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

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.

8 Specify the methods used to decide whether a study met the inclusion criteria of the review, including how many reviewers screened each record and each report retrieved, whether they worked independently, and if applicable, details of automation tools used in the process.
Pg. 4 Data collection process 9 Specify the methods used to collect data from reports, including how many reviewers collected data from each report, whether they worked independently, any processes for obtaining or confirming data from study investigators, and if applicable, details of automation tools used in the process.
Pg. 4-5 Data items 10a List and define all outcomes for which data were sought. Specify whether all results that were compatible with each outcome domain in each study were sought (e.g. for all measures, time points, analyses), and if not, the methods used to decide which results to collect.
Pg. 4-5 10b List and define all other variables for which data were sought (e.g. participant and intervention characteristics, funding sources). Describe any assumptions made about any missing or unclear information.
Pg. 4-5 Study risk of bias assessment 11 Specify the methods used to assess risk of bias in the included studies, including details of the tool(s) used, how many reviewers assessed each study and whether they worked independently, and if applicable, details of automation tools used in the process.
Pg. 5 Effect measures 12 Specify for each outcome the effect measure(s) (e.g. risk ratio, mean difference) used in the synthesis or presentation of results. N/A Synthesis methods 13a Describe the processes used to decide which studies were eligible for each synthesis (e.g. tabulating the study intervention characteristics and comparing against the planned groups for each synthesis (item #5)).
Pg. 5 13b Describe any methods required to prepare the data for presentation or synthesis, such as handling of missing summary statistics, or data conversions.
Pg. 5 13c Describe any methods used to tabulate or visually display results of individual studies and syntheses. Pg. 5 13d Describe any methods used to synthesize results and provide a rationale for the choice(s). If meta-analysis was performed, describe the Pg. 5 model(s), method(s) to identify the presence and extent of statistical heterogeneity, and software package(s) used.
13e Describe any methods used to explore possible causes of heterogeneity among study results (e.g. subgroup analysis, meta-regression). N/A 13f Describe any sensitivity analyses conducted to assess robustness of the synthesized results. N/A Reporting bias assessment 14 Describe any methods used to assess risk of bias due to missing results in a synthesis (arising from reporting biases). N/A Certainty assessment 15 Describe any methods used to assess certainty (or confidence) in the body of evidence for an outcome. N/A

Study selection
16a Describe the results of the search and selection process, from the number of records identified in the search to the number of studies included in the review, ideally using a flow diagram.
Pg. 5, Fig 1   16b Cite studies that might appear to meet the inclusion criteria, but which were excluded, and explain why they were excluded. Pg. 19 For all outcomes, present, for each study: (a) summary statistics for each group (where appropriate) and (b) an effect estimate and its precision (e.g. confidence/credible interval), ideally using structured tables or plots.
Tables 1 -4, Sup Table S9 Results of syntheses 20a For each synthesis, briefly summarise the characteristics and risk of bias among contributing studies. Pg. 6 -9, Tables 1 -4 20b Present results of all statistical syntheses conducted. If meta-analysis was done, present for each the summary estimate and its precision (e.g. confidence/credible interval) and measures of statistical heterogeneity. If comparing groups, describe the direction of the effect.
Pg. 6 -9, Tables 1 -4 20c Present results of all investigations of possible causes of heterogeneity among study results. N/A 24c Describe and explain any amendments to information provided at registration or in the protocol. N/A Support 25 Describe sources of financial or non-financial support for the review, and the role of the funders or sponsors in the review. Pg. 13 Competing interests 26 Declare any competing interests of review authors. Pg. 13 Availability of data, code and other materials 27 Report which of the following are publicly available and where they can be found: template data collection forms; data extracted from included studies; data used for all analyses; analytic code; any other materials used in the review.