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    Original Research

    Current Situation of Acute Rheumatic Fever and Rheumatic Heart Disease in Latin America and the Caribbean: A Systematic Review

    Authors:

    Maria Alejandra Jaimes-Reyes,

    Fundación del Caribe para la Investigación Biomédica, Carrera 50 # 80–216 Office 201, Barranquilla, Atlántico, CO
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    Manuel Urina-Jassir,

    Fundación del Caribe para la Investigación Biomédica, Carrera 50 # 80–216 Office 201, Barranquilla, Atlántico, CO
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    Manuel Urina-Triana,

    Fundación del Caribe para la Investigación Biomédica, Carrera 50 # 80–216 Office 201, Barranquilla, Atlántico; Facultad de Ciencias de la Salud, Universidad Simón Bolívar, Carrera 59 # 59–65, Barranquilla, Atlántico, CO
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    Miguel Urina-Triana

    Fundación del Caribe para la Investigación Biomédica, Carrera 50 # 80–216 Office 201, Barranquilla, Atlántico; Facultad de Ciencias de la Salud, Universidad Simón Bolívar, Carrera 59 # 59–65, Barranquilla, Atlántico, CO
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    Abstract

    Background: Rheumatic heart disease (RHD) disproportionately affects low-income and middle-income countries. Latin America and the Caribbean (LAC) have been less represented in scientific literature. We aimed to describe the epidemiology, burden and implemented screening and prevention strategies of RHD in LAC.

    Methods: We systematically searched PubMed, Embase, LILACS, and SciELO from 1990 to April 2021. Observational and experimental studies that described data on the epidemiology, burden, or prevention/screening strategies of RHD, regardless of age or language, were included. The risk of bias was assessed by previously published tools depending on their study design. Pre-specified data were independently extracted and presented by each topic (epidemiology, burden, prevention/screening). PROSPERO registration number: CRD42021250043.

    Results: Forty-eight studies out of 1692 non-duplicate records met the eligibility criteria. They were mainly from Brazil, observational in design, and hospital-based. Data on the epidemiology of acute rheumatic fever (ARF) was not recent (most before 2000) with studies describing decreasing incidence through the years. The prevalence of RHD was described in six studies, ranging from 0.24 to 48 per 1,000 among studies evaluating schoolchildren. Nine studies described data based on admissions, ranging from 0.04% to 7.1% in single-center studies. Twenty-four studies assessed the burden of RHD with most of them reporting mortality rates/proportions and complications such as the need for intervention, atrial fibrillation, or embolism. Six preventive strategies were identified that included educational, register-based, and/or secondary prophylaxis strategies. Three well-established echocardiographic screening studies in Brazil and Peru were identified.

    Conclusions: Most ARF/RHD research in LAC comes from a single country, Brazil where preventive/screening efforts have been conducted. There was a paucity of data from several countries in the region, reflecting the need for epidemiological studies from more countries in LAC which will provide a better picture of the current situation of ARF/RHD and guide the implementation of preventive strategies.

    Keywords: rheumatic heart disease, rheumatic fever, epidemiology, Latin America, Caribbean region
    How to Cite: Jaimes-Reyes MA, Urina-Jassir M, Urina-Triana M, Urina-Triana M. Current Situation of Acute Rheumatic Fever and Rheumatic Heart Disease in Latin America and the Caribbean: A Systematic Review. Global Heart. 2022;17(1):65. DOI: http://doi.org/10.5334/gh.1152
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      Published on 02 Sep 2022
    Peer Reviewed
     CC BY 4.0
     Accepted on 06 Aug 2022            Submitted on 03 May 2022

    1. Introduction

    Rheumatic heart disease (RHD) is the resulting chronic valvular damage after a single severe or multiple episodes of acute rheumatic fever (ARF) [1, 2]. The prevalence of RHD has been increasing since 1990 according to data of the Global Burden of Cardiovascular Diseases 2019, with estimates of up to 40.5 million people affected in 2019 [3]. On a positive note, however, the global age-standardized mortality from RHD decreased from 9.2 deaths per 100,000 population in 1990 to 4.8 in 2015 [4]. Despite this, there still exists heterogeneity in the prevalence and mortality rates among countries or regions. For instance, in 2015, 73% of the global cases were concentrated in five countries (India, China, Pakistan, Indonesia, Democratic Republic of Congo), whereas the highest age-standardized death rates occurred in Oceania, South Asia, and central sub-Saharan Africa, indicating an unequal burden of this disease throughout the world [4].

    In the Americas, a region including North America (the United States and Canada) and Latin America and the Caribbean (LAC), the prevalence and mortality estimates due to RHD in 2017 were lower than in the global population, according to a secondary analysis of the Global Burden of Disease (GBD) 2017 study [5]. However, the age-standardized prevalence in 2017 of the LAC subregion (532.8 [513.2–552.8] per 100,000 population) was higher than that of the Americas region as a whole (346.4 [334.1–359.2]) or the global prevalence (500.6 [482.9–519.7]). Nevertheless, there was a reduction in mortality due to RHD in both, the Americas (–48.3%) and the LAC subregion (–59.0%) from 1990 to 2017 with lower mortality age-standardized estimates in 2017 (1.8 [1.7–1.9] and 1.2 [1.2–1.3] per 100,000, respectively) than the global population (3.7 [3.4–3.9]) [5]. In line with the worldwide trends, the burden of premature mortality in the Americas was also described to affect predominantly poorer countries [5]. It is important to note that the GBD studies provide essential estimates for the global patterns, but they have inherent limitations as there exists a lack of quality data from many countries, especially low-and-middle-income, including those in LAC [4, 5].

    Despite the global decreased tendency in the number of deaths, RHD continues to burden many low- and middle-income countries due to its long-term cardiovascular complications including heart failure (HF), pulmonary hypertension (PH), atrial fibrillation (AFib), infective endocarditis (IE), and stroke [6, 7]. Multiple health organizations and world-renowned groups of experts have published recommendations and strategies that aim to reduce the burden of RHD worldwide [8, 9, 10]. The World Heart Federation (WHF) established the goal of reducing 25% of premature deaths from ARF and RHD by 2025 [8]. Consistent with this, the World Health Organization (WHO) Assembly approved a resolution to raise the profile of RHD on the global agenda [9]. Ordunez et al. have raised awareness about this disease in the Americas and LAC, which are regions that are less represented in the published literature on RHD [5]. Considering this, our systematic review aimed to describe the epidemiology of ARF and RHD, the burden of RHD, and the implemented screening and prevention strategies in LAC.

    2. Methods

    This review was reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement (PRISMA) guidelines [11]. The protocol was registered a priori on PROSPERO (CRD42021250043) [12]. The objectives of the review were 1) to describe the epidemiology (e.g., prevalence or incidence) of ARF/RHD, 2) to describe the burden (e.g., complications, need for intervention, or mortality) of RHD, 3) to describe the screening and prevention strategies for RHD, in LAC. In addition, we also aimed to identify possible gaps in the RHD literature in LAC.

