Professor Jonathan Carapetis AM

PneuMum: Impact from a trial of maternal pneumococcal vaccination on middle ear disease amongst Indigenous infants

This study was unable to demonstrate efficacy of 23vPPV in pregnancy against the co-primary outcomes of either all-cause infant ear disease.

Development of Group A streptococcal vaccines: an unmet global health need

This review provides an update on the current status of Group A Streptococcus vaccine development, & describes global efforts to accelerate the development...

Changes in the clinical and epidemiological features of group A streptococcal bacteraemia in Australia's Northern Territory

This study adds to emerging data suggesting increasing importance of iGAS in low- and middle-income settings globally.

Rheumatic heart disease in Indigenous children in northern Australia: Differences in prevalence and the challenges of screening

This study compared regional differences in the prevalence of rheumatic heart disease in Indigenous Australian children, and describes the logistical and...

The global epidemiology of impetigo: A systematic review of the population prevalence of impetigo and pyoderma

We conducted a comprehensive, systematic review of the global childhood population prevalence of impetigo and the broader condition pyoderma.

Global, regional, and national disability-adjusted life years (DALYs) for 306 diseases and injuries and healthy life expectancy (HALE) for 188 countries

These summary measures can also be used to quantify the component of variation in epidemiology that is related to sociodemographic development.

The 2015 revision of the Jones criteria for the diagnosis of acute rheumatic fever: Implications for practice in low-income and middle-income countries

This article discusses the 2015 revision of the Jones criteria by the American Heart Association for the diagnosis of acute rheumatic fever.

Disparity in Mortality From Rheumatic Heart Disease in Indigenous Australians

This study was undertaken to provide a comprehensive examination of rheumatic heart disease mortality rates and trends in Indigenous Australians.

Rheumatic heart disease among adults in a mining community of Papua, Indonesia: findings from an occupational cohort

To describe the pattern of RHD occurrence in a sample of presenting cases from an occupational cohort in Papua Province, Indonesia.

Are minor echocardiographic changes associated with an increased risk of acute rheumatic fever or progression to rheumatic heart disease?

We aimed to determine the significance of minor heart valve abnormalities, including Borderline RHD, in predicting the future risk of acute rheumatic fever.

Comparison of approaches to rheumatic fever surveillance across Organisation for Economic Co-operation and Development countries.

Rheumatic fever (RF) prevention, control and surveillance are increasingly important priorities in New Zealand (NZ) and Australia.

Sore throat: Is it such a big deal anymore?

This review article addresses the driving factors associated with diagnosis and treatment of sore throats caused by Group A streptococcus.

The stark reality of rheumatic heart disease

This editorial refers to ‘Characteristics, complications, and gaps in evidence-based interventions in rheumatic heart disease: the Global Rheumatic Heart...

Impact of an Ivermectin Mass Drug Administration on Scabies Prevalence in a Remote Australian Aboriginal Community.

Scabies is endemic in many Aboriginal and Torres Strait Islander communities, with 69% of infants infected in the first year of life.

Pediatric sepsis in the developing world.

Sepsis is the leading killer of children worldwide, but this is not reflected in estimates of global mortality.

Pneumococcal conjugate vaccines PREVenar13 and SynflorIX in sequence or alone in high-risk indigenous infants (PREV-IX-COMBO)

Otitis media (OM) starts within weeks of birth in almost all Indigenous infants living in remote areas of the Northern Territory (NT).

Evolution, Evidence and Effect of Secondary Prophylaxis Against Rheumatic Fever

The association between group A streptococcal infection and rheumatic fever (RF) was established in the early 20th century.

The prevention, diagnosis and management of central venous line infections in children

With advancing paediatric healthcare, the use of central venous lines has become a fundamental part of management of neonates and children.

Post-infectious group A streptococcal autoimmune syndromes and the heart

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...

Controlling acute rheumatic fever and rheumatic heart disease in developing countries: Are we getting closer?

Improved opportunities for the primary prevention of ARF now exist, because of point-of-care antigen tests for Streptococcus pyogenes, and clinical decision...

The microbiology of impetigo in Indigenous children

Prevalence and antimicrobial resistance of impetigo pathogens in a randomised, controlled trial of impetigo treatment conducted in remote Indigenous communities

Susceptibility to acute rheumatic fever based on differential expression of genes involved in cytotoxicity, chemotaxis, and apoptosis

Differences in the immune response, detectable by gene expression, between individuals who are susceptible to ARF and those who are not

Prevalence of rheumatic heart disease in young adults from New Caledonia

The prevalence of echocardiographically diagnosed RHD in adults in New Caledonia is estimated at 5.9 per 1000

Standardising and assessing digital images for use in clinical trials: A practical, reproducible method that blinds the assessor to treatment allocation

We describe the development and evaluation of a protocol for digital image collection by the non-professional photographer in a remote setting research trial

Management of invasive group A streptococcal infections

Invasive group A streptococcal disease in children includes deep soft tissue infection, bacteraemia, bacteraemic pneumonia, meningitis and osteomyelitis

The case for global investment in rheumatic heart-disease control

The review built a case for extending simple and cost–effective measures to all countries. Had these recommendations been put into action, significant...

Short-course oral co-trimoxazole versus intramuscular benzathine benzylpenicillin for impetigo in a highly endemic region

The major burden of disease is in developing and tropical settings where topical antibiotics are impractical and lead to rapid emergence of antimicrobial...

Invasive group A streptococcal infection in the Northern Territory, Australia: Case report and review of the literature

This review article presents the case of infant Aboriginal twins with invasive group A streptococcal infection complicated by streptococcal toxic shock...

Nitazoxanide for the treatment of infectious diarrhoea in the Northern Territory, Australia 2007-2012

This paper examines the use of a new antibiotic to treat diarrhoea cause by Cryptosporidium infection in Australian Indigenous children.

