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Background: In Victoria, Australia, children with Pacific Islander ('Pacific') ethnicities are overrepresented in acute rheumatic fever (ARF) and rheumatic heart disease (RHD). In June 2023, ARF and RHD became notifiable in Victoria. To inform public health and clinical practice, we described young Pacific patients' and their caregivers' understandings and experiences of ARF/RHD, and identified possible ways to improve the delivery of clinical care., Methods: We established a project reference group including local Pacific people to guide this research. Pacific patients who attended an ARF/RHD clinic at The Royal Children's Hospital, Melbourne, were invited to participate, as were their caregivers. A Samoan researcher conducted qualitative 'talanoa' (conversational) interviews with patients and caregivers. A second researcher conducted semi-structured interviews with treating clinicians and other stakeholders. Interview transcripts underwent thematic analysis guided by the Tuilaepa Youth Mentoring Services Pacific Youth Wellbeing Framework., Results: We interviewed 27 participants. This included nine patients and nine caregivers, all of whom were Samoan. These 18 participants expressed a desire to learn more about ARF/RHD and connect with other affected people. While some shared their experiences of having well-liked and trusted healthcare providers, patients often struggled to have two-way clinical conversations. The need to support clinicians working with high-risk populations to improve their awareness of ARF was identified. Receiving treatment on time was a top priority for affected families, despite injection pain, inconvenience and financial costs. The need to support continuity of care for young adult patients was raised by participants., Conclusions: Pacific people living with ARF/RHD and their families require additional support to receive high quality management in Victoria. Introducing a patient register and a specialist RHD nurse would enhance access to treatment, as would removing cost barriers, improving clinical awareness of ARF/RHD and creating Victoria-specific patient resources., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Oliver et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Streptococcus pyogenes, also known as group A streptococcus (StrepA), is a bacterium that causes a range of human diseases, including pharyngitis, impetigo, invasive infections, and post-infection immune sequelae such as rheumatic fever and rheumatic heart disease. StrepA infections cause some of the highest burden of disease and death in mostly young populations in low-resource settings. Despite decades of effort, there is still no licensed StrepA vaccine, which if developed, could be a cost-effective way to reduce the incidence of disease. Several challenges, including technical and regulatory hurdles, safety concerns and a lack of investment have hindered StrepA vaccine development. Barriers to developing a StrepA vaccine must be overcome in the future by prioritising key areas of research including greater understanding of StrepA immunobiology and autoimmunity risk, better animal models that mimic human disease, expanding the StrepA vaccine pipeline and supporting vaccine clinical trials. The development of a StrepA vaccine is a complex and challenging process that requires significant resources and investment. Given the global burden of StrepA infections and the potential for a vaccine to save lives and livelihoods, StrepA vaccine development is an area of research that deserves considerable support. This report summarises the findings of the Primordial Prevention Working Group-VAX, which was convened in November 2021 by the National Heart, Lung, and Blood Institute. The focus of this report is to identify research gaps within the current StrepA vaccine landscape and find opportunities and develop priorities to promote the rapid and successful advancement of StrepA vaccines., Competing Interests: Competing interests: MWC, JRC and ACS have received funding support from the National Institutes of Health. MWC received fees as a consultant for Vaxform Incorporated, Serum India Institute and Pfizer Incorporated. MWC is the Chief Scientific Officer and co-founder, with financial interest, in Moleculera Labs, a commercial laboratory for diagnostic testing of autoantibodies against the heart and brain., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To determine population-based rates of non-fatal complications of rheumatic heart disease (RHD)., Design: Retrospective cohort study based on multiple sources of routine clinical and administrative data amalgamated by probabilistic record-linkage., Setting: Fiji, an upper-middle-income country, where most of the population has access to government-funded healthcare services., Participants: National cohort of 2116 patients with clinically apparent RHD aged 5-69 years during 2008 and 2012., Primary and Secondary Outcome Measures: The primary outcome was hospitalisation for any of heart failure, atrial fibrillation, ischaemic stroke and infective endocarditis. Secondary outcomes were first hospitalisation for each of the complications individually in the national cohort as well as in hospital (n=1300) and maternity (n=210) subsets. Information on outcomes was obtained from discharge diagnoses coded in the hospital patient information system. Population-based rates were obtained using relative survival methods with census data as the denominator., Results: Among 2116 patients in the national cohort (median age, 23.3 years; 57.7% women), 546 (25.8%) were hospitalised for an RHD complication, a substantial proportion of all cardiovascular admissions in the country during this period in those aged 0-40 years (heart failure, 210/454, 46.3%; ischaemic stroke 31/134, 23.1%). Absolute numbers of RHD complications peaked during the third decade of life with higher population-based rates in women compared with men (incidence rate ratio 1.4, 95% CI 1.3 to 1.6, p<0.001). Hospitalisation for any RHD complication was associated with substantially increased risk of death (HR 5.4, 95% CI 3.4 to 8.8, p<0.001), especially after the onset of heart failure (HR 6.6, 95% CI 4.8 to 9.1, p<0.001)., Conclusions: Our study defines the burden of RHD-attributable morbidity in the general population of Fiji, potentially reflecting the situation in low-income and middle-income countries worldwide. Hospitalisation for an RHD complication is associated with markedly increased risk of death, re-emphasising the importance of effective early prevention., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Aim: To describe the epidemiology and clinical profile of children and adolescents with acute rheumatic fever (ARF) and rheumatic heart disease (RHD) in Victoria, Australia., Methods: A retrospective audit was undertaken of children and adolescents with ARF and RHD attending the Royal Children's and Monash Children's Hospitals in Victoria, Australia between 2010 and 2019. Potential cases were identified by searching multiple sources for relevant ICD-10-AM codes and keywords, then reviewed manually. For confirmed cases, we collected data on patient demographics, clinical features, comorbidities and management., Results: Of 179 participants included, there were 108 Victorian residents and 71 non-Victorian residents. 126 had at least one episode of ARF during the study period and 128 were diagnosed with RHD. In the Victorian resident group, the overall incidence of ARF was 0.8 per 100 000 5-14 year olds. This incidence was higher in Victorian Aboriginal and/or Torres Strait Islander (3.8 per 100 000) and Pacific Islander (32.1 per 100 000) sub-populations. Of 83 Victorian residents who had an ARF episode, 11 (13%) had a recurrence. Most Victorian residents with RHD had mixed aortic and mitral valve pathology (69.4%) and moderate to severe disease (61.9%). Most non-Victorian residents were Aboriginal and/or Torres Strait Islander people (80.3%) and were commonly transferred for tertiary or surgical management of RHD (83.1%)., Conclusions: ARF and RHD continue to affect the health of significant numbers of children and adolescents living in Victoria, including severe and recurrent disease. Specialised services and a register-based control program may help to prevent complications and premature death., (© 2022 The Authors. Journal of Paediatrics and Child Health published by John Wiley & Sons Australia, Ltd on behalf of Paediatrics and Child Health Division (The Royal Australasian College of Physicians).)