    2.1. Information sources and search strategy

    We conducted a systematic literature search in Embase, PubMed, the Latin American and Caribbean System on Health Sciences Information (LILACS, for its acronym in Spanish), and SciELO databases for studies of Acute Rheumatic Fever and/or Rheumatic Heart Disease in Latin America and the Caribbean from 1990 to April 22nd, 2021. We restricted the search to 1990 and onward to obtain information about ARF/RHD in LAC published in the last 30 years. No language restriction was applied. The search strategy is available in Supplementary Table S1-4.

    2.2. Inclusion and exclusion criteria

    Our inclusion criteria included the following: 1) population: subjects of any age from LAC countries, 2) condition: diagnosis of ARF and/or RHD, 3) outcomes/data reported: epidemiologic data (e.g., prevalence, incidence, or admissions), burden data (e.g., morbidity, mortality, or costs), and/or the description of screening/preventive strategies, 4) study designs: primary study designs such as experimental (randomized controlled and non-randomized trials) and observational studies (cross-sectional, cohort, and case-control studies), 5) publication year range: 1990 to April 2021, and 6) language: no restriction. Case reports and series, review articles, systematic reviews/meta-analyses, and guidelines were excluded. International studies that included data not divided by region or country, articles with duplicate information from other reports, and studies based on autopsies or necropsies were also excluded. When encountered with manuscripts on heart or valve diseases, they were included only if outcomes (e.g., prevalence, mortality, etc.) were divided by etiology (i.e., RHD). As being the first systematic review, to our knowledge, addressing these topics of RHD in LAC, we decided to have relatively broad inclusion criteria regarding study design and setting to better capture the status of RHD in this region.

    2.3. Selection process

    Two authors (MAJR and MUJ) independently assessed all records by title and abstract. Then, records were reviewed in full text and selected independently by the same two reviewers according to the eligibility criteria using Rayyan® [13]. Discrepancies between the two reviewers were determined by a consensus-based discussion or by a third reviewer (MUT) if required.

    2.4. Data collection process

    The following items were extracted from each study (if available): 1) general information (author, year of publication, study design and period, country, objectives); 2) population information (study sample, number of participants, gender, and age); 3) diagnostic criteria used for ARF and/or RHD, 4) epidemiologic characteristics (incidence, prevalence, and hospitalization/admission frequency data); 5) burden of RHD (mortality, costs of disease, need for intervention, need for anticoagulation, and complications of RHD [AFib, IE, embolic events (EE) or stroke, HF, PH, and anticoagulated-related complications]); 6) prevention and screening strategies for RHD (type of strategy, description, duration, and results of strategy). All data were independently extracted by two reviewers (MAJR and MUJ) using a spreadsheet with a prespecified extraction form with all the information stated above. Disagreements between the two reviewers were discussed; a final decision was made by mutual consensus or by a third reviewer (MUT).

    2.5. Study risk of bias assessment

    Two reviewers (MAJR and MUJ) independently evaluated the risk of bias for each study. We evaluated the risk of bias or quality of each of the included studies depending on each of their study design. The assessment tools used were the Newcastle-Ottawa Scale (NOS) [14] for cohort studies, the AXIS Critical Appraisal Tool for Cross-Sectional Studies [15], and the Cochrane Revised Tool for Risk of Bias in randomized controlled trials (RoB 2.0) [16] (and its extension for Cluster Randomized Trials [17]). Disagreements were resolved by discussion between authors (MAJR and MUJ) or by a third reviewer (MUT). We did not exclude any studies based on quality assessment.

    2.6. Synthesis methods

    Due to the high heterogeneity among the studies, we conducted a narrative synthesis divided by each topic: epidemiology of ARF/RHD, the burden of RHD, and prevention and screening strategies of ARF/RHD.

    3. Results

    3.1. Selection of studies

    Our search yielded a total of 2431 records of which 1692 were screened by title/abstract after duplicates were removed. One hundred seventy-nine records were sought for retrieval and ultimately 48 studies fulfilled the eligibility criteria [18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 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, 57, 58, 59, 60, 61, 62, 63, 64, 65]. A PRISMA [11] flow diagram of our search strategy and reasons for the exclusion of full-text articles can be seen in Figure 1.

    PRISMA [11] flow diagram for study selection
    Figure 1 

    PRISMA [11] flow diagram for study selection.

    3.2. Study characteristics

    Studies were from Barbados (n = 1), Brazil (n = 31), Chile (n = 3), Cuba (n = 1), Dominican Republic (n = 1), Guatemala (n = 1), Jamaica (n = 1), Martinique/Guadeloupe (n = 1), Mexico (n = 2), Nicaragua (n = 1), Peru (n = 2), Uruguay (n = 1), and Venezuela (n = 1). Additionally, one study included Bolivia, El Salvador, and Jamaica as the ‘Americas’ [64]. They were published between 1990 and 2021 with most studies published during or after 2010 (n = 26).

    Data on epidemiology, burden, and prevention/screening strategies were extracted from 23, 24, and 11 studies, respectively. Regarding the setting, studies were hospital-based (n = 28), school-based (n = 5), community-based (n = 3), or population-based (n = 8). In addition, four studies evaluated schoolchildren in addition to another setting (hospital or community). Supplementary Table S5 describes the general characteristics of each reference.

    3.3. Risk of bias among included studies

    3.3.1. Cross-sectional studies

    Among the 30 cross-sectional studies, AXIS scores ranged from 8 to 20. Most studies lack sample size justification (Question 3) and non-responders’ characterization (Question 7). Other common flaws were lack of description of statistical significance (Question 10) or limitations acknowledgment in the discussion section (Question 18) (Supplementary Table S6).

    3.3.2. Cohort studies

    The NOS scores of the 16 cohort studies ranged from five to nine stars. Those studies with a higher risk of bias were due to not describing adequately the ‘Comparability of cohorts’ as indicated in the NOS. Individual scores are presented in Supplementary Table S7.

    3.3.3. Randomized controlled trials

    Two randomized controlled trials (RCTs) were included. Both RCTs were found to have an overall risk of bias of ‘Some Concerns’. None had ‘High Risk of Bias’ in any section; a detailed assessment for each section is presented in Supplementary Table S8.

    3.4. Epidemiology of ARF and RHD in Latin America and the Caribbean

    Twenty-three studies assessed epidemiological data of patients with either ARF, RHD, or both. Fifteen of them presented incidence or prevalence data whereas nine studies evaluated admissions-based data (one study assessed both). Tables 1 and 2 summarize the epidemiological data per study.

    Table 1

    Prevalence and incidence of acute rheumatic fever and rheumatic heart disease in Latin America and the Caribbean.

