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

Abstract

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.

Nonstandard Abbreviations and Acronyms

ARF

acute rheumatic fever

GAS

Group A Streptococcus

RHD

rheumatic heart disease

Research Perspective.

What Is New?

• Evidence on implementing rheumatic heart disease prevention interventions in low‐middle–income countries, particularly sub‐Saharan Africa, remains limited.

What Question Should Be Addressed Next?

• The feasibility and advisability of school‐based primary prevention and community programs in low‐middle–income countries warrant exploration.

• Further research is essential to evaluate the actual effectiveness of current interventions in reducing the rheumatic heart disease burden.

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. RHD is a significant public health problem and is among the leading causes of cardiovascular morbidity and mortality, with an estimated 40.5 million people affected and approximately 305 000 deaths occurring annually. ¹ RHD is a disease caused by progressive fibrotic changes due to avascularized valvular tissues from the inflammation of the heart valves. The inflammation is a result of acute rheumatic fever (ARF), which is an autoimmune response to antigenic mimicry of a certain Group A Streptococcus (GAS) antigenic protein during a GAS bacterial infection of the pharynx. ²

Preventing RHD requires a multifaceted approach of primordial, primary, secondary, and tertiary interventions. Primordial prevention focuses on mitigating social determinants of health to reduce the risk of GAS transmission. Primary prevention involves timely diagnosis and treatment of GAS infections with penicillin antibiotic treatment to prevent ARF. Secondary prevention entails continuous benzathine penicillin prophylaxis to prevent the recurrence of ARF, as well as early detection and management of RHD to prevent complications. Tertiary interventions involve heart surgery and chronic medical treatment for the management of chronic RHD. ³ , ⁴ , ⁵

Despite being a major public health concern, RHD has been neglected in the past, primarily because of the reduction of RHD in high‐income countries due to economic improvements and previous World Health Organization programs. ⁶ Around the year 2000 new interest emerged that resulted in RHD being placed on the international agenda. For example, in 2013 to 2014 the World Heart Federation set a goal of reducing premature deaths from RHD in individuals younger than 25 years of age by 25% by the year 2025. ⁷ As a result, resolutions and guidelines on ARF and RHD have been developed to provide technical guidance for actions to prevent and eradicate RHD. ⁸ , ⁹ , ¹⁰ , ¹¹ One of the key resolutions is implementing country‐level comprehensive programs including components from each level of prevention. The proposal includes the strategies advocacy, surveillance, awareness, and prevention. ⁹ Earlier programs implemented (in the 1980s and 1990s) in Cuba, ¹² Caribbean island countries, ¹³ and other countries, ⁶ provided evidence supporting the effectiveness of primary and secondary interventions in reducing the burden of RHD. However, the effectiveness of primordial interventions has been less clear.

With the new interest and resolutions, various preventive interventions have been implemented in various settings, including community‐based outreach programs, school‐based programs, and screening‐based interventions, including the expansion of penicillin prophylaxis and surveillance. ¹⁴ , ¹⁵ , ¹⁶ However, there is a paucity of evidence regarding the effectiveness of these recent interventions added to the interventions in the 1980s and 1990s. It is important to synthesize as much current evidence as possible to determine the effectiveness of these interventions to provide guidance for policy and practice and also highlight the work that has been done in the 21st century so far in response to the new resolutions.

The objectives of this systematic review are to evaluate the effectiveness of preventive interventions in reducing the incidences of ARF and RHD, as well as to describe the different strategies employed by the interventions.

METHODS

The review followed the Cochrane Collaboration Handbook for Systematic Reviews ¹⁷ and the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guidelines (Table S1). ¹⁸ The review protocol was registered in PROSPERO (International Prospective Register of Systematic Reviews; CRD42020170503; https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020170503). Additional information about the review protocol can be found in a separate publication. ¹⁹ Authors declare that supporting materials for the review are in the article. Further information is available from the corresponding author on request. As this systematic review used published data, ethical approval and informed consent were not required.

