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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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Prevalence of group A Streptococcal infection in Africa to inform GAS vaccines for rheumatic heart disease: A systematic review and meta-analysisThe prevalence of group A streptococcal disease remains high among symptomatic individuals residing in Africa
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Establishing the lowest penicillin concentration to prevent pharyngitis due to Streptococcus pyogenes using a human challenge model (CHIPS)The in-vivo plasma concentration of penicillin needed to prevent Streptococcus pyogenes pharyngitis, recurrent acute rheumatic fever, and progressive rheumatic heart disease is not known. We used a human challenge model to assess the minimum penicillin concentration required to prevent streptococcal pharyngitis.
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The need for community-controlled tools to monitor health impacts of housing and living conditions in AustraliaDespite millennia of strong and continuous culture, inadequate housing has profound consequences on the health and wellbeing of Aboriginal and Torres Strait Islander people in Australia. For example, the excessive and inequitable burden of childhood skin infections, rheumatic fever, gastrointestinal disease and ear infections can all be linked to failures in housing policy, funding and maintenance.
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Global, regional, & national burden of rheumatic heart disease, 1990-2015We estimated the global disease prevalence of and mortality due to rheumatic heart disease over a 25-year period
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Acceptability and Implementation Challenges of Benzathine Penicillin G Secondary Prophylaxis for Rheumatic Heart Disease in Ethiopia: A Qualitative StudyMonthly intramuscular injections of benzathine penicillin G (BPG) remain the cornerstone of secondary prophylaxis for acute rheumatic fever and rheumatic heart disease (RHD). The barriers to successful delivery of BPG may be patient- or service-delivery-dependent.
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High dose, subcutaneous injections of benzathine penicillin G (SCIP) to prevent rheumatic fever: A single arm, phase IIa trial of safety and pharmacokineticsThis Phase-IIa trial evaluates the safety and pharmacokinetics of high-dose, 10 weekly subcutaneous injections of penicillin (SCIP) in young people with a history of acute rheumatic fever (ARF).
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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.