Background: Rheumatic heart disease affects more than 40.5 million people worldwide and results in 306,000 deaths annually. Echocardiographic screening detects rheumatic heart disease at an early, latent stage. Whether secondary antibiotic prophylaxis is effective in preventing progression of latent rheumatic heart disease is unknown., Methods: We conducted a randomized, controlled trial of secondary antibiotic prophylaxis in Ugandan children and adolescents 5 to 17 years of age with latent rheumatic heart disease. Participants were randomly assigned to receive either injections of penicillin G benzathine (also known as benzathine benzylpenicillin) every 4 weeks for 2 years or no prophylaxis. All the participants underwent echocardiography at baseline and at 2 years after randomization. Changes from baseline were adjudicated by a panel whose members were unaware of the trial-group assignments. The primary outcome was echocardiographic progression of latent rheumatic heart disease at 2 years., Results: Among 102,200 children and adolescents who had screening echocardiograms, 3327 were initially assessed as having latent rheumatic heart disease, and 926 of the 3327 subsequently received a definitive diagnosis on the basis of confirmatory echocardiography and were determined to be eligible for the trial. Consent or assent for participation was provided for 916 persons, and all underwent randomization; 818 participants were included in the modified intention-to-treat analysis, and 799 (97.7%) completed the trial. A total of 3 participants (0.8%) in the prophylaxis group had echocardiographic progression at 2 years, as compared with 33 (8.2%) in the control group (risk difference, -7.5 percentage points; 95% confidence interval, -10.2 to -4.7; P<0.001). Two participants in the prophylaxis group had serious adverse events that were attributable to receipt of prophylaxis, including one episode of a mild anaphylactic reaction (representing <0.1% of all administered doses of prophylaxis)., Conclusions: Among children and adolescents 5 to 17 years of age with latent rheumatic heart disease, secondary antibiotic prophylaxis reduced the risk of disease progression at 2 years. Further research is needed before the implementation of population-level screening can be recommended. (Funded by the Thrasher Research Fund and others; GOAL ClinicalTrials.gov number, NCT03346525.)., (Copyright © 2021 Massachusetts Medical Society.)

Background: Rheumatic heart disease (RHD) is associated with high morbidity and mortality, especially in those with severe RHD or progression of valvular disease (VD). Evaluation of the factors that predict valvular progression is important in order to improve clinical outcome., Aim: To evaluate outcome and clinical predictors of valvular progression in children with newly diagnosed RHD., Methods: A retrospective cohort study was conducted in children with newly diagnosed RHD at Dr Sardjito Hospital, Yogyakarta, Indonesia during 2013-2020. Clinical and echocardiography data at the time of diagnosis were collected and patients were followed up for 1 year. Echocardiography evaluations were undertaken to determine the progression of VD. Independent predictors of valvular progression were identified by Cox regression analysis., Results: A total of 77 patients were recruited, 36 (46.7%) of whom were male, and the median age (range) was 12.3 years (5.9-17.8). Thirty-three (42.8%) had progression of VD in the year after diagnosis. By multivariable analysis, an age at diagnosis of >10 years and high C-reactive protein (CRP) were independently associated with an increased risk of valvular progression with an adjusted hazard ratio (95% CI) of 3.23 (1.09-9.60) and 3.69 (1.45-9.67), respectively., Conclusion: After only 1 year of follow-up, approximately four in 10 children with newly diagnosed RHD developed progression of VD. An increased risk of valvular progression was associated with being over 10 years of age and a high level of CRP.

Background: In 2012, the World Heart Federation (WHF) published guidelines for the echocardiographic diagnosis of rheumatic heart disease (RHD). This study assesses individual reviewer performance and inter-rater agreement and reliability on the presence of any RHD, as well classification of RHD based on the 2012 WHF criteria., Methods: Four cardiologists individually reviewed echocardiograms in the context of a randomized clinical trial (ClinicalTrials.gov:NCT03346525) and participated in a blinded adjudication panel. Panel decision was the reference standard for diagnosis. Performance of individual reviewers to panel adjudication was compared through sensitivity and specificity analyses and inter-rater reliability was assessed between individual panelists using Fleiss free marginal multirater kappa., Results: Echocardiograms from 784 children had two independent reports and panel adjudication. The accuracy of independent reviewers for any RHD had high sensitivity (94%, 95% CI 93-95%) and moderate specificity (62%, 95% CI 53-70%). Sensitivity and specificity for definite RHD was 61.3 (95% CI, 55.3-67.1) and 93.1 (95% CI, 91.6-94.4), with 86.8 (84.7-88.7) and 65.8 (61.0-70.4) for borderline RHD. There was moderate inter-rater agreement (κ = 0.66) on the presence of any RHD while agreement for specific 2012 WHF classification was only fair (κ = 0.51)., Conclusions: The 2012 WHF guidelines are moderately reproducible when used by expert cardiologists. More cases of RHD were diagnosed by an consensus panel than by individual reviewers. A revision to the criteria is now warranted to further increase the reliability of the WHF criteria., Competing Interests: Declaration of Competing Interest The authors report no relationships that could be construed as a conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Aim: Acute rheumatic fever (ARF) most commonly presents in children aged 5-14 years old. Lifelong rheumatic heart disease (RHD) can result. This study investigated time trends in ARF and RHD using inpatient data from the Royal Children's Hospital, Melbourne (RCH)., Methods: A retrospective cohort study covering the period 1937-2013 was conducted using records from RCH, a quaternary paediatric hospital in Melbourne, Victoria, Australia. Patient data were identified using RCH classification of diseases coding for ARF or RHD for years <1952. For the period 1952-1987, this system was used in addition to identifying International Classification of Disease (ICD) discharge codes that corresponded to ARF or RHD. From 1988-2013, only ICD codes were used to identify patient data. Descriptive epidemiological analyses were performed, including incidence rate calculations using historical census population denominator data. Analyses focussed on children in the peak age group., Results: Among children aged five to 14 years, a total of 4337 RCH admissions with ARF/RHD occurred for 3015 patients. A sharp decline in first ARF/RHD hospitalisations at RCH occurred from 1959, following a peak mean annual incidence rate during 1944-1947 of 40.1/100 000 children (95% confidence interval (CI): 36.6-43.9; P < 0.05). Over 1996-2013, the mean annual incidence rate was 1.6/100 000 (95% CI: 1.3-1.8) and reached 2.3/100 000 (95% CI: 1.3-3.7) in 2005., Conclusion: The burden of ARF and RHD treated at RCH declined following the 1940s, mirroring changes seen in North America and Europe. Despite this, inpatient treatment for these conditions continued to be provided right up until the end of the study period., (© 2020 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).)

