BACKGROUND:In sub-Saharan Africa (SSA), people with HIV continue to present with advanced HIV disease (AHD), putting them at high risk of life-threatening opportunistic diseases. We aimed to estimate mortality among this population. METHODS:We conducted a systematic review and meta-analysis of studies reporting one-year mortality among adults living with HIV and presenting to care with CD4 + cell count ≤200 cells/mm 3 in SSA. MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched for studies (comprising >500 participants) published between January 1, 2016 and March 21, 2025. Screening and data extraction were done in duplicate. Pooled mortality proportions across CD4 + cell count and time strata were calculated using a generalized linear mixed model. Risk of bias was assessed using a modified Newcastle-Ottawa scale. The protocol is registered with PROSPERO, CRD42023451498. RESULTS:Thirty-six studies with 313 362 participants were included. The weighted median age was 35 years, 64% were female, and 98.9% were antiretroviral therapy-naive. One-year mortality was 12% (95% CI 8-16) among people with CD4 + cell count ≤200 cells/mm 3 and increased with lower CD4 + cell count (≤100 cells/mm 3 , 15% (95% CI 11-19); ≤50 cells/mm 3 , 20% (95% CI 12-31)). Most deaths occurred within the first 3 months after AHD presentation. Heterogeneity was substantial. Risk of bias was high in 18 (50%) of 36 included studies. DISCUSSION:There is high 1-year mortality among people presenting with AHD in SSA. It is a priority to identify AHD with CD4 + testing, improve retention in care, and evaluate additional interventions to reduce mortality in this population.

Background:The transmission of Group A Streptococcus (Strep A) through respiratory droplets has been considered the dominant mode of transmission to date; however, little is known about the relative contribution of other modes of transmission. This review systematically summarises the contemporary evidence regarding the transmission of Strep A. Methods:A comprehensive search strategy was implemented to identify studies on Strep A transmission published in English between 1980 and 2019. Full-text articles were screened and included based on the predefined criteria. Studies were included if molecular techniques were used to identify the same Strep A strain in both clinical and environmental swabs. A random-effects meta-analysis model was used to aggregate attack rate estimates with 95% confidence intervals (CI), incorporating the Freeman-Tukey transformation to account for variability between studies. Results:A total of 34 transmission cohorts were included in this study. The overall attack rate of Strep A was 18.4% (95% CI, 13.1-24.2%, I2 = 95.9%), for direct contact, it was 20.5% (95% CI, 8.3-35.4%), and for indirect contact, it was 19.1% (95% CI, 13.2-25.7%). When pooled by geographical location, the attack rate was 30.38% (95% CI, 20.89-40.75%) in non-urban settings and 7.36% (95% CI, 2.60-14.21%) in urban settings. Conclusion:Direct contact is no longer the dominant form of Strep A transmission. Our contemporary findings have implications for the development of evidence-based environmental health strategies aimed at reducing Strep A transmission. Systematic review registration:https://www.crd.york.ac.uk/PROSPERO/view/CRD42019138472, CRD42019138472.

Objectives:Acute rheumatic fever (ARF) and rheumatic heart disease (RHD) are potential sequelae of untreated group A streptococcal (Strep A) infections. Guidelines focus on treating Strep A pharyngitis but seldom on skin infections. This systematic review explored whether directed antibiotic therapy for superficial Strep A skin infections prevents ARF/RHD. Methods:We searched PubMed, Scopus, Cochrane Library, and clinical trial registries for published and ongoing trials measuring the eradication of Strep A and clinical resolution of polymicrobial infections with antibiotics through December 13, 2024. We calculated risk ratios and absolute risk differences, using the grading of recommendations, assessment, development, and evaluation (GRADE) to assess the certainty of evidence. Results:No trials were reported on ARF/RHD outcomes. However, we identified 12 trials and pooled data comparing penicillin, cotrimoxazole, macrolides, and cephalosporins. There was probably no difference between interventions for eradicating Strep A (very low certainty evidence). For clinical resolution, cotrimoxazole was comparable to intramuscular benzathine benzylpenicillin and macrolides to penicillin (moderate certainty evidence). First- and second-generation cephalosporins showed no difference (low certainty evidence), whereas third-generation cephalosporins demonstrated improved clinical response (moderate certainty evidence). Benzathine benzylpenicillin-associated injection-site pain and oral antibiotic-associated gastrointestinal disorders were commonly reported. Conclusions:The available evidence for directed treatment of Strep A skin infections to prevent ARF/RHD is uncertain, requiring further research, with consideration of antimicrobial resistance and the limited antibiotic pipeline.