    REFERENCE COUNTRY SETTING TARGET POPULATION DIAGNOSTIC CRITERIA PERIOD PREVALENCE INCIDENCE
    Acute Rheumatic Fever
    Noah, 1994 [47] Barbados Population Children Total Jones 1971–1990 NR Total population:
    1971–1972: 13/100,000
    1973: 12/100,000
    1974: 5/100,000
    1975: 8/100,000
    1976–1977: 7/100,000
    1978: 9/100,000
    1979: 8/100,000
    1980: 5/100,000
    1981: 3/100,000
    1982–1984: 5/100,000
    1985: 3/100,000
    1986–1990: 2/100,000

    Childhood population (<19 years)‘Since 1986’: 8/100,000
    Alves Meira et al., 1995 [18] Brazil School 10–20 years Jones 1992 3.6/1,000 NR
    Berrios et al., 1993 [21] Chile Community N/A Jones 1982–1986 NR 1982–1985: 22.5 per year
    1986(6–14-years): 21.7/100,000
    Luque et al., 2006 [38] Chile Population N/A N/A 1978–1998 NR 1978: 2.2/100,000
    1979: 3.2/100,000
    1980: 1.4/100,000
    1981: 1.6/100,000
    1982: 2.4/100,000
    1983: 3/100,000
    1984: 2.5/100,000
    1985: 2/100,000
    1986: 1.9/100,000
    1987: 1.3/100,000
    1988–89: 1/100,000
    1990: 0.6/100,000
    1991–92: 0.5/100,000
    1993: 0.3/100,000
    1994–95: 0.2/100,000
    1996–97: 0.1/100,000
    1998: 0/100,000
    Nordet et al., 2008 [48] Cuba School 5–14 years Inactive RF: ‘History of ARF without established RHD’ 1985, 1996 1985: 1.75/1,000
    1996: 5.78/1,000    		 See below in ARF/RHD section for incidence
    Bach et al., 1996 [19] Martinique Guadeloupe School Hospital <20 years Jones 1982–1983 NR Martinique: 19.6/100,000
    Guadeloupe: 17.4/100,000
    Soto Lopez et al., 2001 [58] Mexico Population 5–20 years Jones 1994–1999 NR ‘Annual incidence tendency decreased from 1.3% to 0.3%’
    Rheumatic Heart Disease
    Meira et al., 2005 [39] Brazil Hospital Children Adolescent Echo2 1983–1998 NR 186 (72.1%) – Severe: 41 (15.9%) out of 258 with ARF
    Miranda et al., 2014 [43] Brazil School Children Adolescent Auscultation Echo (WHO) 2010–2011 Clinical:
    AR: 3.7/1,000
    MR: 3.7/1,000

    Echo:
    AR: 7.5/1,000
    MR: 18.7/1,000    		 NR
    Nascimento et al., 2018 [46] Brazil School Primary care centers Children Adolescent Echo (WHF) 2014–2016 Borderline RHD:
    4% (478/12,048)
    Definite RHD:
    0.5% (63/12,048)    		 NR
    Nascimento et al., 2021 [45] Brazil Community Pregnant Echo (ASE-REWARD study) 2018–2019 Hand-held echo screening: 3.2% (36/1,112)
    Standard echo: 1.2% (12/1,112)    		 NR
    Nordet et al., 2008 [48] Cuba School 5–14 years Echo3 1985, 1996 1985: 2.27/1,000
    1996: 0.24/1,000    		 See below in ARF/RHD section for incidence
    Paar et al., 2010 [51] Nicaragua Community Children Adult Echo (WHO) 2006–2009 Pediatric: 48/1,000

    Adult: 22/1,000    		 NR
    Spitzer et al., 2015 [60] Peru School Children Adolescent Echo (WHO & WHF) 2014 WHO: 19.7/1,000 children

    WHF: 3.9/1,000 children    		 NR
    Acute Rheumatic Fever/Rheumatic Heart Disease1
    Souza et al., 1990 [59] Brazil School Community Children Adolescent Jones N/A 20.3% (198/972) NR
    WHO Cardiovascular Diseases Unit, 19924 [64] Bolivia El Salvador Jamaica (Americas) School Children N/A 1986–1990 Americas:1.5 (0.1–7.9)/1,000

    Bolivia: 7.9/1,000    		 NR
    Nordet et al., 2008 [48] Cuba Population (Incidence)School (Prevalence) 5–25 years Inactive RF: ‘History of ARF without heart valve damage’RHD: Echo3 1986, 1996, 2002 5–14 years:
    1985: 8.01/1,000
    1996: 1.99/1,000    		 5–25 years:
    1986: 18.6/100,000
    1996: 2.5/100,000
    2002: 2.4/100,000

    5–14 years
    1986: 28.4/100,000
    1996: 2.7/100,000
    2002: 2.8/100,000

    1 Studies that reported the epidemiologic data combining both terms ARF and RHD or referred to them as ‘ARF/RHD’.

    2 Reported as ‘the Doppler echocardiography criteria adopted by the echo lab of Universidad Federal Minas Gerais’ [39].

    3 Reported as ‘typical RHD valve damage supported by echocardiogram’ [48].

    4 The manuscript includes data from 16 countries divided into 5 regions; only data of the Americas region was extracted.

    Abbreviations: ASE: American Society of Echocardiography; AR: Aortic regurgitation; ARF: Acute rheumatic fever; ICD: International Classification of Diseases; MR: Mitral regurgitation; N/A: Not available; NR: Not reported; RF: Rheumatic fever; RHD: Rheumatic heart disease; WHF: World Heart Federation; WHO: World Health Organization.

    Table 2

    Admissions-based data of acute rheumatic fever and rheumatic heart disease in Latin America and the Caribbean.

    REFERENCE COUNTRY TARGET POPULATION PERIOD DIAGNOSTIC CRITERIA N/N (%) DESCRIPTION
    Acute Rheumatic Fever
    Silva et al., 2010 [57] Brazil Children Adolescent 1986, 1991, 1996, 2001, 2006 Jones 1986: 59/4206 (1.4%)
    1991: 17/5206 (0.3%)
    1996: 8/5196 (0.15%)
    2001: 12/6777(0.18%)
    2006: 3/8203 (0.04%)    		 # of ARF admissions/# of admissions in each period in a single pediatric center
    de Araújo Fonseca et al., 2020 [26] Brazil N/A 2008–2017 ICD-10 42,720/11,345,821 (0.4%) # of ARF admissions/# of CVD admissions in Brazil 2008–2017
    Defilló Ricart et al., 1991 [27] Dominican Republic Children 1969–1989 Jones 121/19,483 (0.62%) # of ARF cases/# of admissions in Cardiology Department of Pediatric Hospital
    Stokes Baltazar, 2007 [61] Guatemala Children AdolescentAdult 2000–2005 Jones 246/3422 (7.1%) # of ARF cases/# of admissions from a single center
    Millard-Bullock, 2012 [42] Jamaica Children 1975–19851989–1995 Jones 1975–1985: 54% (total pop.: 1079)
    1989–1995: 55% (total pop.: 512)    		 % of patients with ARF among children admitted to hospitals in Jamaica (1975–1985: 4 hospitals, 1989–1995: 3 hospitals)
    Soto Lopez et al., 2001 [58] Mexico Children Adolescent 1994–1999 Jones Incidence: 6.6 per 1,000