Search Strategy

A comprehensive search was conducted in electronic databases, including PubMed, Scopus, and Web of Science, covering publications from January 2000 to February 2023. Additionally, the reference lists of retrieved articles were manually searched for possible relevant studies. The search strategy used the Medical Subject Headings terms and keywords rheumatic heart disease, acute rheumatic fever, rheumatic fever, Group A Streptococcus, intervention, and Program (Table S2).

Intervention

In the context of the review, the concept of intervention refers to activities or measures undertaken with the aim of reducing the incidences or prevalence of either GAS, ARF, or RHD in populations classified as at high risk of RHD. These interventions can include a wide range of strategies, such as public health campaigns, education programs, vaccination initiatives, improved access to health care services, screening and early detection programs, penicillin antibiotic prophylaxis, and other preventive measures. The intervention should be clearly described and focused on reducing the incidence or prevalence of GAS, ARF, and RHD.

Study Selection and Inclusion Criteria

The search results were imported to Clarivate Endnote 20. After removing duplicates, 1 author (P.P.S.) screened the titles of the retrieved studies. Two authors (P.P.S. and T.W.S.) independently screened the abstracts of the selected articles, and the full texts of potentially relevant articles were assessed for eligibility. Articles for which the relevance was not immediately clear were discussed until resolution, sometimes with a third reviewer (F.N.) when necessary. To assess effectiveness, we included studies that met the following criteria: (1) evaluated the effectiveness of preventive interventions and reported outcomes regarding the impact on the incidence or prevalence of GAS, ARF, and RHD; (2) reported an intervention implemented in January 2000 or later; and (3) provided a clear description of the intervention aimed at reducing the incidence or prevalence of GAS, ARF, and RHD. We excluded studies that did not report outcomes related to disease incidence or prevalence, as these were necessary for determining an intervention's effectiveness. Studies lacking a clear description of the intervention as targeting the prevention of GAS, ARF, and RHD were excluded, as were articles about a population that the authors classified as not at risk of ARF or RHD based on the prevalence rates or considered not endemic. Studies with full text not written in English were categorized as awaiting classification due to the unavailability of translators and were not used for this paper.

Quality Appraisal and Risk of Bias

The quality appraisal of the included studies was assessed independently by 2 reviewers (P.P.S. and T.W.S.) using the Joanna Briggs Institute critical appraisal checklists for nonrandomized studies of interventions. ²⁰ , ²¹ The checklists contains questions that assesses different broad areas of methodological quality of the studies. The checklists have a scoring framework of yes, no, unclear, and not applicable. All the included studies had a relatively good methodological quality and thus were retained for analysis.

Synthesis Methods

Due to the heterogeneity among the included studies, encompassing methodology, outcomes, and contexts, we used a narrative synthesis approach based on the relevance and applicability of the findings in various settings.

RESULTS

Selection of Studies

A summary of the review processes and selection of studies is presented in the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses flow diagram (Figure). ¹⁸ The search identified 3037 publications. After removing 516 duplicate articles, 2520 titles were screened, and a total of 2485 studies excluded after screening for title and abstract. For the remaining 35 publications, full‐text reviews were conducted to determine their inclusion. Subsequently, 7 studies describing disease incidence or prevalence outcomes were included in the analysis (Table 1). ²² , ²³ , ²⁴ , ²⁵ , ²⁶ , ²⁷ , ²⁸

Figure  . Preferred Reporting Items for Systematic Reviews and Meta‐Analyses flow diagram for study selection.

ARF indicates acute rheumatic fever.

Table 1.