Introduction Infant mortality in low or middle-income countries (LoMICs) is still triple that of high-income countries (HICs), and the high mortality burden regions are also weighed down by a triple or quadruple burden of disease such as HIV and tuberculosis; chronic illness; mental health; injury and violence; and maternal, neonatal and child mortality. Emerging data suggest that the sudden unexpected death in infancy (SUDI) burden in LoMICs is at least 10-fold that in HICs. While ending preventable deaths in the neonatal period has received some global attention, the postnatal period where SUDIs occur is a poorly understood and data-poor area in LoMICs. We propose conducting a systematic review to evaluate the burden and trends of SUDIs in LoMICs since 2004.Methods and analysis We will systematically search PubMed, Web of Science, Scopus, African Index Medicus, EBSCOHost, Google Scholar, WHOIS and WHO database to identify studies published from July 2004 until October 2024. Two reviewers will screen titles and abstracts and select full-text articles independently for review. We will use the tool developed by the South African Medical Research Council—Burden of Disease Review Manager (BODRevMan)—to assess the risk of bias for each included study. Risk of bias will be assessed for each included study. Information on the prevalence and/or incidence of SUDI and its subcategories and case definitions will be extracted from each article. Where possible, data on prevalence, incidence and subcategories will be pooled using a random effects meta-analysis to account for variability between estimates. The I2 statistic will establish the level of heterogeneity due to variation in estimates rather than chance. Results will be presented in tables and graphs. The systematic review will be reported according to the PRISMA 2020 checklist.Ethics and dissemination Ethical approval is not required as this is a protocol for a systematic review. Findings will be disseminated through peer-reviewed publications and conference presentations.PROSPERO registration number CRD42023466162.

BACKGROUND:Group A β-haemolytic Streptococcus, also known as Streptococcus pyogenes, commonly causes childhood pharyngitis and can lead to severe complications like acute rheumatic fever and rheumatic heart disease. Timely penicillin treatment is vital in preventing these issues. However, data on the prevalence of Group A β-haemolytic Streptococcus pharyngitis in Botswana are limited, and there is no national surveillance for Group A β-haemolytic Streptococcus infections. OBJECTIVES:This study aimed to determine the prevalence of Group A β-haemolytic Streptococcus pharyngitis among children aged 8 and 18 years presenting with sore throats in selected Gaborone clinics and assess the antibiotic sensitivity patterns of Group A β-haemolytic Streptococcus isolates. METHODS:A cross-sectional study was conducted among children aged 8-18 years suspected of pharyngitis at Nkoyaphiri and Mafitlhakgosi clinics in Gaborone. Participants were selected based on a modified Centor score of 2 or higher. Throat swabs were processed for culture, identification, and antibiotic sensitivity testing. RESULTS:The prevalence of Group A β-haemolytic Streptococcus pharyngitis was 7.5% (24/322; 95% CI: 0.50%-0.11%). The mean age of the participants was approximately 12 years. Group A β-haemolytic Streptococcus isolates remained fully susceptible to penicillin, the treatment of choice, but concerns about macrolide resistance were observed in some strains. CONCLUSIONS:Group A streptococcal pharyngitis was found in 7.5% of children with sore throats in Gaborone, Botswana. All Group A β-haemolytic Streptococcus strains were susceptible to penicillin, affirming its continued use as the preferred treatment. These results emphasize the need for accurate diagnosis and targeted antibiotic therapy to prevent complications like acute rheumatic fever and rheumatic heart disease.