Background: Rheumatic heart disease (RHD) is a chronic valvular heart disease that is responsible for a heavy burden of premature mortality in low- and middle-income countries. The total costs of RHD are important to health policy and research investment decisions. We estimate for the first time the total cost of RHD for Fiji (2008-2012) using a cost-of-illness approach and novel primary data on RHD disease burden and costs., Methods: RHD cases were identified using probabilistic record linkage across four routine data sources: (1) the Fiji RHD Control Program, (2) national hospital admissions records, (3) the Ministry of Health database of cause-specific deaths and (4) hospital ECG clinic registers. For each individual with RHD, we obtained information on RHD hospital admissions, treatment and death. We conducted a prevalence-based cost-of-illness analysis, including bottom-up assessment of indirect and direct (healthcare) costs., Results: The estimated cost of RHD in Fiji for 2008-2012 was year-2010 $FJ91.6 million (approximately US$47.7 million). Productivity losses from premature mortality constituted the majority of costs (71.4%). Indirect costs were 27-fold larger than the direct costs., Conclusions: RHD leads to a heavy economic burden in Fiji. Improved prevention strategies for RHD will likely confer substantial economic benefits to the country., (© The Author(s) 2020. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

Rheumatic heart disease (RHD), an autoinflammatory heart disease, was recently declared a global health priority by the World Health Organization. Here we report a genome-wide association study (GWAS) of RHD susceptibility in 1,163 South Asians (672 cases; 491 controls) recruited in India and Fiji. We analysed directly obtained and imputed genotypes, and followed-up associated loci in 1,459 Europeans (150 cases; 1,309 controls) from the UK Biobank study. We identify a novel susceptibility signal in the class III region of the human leukocyte antigen (HLA) complex in the South Asian dataset that clearly replicates in the Europeans (rs201026476; combined odds ratio 1.81, 95% confidence intervals 1.51-2.18, P = 3.48×10 -10 ). Importantly, this signal remains despite conditioning on the lead class I and class II variants (P = 0.00033). These findings suggest the class III region is a key determinant of RHD susceptibility offering important new insight into pathogenesis while partly explaining the inconsistency of earlier reports.

Background: Despite the substantial global burden of disease, rheumatic heart disease research receives little funding globally., Methods: Using data from the Global Burden of Disease Study and funding from the G-FINDER database, we propose a novel logarithmic disability neglect index (DNI) to describe disease burden using disability-adjusted life years relative to funding for 16 major tropical diseases., Results: Across a range of diseases, rheumatic heart disease received the least funding relative to disease burden (DNI=3.83). Other diseases facing similar underfunding include cysticercosis (DNI=2.71) and soil-transmitted helminths (DNI=2.41)., Conclusions: Rheumatic heart disease remains severely underfunded relative to disease burden., (© The Author(s) 2019. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

Background: Rheumatic heart disease remains an important preventable cause of cardiovascular death and disability, particularly in low-income and middle-income countries. We estimated global, regional, and national trends in the prevalence of and mortality due to rheumatic heart disease as part of the 2015 Global Burden of Disease study., Methods: We systematically reviewed data on fatal and nonfatal rheumatic heart disease for the period from 1990 through 2015. Two Global Burden of Disease analytic tools, the Cause of Death Ensemble model and DisMod-MR 2.1, were used to produce estimates of mortality and prevalence, including estimates of uncertainty., Results: We estimated that there were 319,400 (95% uncertainty interval, 297,300 to 337,300) deaths due to rheumatic heart disease in 2015. Global age-standardized mortality due to rheumatic heart disease decreased by 47.8% (95% uncertainty interval, 44.7 to 50.9) from 1990 to 2015, but large differences were observed across regions. In 2015, the highest age-standardized mortality due to and prevalence of rheumatic heart disease were observed in Oceania, South Asia, and central sub-Saharan Africa. We estimated that in 2015 there were 33.4 million (95% uncertainty interval, 29.7 million to 43.1 million) cases of rheumatic heart disease and 10.5 million (95% uncertainty interval, 9.6 million to 11.5 million) disability-adjusted life-years due to rheumatic heart disease globally., Conclusions: We estimated the global disease prevalence of and mortality due to rheumatic heart disease over a 25-year period. The health-related burden of rheumatic heart disease has declined worldwide, but high rates of disease persist in some of the poorest regions in the world. (Funded by the Bill and Melinda Gates Foundation and the Medtronic Foundation.).

Background: Echocardiographic screening is under consideration as a disease control strategy for rheumatic heart disease (RHD). However, clinical outcomes of young people with screening-detected RHD are unknown. We aimed to describe the outcomes for a cohort with screening-detected RHD, in comparison to patients with clinically-diagnosed RHD., Methods: A retrospective cohort study included all young people with screening-detected RHD in the Central Division of Fiji in the primary cohort. Screen-negative and clinically-diagnosed comparison groups were matched 1:1 to the primary cohort. Data were collected on mortality, clinical complications and healthcare utilisation from the electronic and paper health records and existing databases., Results: Seventy participants were included in each group. Demographic characteristics of the groups were similar (median age 11years, 69% female, median follow-up 7years). There were nine (12.9%) RHD-related deaths in the clinically-diagnosed group and one (1.4%) in the screening-detected group (Incident Rate Ratio: 9.6, 95% CI 1.3-420.6). Complications of RHD were observed in 39 (55.7%) clinically-diagnosed cases, four (20%) screening-detected cases and one (1.4%) screen-negative case. There were significant differences in the cumulative complication curves of the groups (p<0.001). Rates of admission and surgery were highest in the clinically-diagnosed group, and higher in the screening-detected than screen-negative group., Conclusions: Young people with screening-detected RHD have worse health outcomes than screen-negative cases in Fiji. The prognosis of clinically-diagnosed RHD remains poor, with very high mortality and complication rates. Further studies in other settings will inform RHD screening policy. Comprehensive control strategies are required for disease prevention., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The indigenous populations of the South Pacific experience a high burden of rheumatic heart disease (RHD). Here we report a genome-wide association study (GWAS) of RHD susceptibility in 2,852 individuals recruited in eight Oceanian countries. Stratifying by ancestry, we analysed genotyped and imputed variants in Melanesians (607 cases and 1,229 controls) before follow-up of suggestive loci in three further ancestral groups: Polynesians, South Asians and Mixed or other populations (totalling 399 cases and 617 controls). We identify a novel susceptibility signal in the immunoglobulin heavy chain (IGH) locus centring on a haplotype of nonsynonymous variants in the IGHV4-61 gene segment corresponding to the IGHV4-61*02 allele. We show each copy of IGHV4-61*02 is associated with a 1.4-fold increase in the risk of RHD (odds ratio 1.43, 95% confidence intervals 1.27-1.61, P=4.1 × 10 -9 ). These findings provide new insight into the role of germline variation in the IGH locus in disease susceptibility.