    (Total pop.: 3392)    		 Incidence of new ARF cases out of the total admissions among 5–20-year-olds in a single Cardiology center
    Giachetto et al., 1994 [31] Uruguay Children Adolescent 1990–1993 Jones 1990: 14/1731 (0.82%)
    1991: 8/2032 (0.39%)
    1992: 18/2063 (0.87%)
    1993: 18/2256 (0.79%)Total: 58/8,082 (0.71%)    		 # of ARF admissions/# of children aged 2–14 admissions in a single pediatric center
    Rheumatic Heart Disease
    Haddad and Bittar, 2005 [32] Brazil N/A 1988–2003 ICD-9 (1988–94)ICD-10 Men: 3.1%
    Women: 9.8%    		 Mean relative percentage per month of RHD diagnosis out of the total admissions in a single CVD center
    de Araújo Fonseca et al., 2020 [26] Brazil N/A 2008–2017 ICD-10 78,966/11,345,821 (0.7%) # of RHD admissions/# of CVD admissions in Brazil 2008–2017
    Acute Rheumatic Fever/Rheumatic Heart Disease1
    Salinas Mondragón et al., 1995 [54] Peru Children Adolescent 1989–1993 Jones 1989: 9/174 (5.1%)
    1990: 10/215 (4.6%)
    1991: 16/177 (9.0%)
    1992: 15/263 (5.7%)
    1993: 16/245 (6.5%)
    Total: 66/1074 (6.1%)    		 # of hospital discharges with ARF/RHD/# discharges in a single pediatric center

    1 Studies that reported the epidemiologic data combining both terms ARF and RHD or referred to them as ‘ARF/RHD’.

    Abbreviations: ARF: Acute rheumatic fever; CVD: cardiovascular diseases; ICD: International Classification of Diseases; N/A: Not available; RHD: Rheumatic heart disease.

    3.4.1. Prevalence of ARF and RHD in Latin America and the Caribbean

    Data on the prevalence of each study are described in Table 1. Two studies from Brazil [18] and Cuba [48] reported the prevalence of ARF with one using Jones Criteria for case definition [18]. The prevalence in the Brazilian study was 3.6 per 1,000 among schoolchildren from Belo Horizonte in 1992 [18]. Whereas Nordet et al. described a prevalence of 1.75 and 5.78 per 1,000 in 1985 and 1996, respectively, in a Cuban study [48]. On the other hand, six studies evaluated data on RHD [43, 45, 46, 48, 51, 60], whereas three from Brazil, Cuba, and the Americas region described epidemiological data combining both terms (ARF/RHD) [48, 59, 64]. The latter corresponds to data collected by the World Health Organization program from 1986 to 1990 in Bolivia, El Salvador, and Jamaica, where a prevalence of 1.5 per 1,000 (ranging from 0.1 to 7.9 among the countries) was identified [64].

    The prevalence of RHD was described in three Brazilian studies [43, 45, 46] as well as studies from Cuba [48], Nicaragua [51], and Peru [60]. All studies based their diagnosis on echocardiographic criteria; two of the Brazilian reports were based on the Rheumatic Valve Disease Screening Program (PROVAR) and its extension (PROVAR+) [45, 46]. The population assessed was mostly focused on the non-adult population, whereas one study evaluated pregnant women [45] and another study included adults in addition to the pediatric population [51]. The prevalence among studies assessing children or adolescent population ranged from 0.24 per 1,000 (Cuba, 1996) [48] to 48 per 1,000 (Nicaragua, 20062009) [51]. Furthermore, the prevalence of RHD among pregnant women in the primary care setting in Minas Gerais, Brazil was 1.2% [45].

    3.4.2. Incidence of ARF and RHD in Latin America and the Caribbean

    Table 1 presents the incidence of ARF and RHD per study. Most studies reported the incidence of ARF; these were from Barbados, Chile, Martinique, Guadeloupe, and Mexico [19, 21, 38, 47, 58]. All except for one, where the definition was not described [38], used Jones criteria for case definition. When data from more than one year was available, the studies from Barbados, Chile, and Mexico described a lower incidence throughout their study years [38, 47, 58]. For instance, the incidence of ARF in Chile decreased from 2.2 per 100,000 in 1978 to 0 in 1998 [38] and in Barbados from 13 per 100,000 in 1971 to 2 per 100,000 in 1990 [47]. No data from the 2000s, 2010s, and 2020s were identified about ARF incidence. One study prospectively followed Brazilian children and adolescents with ARF to evaluate the progression to RHD; these authors found that 72.1% (186/258) developed chronic disease [39]. Moreover, one study assessed the incidence of combined ARF/RHD in two different age groups in Cuba, identifying a decreasing incidence from 1986 to 2002 [48].

    3.4.3. Admissions-based data on ARF and RHD in Latin America and the Caribbean

    Data on admissions or discharges of ARF, RHD, or both were assessed in nine studies from Brazil, Dominican Republic, Guatemala, Jamaica, Mexico, Peru, and Uruguay [26, 27, 31, 32, 42, 54, 57, 58, 61]. Most of them were based on single-center experiences except for two studies [26, 42]. A Brazilian study evaluated all the cardiovascular admissions in the country over 10 years, identifying that 0.4% and 0.7% of them were due to ARF and RHD, respectively [26]. Furthermore, Millard-Bullock assessed the data from three and four Jamaican hospitals in two study periods, 1975–1985 and 1989–1995, respectively, with a high frequency of admitted patients with ARF (54% and 55%, respectively) [42]. Among single-center studies on either ARF or ARF/RHD, the percentage of patients with this diagnosis ranged from 0.04% (Brazil, 2006) [57] to 7.1% (Guatemala, 2000–2005) [61]. A summary of the results of these investigations is presented in Table 2.

    3.5. Burden of RHD in Latin America and the Caribbean

    Twenty-four studies described data on the burden of RHD. Fifteen reports were based on solely surgical or percutaneously intervened subjects whereas the other studies included subjects with RHD regardless of their treatment (general studies).

    3.5.1. Mortality of RHD

    Seven studies reported RHD mortality regardless of their treatment; five were from Brazil [30, 33, 37, 49, 63], while the other two were from Peru [54] and Venezuela [34]. Studies reported data with different measures (e.g., proportions, rates) with four of them reporting mortality rates. Two of them assessed mortality rates among women of reproductive age in Brazil; Lolio et al. reported a mortality rate of 2.6 per 100,000 women in 1986 while Haddad and Silva described 1.58 per 100,000 women from 1991 to 1995 [33, 37]. More recently, Figueiredo et al. utilized data from the Brazilian health system and described RHD mortality rates of 5.77 and 8.22 in 1998 and 2016, respectively [30]. A Venezuelan cross-sectional study reported adjusted mortality rates from data from the Health Ministry, with rates per 100,000 declining from 7.06 in 1955 to 1.05 in 1994 [34]. From the studies reporting the proportion of demised patients, this ranged from 0.8% to 6% [49, 54, 63]. Further data on mortality among general studies are presented in Table 3 and Supplementary Table S9.

    Table 3

    Burden of rheumatic heart disease in Latin America and the Caribbean*.

