc. 2017, 6, e004515.
  150. Zachariah JP and Samnaliev, M. Echo-based screening of rheumatic heart disease in children: A cost-effectiveness Markov model. J. Med. Econ. 2015, 18, 410–419.
  151. Ubels, J.; Sable, C.; Beaton, A.Z.; Nunes, M.C.P.; Oliveira, K.K.B.; Castro, L.C.; Teixeira, I.M.; Ruiz, G.Z.L.; Rabelo, L.M.M.; Tompsett, A.R.; et al. Cost-Effectiveness of Rheumatic Heart Disease Echocardiographic Screening in Brazil: Data from the PROVAR+ Study: Cost-effectiveness of RHD screening in Brazil. Glob. Heart 2020, 15, 18.
  152. Roberts, K.V.; Maguire, G.P.; Brown, A.; Atkinson, D.N.; Remenyi, B.; Wheaton, G.; Ilton, M.; Carapetis, J. Rheumatic heart disease in Indigenous children in northern Australia: Differences in prevalence and the challenges of screening. Med J. Aust. 2015, 203, 221.
  153. Coates, M.M.; Sliwa, K.; A Watkins, D.; Zühlke, L.; Perel, P.; Berteletti, F.; Eiselé, J.-L.; Klassen, S.L.; Kwan, G.F.; O Mocumbi, A.; et al. An investment case for the prevention and management of rheumatic heart disease in the African Union 2021–30: A modelling study. Lancet Glob. Heath 2021, 9, e957–e966.
  154. Opara, C.C.; Du, Y.; Kawakatsu, Y.; Atala, J.; Beaton, A.Z.; Kansiime, R.; Nakitto, M.; Ndagire, E.; Nalubwama, H.; Okello, E. Household Economic Consequences of Rheumatic Heart Disease in Uganda. Front. Cardiovasc. Med. 2021, 680.
  155. Oyebamiji, O. The Household Economic Impact of Rheumatic Heart Disease (RHD) in South Africa. Master’s Thesis, University of Cape Town, Cape Town, South Africa, 2018.
  156. Hellebo, A.G.; Zuhlke, L.J.; Watkins, D.A.; Alaba, O. Health system costs of rheumatic heart disease care in South Africa. BMC Public Health 2021, 21, 1303.
  157. Mocumbi, A.O. Out-of-pocket costs in rheumatic heart disease care: A major barrier to equity in cardiovascular health. Indian Heart J. 2021, 73, 141–142.
  158. Arvind, B.; Saxena, A.; Kazi, D.S.; Bolger, A.F. Out-of-pocket expenditure for administration of benzathine penicillin G injections for secondary prophylaxis in patients with rheumatic heart disease: A registry-based data from a tertiary care center in Northern India. Indian Heart J. 2021, 73, 169–173.
  159. Watkins, D.; Daskalakis, A. The economic impact of rheumatic heart disease in developing countries. Lancet Glob. Health 2015, 3, S37.
  160. World Health Organization. 71st World Health Assembly Adopts Resolution Calling for Greater Action on Rheumatic Heart Disease; World Health Organization: Geneva, Switzerland, 2018.
  161. White, A. WHO Resolution on rheumatic heart disease. Eur. Heart J. 2018, 39, 4233.
  162. World Health Organization. Rheumatic fever and rheumatic heart disease. In Report by the Director General. Seventy-First World Health Assembly; World Health Organization: Geneva, Switzerland, 2018; Available online: https://apps.who.int/gb/ebwha/pdf_files/WHA71/A71_25-en.pdf (accessed on 15 October 2021).
  163. Mayosi, B.M.; Gamra, H.; Dangou, J.-M.; Kasonde, J. Rheumatic heart disease in Africa: The Mosi-o-Tunya call to action. Lancet Glob. Health 2014, 2, e438–e439.
  164. Mayosi, B.M. The Four Pillars of Rheumatic Heart Disease Control. S. Afr. Med. J. 2010, 100, 506.
  165. Beaton, A.; Sable, C. Reducing rheumatic heart disease in Africa—Time for action. Nat. Rev. Cardiol. 2016, 13, 190–191.
  166. Mayosi, B.; Robertson, K.; Volmink, J.; Adebo, W.; Akinyore, K.; Amoah, A.; Bannerman, C.; Biesman-Simons, S.; Carapetis, J.; Cilliers, A.; et al. The Drakensberg declaration on the control of rheumatic fever and rheumatic heart disease in Africa. S. Afr. Med. J. 2006, 96, 246.
  167. Watkins, D.; Zuhlke, L.; Engel, M.; Daniels, R.; Francis, V.; Shaboodien, G.; Mayosi, B.M.; Kango, M.; Abul-Fadl, A.; Adeoye, A. Seven key actions to eradicate rheumatic heart disease in Africa: The Addis Ababa communiqué: Cardiovascular topics. Cardiovasc. J. Afr. 2016, 27, 184–187.
  168. Ogola, E.; Omokhodion, S.; Palweni, C.; Pearce, A.; Salo, A.; Thomas, B.; Walker, K.; Wiysonge, C.; Zaher, S. The Drakensberg declaration on the control of rheumatic fever and rheumatic heart disease in Africa. South Afr. Med. J. 2006, 96, 246.
  169. Remenyi, B.; Carapetis, J.; Wyber, R.; Taubert, K.; Mayosi, B.M. Position statement of the World Heart Federation on the prevention and control of rheumatic heart disease. Nat. Rev. Cardiol. 2013, 10, 284–292.
  170. Beaton, A.; Kamalembo, F.B.; Dale, J.; Kado, J.H.; Karthikeyan, G.; Kazi, D.S.; Longenecker, C.T.; Mwangi, J.; Okello, E.; Ribeiro, A.L.P.; et al. The American Heart Association’s Call to Action for Reducing the Global Burden of Rheumatic Heart Disease: A Policy Statement From the American Heart Association. Circulation 2020, 142, e358–e368.
More
© Text is available under the terms and conditions of the Creative Commons Attribution (CC BY) license; additional terms may apply. By using this site, you agree to the Terms and Conditions and Privacy Policy.
Upload a video for this entry
Information
Subjects: Health Care Sciences & Services
Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register :
Andrew Chang
,
JOSELYN RWEBEMBERA
,
,
Bruno Galdino
,
Walderez Dutra
View Times: 627
Entry Collection: Hypertension and Cardiovascular Diseases
Revisions: 3 times (View History)
Update Date: 19 May 2022
Table of Contents
    1000/1000
    Hot Most Recent
    Video Production Service
    Feedback