Ficolin-3 is a crucial protein for the activation of the complement system. Previous work has indicated this protein may play a role in the pathogenesis of rheumatic heart disease (RHD), and it has been hypothesised that ficolin-3 has potential as a biomarker for early identification of patients with suspected RHD. This study investigated FCN3 gene polymorphisms rs532781899 (c.349del) and rs4494157 (c.658 + 250 C > A) and ficolin-3 serum concentrations in an ethnically diverse cohort of 53 RHD cases and 45 healthy controls from across Africa. Ficolin-3 was found to be increased by 16

Background There is concern regarding the increasing resistance of Group A streptococcus (GAS) to routinely used antibiotics. GAS is a common cause of bacterial pharyngitis and more severe invasive infections such as septicaemia. Furthermore, GAS pharyngitis is the antecedent for serious conditions such as rheumatic fever and rheumatic heart disease. The study aimed to determine the antimicrobial susceptibility patterns of GAS cultured from patients with invasive and non-invasive infections from Cape Town, as part of the AFROStrep Registry. Methods Samples were provided by the AFROStrep Registry, a continental endeavour aiming to document Streptococcus pyogenes infection in Africa and create the first biorepository of its kind. Ninety-five GAS isolates (invasive, n = 40; non-invasive, n = 55) were evaluated for resistance to a panel of 20 antibiotics using the Sensititre® STP6F system with MICs interpreted by CLSI break points. Results Amongst all isolates, highest levels of resistance were observed with respect to tetracycline (8.33 %), followed by azithromycin (1.04 %) and erythromycin (1.04 %). No resistance to the remaining antibiotics was detected amongst all isolates. No differences with regard to MIC values were observed between isolates from invasive and non-invasive infections (p-value >0.05 for all antibiotics). Conclusion GAS remains susceptible to routine-antimicrobial agents used in our low-resourced setting. Eight percent of the GAS isolates were resistant to tetracycline, and we did not observe macrolide resistance as reported in high income countries. This is the first study to report on the antimicrobial patterns of GAS in South Africa. These results address a critical gap in the available data on GAS in Africa and specifically South Africa and, thus, aid in avoiding therapeutic failures.

Introduction: Mobile phone text message reminders (MPTMRs) have been implemented globally to promote vaccination uptake and recall rates. This systematic review evaluated the effectiveness of MPTMRs on vaccination recall rates. Methods: We included randomized controlled trials of caregivers of children, adolescents, or adults who received MPTMRs for improving vaccine uptake and recall visits. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, and Scopus to identify relevant studies published up to 24 January 2024. We used Cochrane’s Risk of Bias tool to assess the included studies and reported the results as risk ratios with 95% confidence intervals, using a random effects model. Results: We identified 25 studies for inclusion. All studies were assessed as having a low risk of bias. The evidence supports MPTMRs for improving vaccination uptake compared to usual care (RR = 1.09 [95%CI: 1.06, 1.13], I2 = 76%). Intervention characteristics, country setting, country economic status, and vaccination type had no bearing on the effectiveness of the intervention. Conclusions: MPTMRs have a positive effect, albeit relatively small, on vaccination uptake. These findings may assist public health practitioners, policymakers, and vaccine researchers in evidence-based decision making that focuses on MPTMRs and their impact on vaccination coverage.