    COMPLICATION REPORTED DATA AND REFERENCES
    General studies1 Intervention-only studies1
    Mortality Rates
    BR:
    2.6/100,000 women (1986) [37]
    1.58/100,000 women (1991–1995) [33]
    5.77 (1998), 8.22 (2016) [30]

    VE: 7.06 (1955), 3.04 (1966), 0.78 (1975), 1.66 (1985), 1.05 (1994)/100,000 [34]

    Proportions
    BR:
    0.8% (2007–2011) [49]
    6.2% (2010–2019) [63]

    PE: 6% (1989–1993) [54]    		 Operative:
    BR:
    0% (1994–2005) [56]
    2.7% (1996–2005) [62]
    13% (2008–2009) [22]

    CL: 9.4% (1990–2004) [55]

    In-hospital or <30 days:
    BR:
    5.4% (1991–1994) [35]
    0% (1994–2005) [56]
    9% (2002–2005) [53]
    19.2% (2007–2011) [29]
    10% (2010–2011) [52]
    7.8% (2013–2014) [24]
    3.51% (2010–2015) [40]

    Follow-up:
    BR:
    2-month: 0% (2011–2017) [25]
    3-month: 0% (2010–2012) [28]
    1-year: 0% (2013–2014) [24]
    38.5–41.1-month: 7.3% (1991–1994) [35]
    63 ± 39-month: 2.9% (1994–2005) [56]

    CL: 6.67–7.89-years: 17.7% (1990–2004) [55]

    Overall
    BR:
    0.6% (1987–2010) [41]
    8.2% (1996–2005) [62]

    MX: 20% [65]
    Need for intervention2 At baseline
    BR:
    27% (2007–2011) [49]
    25% (2010–2019) [63]

    During follow-up
    BR:
    34.4% (2007–2011) [49]
    21.5% (2010–2019) [63]

    Overall

    CU: 4.5% (1986–1990), 0.5%(1991–1996) [48]
    PE: 12.1% (1989–1993) [54]    		 At baseline
    BR:
    30% (2002–2005) [53]
    38% (2007–2011) [29]
    63% (2010–2011) [52]

    Reintervention
    BR:
    11.5% (1994–2005) [56]
    12.7% (1996–2005) [62]
    23.07% (2007–2011) [29]
    8.3% (Surgery), 10% (PBMV) (1987–2010) [41]
    10% (2010–2011) [52]
    27.9% (First), 14.8% (Second) (2010–2015) [40]
    5.6% (2011–2017) [25]

    CL: 4.7% (1990–2004) [55]
    Heart failure CU: 11.2% (1986–1990), 1.5% (1991–1996) [48] BR:
    22.3% (2009) [23]
    7.4% (Postop.) (2011–2017) [25]

    CL: 5.1% (1990–2004) [55]
    Atrial fibrillation BR:
    14% (2007–2011) [49]
    30% (2010–2019) [63]    		 BR:
    12.5% (1987–2010) [41]
    28% (2007–2011) [29]
    53.1% (2009) [23]
    0% (2011–2017) [25]

    CL: 65.6% (Preop.), 63.3% (Postop.) (1990–2004) [55]
    Infective endocarditis CU: 0% (1986–1996) [48]
    PE: 23% (1989–1993) [54]    		 BR:
    2.8% (1996–2005) [62]
    1.9% (2008–2009) [22]
    16% (2010–2011) [52]

    CL: 1.4% (1990–2004) [55]

    MX: 7.1% [65]
    Stroke BR:
    18% (Baseline), 5.2% (Follow-up) (2010–2019) [63]
    12.7% [36]

    PE: 1.5% (1989–1993) [54]    		 BR:
    4.2% (1996–2005) [62]
    7.5% (2008–2009) [22]
    2.7% (2010–2012) [28]
    10.5% (Baseline), 1% (Postop.) (2013–2014) [24]

    CL: 2.8% (1990–2004) [55]
    Embolic events BR: 4.4% [36] BR: 16.4% (Baseline), 12.7% (Postop.) (1991–1994) [35]
    MX: 7.1% [65]
    Pulmonary hypertension PE: 16.7% (1989–1993) [54] BR:57.5% (2009) [23]
    77.6% (Preop.), 18.4% (Postop.) (2011–2017) [25]

    * Supplementary Table S9 includes the information on burden of RHD per each included study.

    1 Several studies (‘Intervention-only studies’) that assessed solely surgical or percutaneously intervened RHD patients while others (‘General studies’) assessed patients receiving any kind of treatment.

    2 ‘Need for intervention’ includes any surgical (initial or reoperation) or percutaneous intervention (initial or reintervention).

    Abbreviations: BR: Brazil, CL: Chile, CU: Cuba, MX: Mexico, PBMV: Percutaneous Balloon Mitral Valvuloplasty; PE: Peru, Postop.: postoperative, Preop.: preoperative, VE: Venezuela.

    Among the studies assessing surgically or percutaneously intervened, thirteen were from Brazil, one from Chile [55], and one from Mexico [65]. All, except one [23], reported data on mortality, which timeframes varied among studies. Among those reporting operative mortality, proportions ranged from 0 to 13% [22, 55, 56, 62], whereas in those reporting in-hospital or <30 days mortality, it ranged from 0% to 19.2% [24, 29, 35, 40, 52, 53, 56]. Some authors reported distinct follow-up periods for longer-term mortality (from 2 months up to 8 years of follow-up) [24, 25, 28, 35, 55, 56] whereas others reported overall mortality during their total study period ranging from 0.6% to 20% [41, 62, 65]. Moreover, Ribeiro et al. reported the mean annual incidence of in-hospital mortality (0.25 per 100,000) and of open-heart surgery for RHD (2.86 per 100,000) in Salvador, Brazil [53] (Table 3 and Supplementary Table S9).

    3.5.2. Morbidity of RHD

    Among general studies, burden was represented as the need for an intervention [48, 49, 54, 63], need for anticoagulation [63], HF [48], AFib [49, 63], IE [48, 54], stroke or EE [36, 54, 63], and PH [54]. Regarding the need for surgery or percutaneous intervention, this varied among studies from 0.5% [48] to 34.4% [49]. Two studies reported that patients with RHD had concomitant AFib in 14% and 30%, respectively [49, 63]. Lavitola et al. reported an incidence of EE of 3.7% patient/year in an RCT of warfarin versus aspirin among RHD patients [36]. Recently, Vasconcelos et al. reported an incidence of 1.47 strokes per 100 patient-years in a prospective cohort study among Brazilian adults with RHD [63]. The proportion of other complications (with more than one study reporting the variable) ranged from 0%–23% for IE [48, 54] and 1.5%–18% for stroke/EE [36, 54, 63]. Information on the burden data per study is shown in Table 3 and Supplementary Table S9.

    Burden was also assessed from surgical or percutaneously intervened studies. The need for reoperation or reintervention was commonly described in the studies [25, 29, 40, 41, 52, 55, 56, 62]. Other complications of RHD reported among interventional studies were HF (5.1%–22.3%) [23, 25, 55], AFib (0%–65.6%) [23, 25, 29, 41, 55], IE (1.4%–16%) [22, 52, 55, 62, 65], stroke (2.7%–10.5%) [22, 24, 28, 55, 62], EE (7.1%–16.4%) [35, 65], and PH [23, 25]. Table 3 and Supplementary Table S9 present data on burden per study.