Working towards a Group A Streptococcal vaccine: Report of a collaborative Trans-Tasman workshop

This paper is a report on progress towards a joint Australian and New Zealand vaccination program for Group A Streptococcus bacteria, which causes serious...

A systematic and functional classification of Streptococcus pyogenes that serves as a new tool for molecular typing and vaccine development.

This publication is a systematic analysis of all Group A Streptococcus M protein variants, to assist in the development of a vaccine.

Effectiveness of clindamycin and intravenous immunoglobulin, and risk of disease in contacts, in invasive group a streptococcal infections

This paper reports on treatment, and preventing infection in close contact, of invasive group A streptococcal (iGAS) using the antibiotic clindamycin and...

Formal infectious diseases consultations at a tertiary pediatric hospital: A 14-year review

We analyzed the formal consultations seen by the infectious diseases service over a 14-year period at one of the largest pediatric hospitals in Australia.

Invasive Staphylococcus aureus Infections in Children in Tropical Northern Australia

We conducted a retrospective review for all cases of S aureus bacteremia and sterile site infections, for children under 15 years, in northern Australia over...

Echocardiographic screening for rheumatic heart disease in high and low risk Australian children

We aimed to establish the prevalence of RHD in high-risk Indigenous Australian children using these criteria and to compare the findings with a group of...

Echocardiographic screening in a resource poor setting: Borderline rheumatic heart disease could be a normal variant

Cross-sectional observational study across ten primary schools in Fiji in school children aged 5-14 years.

Changes in the clinical and epidemiological features of group A streptococcal bacteraemia in Australia's northern territory

We aimed to measure the incidence and severity of invasive Group A Strep disease in the NT since 1996.

The clinical and molecular epidemiology of Staphylococcus aureus infections in Fiji

We observed S. aureus infections in Fiji in both community and hospital settings with an emphasis on clonal complex genotyping and antimicrobial susceptibility.

Global, regional, and national levels of neonatal, infant, and under-5 mortality during 1990-2013

We generated updated estimates of child mortality in various age groups for 188 countries from 1970 to 2013.

Extensive Diversity of Streptococcus pyogenes in a Remote Human Population Reflects Global-Scale Transmission Rather than Localised Diversification

The Indigenous population of the Northern Territory of Australia (NT) suffers from a very high burden of Streptococcus pyogenes disease, including cardiac...

Continued challenge of rheumatic heart disease: The gap of understanding or the gap of implementation?

We still do not have a RF vaccine, although the recent announcement that the Australian and New Zealand governments are jointly sponsoring a program to fast...

The second rheumatic heart disease forum report

Building on the foundation of the first RHD forum, over 150 interested participants met to discuss critical issues on the RHD landscape.

Utility of auscultatory screening for detecting rheumatic heart disease in high-risk children in Australia's Northern Territory

Sensitivity and positive predictive value of cardiac auscultation compared with echocardiography is poor, regardless of the expertise of the auscultator.

Acute rheumatic fever and rheumatic heart disease: Incidence and progression in the Northern Territory of Australia 1997 -2010

The reduction in ARF recurrence indicates that the RHD control program has improved secondary prophylaxis; a decline in RHD incidence is expected to follow.

Updated model of group A Streptococcus M proteins based on a comprehensive worldwide study

Group A Streptococcus (GAS) M protein is an important virulence factor and potential vaccine antigen, and constitutes the basis for strain typing (emm-typing).

Position statement of the World Heart Federation on the prevention and control of rheumatic heart disease

In the 21st century, rheumatic fever (RF) and rheumatic heart disease (RHD) are neglected diseases of marginalized communities.

Comparison of three methods for the recovery of skin pathogens from impetigo swabs collected in a remote community of Northern Territory, Australia

Immediate plating of impetigo swabs is the gold standard for bacterial recovery but is rarely feasible in remote regions.

Group A streptococcal vaccines: Paving a path for accelerated development

Vaccine prevention of GAS infections and their immunological complications has been a goal of researchers for decades.

Attendances during the First 12 Months of Life for Aboriginal Children in Five Remote Communities of Northern Australia

The median number of presentations per child in the first year of life was 21 with multiple reasons for presentation.

Progress toward a global group a streptococcal vaccine

The desire for an effective vaccine arises from the large burden of disease caused by the bacterium, particularly rheumatic fever and rheumatic heart disease.

Acute Rheumatic Fever and Chronic Rheumatic Disease

This chapter describes the epidemiology, pathogenesis, clinical manifestations, diagnostic criteria, and management principles of acute rheumatic fever.

Swimming pools in remote Aboriginal communities

Providing remote communities with access to chlorinated swimming pools has been considered as a possible strategy for reducing ear and skin infection rates...

A national prospective surveillance study of acute rheumatic fever in Australian children

Acute rheumatic fever (ARF) is an important cause of heart disease in Indigenous people of northern and central Australia.

Screening for rheumatic heart disease: current approaches and controversies

In endemic areas, RHD has long been a target of screening programmes that, historically, have relied on cardiac auscultation.

Group A Streptococcal Diseases and Their Global Burden

We review GAS transmission characteristics and prevention strategies, historical and geographical trends and report on the estimated global burden disease...

Preventing urinary tract infections in early childhood

Urinary tract infection (UTI) is common in children, causes them considerable discomfort, as well as distress to parents and has a tendency to recur.

The Australian guideline for prevention, diagnosis and management of acute rheumatic fever and rheumatic heart disease

Acute rheumatic fever (ARF) and rheumatic heart disease (RHD) occur at very high rates among Aboriginal and Torres Strait Islander people.

Preventing heart failure: a position paper of the Heart Failure Association in collaboration with the European Association of Preventive Cardiology

The heart failure epidemic is growing and its prevention, in order to reduce associated hospital readmission rates and its clinical and economic burden, is a key issue in modern cardiovascular medicine. The present position paper aims to provide practical evidence-based information to support the implementation of effective preventive measures.