IntroductionIt is currently unclear what the role of Group A streptococcus (GAS) virulence factors (VFs) is in contributing to the invasive potential of GAS. This work investigated the evidence for the association of GAS VFs with invasive disease.MethodsWe employed a broad search strategy for studies reporting the presence of GAS VFs in invasive and non-invasive GAS disease. Data were independently extracted by two reviewers, quality assessed, and meta-analyzed using Stata®.ResultsA total of 32 studies reported on 45 putative virulence factors [invasive (n = 3,236); non-invasive (n = 5,218)], characterized by polymerase chain reaction (PCR) (n = 30) and whole-genome sequencing (WGS) (n = 2). The risk of bias was rated as low and moderate, in 23 and 9 studies, respectively. Meta-,analyses of high-quality studies (n = 23) revealed a significant association of speM [OR, 1.64 (95%CI, 1.06; 2.52)] with invasive infection. Meta-analysis of WGS studies demonstrated a significant association of hasA [OR, 1.91 (95%CI, 1.36; 2.67)] and speG [OR, 2.83 (95%CI, 1.63; 4.92)] with invasive GAS (iGAS). Meta-analysis of PCR studies indicated a significant association of speA [OR, 1.59 (95%CI, 1.10; 2.30)] and speK [OR, 2.95 (95%CI, 1.81; 4.80)] with invasive infection. A significant inverse association was observed between prtf1 [OR, 0.42 (95%CI, 0.20; 0.87)] and invasive infection.ConclusionThis systematic review and genomic meta-analysis provides evidence of a statistically significant association with invasive infection for the hasA gene, while smeZ, ssa, pnga3, sda1, sic, and NaDase show statistically significantly inverse associations with invasive infection. SpeA, speK, and speG are associated with GAS virulence; however, it is unclear if they are markers of invasive infection. This work could possibly aid in developing preventative strategies.

Background: The prevalence of tuberculosis (TB)-associated pulmonary hypertension (PH) has not previously been quantified, resulting in an underappreciated burden of disease. We aimed to estimate the prevalence of PH in post-TB and active TB populations. Methods: In this systematic review and meta-analysis, we searched PubMed/Medline, Cochrane Library, EBSCOhost, Scopus, African Journals Online and Google Scholar, with no language restriction, for available literature published after 1950. Eligible studies described adult participants (≥16 years), with documented evidence of active or prior TB, diagnosed with PH. Study quality was assessed using a risk of bias tool specifically developed for prevalence studies. Aggregate prevalence estimates with 95% confidence intervals were synthesised using a random-effects meta-analysis model, incorporating the Freeman–Tukey transformation. Subgroup analysis was conducted to ascertain prevalence estimates in specific patient populations. Results: We identified 1452 unique records, of which 34 met our inclusion criteria. 23 studies, with an acceptable risk of bias and where PH was diagnosed at right heart catheterisation or echocardiography, were included in the meta-analysis. In post-TB studies (14/23), the prevalence of PH was 67.0% (95% CI 50.8–81.4) in patients with chronic respiratory failure, 42.4% (95% CI 31.3–54.0) in hospitalised or symptomatic patients and 6.3% (95% CI 2.3–11.8) in nonhealthcare-seeking outpatients (I 2 =96%). There was a lower estimated prevalence of PH in studies of populations with active TB (9.4%, 95% CI 6.3–13.0), I 2 =84%). Conclusion: Our results highlight the significant burden of PH in post-TB and active TB populations. We emphasise the need for increased recognition of TB-associated PH and additional high-quality prevalence data.

Background:Computer-aided detection (CAD) may be a useful screening tool for tuberculosis (TB). However, there are limited data about its utility in active case finding (ACF) in a community-based setting, and particularly in an HIV-endemic setting where performance may be compromised. Methods:We performed a systematic review and evaluated articles published between January 2012 and February 2023 that included CAD as a screening tool to detect pulmonary TB against a microbiological reference standard (sputum culture and/or nucleic acid amplification test [NAAT]). We collected and summarized data on study characteristics and diagnostic accuracy measures. Two reviewers independently extracted data and assessed methodological quality against Quality Assessment of Diagnostic Accuracy Studies-2 criteria. Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Diagnostic Test Accuracy Studies (PRISMA-DTA) guidelines were followed. Results:Of 1748 articles reviewed, 5 met with the eligibility criteria and were included in this review. A meta-analysis revealed pooled sensitivity of 0.87 (95% CI, 0.78-0.96) and specificity of 0.74 (95% CI, 0.55-0.93), just below the World Health Organization (WHO)-recommended target product profile (TPP) for a screening test (sensitivity ≥0.90 and specificity ≥0.70). We found a high risk of bias and applicability concerns across all studies. Subgroup analyses, including the impact of HIV and previous TB, were not possible due to the nature of the reporting within the included studies. Conclusions:This review provides evidence, specifically in the context of ACF, for CAD as a potentially useful and cost-effective screening tool for TB in a resource-poor HIV-endemic African setting. However, given methodological concerns, caution is required with regards to applicability and generalizability.