Characteristics of Included Studies With Effectiveness Measures (n=7)

Reference/country	Intervention	Control/comparator	Setting	Participants	Results	Outcomes	Prevention
Ali and Subahi 2020 22 Sudan	RHD control center led by a community nurse and 3 physicians. Surveillance: Electronic register Education: Eight training workshops for health workers (n=350) Awareness: Public awareness in 4 districts using local media in the community and schools Echo screening and initiating benzathine penicillin G treatment Advocacy: Collaboration with ministry of health	None	Community and health facilities	Patients with RHD Health workers	Reported declining trends in RHD burden; however, the study did not report the size of the effect as the outcomes were not formally assessed at the time of the study.	Identified high‐burden areas RHD control center established in high‐prevalence areas Program integrated into the Package of Noncommunicable Disease Trends of a possible decline in the RHD burden observed.	Primary Secondary
Anderson et al, 2016 23 New Zealand	Registered nurse led ARF school clinic: 1 registered nurse and support worker (n=61 schools) Strategies: 1. Daily assessment and treatment of sore throat using a manual of operation 2. Engagement and awareness creation for children and parents Students Period: February 2013–September 2014	Preintervention	Schools	School children (n=23 756) Parents (n=439)	Pharyngeal GAS prevalence rates=26% (95% CI 20%–34%) and 14% (11%–18%) for 2013 and 2014 (P=0.01) GAS+ relative risk=1.8 (95% CI, 1.3–2.3) in 2013 compared with 2014 3 Percentage of GAS‐positive swabs= 3 10.8% in 2013 to 5% in 2014. 4 Family awareness of ARF and RHD: 2013=71% to 2014=89%	Difference in pharyngeal GAS prevalence rates. Decreasing percentage of GAS‐positive swabs by month. Improved awareness ARF and RHD awareness among family and children. Improved health literacy/knowledge on sore throat, ARF, medication adherence.	Primary
Jack et al, 2018 24 New Zealand	School‐based sore throat services for case finding and treatment (n=244 schools). Strategies: 1. Throat swab and 10‐day course of oral amoxicillin Period: January 2012–December 2016	Baseline data from 2009 to 2011 used to compare with intervention period.	Schools	School children (n=53 376)	Overall intervention effectiveness was 23% (95% CI, 6%–44%); RR, 0.77 (95% CI, 0.56–1.06) Sore throat swab rates=62/1000‐1177/1000 (59% schools, 41% primary care) National ARF incidences decline (28%): 4.0/100 000 (95% CI, 3.5–4.6) at baseline to 2.9/100 000 (95% CI, 2.4–3.4, P<0.01)	Sore throat swabbing increased in schools and primary care Observed a decline in the national ARF incidences rates after intervention	Primary
Lennon et al, 2017 25 New Zealand	School‐based sore throat services (n=61 schools). Registered nurse and community health worker. Strategies: 1. Daily visit to classrooms and identify children with a sore throat for swabbing. 2. GAS‐positive treated with a 10‐day course of oral amoxicillin Period: July 2012–May 2014	Baseline data before clinic	Schools	School children (n=25 000)	58% reduction in ARF rates among school children (88/100 000 [95% CI, 79–111] to 37/100 000 [95% CI, 15–83]) GAS prevalence=preprogram: 22.4% (95% CI, 16.5–30.5) vs 11.4% (95% CI, 8.2–15.7), P=0.005	1. There was a reduction (58%) of first presentation ARF rates after introduction of the clinics. 2. There was a significant reduction in GAS prevalence after introduction of clinics.	Primary
Regmi 2016 26 Nepal	National comprehensive program Main strategies: 1. Advocacy, awareness, and training 2. Rheumatic fever/RHD registers and penicillin injection cards (national, hospitals, primary health centers) 3. Training of community health workers 4. Early diagnosis and treatment of GAS	Preprogram	Community and health facilities	National	RHD prevalence reduced from 1.2/1000 to 0.8/1000. RHD admissions reduced from 14.5% to 6.0%	The burden of RHD reduced with the program.	Primordial Primary Secondary
Walsh et al, 2020 27 New Zealand	School‐based sore throat services. Cohort 1: Nurse‐led school‐based program with GP support: throat swabbing and treatment Cohort 2: GP management without school‐based programs Cohort 3: GP management with limited school program	Cohort 1: School‐based program with GP support (n=26) Cohort 2: GP management without school‐based (n=19) programs Cohort 3: GP management with limited school program (n=3)	Schools	School children	ARF incidences reduction: C1‐reduced (60%): 148 to 59/100 000/year, RR, 0.40 (95% CI, 0.22–0.73) P=0.002 C2‐increase: 30 to 69/100000/year RR, 2.28 (95% CI, 0.99–5.27) P=0.047 C3‐reduced (48%): 50 to 26/100000/year RR, 0.52 (95% CI, 0.27–0.99) P=0.044	ARF declined in the cohorts with school‐based programs.	Primary
Ralph et al, 2022 28 Australia	Community‐based outreach‐to‐household services for support and awareness creation by community health workers Strategies: 1 Engage people with ARF or RHD and their families 2 Support reporting and repairs of faulty health hardware including showers 3 Provide health care navigation for families 1 Period: February 2018–January 2022	Baseline, preintervention	Community	People with ARF and RHD (n=29 individuals, 26 households) People at risk of ARF and RHD	The ARF incidences reduced during the intervention: Baseline=6 Year 1=5 Year 2=1 Year 3=0	The intervention contributed to a reduction of ARF incidences.	Primordial Primary