Background: Secondary prevention is an effective treatment for rheumatic heart disease (RHD), but ensuring high adherence to prophylaxis over many years is challenging and requires understanding of local factors., Methods: Participants were young people diagnosed with RHD through echocardiographic screening in Fiji. We used a structured interview to evaluate the following: health seeking behaviours; attitudes, practice, barriers and potential improvement strategies for adherence to antibiotic prophylaxis; and adolescent-friendly qualities of the health service., Results: One hundred and one participants were interviewed (median age, 17.2 years). Adherence was very low overall (adequate in 6%). Sore throat and fever with sore joints were experienced in the preceding year by 42% and 28%, respectively. Barriers to receiving treatment included taking alternate treatments and the perception that symptoms were benign and self-limiting. Reasons for missing prophylaxis injections included lack of awareness, feeling well, transport cost and access, and medication unavailability (>40% of participants each). The injection health service had many perceived strengths, but inclusion of adolescents in decision making, and quality of educational materials were deficiencies. Reminder strategies, particularly phone-based reminders, were considered helpful by 94%., Conclusions: We identified several factors influencing secondary prevention that may be used to develop interventions to improve adherence., (© The Author 2017. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The implementation of screening for rheumatic heart disease at a population-scale would require a considerable increase in human resources. Training nonexpert staff in echocardiography requires appropriate methods and materials., Objectives: This pre/post study aims to measure the change in the knowledge and confidence of a group of health workers after a computer-assisted training intervention in basic echocardiography for rheumatic heart disease., Methods: A syllabus of self-guided, computer-based modules to train nonexpert health workers in basic echocardiography for rheumatic heart disease was developed. Thirty-eight health workers from Uganda participated in the training. Using a pre/post design, identical test instruments were administered before and after the training intervention, assessing the knowledge (using multiple-choice questions) and confidence (using Likert scale questions) in clinical science and echocardiography., Results: The mean total score on knowledge tests rose from 44.8% to 85.4% (mean difference: 40.6%, 95% confidence interval [CI]: 35.4% to 45.8%), with strong evidence for an increase in scores across all knowledge theme areas (p < 0.001). Increased confidence with each key aspect was reported, and there was strong evidence for an increase in the mean score for confidence scales in clinical science (difference: 7.1, 95% CI: 6.2 to 8.0; p < 0.001) and echocardiography (difference: 18.3, 95% CI: 16.6 to 20.0; p < 0.001)., Conclusions: The training program was effective at increasing knowledge and confidence for basic echocardiography in nonexpert health workers. Use of computer-assisted learning may reduce the human resource requirements for training staff in echocardiography., (Copyright © 2016 World Heart Federation (Geneva). Published by Elsevier B.V. All rights reserved.)

Objectives: Echocardiographic screening for rheumatic heart disease (RHD) can detect subclinical cases; however, adequate adherence to secondary antibiotic prophylaxis (SAP) is required to alter disease outcomes. We aimed to investigate the adherence to SAP among young people with RHD diagnosed through echocardiographic screening in Fiji and to investigate factors associated with adherence., Methods: Patients diagnosed with RHD through echocardiographic screening in Fiji from 2006 to 2014 were included. Dates of benzathine penicillin G injections were collected from 76 health clinics nationally from December 2011 to December 2014. Adherence was measured using the proportion of days covered (PDC). Multivariate logistic regression analysis was used to identify characteristics associated with any adherence (≥1 injection received) and adequate adherence (PDC ≥0.80)., Results: Of 494 patients, 268 (54%) were female and the median age was 14 years. Overall, 203 (41%) had no injections recorded and just 33 (7%) had adequate adherence. Multivariate logistic regression showed increasing age (OR 0.93 per year, 95% CI 0.87-0.99) and time since diagnosis ≥1.5 years (OR 0.53, 95% CI 0.37-0.79) to be inversely associated with any adherence. Non-iTaukei ethnicity (OR 2.58, 95%CI 1.04-6.33) and urban residence (OR 3.36, 95% CI 1.54-7.36) were associated with adequate adherence, whereas time since diagnosis ≥1.5 years (OR 0.38, 95%CI 0.17-0.83) was inversely associated with adequate adherence., Conclusions: Adherence to SAP after screening in Fiji is currently inadequate for individual patient protection or population disease control. Secondary prevention should be strengthened before further screening can be justified., (© 2016 John Wiley & Sons Ltd.)

Background: Echocardiographic screening for rheumatic heart disease (RHD) can identify individuals with subclinical disease who could benefit from antibiotic prophylaxis. However, most settings have inadequate resources to implement conventional echocardiography and require a feasible, accurate screening method. We aimed to investigate the accuracy of screening by non-expert operators using focused cardiac ultrasound (FoCUS)., Methods: In this prospective study of diagnostic accuracy, we recruited schoolchildren aged 5 to 15 years in Fiji to undergo two blinded tests. The index test was a FoCUS assessment of mitral and aortic regurgitation, performed by nurses after an 8-week training programme. The reference standard was the diagnosis of RHD by a paediatric cardiologist, based on a standard echocardiogram performed by a skilled echocardiographer. The primary outcome was the accuracy of the index test with use of the most sensitive criteria (any regurgitation)., Findings: We included 2004 children in the study. The index tests were done between September, 2012, and September, 2013, by seven nurses in eight schools in Fiji. The diagnostic accuracy of the screening test (area under receiver operator characteristic curve) was 0·89 (95% CI 0·83-0·94). When the primary cut-off point (any regurgitation) was used for analysis, sensitivity was 84·2% (72·1-92·5) and specificity was 85·6% (83·9-87·1). The sensitivity of individual nurses ranged from 66·7% to 100% and specificity 74·0% to 93·7%., Interpretation: Screening by briefly trained nurses using FoCUS was accurate for the diagnosis of RHD. Refinements to training and screening test methods should be studied in a range of settings, and in parallel with investigations of the long-term clinical and cost-effectiveness of screening for RHD., Funding: Cure Kids, New Zealand; the Fiji Water Foundation provided funding for portable ultrasound equipment; see acknowledgments for further details of funders., (Copyright © 2016 Engelman et al. Open Access article distributed under the terms of CC BY-NC-ND. Published by Elsevier Ltd.. All rights reserved.)