Background: Acute rheumatic fever (ARF) and rheumatic heart disease (RHD) are potential sequelae of untreated group A streptococcal (Strep A) infections. Guidelines often focus on Strep A pharyngitis, but seldom on skin infections. Laboratory confirmation of causative pathogens may assist to direct antibiotic therapy of clinically−suspected skin infections. In this systematic review, we explored whether routine use of directed therapy for superficial Strep A skin infections, compared to no treatment or an alternative antibiotic, prevents ARF/RHD.Method: We searched, with no restrictions, PubMed, Scopus, Cochrane Library, and clinical trial registries for published, completed and ongoing trials through 1 December 2022. Trials measuring eradication of Strep A, and clinical resolution of polymicrobial infections using antibiotic therapy, were included. We calculated random−effects risk ratios with (95% confidence intervals) and absolute risk differences. We used GRADE to rate the certainty of evidence.Findings: We identified twelve trials, and pooled data for three therapeutic comparisons: cotrimoxazole vs penicillin, macrolide vs penicillin, and second− vs first−generation cephalosporins. Overall, very low certainty evidence suggests no difference between interventions for eradication of Strep A. For clinical resolution, cotrimoxazole was comparable to intramuscular benzathine benzylpenicillin, and macrolides to penicillin, moderate certainty evidence. Similarly, cephalosporins were comparable to other antibiotics (fluoroquinolones, linezolid, topical mupirocin), low to very low certainty evidence. There were more treatment failures with topical bacitracin compared to oral cephalexin, very low certainty evidence. Intraclass oral cephalosporin comparisons showed no difference between first−- and second−generation therapies, low certainty evidence, whilst third−generation cephalosporins demonstrated improved clinical response compared to older-generation cephalosporins, moderate certainty evidence.Benzathine benzylpenicillin associated injection−site pain and oral antibiotic-associated gastrointestinal disorders were commonly reported. No trials reported on ARF/ RHD outcomes.Interpretation: Available evidence for laboratory−directed treatment of Strep A skin infections to prevent ARF/RHD is uncertain. Studies with larger sample sizes and longer follow up are necessary to explore this further.Funding: World Health Organization and READ-It.Declaration of Interest: MEE is a member of the RHD Taskforce of the Pan African Society of Cardiology. MEE does not receive any commercial funding. TK is a member of the National Essential Medicines Committee informing national guidance across all levels of care, a member of the National Ministerial Advisory Committee for Vaccines for Covid-19, co-leads the South African GRADE Network and co-Directs Cochrane Africa. TDL, AH, FB, DM, JO, NB, and TK do not receive any commercial funding, although the organisation they work for, the South African Medical Research Council, receives a variety of income from pharmaceutical and other commercial companies.Ethical Approval: Our author group conducted a systematic review of published and publicly available randomised controlled trials. We did not undertake any primary data collection with participants or engage patients or the public with our work. Therefore, no ethics approval was required for this research.