ARF indicates acute rheumatic fever; GAS, Group A Streptococcus; GAS+, Group A Streptococcus positive diagnosis; GP, general practitioner; and RHD, rheumatic heart disease; and RR, rate ratio.

The remaining 28 publications were excluded due to their failure to describe the outcomes of interest or to meet other inclusion criteria (Table S3). ²⁹ , ³⁰ , ³¹ , ³² , ³³ , ³⁴ , ³⁵ , ³⁶ , ³⁷ , ³⁸ , ³⁹ , ⁴⁰ , ⁴¹ , ⁴² , ⁴³ , ⁴⁴ , ⁴⁵ , ⁴⁶ , ⁴⁷ , ⁴⁸ , ⁴⁹ , ⁵⁰ , ⁵¹ , ⁵² , ⁵³ , ⁵⁴ , ⁵⁵ , ⁵⁶ Among the excluded studies, 17 described interventions but did not report the impact on the incidence or prevalence of the diseases. ²⁹ , ³⁰ , ³¹ , ³² , ³³ , ³⁴ , ³⁵ , ³⁶ , ³⁷ , ³⁸ , ³⁹ , ⁴⁰ , ⁴¹ , ⁴² , ⁴³ , ⁴⁴ , ⁴⁵ Five studies described interventions that were implemented before the year 2000. ⁴⁶ , ⁴⁷ , ⁴⁸ , ⁴⁹ , ⁵⁰ Two studies described interventions in Finland and Italy but did not give a clear description as to their targeting of ARF and RHD, ⁵¹ , ⁵² and the population was considered as not at risk of RHD. Two papers were written in Russian and excluded due to unavailability of translators. ⁵³ , ⁵⁴ Finally, 2 studies did not report on actually implemented interventions, only on clinical activities. ⁵⁵ , ⁵⁶

Characteristics of the Included Studies

Table 1 presents details about the 7 studies that described outcomes of the interventions on disease incidence or prevalence. Among the included studies, 5 were conducted in Australia and New Zealand, which are high‐income countries. ²³ , ²⁴ , ²⁵ , ²⁷ , ²⁸ The study designs of these studies consisted of 2 cross‐sectional studies, ²³ , ²⁵ 2 retrospective cohorts, ²⁴ , ²⁷ and 1 pragmatic intervention study. ²⁸ Two studies were conducted in Nepal and Sudan, which are low‐middle–income countries. ²² , ²⁶ Both of these studies were descriptive in nature. All of the included studies aimed to investigate primary and secondary prevention of RHD, with 1 study from Australia also including a primordial prevention component. ²⁸

Four studies conducted in New Zealand described school‐based primary prevention clinics led by nurses who applied strategies of screening school children and treating sore throats using oral penicillin antibiotic. ²³ , ²⁴ , ²⁵ , ²⁷ The school‐based clinics appeared to have a positive effect on reducing the incidence of GAS and ARF among school children. One study demonstrated that the prevalence of GAS decreased from 22.4% to 11.4% after implementing a school‐based clinic intervention over a span of 2 years and furthermore that there was a 58% decline in ARF rates following the intervention. ²⁵ Another study observed a decrease in pharyngeal GAS infections after implementing the intervention for 19 months. The study found a statistically significant reduction (P=0.01) in the pharyngeal GAS burden, with adjusted rates of 26% before the intervention and 14% after the intervention. ²³