Background: Echocardiographic screening for rheumatic heart disease (RHD) has the potential to detect subclinical cases for secondary prevention, but is constrained by inadequate human resources in most settings. Training non-expert health workers to perform focused cardiac ultrasound (FoCUS) may enable screening at a population-level. We aimed to evaluate the quality and agreement of FoCUS for valvular regurgitation by briefly trained health workers., Methods: Seven nurses participated in an eight week training program in Fiji. Nurses performed FoCUS on 2018 children aged five to 15 years, and assessed any valvular regurgitation. An experienced pediatric cardiologist assessed the quality of ultrasound images and measured any recorded regurgitation. The assessment of the presence of regurgitation and measurement of the longest jet by the nurse and cardiologist was compared, using the Bland-Altman method., Results: The quality of FoCUS overall was adequate for diagnosis in 96.6%. There was substantial agreement between the cardiologist and the nurses overall on the presence of mitral regurgitation (κ = 0.75) and aortic regurgitation (κ = 0.61) seen in two views. Measurements of mitral regurgitation by nurses and the cardiologist were similar (mean bias 0.01 cm; 95% limits of agreement -0.64 to 0.66 cm)., Conclusions: After brief training, health workers with no prior experience in echocardiography can obtain adequate quality images and make a reliable assessment on the presence and extent of valvular regurgitation. Further evaluation of the imaging performance and accuracy of screening by non-expert operators is warranted, as a potential population-level screening strategy in high prevalence settings.

Background: Rheumatic heart disease (RHD) is considered a major public health problem in developing countries, although scarce data are available to substantiate this. Here we quantify mortality from RHD in Fiji during 2008-2012 in people aged 5-69 years., Methods and Findings: Using 1,773,999 records derived from multiple sources of routine clinical and administrative data, we used probabilistic record-linkage to define a cohort of 2,619 persons diagnosed with RHD, observed for all-cause mortality over 11,538 person-years. Using relative survival methods, we estimated there were 378 RHD-attributable deaths, almost half of which occurred before age 40 years. Using census data as the denominator, we calculated there were 9.9 deaths (95% CI 9.8-10.0) and 331 years of life-lost (YLL, 95% CI 330.4-331.5) due to RHD per 100,000 person-years, standardised to the portion of the WHO World Standard Population aged 0-69 years. Valuing life using Fiji's per-capita gross domestic product, we estimated these deaths cost United States Dollar $6,077,431 annually. Compared to vital registration data for 2011-2012, we calculated there were 1.6-times more RHD-attributable deaths than the number reported, and found our estimate of RHD mortality exceeded all but the five leading reported causes of premature death, based on collapsed underlying cause-of-death diagnoses., Conclusions: Rheumatic heart disease is a leading cause of premature death as well as an important economic burden in this setting. Age-standardised death rates are more than twice those reported in current global estimates. Linkage of routine data provides an efficient tool to better define the epidemiology of neglected diseases.

There is a pressing need to reduce the high global disease burden of rheumatic heart disease (RHD) and its harbinger, acute rheumatic fever (ARF). ARF is a classical example of an autoimmune syndrome and is of particular immunological interest because it follows a known antecedent infection with group A streptococcus (GAS). However, the poorly understood immunopathology of these post-infectious diseases means that, compared to much progress in other immune-mediated diseases, we still lack useful biomarkers, new therapies or an effective vaccine in ARF and RHD. Here, we summarise recent literature on the complex interaction between GAS and the human host that culminates in ARF and the subsequent development of RHD. We contrast ARF with other post-infectious streptococcal immune syndromes - post-streptococcal glomerulonephritis (PSGN) and the still controversial paediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS), in order to highlight the potential significance of variations in the host immune response to GAS. We discuss a model for the pathogenesis of ARF and RHD in terms of current immunological concepts and the potential for application of in depth "omics" technologies to these ancient scourges., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: Recent estimates of the global burden of rheumatic heart disease (RHD) have highlighted the paucity of reliable RHD mortality data from populations most affected by RHD., Methods and Results: We investigated RHD mortality rates and trends for Indigenous and non-Indigenous Australians in the Northern Territory (NT) for the period 1977-2005 and seminationally (NT plus 4 other states, covering 89% of Indigenous Australians) from 1997 to 2005 using vital statistics data. All analysis was undertaken by Indigenous status, sex, and age at death. In the NT, 90% of all deaths from RHD were among Indigenous persons; however, the Indigenous population makes up only 30.4% of the NT population. The death rate ratio (Indigenous compared with non-Indigenous) was 54.80 in the NT and 12.74 in the other 4 states (estimated at the median age of 50 years). Non-Indigenous death rates were low for all age groups except ≥65 years, indicating RHD deaths in the elderly non-Indigenous population. Death rates decreased at a more rapid rate for non-Indigenous than Indigenous persons in the NT between 1997 and 2005. Indigenous persons in other parts of Australia showed lower death rates than their NT counterparts, but the death rates for Indigenous persons in all states were still much higher than rates for non-Indigenous Australians., Conclusions: Indigenous Australians are much more likely to die from RHD than other Australians. Among the Indigenous population, RHD mortality is much higher in the NT than elsewhere in Australia, exceeding levels reported in many industrialized countries more than a century ago. With the paucity of data from high-prevalence areas, these data contribute substantially to understanding the global burden of RHD mortality., (© 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

We designed a pilot study of a training module for nurses to perform rheumatic heart disease echocardiography screening in a resource-poor setting. The aim was to determine whether nurses given brief, focused, basic training in echocardiography could follow an algorithm to potentially identify cases of rheumatic heart disease requiring clinical referral, by undertaking basic two-dimensional and colour Doppler scans. Training consisted of a week-long workshop, followed by 2 weeks of supervised field experience. The nurses' skills were tested on a blinded cohort of 50 children, and the results were compared for sensitivity and specificity against echocardiography undertaken by an expert, using standardised echocardiography definitions for definite and probable rheumatic heart disease. Analysis of the two nurses' results revealed that when a mitral regurgitant jet length of 1.5 cm was used as the trigger for rheumatic heart disease identification, they had a sensitivity of 100% and 83%, respectively, and a specificity of 67.4% and 79%, respectively. This pilot supports the principle that nurses, given brief focused training and supervised field experience, can follow an algorithm to undertake rheumatic heart disease echocardiography in a developing country setting to facilitate clinical referral with reasonable accuracy. These results warrant further research, with a view to developing a module to guide rheumatic heart disease echocardiographic screening by nurses within the existing public health infrastructure in high-prevalence, resource-poor regions.