Secondary Antibiotic Prophylaxis for Latent Rheumatic Heart Disease

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.

Preventing heart failure: a position paper of the Heart Failure Association in collaboration with the European Association of Preventive Cardiology

The heart failure epidemic is growing and its prevention, in order to reduce associated hospital readmission rates and its clinical and economic burden, is a key issue in modern cardiovascular medicine. The present consensus document aims to provide practical evidence-based information to support the implementation of effective preventive measures.

Pediatric Staphylococcus aureus Bacteremia: Clinical Spectrum and Predictors of Poor Outcome

Staphylococcus aureus is a common cause of bacteremia, yet the epidemiology and predictors of poor outcome remain inadequately defined in childhood. ISAIAH (Invasive Staphylococcus aureus Infections and Hospitalizations in children) is a prospective, cross-sectional study of S. aureus bacteremia in children hospitalized in Australia and New Zealand over 24 months.

Improving primary prevention of acute rheumatic fever in Australia: consensus primary care priorities identified through an eDelphi process

To establish the priorities of primary care providers to improve assessment and treatment of skin sores and sore throats among Aboriginal and Torres Strait Islander people at risk of acute rheumatic fever (ARF) and rheumatic heart disease (RHD).

Modelling study of the ability to diagnose acute rheumatic fever at different levels of the Ugandan healthcare system

To determine the ability to accurately diagnose acute rheumatic fever given the resources available at three levels of the Ugandan healthcare system.

Missing Piece Study protocol: Prospective surveillance to determine the epidemiology of group A streptococcal pharyngitis and impetigo in remote Western Australia

Group A β-haemolytic Streptococcus (GAS), a Gram-positive bacterium, causes skin, mucosal and systemic infections. Repeated GAS infections can lead to autoimmune diseases acute rheumatic fever (ARF) and rheumatic heart disease (RHD). Aboriginal and Torres Strait Islander peoples in Australia have the highest rates of ARF and RHD in the world.

Whole genome sequencing and molecular epidemiology of paediatric Staphylococcus aureus bacteraemia

The role Staphylococcus aureus antimicrobial resistance genes and toxins play in disease severity, management and outcome in childhood is an emerging field requiring further exploration.

The global burden of sore throat and group A Streptococcus pharyngitis: A systematic review and meta-analysis

Contemporary data for the global burden of sore throat and group A Streptococcus (Strep A) pharyngitis are required to understand the frequency of disease and develop value propositions for Strep A vaccines.

Penicillin G concentrations required for prophylaxis against Group A Streptococcus infection evaluated using a hollow fibre model and mathematical modelling

Acute rheumatic fever (ARF), an autoimmune reaction to Group A Streptococcus (Streptococcus pyogenes; Strep A) infection, can cause rheumatic heart disease (RHD). New formulations of long-acting penicillins are being developed for secondary prophylaxis of ARF and RHD.

Immunogenicity, otitis media, hearing impairment, and nasopharyngeal carriage 6-months after 13-valent or ten-valent booster pneumococcal conjugate vaccines, stratified by mixed priming schedules: PREVIX_COMBO and PREVIX_BOOST randomised controlled trials

Australian First Nations children are at very high risk of early, recurrent, and persistent bacterial otitis media and respiratory tract infection. With the PREVIX randomised controlled trials, we aimed to evaluate the immunogenicity of novel pneumococcal conjugate vaccine (PCV) schedules.

Roadmap to incorporating group A Streptococcus molecular point-of-care testing for remote Australia: a key activity to eliminate rheumatic heart disease

The burden of bacterial skin infection, scabies and atopic dermatitis among urban-living Indigenous children in high-income countries: a protocol for a systematic review

Bacterial skin infections and scabies disproportionately affect children in resource-poor countries as well as underprivileged children in high-income countries. Atopic dermatitis is a common childhood dermatosis that predisposes to bacterial skin infection.

Risk factors for group A streptococcal pharyngitis and skin infections: A case control study

Group A streptococcal (GAS) infections can trigger an immune-mediated response resulting in acute rheumatic fever. The role of social and environmental risk factors for GAS pharyngitis and skin infections are not well understood.

A Systematic Framework for Prioritizing Burden of Disease Data Required for Vaccine Development and Implementation: The Case for Group A Streptococcal Diseases

Vaccine development and implementation decisions need to be guided by accurate and robust burden of disease data. We developed an innovative systematic framework outlining the properties of such data that are needed to advance vaccine development and evaluation, and prioritize research and surveillance activities.

Population pharmacokinetic study of benzathine penicillin G administration in Indigenous children and young adults with rheumatic heart disease in the Northern Territory, Australia

Benzathine penicillin G is the cornerstone of secondary prophylaxis to prevent Streptococcus pyogenes infections, which precede acute rheumatic fever.

The burden of atopic dermatitis and bacterial skin infections among urban-living Indigenous children and young people in high-income countries: A systematic review

A high burden of bacterial skin infections is well documented in remote-living Indigenous children and young people in high-income countries.

Starting the SToP trial: Lessons from a collaborative recruitment approach

Recruitment in research can be challenging in Australian Aboriginal contexts. We aimed to evaluate the SToP (See, Treat, Prevent skin infections) trial recruitment approach for Aboriginal families to identify barriers and facilitators and understand the utility of the visual resource used.

Host-dependent resistance of Group A Streptococcus to sulfamethoxazole mediated by a horizontally-acquired reduced folate transporter

Described antimicrobial resistance mechanisms enable bacteria to avoid the direct effects of antibiotics and can be monitored by in vitro susceptibility testing and genetic methods. Here we describe a mechanism of sulfamethoxazole resistance that requires a host metabolite for activity.