Another study reported a 28% decline in the national ARF incidence rate after implementing school‐based sore throat services, with an overall effectiveness of 23% (95% CI, −6% to 44%; rate ratio [RR], 0.77 [95% CI, 0.56–1.06]). ²⁴ The fourth New Zealand study compared 3 different approaches to school‐based sore throat clinics showing that areas with full school programs supported by a general practitioner experienced a 60% reduction in ARF incidence, compared with a 48% reduction in areas where predominantly general practitioners provided limited school services and a 30% reduction in areas without any school services. ²⁷

A fifth study, conducted in Australia, reported on a pragmatic intervention, namely a community‐based outreach program with a primary focus on the primordial and primary prevention of ARF; this study reported a decreasing trend in the annual number of first‐known ARF cases. During the baseline period, 6 cases were recorded, which decreased to 5, then 1, and finally reached 0 cases over the course of the following 3 years. ²⁸ However, it is important to note that the study's sample size was small, consisting of only 29 individuals from 26 households. Consequently, the generalizability of the findings to other populations may be limited. The intervention was led by trained community workers who aimed to disseminate ARF knowledge, assist families in accessing health care, and promote hygiene practices within households.

The sixth study reported on a comprehensive program in Nepal, which contributed to a decrease in national RHD prevalence from 1.2/1000 to 0.8/1000 over a period of 10 years. ²⁶ The seventh study reported on a similar program implemented in Sudan that was associated with declining trends in RHD burden; however, the study did not report the size of the effect as the outcomes were not formally assessed at the time of the study. ²² These programs included echocardiogram screening, awareness and knowledge campaigns, penicillin antibiotic prophylaxis, surveillance registers, and tertiary care. Such findings are highly relevant and demonstrate the potential capacity in low‐middle–income countries to adopt and implement the multiple global resolutions for the control and elimination of RHD.

The studies from Australia, ²⁸ Nepal, ²⁶ and Sudan ²² described the components and frameworks of the implemented interventions for preventing ARF and RHD and included the recommended components of awareness, surveillance, advocacy, and prevention to address the various social, cultural, and economic factors that contribute to the development and spread of GAS (Table 2).

Table 2.

Intervention Framework and Strategies in the Included Studies With Comprehensive Interventions (n=3)

Reference/country/level	Advocacy	Surveillance	Awareness	Prevention
Ali and Subahi, 2020 22 Sudan Level: Health system	Raised funds for the program. Integrated the program into existing programs in primary care, and education curricula. Gained support from ministry of health	Mapped high‐burden areas. Developed registers and surveillance centers. Echocardiogram screening	Developed health education materials. Conducted community health education Conducted training for health workers.	Echocardiogram screening by physician and refer to the cardiologist. Modified screening and treatment tools All RHD‐positive cases started on benzathine G penicillin prophylaxis
Regmi, 2016 26 Nepal Level: Health system	Collaborated with the government Integrated the program into existing health system Free treatment and surgery for RF and RHD Integrated the program into medical school curricula	Mapped high‐burden areas Developed national RF/RHD register Developed hospital registers forwarding data to the national register. Echocardiogram screening	Developed health education materials Conducted country‐wide community health education (ie, films on TV) Conducted training for health workers (ie, 1500 community health workers)	Recommendations on penicillin allergy skin tests. Treatment guidelines for sore throat Heart screening for school children Free treatment for primary and secondary prophylaxis Benzathine G penicillin procurement, storage, and supply
Ralph et al, 2022 28 Australia Level: Community	Recruitment, retention of ACW Advocacy by ACW for household members to seek care for sore throat Advocacy by ACW for people living with RHD to attend secondary prophylaxis injections	Household surveys RHD register	Community awareness and empowerment of community members. Household education School‐based education Health care provider education Training of ACWs	Housing and environmental health support (ie, repair of housing equipment) Assist clients to access health services (health navigation) Primary and secondary prophylaxis

ACW indicates Aboriginal community worker; RF, rheumatic fever; and RHD, rheumatic heart disease.