Purpose of Review: In resource-limited tropical settings, both impetigo and rheumatic disease are endemic. The major cause of impetigo in these regions is the group A streptococcus and there is a growing body of opinion implicating impetigo in the pathogenesis of rheumatic fever and rheumatic heart disease (RHD). This potentially has major implications for control of these neglected diseases, which account for at least 350  000 deaths worldwide, annually. In this review, we summarize recent advances in the epidemiology of group A streptococcal skin disease and examine evidence for the relationship between group A streptococcal skin disease and rheumatic fever., Recent Findings: Detailed epidemiologic studies of impetigo, particularly among indigenous communities in the Pacific among whom rheumatic fever is endemic, find the disease remarkably prevalent. In contrast, group A streptococcal pharyngitis occurs no more frequently than in regions wherein rheumatic fever is now rare. Studies of molecular epidemiology reveal that overall there is a greater diversity of group A streptococcal strains in tropical regions, and skin-associated strains appear predominant. These skin strains may move between skin and throat, and there is increasing evidence of skin-associated strains being linked to cases of rheumatic fever., Summary: The available data support the hypothesis that group A streptococcal impetigo plays a role in the pathogenesis of RHD. There is considerable scope to investigate this question through studies of pathogenesis, employing advances in both human and bacterial genetics, molecular immunology, and carefully designed trials aimed at control of impetigo.

Rheumatic heart disease (RHD) is an important cause of cardiac morbidity and mortality globally, particularly in the Pacific region. Susceptibility to RHD is thought to be due to genetic factors that are influenced by environmental factors, such as crowding and poverty. However, there are few data relating to these environmental factors in the Pacific region. We conducted a case-control study of 80 cases of RHD with age- and sex-matched controls in Fiji using a questionnaire to investigate associations of RHD with a number of environmental factors. There was a trend toward increased risk of RHD in association with poor-quality housing and lower socioeconomic status, but only one factor, maternal unemployment, reached statistical significance (OR 2.6, 95% confidence interval 1.2-5.8). Regarding crowding, little difference was observed between the two groups. Although our data do not allow firm conclusions, they do suggest that further studies of socioeconomic factors and RHD in the Pacific are warranted. They also suggest that genetic studies would provide an insight into susceptibility to RHD in this population.

Acute rheumatic fever and rheumatic heart disease are diseases of socioeconomic disadvantage. These diseases are common in developing countries and in Indigenous populations in industrialized countries. Clinicians who work with Indigenous populations need to maintain a high index of suspicion for the potential diagnosis of acute rheumatic fever, particularly in patients presenting with joint pain. Inexpensive medicines, such as aspirin, are the mainstay of symptomatic treatment of rheumatic fever; however, antiinflammatory treatment has no effect on the long-term rate of progression or severity of chronic valvular disease. The current focus of global efforts at prevention of rheumatic heart disease is on secondary prevention (regular administration of penicillin to prevent recurrent rheumatic fever), although primary prevention (timely treatment of streptococcal pharyngitis to prevent rheumatic fever) is also important in populations in which it is feasible.

Rheumatic fever and rheumatic heart disease continue to be a huge public-health burden on many Pacific Island countries. Prevalence reported in some nations are some of the highest seen globally, yet many countries in the region do not have national disease registers. Despite the will of many Pacific Island countries, there are a number of barriers to the implementation and sustainability of effective coordinated prevention programs, including limited funding and competing health priorities. In promising recent developments, a number of countries in the region have been able to develop or strengthen national rheumatic heart disease registers. These registers allow for more effective delivery of secondary prophylaxis, the mainstay of disease control in the Pacific. Primary prevention of rheumatic fever and screening for rheumatic heart disease are important adjunctive strategies. Recent advances in screening methods, focusing on portable echocardiography, may allow for the early detection of rheumatic heart disease in the community.

The prevalence of rheumatic heart disease (RHD) in industrialized countries has declined dramatically over the last century, but the disease remains an important global health problem with the burden of disease shouldered by developing countries. Indeed, data from epidemiologic surveys, which used echocardiography as the primary screening tool, indicate that the prevalence of RHD in developing nations might have been substantially underestimated. Despite the high burden of disease globally, there has never been a sustained and comprehensive international strategy to control RHD. The current focus of global efforts to combat the disease is on strengthening secondary prophylaxis strategies, although very few active national programs have been implemented. RHD will continue to cause high morbidity and mortality among the world's poorest populations unless current prevention initiatives expand and new programs are established.

Background and Aim of the Study: Rheumatic heart disease (RHD) is an important cause of morbidity and mortality in young people in developing countries. Many cases of RHD are first detected when they progress to cardiac failure. Screening for RHD represents a means of detecting cases early so that preventative measures to halt the disease progression can be put into place., Methods: A cross-sectional screening survey of RHD in 3,462 children aged 5 to 15 years in Fiji was performed in 2006. A three-stage screening method was used: stage 1 involved auscultatory screening; stage 2 was a limited echocardiography of children identified as having a suspicious murmur in stage 1; and stage 3 involved a full echocardiography of children identified as having pathology in stage 2., Results: Among the 3,462 children screened, 359 (10.4%) had a significant murmur; subsequent echocardiography was performed on 331 of these children, with RHD being detected in 29 cases. The prevalence of definite RHD was 4.1 per 1,000 (95% CI 2.2-6.8), and the overall prevalence (definite or probable RHD) was 8.4 cases per 1,000 (95% CI 5.6-12)., Conclusion: The study results suggest that there is a significant burden of undetected RHD in Fiji. The three-stage approach described here represents a practical means of screening for clinical RHD in developing countries, although it does not allow detection of the subclinical disease.