    3.5.3. Economic impact of RHD

    Three studies assessed the economic consequences of RHD in LAC countries [30, 42, 48]. In Pinar del Rio, Cuba, the estimated mean cost per year due to ARF/RHD care was $97,457.00 USD from 1986 to 1996 [48]. Figueiredo et al. reported that the total costs due to RHD increased from $7,006,288.21 USD (1998) to $25,526,924.01 USD (2016) in Brazil [30]. Furthermore, Millard-Bullock commented on a total hospitalization cost for ARF/RHD of $17 million Jamaican Dollars (JMD) per year among the three hospitals assessed in 1989–1995 in Jamaica [42].

    3.6. RHD prevention and screening strategies in Latin America and the Caribbean

    3.6.1. RHD prevention programs in Latin America and the Caribbean

    Different prevention programs have been launched in Brazil [44], Chile [21], Cuba [48], Jamaica [42], Martinique, Guadeloupe [19], Bolivia, El Salvador, and Jamaica [64]. The study periods of these strategies ranged from 1975 to 2001. Four of these strategies included case finding or registries of patients with ARF/RHD [19, 42, 48, 64]. Chemoprophylaxis for secondary prevention was a part of five of the prevention programs [21, 42, 44, 48, 64]. Another common aspect of the projects was the education of the general population, teachers, and/or healthcare workers [19, 42, 48, 64]. Three of these strategies described a decrease in unfavorable outcomes including cases/recurrences [19, 44, 48], severity [48], hospital admissions [44], surgeries [19, 44], deaths [44], and costs [19, 48]. The specific description and the results obtained during each program are presented in Table 4.

    Table 4

    Preventive and screening strategies for rheumatic heart disease in Latin America and the Caribbean.

    REFERENCE COUNTRY STUDY PERIOD DESCRIPTION RESULTS
    Prevention programs
    Mota et al., 2015 [44] Brazil 1977–2000 Prevention Program for ARF-UFMG (since 1988)
    1. HCW education.
    2. Outpatient clinic for ARF with routine follow-up.
    3. Echocardiographic screening for definite or suspected cases of ARF or RHD.
    4. Distribution of free medication.
    5. Chemoprophylaxis and ‘prophylaxis card’ to control compliance.
    6. Active searching of missing patients.
    		 Comparing two periods (July 1977–July 1988, n = 248 and August 1988–February 2000, n = 454), the authors identified a decrease in:
    1. Recurrences (22.4 vs 7.4, p = 0.0000)
    2. Hospital admissions (45.4 vs 28.4, p = 0.0000)
    3. Surgeries (13.3 vs 1.5, p = 0.0000)
    4. Deaths (5.4 vs 0.4, p = 0.0000)
    Berrios et al., 1993 [21] Chile 1982–1988 ARF Control and Prevention Program of Southeast Health District (Catholic University Medical School, Santiago, Chile)
    1. Chemoprophylaxis: benzathine penicillin G every 28 days (nonpenicillin allergic) or oral sulfadiazine daily (penicillin allergic)
      • Duration: no carditis: 5 years or until age 18; carditis: 10 years or until age 25; aortic involvement, mitral stenosis or multivalvular: for life.
    2. Follow-up after cessation: regular visits every 3 months, annual examination by cardiologist.
    1. 59 post prophylactic patients (1032 scheduled visits and 3346 patient- months)
    2. Recurrence rate of 0.72 (CI, 0.2 to 2.6) per 100 patients-years of prospective surveillance.
    Nordet et al., 2008 [48] Cuba 1986–2001 Pinar del Rio Project
    1. Primary prevention of ARF/RHD: diagnosis and treatment of GAS pharyngitis.
    2. Secondary prevention of ARF/RHD: case finding, referral, permanent register, surveillance, and chemoprophylaxis for ARF/RHD.
    3. Educational program and personnel training.
    4. Two cross-sectional studies for ARF/RHD prevalence in schoolchildren (5–15 year) were conducted in 1985 and 1996.
    1. Decline in the occurrence and severity of RF/RHD. (See Results section, Tables 1 and 3)
    2. Decline of ARF/RHD incidence in schoolchildren and 5–25-year-olds. (See Results section, Table 1)
    3. Increase in secondary prophylaxis compliance: 1986 (50% regular, 36.5% irregular and 13.5% non-compliance) to 1996 (93.8% regular, 6.2% irregular).
    4. Decline in estimated direct costs of RF/RHD: 145519 USD per year (1986–1990) to 49376 USD per year (1991–1996).
    Millard-Bullock, 2012 [42] Jamaica 1975–1985, 1989–1995 The ARF and RHD Control Program – Jamaica
    1. Primary prevention of ARF (identification and treatment of GAS infections).
    2. Secondary prevention with 4-weekly injections of benzathine penicillin.
    3. Case-finding, registration, and surveillance of patients.
    4. Health education to patients, families, and the public. (Conferences, seminars, posters, etc.)
    1. ARF cases surveys (See Results section, Table 2)
    2. ARF/RHD’s hospitalization cost (1989–1995): J$17 million per year for 3 hospitals.
    Bach et al., 1996 [19] Martinique Guadeloupe 1982–1992 Martinique/Guadeloupe eradication program
    1. Registry of all cases.
    2. Educational program (pamphlets, posters, films, etc.) on sore throat, ARF, and HCW education.
    3. Research (immunological, bacteriological, or genetic studies) on patients with ARF.
    1. Decline of ARF cases in both islands. (78% reduction in Martinique and 74% in Guadeloupe)
    2. Decline of patients requiring open heart surgery due to rheumatic fever carditis before age 18.
    3. Cost reduction of recent childhood rheumatic fever from USD 1,426,000 to USD 100,000 (86% decrease)
    WHO Cardiovascular Diseases Unit, 1992 [64] BoliviaEl SalvadorJamaica
    (‘Americas’)    		 1986–1990 WHO program for the prevention of ARF/RHD in 16 developing countries
    The Americas region was one of the five regions assessed and included Bolivia, El Salvador, and Jamaica. The program included:
    1. Case finding via screening surveys of schoolchildren, hospital retrospective case surveys, and continuing detection/referral of any ARF/RHD confirmed or suspected case from health centers.
    2. Central register of all confirmed ARF/RHD patients.
    3. Follow-up consultation and secondary prophylaxis in local centers.
    4. Personnel (schoolteachers and HCW) training and health education.
    		 The Americas region results:
    1. Five surveys (n: 23,328 schoolchildren) conducted for ARF/RHD prevalence (See Results section, Table 1)
    2. Case detection and registration; a total of 9,645 on the register (35 detected in screening, 881 from other sources and 8,729 known cases)
    3. Rate of coverage of prophylaxis: 47.2% (23.8–75.6%) per 100 patients registered for secondary prophylaxis per month. El Salvador had one of the lowest rates among all 16 countries: 23.8%.
    4. Training of personnel: 2,080 (123 doctors, 1,147 other HCW, and 819 schoolteachers)
    5. Activities for health education: pamphlets and brochures: 24,304, posters: 28, radio/TV programs: 22, and group sessions: 93.
    Screening programs
    Beaton et al., 2016 [20]
    Nascimento et al., 2018 [46]    		 Brazil 2014–2016 PROVAR: Rheumatic Valve Disease Screening Program
    1. RHD echocardiographic screening program in Minas Gerais, Brazil.
      • Image acquisition by nonexperts on portable and/or handheld devices.
      • Telemedicine interpretation by experts in Brazil and USA (WHF 2012 criteria).
      • Patients with confirmed abnormalities referred for clinical and echocardiographic follow-up.
    2. RHD educational curriculum delivered in schools and in primary care (See Oliveira et al., 2020 below).
    3. Echocardiographic education of non-experts (n: 6): self-directed educational experience followed by field-testing of school-based handheld echocardiography screening [20].
    1. Screening in 52 public schools, 2 private schools and 3 primary care centers. (See Results Section, Table 1)
    2. Educational curriculum delivered to 29,695 children.
    3. Non-experts’ interpretation of echocardiography: sensitivity 83% and specificity 85% for detecting RHD (borderline or definite) [20].
    Nascimento et al., 2021 [45] Brazil 2018–2019 PROVAR+: Programa de RastreamentO da VAlvopatia Reumatica e outras Doenças Cardiovasculares
    A continuation of PROVAR [46]. This publication involved an echocardiographic screening program among pregnant women in prenatal care:
    1. Image acquisition by nonexperts on hand-held devices.
    2. Telemedicine image interpretation by experts in Brazil and USA.
    3. HCW received educational curriculum on echocardiography.
    4. Standard echocardiogram was scheduled for those with significant abnormalities during screening.
    1. 1112 pregnant women were screened. (See Results section, Table 1)
    2. Authors concluded that integrating this type of strategies is possible in the Brazilian system.
    Spitzer et al., 2015 [60] Peru 2014 Echocardiopraphic Screening Program on Schoolchildren at Arequipa, Peru
    1. RHD echocardiographic screening program among schoolchidren (5–16 years) in Arequipa, Peru.
      • Cardiac auscultation.
      • Portable echocardiography by cardiologist.
      • If pathologic findings, a detailed echo by local cardiologist was offered.
      • WHO and WHF classifications were evaluated by 5 cardiologists from Bern University Hospital.
    2. Secondary prophylaxis and regular follow-up for children with borderline/definite (WHF) or probable/definite (WHO) RHD.
    1. 1023 children were screened and pathological findings on echocardiography were reported in 59 children (5.8%) and 45 underwent confirmatory echocardiogram. (See Results section, Table 1)
    2. 21 children (4 with concomitant RHD) had congenital heart disease.
    3. Secondary prophylaxis in six children with WHO definite/probable. RHD, and one with WHF borderline RHD.
    Educational programs/interventions
    Oliveira et al., 2020 [50] Brazil 2016–2017 RHD educational strategy by PROVAR researchers
    Two educational strategies were assessed by a cluster randomized trial among schoolchildren:
    1. ‘Conventional’: classes with slide presentations provided by a research nurse.
    2. ‘Experimental’: individual interactive modules provided in tablets.
    1. Baseline knowledge of ARF/RHD was low.
    2. Improvement in knowledge was similar immediately after intervention.
    3. After 3 months, worsening in knowledge was observed (similar in both groups).
    4. Authors concluded that these educational strategies improve knowledge (which may be important in prevention). However, retention of knowledge was low.