In the Australian study, ²⁸ the intervention aimed to prevent GAS infections and improve the diagnosis and management of ARF and RHD in indigenous communities through a coordinated, multidisciplinary approach. This approach included disseminating knowledge, assisting families in accessing care, and promoting household environmental hygiene.

Similarly, the programs in Nepal ²⁶ and Sudan ²² focused on improving access to essential medicines and increasing awareness of ARF and RHD through community education and awareness campaigns. Additionally, the programs established echocardiogram screening and surveillance systems to monitor cases of ARF and RHD and provide timely treatment.

Quality Appraisal and Risk of Bias

Five of the included studies used a cross‐sectional in design and were assessed for methodological quality and risk of bias using the Joanna Briggs Institute Critical Appraisal Checklist for studies reporting prevalence data (Table 3). Two studies used a cohort design and were evaluated using the Joanna Briggs Institute Critical Appraisal Checklist for Cohort Studies (Table 4).

Table 3.

Critical Appraisal Results for Included Studies Using the JBI‐Prevalence Critical Appraisal Checklist

Study	Q1	Q2	Q3	Q4	Q5	Q6	Q7	Q8	Q9
Ali and Subahi, 2020 22	U	U	U	Y	U	Y	Y	N	U
Anderson et al, 2016 23	Y	Y	U	Y	Y	Y	Y	Y	U
Lennon et al, 2017 25	Y	Y	Y	Y	Y	Y	Y	Y	Y
Regmi, 2016 26	U	U	U	Y	U	Y	Y	U	U
Ralph et al, 2022 28	Y	Y	N	Y	Y	Y	Y	Y	Y

N indicates no; Q, question; U, unclear; and Y, yes.

Table 4.

Critical Appraisal Results for Included Studies Using the JBI‐Cohort Critical Appraisal Checklist

Study	Q1	Q2	Q3	Q4	Q5	Q6	Q7	Q8	Q9	Q10	Q11
Jack et al, 2018 24	Y	Y	Y	U	U	N	Y	Y	Y	NA	Y
Walsh et al, 2020 27	Y	Y	Y	U	U	U	Y	Y	Y	NA	Y

N indicates no; NA, not applicable; Q, question; U, unclear; and Y, yes.

Overall, the included cross‐sectional studies were considered to have a good methodological quality concerning the primary outcomes of disease prevalence. ²² , ²³ , ²⁵ , ²⁶ , ²⁸ However, 1 study had a small sample size and lacked a concise description of the sampling frame as the participants were divided into 3 distinct groups. ²⁸ However, the study's reported outcomes, which are in line with our study objectives, focused on the prevalence within the overall population rather than comparisons between groups.

Both of the included cohort studies lacked a clear presentation of the identification and control of confounding factors within the intervention. Additionally, these studies did not provide a comprehensive description of follow‐up strategies, which could be related to the primary outcomes focused on the prevalence within the entire study population. ²⁴ , ²⁷

Two studies used a narrative descriptive approach of the programs evaluated, leading to an overall rating of Unclear for their methodological quality. ²² , ²⁶ This uncertainty is based on the absence of a concise methodology section.

Considering the complexity in evaluating RHD interventions, we did not exclude studies on their quality appraisal (Tables S4–S10). Nevertheless, the quality assessments indicated the potential of bias based on the identified limitations. The main concerns are related to in methodological descriptions, including aspects of sample size and controlling for confounders.