Objectives: To determine the incidence and clinical features of acute rheumatic fever (ARF) in Fiji, and the clinical features of patients presenting to hospital in Fiji with rheumatic heart disease (RHD)., Design and Setting: A prospective surveillance study at the Colonial War Memorial Hospital in Suva over a 23-month period from December 2005 to November 2007., Main Outcome Measures: Incidence of ARF; clinical features of ARF and RHD., Results: The average annualised incidence of definite cases of ARF in children aged 5-15 years was 15.2 per 100,000 (95% CI, 9.0-22.6). The clinical features of ARF were similar to those in classic descriptions. Carditis was very common, occurring in 79% of cases. There were 103 admissions for RHD in which detailed information was collected, with the most common reason for admission being cardiac failure (51%). The median age at admission with RHD was 26.8 years, and there were 10 deaths of patients with RHD (case fatality rate, 9.7%)., Conclusions: Although apparently declining in incidence since the middle of the 20th century, ARF remains a significant health problem in Fiji. RHD affects young people, leading to premature morbidity and mortality. There is an urgent need for effective control of ARF and RHD in Fiji.

Background: Rheumatic heart disease (RHD) is an important problem in developing countries; however, many cases are detected only when the disease has progressed to cardiac failure. Screening can detect cases earlier, but there are no screening guidelines., Methods: We performed a cross-sectional screening study in Tonga among 5,053 primary school children, in whom auscultation followed by echocardiography of those with heart murmurs were used to identify RHD. We also analyzed whether a three-stage screening protocol of auscultation performed by a medical student to detect any heart murmur, second-stage auscultation performed by a local pediatrician to differentiate pathological from innocent murmurs and echocardiography of those with pathological murmurs altered outcomes., Results: The prevalence of definite RHD was 33.2 per 1,000. The prevalence of RHD increased significantly with age, peaking at 42.6 per 1,000 in children aged 10-12 years. Most valve lesions (91 [54%] of 169) were mild. Auscultation to detect pathological murmurs was poorly sensitive (46.4%), and the finding of any murmur on auscultation did not affect the likelihood of detecting pathology on echocardiography. The finding of a pathological murmur did significantly increase the likelihood of detecting pathology on echocardiography, but still missed 54% of those with pathology (mainly RHD) detected on echocardiography., Conclusions: Screening is a useful method for detecting asymptomatic RHD in regions of high prevalence and we report a high echocardiographically confirmed prevalence. The most appropriate screening strategy remains to be confirmed, however, and implementation will depend on the availability of echocardiography and trained staff.

Rheumatic heart disease causes more than 200,000 deaths worldwide annually, with the vast majority of these deaths occurring in developing countries, yet there are few autopsy studies of rheumatic heart disease in these countries. We performed a retrospective review of 6218 autopsies performed during the period from 1990 through 2006, searching for cases of rheumatic heart disease based upon the macroscopic pathologic examination of the heart. We found 147 cases (2.4%) of rheumatic heart disease. There was an apparent increase in the number of cases in the past 5 years. There were 95 deaths that were directly attributable to rheumatic heart disease, with congestive cardiac failure being the most common cause of death in 75 cases. The mean age at death due to rheumatic heart disease was 38 years. There were more cases of rheumatic heart disease in Indigenous Fijians than Indo-Fijians, with an adjusted relative risk of 1.26 (95% confidence intervals from 0.87 to 1.86). Our findings reflect the high burden and early age of death due to rheumatic heart disease in Fiji and the Pacific region generally, and underline the need for early detection and adequate secondary penicillin prophylaxis in this region.

Group A Streptococcus (GAS) infections result in a considerable underappreciated burden of acute and chronic disease globally. A 2018 World Health Assembly resolution calls for better control and prevention. Providing guidance on global health research needs is an important World Health Organization (WHO) activity, influencing prioritization of investments. Here, the role, status, and directions in GAS vaccines research are discussed. WHO preferred product characteristics and a research and development technology roadmap, briefly presented, offer an actionable framework for vaccine development to regulatory and policy decision making, availability, and use. GAS vaccines should be considered for global prevention of the range of clinical manifestations and associated antibiotic use. Impediments related to antigen diversity, safety concerns, and the difficulty to establish vaccine efficacy against rheumatic heart disease are discussed. Demonstration of vaccine efficacy against pharyngitis and skin infections constitutes a key near-term strategic goal. Investments and collaborative partnerships to diversify and advance vaccine candidates are needed. [ABSTRACT FROM AUTHOR]

Streptococcus pyogenes is an important global pathogen, causing considerable morbidity and mortality, especially in low and middle income countries where rheumatic heart disease and invasive infections are common. There is a number of promising vaccine candidates, most notably those based on the M protein, the key virulence factor for the bacterium. Vaccines against Streptococcus pyogenes are considered as impeded vaccines because of a number of crucial barriers to development. Considerable effort is needed by key players to bring current vaccine candidates through phase III clinical trials and there is a clear need to develop a roadmap for future development of current and new candidates. [ABSTRACT FROM AUTHOR]

Screening for rheumatic heart disease (RHD) requires workers skilled in echocardiography, which typically involves prolonged, specialized training. Task shifting echocardiographic screening to nonexpert health workers may be a solution in settings with limited human resources. An 8-week training program was designed to train health workers without any prior experience in focused echocardiography for RHD screening. Seven health workers participated. At the completion of training, the health workers performed unsupervised echocardiography on 16 volunteer children with known RHD status. A pediatric cardiologist assessed image quality. Participants provided qualitative feedback. The quality of echocardiograms were high at completion of training (55 of 56 were adequate for diagnosis) and all cases of RHD were identified. Feedback was strongly positive. Training health workers to perform focused echocardiography for RHD screening is feasible. After systematic testing for accuracy, this training program could be adapted in other settings seeking to expand echocardiographic capabilities. [ABSTRACT FROM AUTHOR]