    Abbreviations: ARF: Acute rheumatic fever; GAS: Group A Streptococcus; HCW: Healthcare workers; J$: Jamaican Dollars; UFMG: Federal University of Minas Gerais; PROVAR: Rheumatic Valve Disease Screening Program; PROVAR+: Programa de RastreamentO da VAlvopatia Reumática e outras Doenças Cardiovasculares; RHD: Rheumatic Heart Disease; TV: Television; USD: United States Dollars; WHF: World Heart Federation; WHO: World Health Organization.

    3.6.2. RHD screening programs in Latin America and the Caribbean

    The Rheumatic Valve Disease Screening Program (PROVAR) in Minas Gerais, Brazil, consisted of the use of handheld devices to obtain cardiac imaging among approximately 12,000 children; these images were then reviewed by experts, and those with abnormal findings were offered follow-up [46]. Additionally, as part of this program, non-experts were also educated on echocardiography [20]. Consequently, this strategy was expanded to include other populations (PROVAR+) such as pregnant women in their prenatal care [45]. An educational strategy on ARF/RHD by the PROVAR researchers was also conducted, comparing two educational methods among schoolchildren [50]. Spitzer et al. conducted echocardiographic screening among schoolchildren in Arequipa, Peru. In this project, imaging was obtained by a cardiologist and two distinct classifications were assessed by other experts abroad and those with abnormal findings were offered follow-up [60] (Table 4).

    4. Discussion

    This systematic review provides an overview of the status of the epidemiology, burden, and preventive strategies of rheumatic heart disease in Latin America and the Caribbean. Forty-eight observational and experimental studies fulfilled eligibility criteria and are presented to describe the continuous burden of this disease in the region.

    4.1. Epidemiology

    We identified relevant data of the epidemiology on ARF/RHD in LAC. As expected, the studies varied in central aspects such as study periods, case definitions, and target population. Overall, the first main finding of our review is the paucity of recent data on the incidence or prevalence of ARF; the included studies mostly assessed data collected before the 2000s. On the other hand, studies on RHD have been more constant and have been published throughout the decades. We identified echocardiographic studies conducted in Brazil [43, 45, 46], Nicaragua [51], and Peru [60]. These investigations were mostly targeting children and adolescents and generally utilized either the WHO or WHF echocardiographic criteria. A meta-analysis assessing echocardiographic studies in school and community settings described a global prevalence of RHD that ranged from 5.2‰ (95% CI, 3.0–8.0) to 26.1‰ (95% CI, 19.2–33.1) according to the studies’ diagnostic criteria [66]. This type of study provides two crucial aspects. First, valuable epidemiological information, and second, the opportunity to offer follow-up and secondary prophylaxis to those with RHD findings [2]. The latter is supported by the recently published GOAL trial which provides evidence that secondary chemoprophylaxis reduced the risk of progression among subjects with latent RHD in a two year follow up [67]. Despite the recent echocardiographic studies in the mentioned countries, there is still room for launching similar strategies in LAC, considering the benefits of early diagnosis and secondary prophylaxis among patients with RHD.

    Furthermore, we also evaluated the hospital-based data on ARF/RHD in LAC. Most studies were based on single-center experiences and reported the frequency or percentage of ARF/RHD out of the total number of admissions. There are clear limitations to hospital-based data such as selection bias (e.g., missing of asymptomatic, or mildly symptomatic patients), variations in each hospital’s admission criteria, and patient’s access to healthcare [68]. However, data as that reported by de Araújo Fonseca et al., using a nationwide hospital admissions registry, are useful to provide an estimate on the general picture of the disease in a certain population [26]. It’s important that further studies using this type of data also assess trends of ARF/RHD throughout the years [68].

    The GBD studies have generated essential estimates on RHD worldwide and in the Americas through well-established models [4, 5]. Based on these data, the Americas have been identified as a region in a more favorable situation when compared to the global picture of RHD [5]. However, consistent with our findings, Ordunez et al. indicate the lack in quantity and quality of data on certain countries in the region [5]. There is a clear need for epidemiologic surveillance on these diseases in LAC, a global barrier identified by the WHF position statement [8]. Possible strategies to tackle this issue have been described by experts in other countries. For example, a possible strategy to obtain updated information is including ARF and RHD as part of the diseases that require mandatory notification in each country [68, 69]. Other more sophisticated strategies to identify contemporary data include the use of data linkage of multiple sources as employed by Katzenellenbogen et al. in Australia [70].