Study protocol for controlled human infection for penicillin G against Streptococcus pyogenes: a double-blinded, placebo-controlled, randomised trial to determine the minimum concentration required to prevent experimental pharyngitis (the CHIPS trial)

Regular intramuscular benzathine penicillin G injections have been the cornerstone of rheumatic heart disease (RHD) secondary prophylaxis since the 1950s. As the pharmacological correlate of protection remains unknown, it is difficult to recommend changes to this established regimen. Determining the minimum effective penicillin exposure required to prevent Streptococcus pyogenes infection will accelerate development of new long-acting penicillins for RHD prevention as well as inform opportunities to improve existing regimens. The CHIPS trial will address this knowledge gap by directly testing protection afforded by different steady state plasma concentrations of penicillin in an established model of experimental human S. pyogenes pharyngitis.

Clinical Evaluation and Diagnosis of Acute Rheumatic Fever

The diagnosis of acute rheumatic fever relies on a combination of clinical evaluation and laboratory studies. Diagnosis is usually made using the Jones criteria, which have recently been updated in 2015.

The economic and health burdens of diseases caused by group A Streptococcus in New Zealand

In preparation for the future arrival of a group A Streptococcus (GAS) vaccine, this study estimated the economic and health burdens of GAS diseases in New Zealand. The annual incidence of GAS diseases was based on extrapolation of the average number of primary healthcare episodes managed each year in general practices (2014-2016) and on the average number of hospitalizations occurring each year (2005-2014). Disease incidence was multiplied by the average cost of diagnosing and managing an episode of disease at each level of care to estimate the annual economic burden.

Interchangeability, immunogenicity and safety of a combined 10-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine (Synflorix) and 13-valent-PCV (Prevenar13) schedule at 1-2-4-6 months: PREVIX_COMBO, a 3-arm randomised controlled trial

Aboriginal children living in remote communities are at high risk of early and persistent otitis media. Streptococcus pneumoniae and non-typeable Haemophilus influenzae (NTHi) are primary pathogens. Vaccines with potential to prevent early OM have not been evaluated in this population. We compared immunogenicity (ELISA and opsonophagocytic activity) of a combination of Synflorix™ (PHiD-CV10, 10 serotypes and protein D of NTHi) and Prevenar13™ (PCV13, 10 serotypes plus 3, 6A, and 19A), with recommended schedules.

Modes of transmission and attack rates of group A Streptococcal infection: a protocol for a systematic review and meta-analysis

Group A Streptococcus (Strep A) is an important cause of mortality and morbidity globally. This bacterium is responsible for a range of different infections and post-infectious sequelae. Summarising the current knowledge of Strep A transmission to humans will address gaps in the evidence and inform prevention and control strategies. The objective of this study is to evaluate the modes of transmission and attack rates of group A streptococcal infection in human populations.

A controlled human infection model of Streptococcus pyogenes pharyngitis (CHIVAS-M75): an observational, dose-finding study

Streptococcus pyogenes is a leading cause of infection-related morbidity and mortality. A reinvigorated vaccine development effort calls for new clinically relevant human S pyogenes experimental infection models to support proof of concept evaluation of candidate vaccines. We describe the initial Controlled Human Infection for Vaccination Against S pyogenes (CHIVAS-M75) study, in which we aimed to identify a dose of emm75 S pyogenes that causes acute pharyngitis in at least 60% of volunteers when applied to the pharynx by swab.

Rheumatic heart disease in Indigenous young peoples

Indigenous children and young peoples live with an inequitable burden of acute rheumatic fever and rheumatic heart disease. In this Review, we focus on the epidemiological burden and lived experience of these conditions for Indigenous young peoples in Australia, New Zealand, and Canada. We outline the direct and indirect drivers of rheumatic heart disease risk and their mitigation.

Increasing incidence of invasive group A streptococcal disease in Western Australia, particularly among Indigenous people

The incidence of invasive GAS disease in WA increased between 2000 and 2018, particularly among Indigenous Australians. Mandatory notification of invasive GAS disease would therefore be appropriate. The social determinants of differences in incidence should be addressed, and other relevant host, pathogen, and health system factors investigated.

Time to address the neglected burden of group A Streptococcus

High risk of early sub-therapeutic penicillin concentrations after intramuscular benzathine penicillin G injections in Ethiopian children and adults with rheumatic heart disease

Intramuscular benzathine penicillin G (BPG) injections are a cornerstone of secondary prophylaxis to prevent acute rheumatic fever (ARF) and rheumatic heart disease (RHD). Uncertainties regarding inter-ethnic and preparation variability, and target exposure profiles of BPG injection are key knowledge gaps for RHD control.

Global epidemiology of valvular heart disease

Valvular heart disease is a major contributor to loss of physical function, quality of life and longevity. The epidemiology of VHD varies substantially around the world, with a predominance of functional and degenerative disease in high-income countries, and a predominance of rheumatic heart disease in low-income and middle-income countries. Reflecting this distribution, rheumatic heart disease remains by far the most common manifestation of VHD worldwide and affects approximately 41 million people.

Searching for a technology-driven acute rheumatic fever test: the START study protocol

The absence of a diagnostic test for acute rheumatic fever (ARF) is a major impediment in managing this serious childhood condition. ARF is an autoimmune condition triggered by infection with group A Streptococcus.

Incidence of acute rheumatic fever in northern and western Uganda: a prospective, population-based study

Acute rheumatic fever is infrequently diagnosed in sub-Saharan African countries despite the high prevalence of rheumatic heart disease. We aimed to determine the incidence of acute rheumatic fever in northern and western Uganda.

Rheumatic heart disease in The Gambia: clinical and valvular aspects at presentation and evolution under penicillin prophylaxis

Rheumatic heart disease (RHD) remains the leading cause of cardiac-related deaths and disability in children and young adults worldwide. In The Gambia, the RHD burden is thought to be high although no data are available and no control programme is yet implemented. We conducted a pilot study to generate baseline data on the clinical and valvular characteristics of RHD patients at first presentation, adherence to penicillin prophylaxis and the evolution of lesions over time.