Background: Scabies is recognised as a major public health problem in many countries, and is responsible for significant morbidity due to secondary bacterial infection of the skin causing impetigo, abscesses and cellulitis, that can in turn lead to serious systemic complications such as septicaemia, kidney disease and, potentially, rheumatic heart disease. Despite the apparent burden of disease in many countries, there have been few large-scale surveys of scabies prevalence or risk factors. We undertook a population-based survey in Fiji of scabies and impetigo to evaluate the magnitude of the problem and inform public health strategies. Methodology/Principal Findings: A total of 75 communities, including villages and settlements in both urban and rural areas, were randomly selected from 305 communities across the four administrative divisions, and all residents in each location were invited to participate in skin examination by trained personnel. The study enrolled 10,887 participants. The prevalence of scabies was 23.6%, and when adjusted for age structure and geographic location based on census data, the estimated national prevalence was 18.5%. The prevalence was highest in children aged five to nine years (43.7%), followed by children aged less than five (36.5%), and there was also an indication of prevalence increasing again in older age. The prevalence of scabies was twice as high in iTaukei (indigenous) Fijians compared to Indo-Fijians. The prevalence of impetigo was 19.6%, with a peak in children aged five to nine years (34.2%). Scabies was very strongly associated with impetigo, with an estimated 93% population attributable risk. Conclusions: As far as we are aware, this is the first national survey of scabies and impetigo ever conducted. We found that scabies occurs at high levels across all age groups, ethnicities, and geographical locations. Improved strategies are urgently needed to achieve control of scabies and its complications in endemic communities. Author Summary: Recently added to the World Health Organization list of neglected tropical diseases, scabies is an under-recognised cause of morbidity in many developing countries, due to secondary bacterial infection of the skin that can in turn lead to serious systemic complications such as kidney disease and, potentially, rheumatic heart disease. Despite the apparent burden of disease in many countries, there have been few large-scale surveys of scabies prevalence or risk factors. We undertook a population-based survey in Fiji of scabies and impetigo to evaluate the magnitude of the problem and inform public health strategies. We examined 10,887 people across 75 communities in all four geographical divisions of Fiji, covering both urban and rural areas. The national prevalence of scabies and impetigo was 23.6% and 19.6% respectively, and highest in children aged 5–9 years. We found that scabies was very strongly associated with impetigo. Scabies was twice as high in iTaukei (indigenous) Fijians compared to Indo-Fijians. Our study shows that scabies occurs at high levels across all age groups, ethnicities, and geographical locations. Improved strategies are urgently needed to achieve control of scabies and its complications in endemic communities. [ABSTRACT FROM AUTHOR]

Few diseases have experienced such a remarkable change in their epidemiology over the past century, without the influence of a vaccine, than rheumatic fever. Rheumatic fever has all but disappeared from industrialised countries after being a frequent problem in the 1940s and 1950s. That the disease still occurs at high incidence in resource limited settings and in Indigenous populations in industrialised countries, particularly in Australia and New Zealand, is an indication of the profound effect of socio-economic factors on the disease. Although there have been major changes in the epidemiology of rheumatic fever, diagnosis remains reliant on careful clinical judgement and management is remarkably similar to that 50 years ago. Over the past decade, increasing attention has been given to rheumatic fever and rheumatic heart disease as public health issues, including in Australia and particularly in New Zealand, as well as in selected low and middle income countries. Perhaps the greatest hope for public health control of rheumatic fever is the development of a vaccine against S treptococcus pyogenes, and there are encouraging initiatives in this area. However, an effective vaccine is some time away and in the meantime public health efforts need to focus on effective translation of the known evidence around primary and secondary prophylaxis into policy and practice. [ABSTRACT FROM AUTHOR]

Streptococcus pyogenes ranks among the main causes of mortality from bacterial infections worldwide. Currently there is no vaccine to prevent diseases such as rheumatic heart disease and invasive streptococcal infection. The streptococcal M protein that is used as the substrate for epidemiological typing is both a virulence factor and a vaccine antigen. Over 220 variants of this protein have been described, making comparisons between proteins difficult, and hindering M protein-based vaccine development. A functional classification based on 48 emm-clusters containing closely related M proteins that share binding and structural properties is proposed. The need for a paradigm shift from type-specific immunity against S. pyogenes to emm-cluster based immunity for this bacterium should be further investigated. Implementation of this emm-cluster-based system as a standard typing scheme for S. pyogenes will facilitate the design of future studies of M protein function, streptococcal virulence, epidemiological surveillance, and vaccine development. [ABSTRACT FROM AUTHOR]

While progress towards a Group A Streptococcus (GAS) vaccine has been stalled by a combination of scientific, regulatory, and commercial barriers, the problem persists. The high and globally-distributed burden of disease attributable to GAS makes vaccination an imperative global public health goal. Advances across a range of scientific disciplines in understanding GAS diseases have made the goal a realistic one and focused attention on the need for coordinated global action. With a view to accelerating GAS vaccine development, the World Health Organization (WHO) and the International Vaccine Institute (IVI) convened a global stakeholder consultation on the 12th and 13th of December 2016, in Seoul, South Korea. Topics discussed included: (1) gaps in current knowledge of global GAS epidemiology, burden of disease, and molecular epidemiology; (2) contribution of pre-clinical models to candidate vaccine evaluation and new immunological assays to address GAS immunology knowledge gaps; (3) status and future of the GAS vaccine development pipeline; and (4) defining a pathway to licensure, policy recommendations and availability of a vaccine. The meeting determined to establish a GAS vaccine working group to coordinate preparation of a global vaccine values proposition, preferred product characteristics, and a technical research and development roadmap. A new global GAS vaccine consortium will drive strategic planning to anticipate requirements for licensure, prequalification, and policy recommendations. [ABSTRACT FROM AUTHOR]

Abstract: Group A streptococci (GAS) are important causes of morbidity and mortality worldwide. These organisms cause a wide spectrum of disease, ranging from uncomplicated sore throat to invasive, life-threatening infections, as well as immune complications such as acute rheumatic fever (ARF), rheumatic heart disease (RHD) and acute post-streptococcal glomerulonephritis (APSGN). Vaccine prevention of GAS infections and their immunological complications has been a goal of researchers for decades. Several vaccine candidates against GAS infection are in various stages of pre-clinical and clinical development, including M protein-based vaccines (N-terminal vaccine candidates and M protein conserved region vaccines), and non-M protein vaccine candidates representing conserved GAS antigens. Some of the obstacles to GAS vaccine development are related to the complexity of the global epidemiology of GAS infections, the limitation in the criteria for selection of antigens to include in combination vaccines as well as the issues around autoimmunity and vaccine safety, among others. Overcoming these obstacles will require collaborative efforts to develop innovative strategies that address key steps in the pre-clinical and clinical development process, as well as clearly defining the global burden of GAS diseases and the molecular epidemiology of infections. Specific recommendations are presented for an accelerated plan leading to the introduction of a broadly protective vaccine designed for deployment in low-, middle-, and high-income countries. [Copyright &y& Elsevier]