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Evaluating the role of asymptomatic throat carriage of Streptococcus pyogenes in impetigo transmission in remote Aboriginal communities in Northern Territory, Australia: a retrospective genomic analysisStreptococcus pyogenes, or group A Streptococcus (GAS), infections contribute to a high burden of disease in Aboriginal Australians, causing skin infections and immune sequelae such as rheumatic heart disease. Controlling skin infections in these populations has proven difficult, with transmission dynamics being poorly understood. We aimed to identify the relative contributions of impetigo and asymptomatic throat carriage to GAS transmission.
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Qualitative assessment of healthy volunteer experience receiving subcutaneous infusions of high-dose benzathine penicillin G (SCIP) provides insights into design of late phase clinical studiesSecondary prophylaxis to prevent rheumatic heart disease (RHD) progression, in the form of four-weekly intramuscular benzathine benzylpenicillin G (BPG) injections, has remained unchanged since 1955. Qualitative investigations into patient preference have highlighted the need for long-acting penicillins to be delivered less frequently, ideally with reduced pain.
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Rheumatic heart disease mortality in Indigenous and non-Indigenous Australians between 2010 and 2017To generate contemporary age-specific mortality rates for Indigenous and non-Indigenous Australians aged <65 years who died from rheumatic heart disease between 2013 and 2017, and to ascertain the underlying causes of death of a prevalent RHD cohort aged <65 years who died during the same period.
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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.
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Starting the SToP trial: Lessons from a collaborative recruitment approachRecruitment 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.
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Lack of effectiveness of 13-valent pneumococcal conjugate vaccination against pneumococcal carriage density in Papua New Guinean infantsPapua New Guinea (PNG) introduced the 13-valent pneumococcal conjugate vaccine (PCV13) in 2014, with administration at 1, 2, and 3 months of age. PCV13 has reduced or eliminated carriage of vaccine types in populations with low pneumococcal carriage prevalence, carriage density and serotype diversity.
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Formative evaluation of a community-based approach to reduce the incidence of Strep A infections and acute rheumatic feverWe explore the acceptability of a novel, outreached-based approach to improve primary and primordial prevention of Strep A skin sores, sore throats and acute rheumatic fever in remote Aboriginal communities. A comprehensive prevention program delivered by trained Aboriginal Community Workers was evaluated using approximately fortnightly household surveys about health and housing and clinical records.
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Subcutaneous infusion of high-dose benzathine penicillin G is safe, tolerable, and suitable for less-frequent dosing for rheumatic heart disease secondary prophylaxis: a phase 1 open-label population pharmacokinetic studySince 1955, the recommended strategy for rheumatic heart disease secondary prophylaxis has been benzathine penicillin G injections administered intramuscularly every 4 weeks. Due to dosing frequency, pain, and programmatic challenges, adherence is suboptimal. It has previously been demonstrated that BPG delivered subcutaneously at a standard dose is safe and tolerable and has favorable pharmacokinetics, setting the scene for improved regimens with less frequent administration.
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Research opportunities for the primordial prevention of rheumatic fever and rheumatic heart disease - streptococcal vaccine development: a national heart, lung and blood institute workshop reportStreptococcus 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.
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Outcomes of rheumatic fever in Uganda: a prospective cohort studyRheumatic heart disease is the largest contributor to cardiac-related mortality in children worldwide. Outcomes in endemic settings after its antecedent illness, acute rheumatic fever, are not well understood. We aimed to describe 3-5 year mortality, acute rheumatic fever recurrence, changes in carditis, and correlates of mortality after acute rheumatic fever.