DISCUSSION

This systematic review identified 7 interventions implemented after 2000 that contributed to a reduction in the incidence or prevalence of GAS infections, acute rheumatic fever (ARF), and rheumatic heart disease in populations at risk of RHD. ²² , ²³ , ²⁴ , ²⁵ , ²⁶ , ²⁷ , ²⁸ The interventions encompassed school‐based sore throat services and community‐based programs that implemented strategies for early detection of GAS infections, ARF, and RHD; penicillin antibiotic treatment; improved health education and literacy; improved access to care; and improved environmental hygiene. Among the studies more closely analyzed, 5 were conducted in high‐income countries, primarily (Australia ²⁸ and New Zealand ²³ , ²⁴ , ²⁵ , ²⁷ ) and only 2 studies were conducted in low‐middle–income countries (Nepal and Sudan ²² , ²⁶ ).The findings of this review hold significant implications for the understanding and implementation of global goals and resolutions aimed at preventing RHD. ⁷ , ⁸ , ⁵⁷

This review highlights that nurse‐led school‐based primary prevention services can play a crucial role in the early diagnosis and treatment of GAS pharyngitis using penicillin antibiotics and therefore they also have the potential to reduce the incidence or prevalence of ARF. ²³ , ²⁴ , ²⁵ , ²⁷ The primary focus of this strategy is to detect and treat GAS pharyngitis early among school children, who are at high risk of ARF. These services involve daily assessments and throat swabbing to accurately diagnose GAS infections. In addition, these services also provide extended support in creating knowledge and awareness among children, teachers, and families about the importance of reporting of sore throats.

This finding aligns with previous evidence highlighting the effectiveness of school‐based services. An earlier meta‐analysis conducted on school and community‐based programs demonstrated a 60% reduction in ARF cases by treating GAS pharyngitis in schools. ⁵⁸ That meta‐analysis primarily reported on interventions before 2000, and our systematic review adds current evidence after 2000. The positive impact noted on disease burden can be attributed to the overall strengths of school‐based services, which improve the detection rates of GAS pharyngitis, adherence to treatment, and awareness and knowledge of ARF and RHD among children and their families. ²³ , ²⁴ , ³³ , ³⁹ , ⁵⁹ The school‐based approach had been found to be acceptable and feasible in low socioeconomic status schools in high‐risk areas, with over 90% uptake rates. ¹⁴

Based on the evidence of the effectiveness of school‐based primary prevention services, it is recommended that communities in low‐middle–income countries, particularly those in sub‐Saharan Africa at high risk of ARF or RHD, consider using school‐based services to identify and treat GAS pharyngitis in order to reduce the burden of ARF and RHD. On a suppositious perspective, this evidence should sufficiently support those decisions on consideration that the affected aboriginal communities in Australia and New Zealand are similar to high‐risk populations in low‐middle–income settings.

The primordial community‐based program implemented in Australia, coordinated by community health workers, offers significant insights into the feasibility and effectiveness of reducing the incidence of first‐known acute ARF. ²⁸ This program adopted a unique approach of using community workers to improve living conditions and environmental hygiene, raise awareness, and support communities in accessing care for GAS, ARF, and RHD. Existing evidence corroborates the crucial role that community health workers play in improving health outcomes in communities for various conditions, such as diabetes, maternal and child health, and vaccination. ⁶⁰ , ⁶¹ , ⁶² It is important to note that this Australian study was conducted in a well‐resourced country, and the sample size for analysis was small (29 individuals), which may limit the generalizability of the findings. However, these results are promising and provide valuable recommendations for low‐resourced countries that have an existing community health worker workforce supporting community health services.

Two comprehensive programs implemented in Nepal and Sudan reported a positive impact on reducing the burden of RHD. ²² , ²⁶ These findings align with existing evidence about the effectiveness of comprehensive community‐based programs implemented in the early 1980s through the 1990s. ⁶ , ¹² , ¹³ However, it is important to note that the previous successful programs may have been influenced by concurrent economic development. The programs employed a diagonal approach, integrating RHD services into existing health care systems to reduce ARF/RHD morbidity and mortality similar to previous programs. This approach included establishing surveillance registers at national, regional, and district levels; training of health workers; extensive community awareness campaigns; advocacy among key stakeholders; and improved access to treatment and surgical care. A main limitation in those studies is a lack of rigorous evaluation of the programs, which is primarily attributable to the challenges associated with assessing complex comprehensive interventions, as their effectiveness is likely to manifest over the long term. ⁶³ However, these studies provide valuable information for planning and implementing comprehensive programs in low‐middle–income countries, with the support of local health governance. Both Nepal's and Sudan's programs were carried out in collaboration with their respective health ministries, integrating them into existing programs and health education curricula. The success of these programs highlights the importance of partnerships with government authorities and the integration of interventions into existing health care systems.