BACKGROUND:Sexually transmitted infections are among the most commonly occurring infections globally, with countries in sub-Saharan Africa exhibiting disproportionately higher prevalence rates. Numerous reports indicate the need for accurate detection, epidemiological characterisation, and appropriate management of these infections. This prospective observational laboratory study sought to determine the occurrence of STI, using a validated molecular assay as a diagnostic and surveillance tool in our setting. METHODS:Urogenital swabs from symptomatic and asymptomatic patients, submitted to the National Health Laboratory Service, at Groote Schuur Hospital, from 04 August 2021-03 February 2022, for routine microbiological investigations, were subjected to the Allplex™ STI Essential Assay (Seegene Inc, South Korea) to determine the distribution of STI pathogens in our setting. This multiplex assay includes C. trachomatis, Mycoplasma genitalium, Mycoplasma hominis, N. gonorrhoeae, Trichomonas vaginalis, Ureaplasma parvum, and Ureaplasma urealyticum. Correlations between detected organisms and participant age and clinical indications for testing were determined using Stata® software. RESULTS:A total of 148 urogenital swabs (91.2% from women) were included in the analysis, of which 56/148 (37.84%) were from symptomatic patients. Up to 83.8% of the samples tested positive for ≥1 organism, with all seven target organisms detected in at least one sample. Ureaplasma parvum was the most common organism detected, followed by N. gonorrhoeae, M. hominis, U. urealyticum, T. vaginalis, C. trachomatis, with M. genitalium being the least detected. All 25 samples submitted for routine antenatal Group B Streptococcal screening were positive for at least one STI organism, and one sample from sexual non-accidental injury tested positive for five different organisms. CONCLUSIONS:STIs comprise a variety of organisms in our setting, with many patients exhibiting coinfection with multiple organisms. This suggests the need for a critical evaluation of current syndromic testing and treatment guidelines so as to stem inadvertent spread of STI organisms and the development of resistance. The use of molecular testing methods may improve detection, especially in resource limited settings, providing speedy results, and thus allowing for guided therapy in only infected patients.

Retrospective studies on artificial intelligence (AI) in screening for diabetic retinopathy (DR) have shown promising results in addressing the mismatch between the capacity to implement DR screening and increasing DR incidence. This review sought to evaluate the diagnostic test accuracy (DTA) of AI in screening for referable diabetic retinopathy (RDR) in real-world settings. We searched CENTRAL, PubMed, CINAHL, Scopus, and Web of Science on 9 February 2023. We included prospective DTA studies assessing AI against trained human graders (HGs) in screening for RDR in patients with diabetes. Two reviewers independently extracted data and assessed methodological quality against QUADAS-2 criteria. We used the hierarchical summary receiver operating characteristics (HSROC) model to pool estimates of sensitivity and specificity and, forest plots and SROC plots to visually examine heterogeneity in accuracy estimates. From our initial search results of 3899 studies, we included 15 studies comprising 17 datasets. Meta-analyses revealed a sensitivity of 95.33% (95%CI: 90.60-100%) and specificity of 92.01% (95%CI: 87.61-96.42%) for patient-level analysis (10 datasets, N = 45,785) while, for the eye-level analysis, sensitivity was 91.24% (95%CI: 79.15-100%) and specificity, 93.90% (95%CI: 90.63-97.16%) (7 datasets, N = 15,390). Subgroup analyses did not provide variations in the diagnostic accuracy of country classification and DR classification criteria. However, a moderate increase was observed in diagnostic accuracy in the primary-level healthcare settings: sensitivity of 99.35% (95%CI: 96.85-100%), specificity of 93.72% (95%CI: 88.83-98.61%) and, a minimal decrease in the tertiary-level healthcare settings: sensitivity of 94.71% (95%CI: 89.00-100%), specificity of 90.88% (95%CI: 83.22-98.53%). Sensitivity analyses did not show any variations in studies that included diabetic macular edema in the RDR definition, nor studies with ≥3 HGs. This review provides evidence, for the first time from prospective studies, for the effectiveness of AI in screening for RDR in real-world settings. The results may serve to strengthen existing guidelines to improve current practices.

