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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.
This 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).
Streptococcus pyogenes (Strep A) is a leading cause of morbidity and mortality across the globe, annually causing hundreds of millions of cases of disease.
Rheumatic heart disease (RHD) is underdiagnosed globally resulting in missed treatment opportunities and adverse clinical outcomes. We describe the protocol for a study which aims to co-design, implement and conduct an evaluation of a task-sharing approach to echocardiographic active case finding for early detection and management of RHD in high-risk settings in Australia and Timor-Leste.
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.
Jonathan Carapetis AM AM MBBS FRACP FAFPHM PhD FAHMS Executive Director; Co-Head, Strep A Translation; Co-Founder of REACH 08 6319 1000 contact@
Jonathan Carapetis AM AM MBBS FRACP FAFPHM PhD FAHMS Executive Director; Co-Head, Strep A Translation; Co-Founder of REACH 08 6319 1000 contact@
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
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.
Secondary 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.