Comparison of group A streptococcal titres in healthy children and those with pharyngitis and skin infections

Rates of acute rheumatic fever, a sequelae of group A Streptococcal (GAS) infection, remain unacceptably high in Indigenous Māori and Pacific children in New Zealand. This prospective study aimed to describe GAS antibody titres in healthy children (5–14 years) by ethnicity, and to determine how paired titres vary with GAS culture positive and negative pharyngitis, and GAS skin infections.

The Spectrum, Severity and Outcomes of Rheumatic Mitral Valve Disease in Pregnant Women in Australia and New Zealand

Rheumatic heart disease (RHD) poses significant perinatal risks. We aimed to describe the spectrum, severity and outcomes of rheumatic mitral valve disease in pregnancy in Australia and New Zealand.

Caring for Pregnant Women with Rheumatic Heart Disease: A Qualitative Study of Health Service Provider Perspectives

Rheumatic heart disease (RHD) persists in low-middle-income countries and in high-income countries where there are health inequities. RHD in pregnancy (RHD-P) is associated with poorer maternal and perinatal outcomes. Our study examines models of care for women with RHD-P from the perspectives of health care providers.

Rheumatic Heart Disease in Pregnancy: New Strategies for an Old Disease?

RHD in pregnancy (RHD-P) is associated with an increased burden of maternal and perinatal morbidity and mortality. A sequellae of rheumatic fever resulting in heart valve damage if untreated, RHD is twice as common in women. In providing an historical overview, this commentary provides context for prevention and treatment in the 21 st century. Four underlying themes inform much of the literature on RHD-P: its association with inequities; often-complex care requirements; demands for integrated care models, and a life-course approach.

Global Burden of Cardiovascular Diseases and Risk Factors, 1990-2019: Update From the GBD 2019 Study

Cardiovascular diseases (CVDs), principally ischemic heart disease (IHD) and stroke, are the leading cause of global mortality and a major contributor to disability. This paper reviews the magnitude of total CVD burden, including 13 underlying causes of cardiovascular death and 9 related risk factors, using estimates from the Global Burden of Disease (GBD) Study 2019. GBD, an ongoing multinational collaboration to provide comparable and consistent estimates of population health over time, used all available population-level data sources on incidence, prevalence, case fatality, mortality, and health risks to produce estimates for 204 countries and territories from 1990 to 2019.

Quality of benzathine penicillin G: A multinational cross-sectional study

Benzathine penicillin G (BPG) is used as first-line treatment for most forms of syphilis and as secondary prophylaxis against rheumatic heart disease (RHD). Perceptions that poor quality of BPG is linked to reported adverse effects and therapeutic failure may impact syphilis and RHD control programs. Clinical networks and web-based advertising were used to obtain vials of BPG from a wide range of countries.

Ending rheumatic heart disease in Australia: the evidence for a new approach

The RHD Endgame Strategy: the blueprint to eliminate rheumatic heart disease in Australia by 2031 (the Endgame Strategy) is the blueprint to eliminate rheumatic heart disease (RHD) in Australia by 2031. Aboriginal and Torres Strait Islander people live with one of the highest per capita burdens of RHD in the world.

Subcutaneous administration of benzathine benzylpenicillin G has favourable pharmacokinetic characteristics for the prevention of rheumatic heart disease compared with intramuscular injection

Benzathine penicillin G has been used as monthly deep intramuscular (IM) injections since the 1950s for secondary prevention of acute rheumatic fever and rheumatic heart disease (RHD). Injection frequency and pain are major programmatic barriers for adherence, prompting calls for development of better long-acting penicillin preparations to prevent RHD.

Estimation of the force of infection and infectious period of skin sores in remote Australian communities using interval-censored data

Prevalence of impetigo (skin sores) remains high in remote Australian Aboriginal communities, Fiji, and other areas of socio-economic disadvantage. Skin sore infections, driven primarily in these settings by Group A Streptococcus (GAS) contribute substantially to the disease burden in these areas. Despite this, estimates for the force of infection, infectious period and basic reproductive ratio-all necessary for the construction of dynamic transmission models-have not been obtained.

Progress towards a coordinated, national paediatric antimicrobial resistance surveillance programme

These data support that children are not just 'little adults' in the AMR era, and analyses by age group are important to detect differences in antibiotic susceptibility

10-Valent pneumococcal non-typeable H. influenzae protein D conjugate vaccine versus 13-valent pneumococcal conjugate vaccine (PCV13) as a booster dose

18 months of age infants receiving 10-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine will have higher antibody levels

Reference exome data for Australian Aboriginal populations to support health-based research

Our data set provides a useful reference point for genomic studies on Aboriginal Australians

Lessons learned in genetic research with Indigenous Australian participants

We reflect on the lessons learned from a recent genome‐wide association study of rheumatic heart disease with Aboriginal Australian participants

RE-AIM evaluation of a teacher-delivered programme to improve the self-regulation of children attending Australian Aboriginal community primary schools

Benefits in teaching the Alert Program® to students in a region with high reported rates of foetal alcohol spectrum disorder and self-regulation impairment

The high prevalence and impact of rheumatic heart disease in pregnancy in First Nations populations in a high-income setting: a prospective cohort study

Rheumatic heart disease in pregnancy persists in First Nations people in Australia and New Zealand and is associated with major cardiac and perinatal morbidity

Barriers and enablers of health service utilisation for childhood skin infections in remote aboriginal communities of Western Australia

Health service utilisation in this setting may be enhanced by improving general awareness of the significance of childhood skin infections

Prevalence of Group A β-hemolytic Streptococcal Throat Carriage and Prospective Pilot Surveillance of Streptococcal Sore Throat in Ugandan School Children

The Group A β-hemolytic Streptococcus pharyngeal carriage rates seen in Uganda (15.9%) are higher than the most recent pooled results globally, at 12%

Acute Rheumatic Fever and Rheumatic Heart Disease

Acute Rheumatic Fever and Rheumatic Heart Disease is a concise, yet comprehensive, clinical resource highlighting must-know information on rheumatic heart disease and acute rheumatic fever from a global perspective