Based on the findings of this review, several recommendations can be made to guide future efforts in preventing and reducing the burden of GAS, ARF, and RHD in populations at high risk of RHD, particularly in low‐middle–income countries.

The effectiveness of school‐based clinics in early detection and treatment of GAS pharyngitis among schoolchildren is supported by our findings. Therefore, it is recommended that communities, particularly those in low‐middle–income countries, consider implementing school‐based primary prevention services. These services should include regular assessments, accurate diagnosis through throat swabbing, and education programs to raise awareness among children, teachers, and families.

Primordial, primary, secondary, and tertiary prevention strategies employed in community‐based programs have shown promising results. It is crucial to strengthen those programs to address the multifaceted social, cultural, and economic factors contributing to the development and spread of these diseases, particularly in low‐middle–income countries. Furthermore, it is important to use community workers in the programs to enhance support for the communities to achieve better health outcomes.

In addition, we advocate integrating RHD services into existing health care systems and fostering collaboration with local health governance. Doing so will foster sustainability, scalability, and effective implementation of the programs by leveraging existing health care infrastructure and resources. Comprehensive programs in Nepal and Sudan have demonstrated the value of integrating RHD services into existing health care systems. This integration will include establishing surveillance registers, training health workers, conducting community awareness campaigns, advocating for RHD prevention, and improving access to treatment and surgical care.

Although the demonstrated effectiveness of these programs is promising, 1 major gap in published research is a lack of studies reporting on the effect of interventions on incidence or prevalence of these conditions. Instead, many studies primarily focus on outcomes like adherence to secondary prophylaxis and awareness levels. For instance, a recent retrospective cohort study conducted in Australia assessed the impact of control programs but only presented outcomes related to disease progression, ARF recurrence, secondary prophylaxis delivery, and early disease detection. ⁵⁹ Future evaluations should also include cost‐effectiveness analyses to assess affordability and guide resource allocation, particularly in resource‐constrained countries. Robust evidence about the true impact on the incidence and prevalence of disease and the cost effectiveness of the interventions should improve policies and prioritization of RHD interventions.

Future studies should also provide comprehensive and detailed information on the designs, structures, and processes employed in planning and implementing interventions. A clear understanding of these processes will enhance knowledge of the best practices and facilitate the adoption of effective strategies in different countries. In particular, countries with limited resources may face challenges in implementing full‐scale programs and can benefit from identifying and implementing specific best strategies. Additionally, such reporting will yield valuable insights for improving future interventions, allowing for continuous refinement and optimization of the interventions.

A main limitation of this review is that we did not conduct further analysis to determine the level of contribution of each intervention activity to the reduction of GAS, ARF, and RHD incidences or prevalence. Although the review identified various interventions that showed promise in reducing the incidences or prevalence of these diseases, it did not investigate the specific impact and effectiveness of each activity. Analysis of these specifics would provide valuable insights into the relative importance and effectiveness of various activities in achieving reductions in incidence and prevalence.

CONCLUSIONS

In conclusion, this systematic review has provided valuable insights into the interventions and approaches that contribute to the prevention and reduction of GAS, ARF, and RHD in populations at risk of RHD. The evidence suggests that implementing school‐based primary prevention services, strengthening community‐based programs, integrating RHD services into existing health care systems through collaboration with local health governance, and conducting rigorous evaluations are crucial steps toward preventing and reducing the burden of GAS, ARF, and RHD. By adopting these recommendations, countries can make significant progress in achieving the global goals and resolutions for the prevention of RHD and ultimately improve the health outcomes of populations at risk.

Sources of Funding

The work was funded by the Erling Persson Foundation. The funder had no role in the design of the study, data collection, analysis, and interpretation of the data and in writing the article.

Disclosures

None.

Supporting information

Tables S1–S10