Background: The genetics of rheumatic heart disease (RHDGen) Network was developed to assist the discovery and validation of genetic variations and biomarkers of risk for rheumatic heart disease (RHD) in continental Africans, as a part of the global fight to control and eradicate rheumatic fever/RHD. Thus, we describe the rationale and design of the RHDGen study, comprising participants from 8 African countries. Methods: RHDGen screened potential participants using echocardiography, thereafter enrolling RHD cases and ethnically-matched controls for whom case characteristics were documented. Biological samples were collected for conducting genetic analyses, including a discovery case-control genome-wide association study (GWAS) and a replication trio family study. Additional biological samples were also collected, and processed, for the measurement of biomarker analytes and the biomarker analyses are underway. Results: Participants were enrolled into RHDGen between December 2012 and March 2018. For GWAS, 2548 RHD cases and 2261 controls (3301 women [69%]; mean age [SD], 37 [16.3] years) were available. RHD cases were predominantly Black (66%), Admixed (24%), and other ethnicities (10%). Among RHD cases, 34% were asymptomatic, 26% had prior valve surgery, and 23% had atrial fibrillation. The trio family replication arm included 116 RHD trio probands and 232 parents. Conclusions: RHDGen presents a rare opportunity to identify relevant patterns of genetic factors and biomarkers in Africans that may be associated with differential RHD risk. Furthermore, the RHDGen Network provides a platform for further work on fully elucidating the causes and mechanisms associated with RHD susceptibility and development.

INTRODUCTION:Rheumatic heart disease (RHD) is responsible for a significant burden of cardiovascular morbidity and mortality, and remains the most common cause of acquired heart disease among children and young adults in low-income and middle-income countries. Additionally, the global COVID-19 pandemic has forced the emergency restructuring of many health systems, which has had a broad impact on health in general, including cardiovascular disease. Despite significant cost to the health system and estimates from 2015 indicating both high incidence and prevalence of RHD in South Africa, no cohesive national strategy exists. An updated review of national burden of disease estimates, as well as literature on barriers to care for patients with RHD, will provide crucial information to assist in the development of a national RHD programme.METHODS AND ANALYSIS:Using predefined search terms that capture relevant disease processes from Group A Streptococcal (GAS) infection through to the sequelae of RHD, a search of PubMed, Scopus, ISI Web of Science, Sabinet African Journals, SA Heart and Current and Completed Research databases will be performed. All eligible studies on RHD, acute rheumatic fever and GAS infection published from April 2014 to December 2022 will be included. Vital registration data for the same period from Statistics South Africa will also be collected. A standardised data extraction form will be used to capture results for both quantitative and qualitative analyses. All studies included in burden of disease estimates will undergo quality assessment using standardised tools. Updated estimates on mortality and morbidity as well as a synthesis of work on primary, secondary and tertiary prevention of RHD will be reported.ETHICS AND DISSEMINATION:No ethics clearance is required for this study. Findings will be disseminated in a peer-reviewed journal and submitted to national stakeholders in RHD.PROSPERO REGISTRATION NUMBER:CRD42023392782.

Background. Rheumatic heart disease (RHD) is a preventable chronic cardiac condition that causes over 350 000 deaths annually, largely in low and middle-income countries, as a direct result of structural inequalities and inadequate access to comprehensive healthcare. People living with and affected by this disease are a key stakeholder group and need to be directing research priorities. Objective. To improve care and provide direction for future research, a group of qualitative researchers and pe living with RHD from six countries convened in Cape Town in 2016. Methods. People with RHD shared their lived experiences while RHD researchers, clinicians and advocates presented a spectrum of qualitative research methods to explore these experiences. The Continuum of Care© (CoC, developed by the Medtronic Foundation) was used as a framework to guide participant discussions. Thematic summaries of the discussions were undertaken in an iterative process throughout the workshop. Results. Three themes emerged in the summaries: there is no ‘typical’ patient journey; a biomedical focus on RHD does not reflect people’s lived experiences; and a diversity of research methods is required to investigate experiences of people living with RHD. Practice implications. Qualitative research methods are invaluable for allowing patient ‘voices’ to be heard. To this end, qualitative approaches should be incorporated in all RHD research to ensure maximum benefit for patients. Conclusion. Greater understanding of the patient journey was gained for strengthening and expanding the global RHD research agenda. Future research should reflect on and incorporate the realities of patients’ lived experiences, and these experiences should be integrated into healthcare models for chronic conditions.