    4.2. Burden of RHD

    Data on the disease burden was the most identified in our review. An overall conclusion of the extracted information is that patients with RHD are heavily burdened by demise, the need for intervention (commonly reintervention), and disease complications particularly AFib, stroke, and HF. However, most publications were based on single-center studies that have inherent limitations as mentioned before. The Addis Ababa communiqué identified the lack of disease surveillance as one of the barriers to the situation of RHD in Africa [71]. The creation of prospective registers for an accurate depiction of the outcomes (morbidity and mortality) of RHD is a proposed solution to this barrier by the Addis Ababa communiqué, the WHF, and the American Heart Association [8, 71, 72]. Of the studies assessing burden, the experience of Nordet et al. in Cuba included the creation of a register of all the cases (5–25-year-olds) and assessing their outcomes, especially the need for admission, HF, and the need for valve surgery [48]. In the last decade, registers have been developed in other regions such as The Global Rheumatic Heart Disease Registry (REMEDY) and the VALVAFRIC [73, 74]. The REMEDY study followed prospectively 3343 patients with RHD from African countries, India, and Yemen, identifying key information on the disease burden such as the severity of the disease and its complications such as HF, PH, AFib, and stroke [73]. On the other hand, the VALVAFRIC study was a retrospective registry that assessed patients with RHD in the hospital setting among eight countries in Western and Central Africa which described a compelling prevalence of in-hospital complications including HF, arrhythmias, IE, and EE as well as a 16% (94/1385) in-hospital mortality rate [74]. Registers aiming to collect information on the negative outcomes of RHD are missing in LAC, these efforts would be important to improve care and follow-up for patients with RHD [72].

    Besides the high burden on the patients’ health, RHD also impacts the economy of each patient, their households, health systems, and governments [7]. Recently, a scoping review assessing the economic consequences of RHD, in which no studies from LAC fulfilled the eligibility criteria, concluded that most information on RHD costs comes from wealthier nations [75]. Consistent with this, our review only identified three studies from Brazil, Cuba, and Jamaica reflecting on the economic impact of RHD in the region [30, 42, 48]. In Africa, Coates et al. conducted a model of an investment case for RHD preventive and management strategies in the African Union from 2021 to 2030. They estimated that the total cost of increasing the coverage of all the interventions related to RHD during the ten-year period was US$3.9 billion [76]. Further investigations in LAC should include economic variables to assess the other side of the burden of RHD.

    4.3. Prevention and screening of RHD

    We identified six prevention programs, predominantly from study periods before 2000, that included a combination of strategies such as educational activities, secondary antibiotic prophylaxis, or the creation of registers. Three of them described a decline in many negative outcomes including the number of cases/recurrences, need for intervention, deaths, and costs [19, 44, 48]. For instance, the 10-year prevention program in Pinar del Rio, Cuba described a reduction in the incidence and severity of ARF/RHD as well as an increase in the compliance to secondary antibiotic prophylaxis [48]. A recent systematic review and meta-analysis described that prevention programs integrated (even if partially) into their country’s health system are beneficial in terms of health outcomes [77]. Moreover, echocardiographic screening programs such as the PROVAR study in Brazil, a large-scale program that focused initially on the echocardiographic screening of schoolchildren in Minas Gerais, have been successful in the early identification and consequent follow-up in patients with RHD [46]. Watkins et al. assessed the cost-effectiveness of the Pinar del Rio Program, a program that used a combination of primary and secondary preventive activities and identified that it was cost saving [78]. Similarly, a cost-effectiveness analysis of the PROVAR study deemed the strategy cost-effective in the Brazilian context [79]. Cost-effectiveness analyses are crucial for the implementation of these strategies by policymakers or health systems, especially in countries with limited resources as are many in LAC [78]. The modelling study by Coates et al. in the African Union described that investing in the prevention and management of RHD could markedly reduce the incidence and deaths due to RHD as well as provide net benefit of US$2.8 billion if coverage for secondary and tertiary care were scaled up [76]. The efforts for the prevention and early diagnosis of RHD in LAC require the involvement of different sectors, including the public health entities, the decision-makers, the scientific organizations, the clinicians, and the community.

    4.4. Limitations

    There are some limitations that are important to mention in our systematic review. First, we did not conduct additional searches for gray literature which could lead to missing information. However, we conducted a thorough search strategy, including two specific Latin American and Caribbean databases where journals from the region are indexed. Second, as we decided to include multiple study settings and methodologies, we could not provide an overall estimate or conclusion on the prevalence, incidence, or mortality of the disease as the studies varied widely in methodology and presented the data using distinct criteria, study periods, and study measures. The region requires updated population-based studies to further clarify the prevalence, incidence, morbidity, and mortality of these diseases. Third, in a similar trend as the previously mentioned limitation, we could not evaluate the trends or changes over time of epidemiological parameters such as prevalence/incidence or mortality due to the heterogeneity the lack of frequency data from multiple time periods among the included studies. This information is needed to assess the changes over time of the disease in LAC. Fourth, data were predominantly from a single nation, Brazil (65% of studies), which limits generalizability to the entire region, but this serves as an example for other countries in LAC to increase their research on RHD. This phenomenon could be explained due to a possible paucity of data or poor data quality in highly burdened regions and better data from regions or countries with better infrastructure [75, 80]. Fifth, data on RHD-prevalence studies were mostly from the pediatric population and information was lacking on young adults and adults. This is an important aspect as according to the most recent GBD study, the peak age of RHD cases worldwide was 20–29 years [3].

    5. Conclusions

    This review summarizes the data from 48 primary studies in Latin America and the Caribbean. Most research and preventive efforts come from a single country, Brazil, thus identifying a need for other nations to ramp up their interest in this public health problem. The initial efforts should be aimed to develop up-to-date epidemiological studies, preferably population-based, or surveillance systems to have an accurate picture of RHD in each country and in the region. These data are crucial for the identification of possible areas, subregions, or countries that would require tailored strategies to reduce the heavy burden of RHD, such as the creation of register-based, echocardiographic screening, or comprehensive prevention programs.

    Data Accessibility Statement

    All data is presented on the main text and supplementary materials (Supplementary Tables S1–S9).

    Additional File

    The additional file for this article can be found as follows:

    Supplementary Material

    Supplementary Tables S1–S9 and PRISMA 2020 Checklist. DOI: https://doi.org/10.5334/gh.1152.s1

    Competing Interests

    The authors have no competing interests to declare.

    Author contributions

    MAJR, MUJ, MUT, and MUT were involved in the conception and design of the study. MAJR and MUJ contributed to the search, article selection, and extraction of data. MAJR, MUJ, MUT, and MUT were involved in the interpretation of results. MAJR and MUJ drafted the manuscript. All authors were involved in critically reviewing the manuscript. MUT and MUT supervised the study. All authors read and approved the final version of the manuscript.

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