Environmental and social determinants of acute rheumatic fever: a longitudinal cohort study

Prevention strategies in ARF endemic settings may be enhanced by targeting new members entering a community and children in environments of close contact

Time to tackle rheumatic heart disease: Data needed to drive global policy dialogues

This report provides an update on the contemporary global and regional policy landscapes relevant to rheumatic heart disease

The fall and rise of Group A Streptococcus diseases

We overview the changing epidemiology of Group A Streptococcus infections and the genetic alterations that accompany the emergence of Group A Streptococcus strains

Seasonal and regional patterns of lower leg cellulitis in Western Australia

In the warmer tropical regions of WA no seasonality was observed, but overall incidence of LLC presentations were higher

Low positive predictive value of International Classification of Diseases, 10th Revision codes in relation to rheumatic heart disease: a challenge for global surveillance

We outline a series of research initiatives to improve identification of RHD in administrative data thereby contributing to monitoring the RHD burden globally

Treatment, prevention and public health management of impetigo, scabies, crusted scabies and fungal skin infections in endemic populations: a systematic review

Systematic review of the treatment, prevention and public health control of skin infections in resource-limited settings where skin infections are endemic

High burden of infectious disease and antibiotic use in early life in Australian Aboriginal communities

Early life infections drive high antibiotic prescribing rates in remote Aboriginal communities

Atlas of group A streptococcal vaccine candidates compiled using large-scale comparative genomics

We identified the existence of more than 290 clinically associated genomic phylogroups across 22 countries, highlighting challenges in designing vaccines of global utility

Severe adverse events following benzathine penicillin G injection for rheumatic heart disease prophylaxis: cardiac compromise more likely than anaphylaxis

These results indicate that anaphylaxis is not a major cause of adverse reactions to benzathine penicillin G

Controlled human infection for vaccination against Streptococcus pyogenes (CHIVAS): Establishing a group A Streptococcus pharyngitis human infection study

We review the Group A Streptococcus Human infection studies and present the study protocol for a dose-ranging inpatient study in healthy adults

Inter-rater and intra-rater reliability and agreement of echocardiographic diagnosis of rheumatic heart disease using the World Heart Federation evidence-based criteria

The WHF echocardiographic criteria enable reproducible categorisation of echocardiograms as definite RHD versus no or borderline RHD

Understanding group A streptococcal pharyngitis and skin infections as causes of rheumatic fever: Protocol for a prospective disease incidence study

This study will identify the incidence of true Group A Streptococcal pharyngitis and serological responses to Group A Streptococcal GAS skin infections

A population pharmacokinetic study of benzathine benzylpenicillin G administration in children and adolescents with rheumatic heart disease

Few children and adolescents receiving BPG as secondary prophylaxis will achieve concentrations >0.02 mg/L for the majority of the time between injections

The Path to Group A Streptococcus Vaccines: World Health Organization Research and Development Technology Roadmap and Preferred Product Characteristics

Here, the role, status, and directions in Group A Streptococcus vaccines research are discussed

SToP (See, Treat, Prevent) skin sores and scabies trial: study protocol for a cluster randomised, stepped-wedge trial for skin disease control in remote Western Australia

Skin infection burden in remote Aboriginal communities can be reduced by the See, Treat, Prevent (SToP skin sores and scabies) trial

Talking skin: Attitudes and practices around skin infections, treatment options, and their clinical management in a remote region in Western Australia

Documenting carer, service provider and healthcare practitioner perspectives on skin infections provides more understanding of the context of treatment decisions

Perinatal risk factors associated with skin infection hospitalisation in Western Australian Aboriginal and Non-Aboriginal children

We have quantified the relative influence of perinatal risk factors associated with skin infection hospitalisations in WA children

Standardizing clinical care measures of rheumatic heart disease in pregnancy: A qualitative synthesis

Pregnancy provides an opportunity to strengthen health system responses and address whole-of-life health for women with rheumatic heart disease

Australian researchers oppose funding from the Foundation for a Smoke-Free World

Research and research funding must be independent of the tobacco industry, which continues to cause so much suffering

How many doses make a difference? An analysis of secondary prevention of rheumatic fever and rheumatic heart disease

increased adherence to penicillin prophylaxis is associated with reduced acute rheumatic fever recurrence and a likely reduction in mortality

Dysregulated IL-1β-GM-CSF Axis in Acute Rheumatic Fever That Is Limited by Hydroxychloroquine

We propose that hydroxychloroquine could be repurposed to reduce the risk of rheumatic heart disease after acute rheumatic fever

An economic case for a vaccine to prevent group A streptococcus skin infections

A vaccine that prevents GAS cellulitis and other skin infections, in addition to throat infections, would maximise its value and commercial viability

Epidemiology and risk factors for recurrent severe lower limb cellulitis: a longitudinal cohort study

Severe lower leg cellulitis recurrences are frequent, and each episode increases the likelihood of subsequent recurrence and length of hospitalization

Severe lower limb cellulitis: Defining the epidemiology and risk factors for primary episodes in a population-based case-control study

Severe lower leg cellulitis presents a major burden to the health sector and is increasing with an ageing population

Primary prevention of rheumatic fever in the 21st century: evaluation of a national programme

Population-based primary prevention of ARF through sore throat management may be effective in well-resourced settings like New Zealand

Investigation of trimethoprim/sulfamethoxazole resistance in an emerging sequence type 5 methicillin-resistant Staphylococcus aureus clone reveals discrepant resistance reporting

Our findings are crucial in demonstrating that the Northern Territory STS clone is not STX resistant

Rheumatic Heart Disease Worldwide: JACC Scientific Expert Panel

The authors present a variety of pressing clinical research questions on optimal RHD prevention and advanced care

Ascertaining infectious disease burden through primary care clinic attendance among young Aboriginal children living in four remote communities in Western Australia

Improved public health measures targeting bacterial skin infections are needed to reduce this high burden of skin infections in Western Australia

Rheumatic heart disease in pregnancy: How can health services adapt to the needs of Indigenous women? A qualitative study

Health systems did not meet the needs of pregnant Aboriginal women with rheumatic heart disease

Scabies and risk of skin sores in remote Australian Aboriginal communities: A self-controlled case series study

The association between scabies and skin sores is highly significant and indicates a causal relationship

Calculation of the age of the first infection for skin sores and scabies in five remote communities in northern Australia

The young age of the first infection with skin sores and scabies reflects the high disease burden in these communities

Fetal Alcohol Spectrum Disorder (FASD): Knowledge, attitudes, experiences and practices of the Western Australian youth custodial workforce

This study aims to establish the current knowledge, attitudes, experiences and practices regarding FASD and other neurodevelopmental impairments among youth custodial officers

Improving delivery of secondary prophylaxis for rheumatic heart disease in a high-burden setting: Outcome of a stepped-wedge, community, randomized trial

This strategy did not improve adherence to rheumatic heart disease secondary prophylaxis within the study time frame.

Qualitative Evaluation of a Complex Intervention to Improve Rheumatic Heart Disease Secondary Prophylaxis

A multifaceted intervention was implemented using quality improvement and chronic care model approaches to improve delivery of penicillin prophylaxis for rheumatic heart disease

Evaluation of safety and immunogenicity of a group a streptococcus vaccine candidate (mj8vax) in a randomized clinical trial

Intramuscular administration of novel acetylated peptide-protein conjugate vaccine candidate MJ8VAX was demonstrated to be safe and immunogenic

Lessons learned in the development of sustained release penicillin drug delivery systems for the prophylactic treatment of rheumatic heart disease (RHD)

The current prophylactic treatment to prevent rheumatic heart disease requires four-weekly intramuscular injection of a suspension of the poorly soluble benzathine salt form of penicillin G (BPG) often for more than 10 years. In seeking to reduce the frequency of administration to improve adherence, biodegradable polymer matrices have been investigated.

Development of an opsonophagocytic killing assay for Group A Streptococcus

Group A Streptococcus (GAS) or Streptococcus pyogenes is responsible for an estimated 500,000 deaths worldwide each year.

Development of an opsonophagocytic killing assay for group a streptococcus

This Group A Streptococcus OPKA assay has the potential to provide a robust and reproducible platform to accelerate GAS vaccine development

Calculation of the age of the first infection for skin sores and scabies in five remote communities in northern Australia

Prevalence of skin sores and scabies in remote Australian Aboriginal communities remains unacceptably high, with Group A Streptococcus (GAS) the dominant pathogen. We aim to better understand the drivers of GAS transmission using mathematical models.

Burden of cardiovascular diseases in the Eastern Mediterranean Region, 1990-2015: findings from the Global Burden of Disease 2015 study

The age-standardized disability-adjusted life years rates in the Eastern Mediterranean Region are considerably higher than the global average

Rheumatic heart disease in Timor-Leste school students: an echocardiography-based prevalence study

The rates of RHD in Timor-Leste are among the highest in the world, and prevalence is higher among girls than boys. Community engagement is essential for ensuring follow-up and the effective delivery of secondary prophylaxis.

Rheumatic heart disease in Timor-Leste school students: an echocardiography-based prevalence study

The rates of RHD in Timor-Leste are among the highest in the world, and prevalence is higher among girls than boys

The NICE-GUT trial protocol: A randomised, placebo controlled trial of oral nitazoxanide for the empiric treatment of acute gastroenteritis among Australian Aboriginal children

Diarrhoeal disease is the second leading cause of death in children under 5 years globally, killing 525 000 annually. Australian Aboriginal and Torres Strait Islander (hereafter Aboriginal) children suffer a high burden of disease.

Rheumatic heart disease across the Western Pacific: not just a Pacific Island problem

We aimed to review RHD burden in Western Pacific Region outside Oceania to identify countries with high RHD burden

Streptococcus, Acute Rheumatic Fever and Rheumatic Heart Disease: Epidemiology and Clinical Considerations

A directed approach to the differential diagnosis of acute rheumatic fever now includes the concept of low-risk versus medium-to-high risk populations

Rheumatic Heart Disease Severity, Progression and Outcomes: A Multi‐State Model

The prognosis of young Indigenous Australians diagnosed with severe RHD is bleak; interventions must focus on earlier detection and treatment

Echocardiographic screening for rheumatic heart disease in indigenous Australian children: A cost-utility analysis

Echocardiographic screening for rheumatic heart disease is cost-effective in our context

Clinical development strategy for a candidate group A streptococcal vaccine

This review outlines a clinical development strategy detailing the phases of development required for registration of a candidate Group A streptococci vaccin

Adherence to secondary prophylaxis for rheumatic heart disease is underestimated by register data.

Adequate resources are needed for maintenance of data quality in acute rheumatic fever/ rheumatic heart disease registers to ensure provision of evidence-based care and accurate assessment of program impact.

Strongyloides seroprevalence before and after an ivermectin mass drug administration in a remote Australian Aboriginal community

We report the impact on Strongyloides seroprevalence after two oral ivermectin mass drug administrations (MDAs) delivered 12 months apart in a remote Australian Aboriginal community.

Repeat pneumococcal polysaccharide vaccine in Indigenous Australian adults is associated with decreased immune responsiveness

These findings highlight the critical need to evaluate the efficacy of future pneumococcal vaccine programs in the Australian Indigenous populations that recommend repeated doses of 23vPPV.

Disparity in Mortality From Rheumatic Heart Disease in Indigenous Australians

Indigenous Australians are much more likely to die from Rheumatic Heart Disease than other Australians.

Burden of cardiovascular diseases in the Eastern Mediterranean Region, 1990-2015: findings from the Global Burden of Disease 2015 study

The age-standardized disability-adjusted life years rates in the Eastern Mediterranean Region are considerably higher than the global average.

Clinical outcomes for young people with screening-detected and clinically-diagnosed rheumatic heart disease in Fiji

Young people with screening-detected RHD have worse health outcomes than screen-negative cases in Fiji.

Global, regional, & national burden of rheumatic heart disease, 1990-2015

We estimated the global disease prevalence of and mortality due to rheumatic heart disease over a 25-year period

Hospital admissions for skin infections among Western Australian children and adolescents from 1996 to 2012

Skin infections are a significant cause of severe disease, requiring hospitalization in Western Australian children, particularly with Aboriginal children

Rheumatic heart disease: infectious disease origin, chronic care approach.

Rheumatic heart disease (RHD) is a chronic cardiac condition with an infectious aetiology, causing high disease burden in low-income settings.

Sulfamethoxazole-Trimethoprim (Cotrimoxazole) for Skin and Soft Tissue Infections Including Impetigo, Cellulitis, and Abscess

We conducted a systematic review of clinical trials and observational studies that address the utility of SXT for SSTI treatment, caused by either GAS or MRSA

Hospital admissions for skin infections among Western Australian children and adolescents from 1996 to 2012

The objective of this study was to describe the occurrence of skin infection associated hospitalizations in children born in Western Australia (WA).

Genome-Wide Analysis of Genetic Risk Factors for Rheumatic Heart Disease in Aboriginal Australians Provides Support for Pathogenic Molecular Mimicry

Rheumatic heart disease (RHD) after group A streptococcus (GAS) infections is heritable and prevalent in Indigenous populations. Molecular mimicry between human and GAS proteins triggers proinflammatory cardiac valve-reactive T cells.

Preliminary consultation on preferred product characteristics of benzathine penicillin G for secondary prophylaxis of rheumatic fever

A sample target product profile for reformulated benzathine penicillin G is presented

Global, regional, and national disability-adjusted life-years (DALYs) for 315 diseases and injuries and healthy life expectancy (HALE), 1990–2015

Total global disability-adjusted life-years remained largely unchanged from 1990 to 2015

Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980–2015

Globally, life expectancy from birth increased from 61·7 years in 1980 to 71·8 years in 2015

Protocol for the systematic review of the prevention, treatment and public health management of impetigo, scabies and fungal skin infections in resource-limited settings

The evidence derived from the review will be used to inform the development of guidelines for the management of skin infections in resource-limited settings

Efficacy of a trivalent influenza vaccine against seasonal strains and against 2009 pandemic H1N1: A randomized, placebo-controlled trial

This study assessed the efficacy of seasonal IIV3s against influenza due to 2008 and 2009 seasonal influenza strains and against the 2009 pandemic H1N1 strain

Long-term outcomes from acute rheumatic fever and rheumatic heart disease

Adverse outcomes for people with acute rheumatic fever and rheumatic heart disease and the effect of comorbidities and demographic factors on these outcomes

Transiently increased IgE responses in infants and pre-schoolers receiving only (DTaP) vaccines compared to those initially receiving at least one dose of DTwP vaccine

Confirm the generalised IgE-trophic activity of the DTaP vaccine in pre-schoolers and demonstrate similar (albeit transient) effects in infants

Impetigo and scabies - Disease burden and modern treatment strategies

Recent data on the epidemiology of impetigo and scabies and describe the current evidence around approaches to individual and community based treatment

Focused cardiac ultrasound screening for rheumatic heart disease by briefly trained health workers: A study of diagnostic accuracy

Echocardiographic screening for rheumatic heart disease (RHD) can identify individuals with subclinical disease who could benefit from antibiotic prophylaxis.

Status of research and development of vaccines for Streptococcus pyogenes

Vaccines against Streptococcus pyogenes are considered as impeded vaccines because of a number of crucial barriers to development

Seven key actions to eradicate rheumatic heart disease in Africa: The Addis Ababa communiqu

Develop a 'roadmap' of key actions that need to be taken by governments to eliminate ARF and eradicate RHD in Africa

The Importance of Scabies Co-Infection in the Treatment Considerations for Impetigo

Treatment success for scabies co-infection was lower than for impetigo overall, with a higher success seen in the co-trimoxazole group than benzylpenicillin

Towards Improving Point-of-Care Diagnosis of Non-malaria Febrile Illness: A Metabolomics Approach

This study demonstrates the potential use of plasma metabolites to identify causality in children with severe febrile illness in malaria-endemic settings

Whole genome sequencing reveals extensive community-level transmission of group A Streptococcus in remote communities

There was evidence of extensive transmission of group A Streptococcus both within households and across the community

Myositis complicating benzathine penicillin-G injection in a case of rheumatic heart disease

A 7-year old boy developed myositis secondary to intramuscular injection of benzathine penicillin-G in the context of secondary prophylaxis for RF

The inequitable burden of group A streptococcal diseases in Indigenous Australians

Given the ongoing mortality and morbidity from GAS infections, we must address more effectively the treatment and prevention of GAS impetigo and pharyngitis

A systematic review of the evidence that swimming pools improve health and wellbeing in remote Aboriginal communities in Australia

The benefits that swimming pools may bring to to ear and eye health in remote Aboriginal communities remains unresolved

Improving delivery of secondary prophylaxis for rheumatic heart disease in remote Indigenous communities

This trial aims to improve uptake of secondary prophylaxis among Aboriginal people with ARF/RHD to reduce progression or worsening of RHD.

Screening for rheumatic heart disease: Quality and agreement of focused cardiac ultrasound by briefly trained health workers

After brief training, health workers with no prior experience in echocardiography can obtain adequate quality images and make a reliable assessment

Acute rheumatic fever and rheumatic heart disease

Acute rheumatic fever (ARF) is the result of an autoimmune response to pharyngitis caused by infection with group A Streptococcus.