Understanding protective plasma levels of penicillin and monitoring antibody responses for the prevention of GAS infection in a paediatric population in New Zealand

Abstract

Acute Rheumatic Fever (ARF) is an autoimmune condition resulting from untreated Group A Streptococcal (GAS) infection of the upper respiratory tract and possibly skin. Repeated untreated and severe episodes of ARF can cause permanent cardiac damage known as Rheumatic Heart Disease (RHD). Rates of ARF in New Zealand and Australia are among the highest in the world, particularly amongst Māori and Pacific and Indigenous Aboriginal children. Monthly injections of Benzathine Penicillin G (BPG) are given intramuscularly to prevent GAS infections that can lead to ARF and cause RHD. Early studies exploring the Pharmacokinetics (PK) properties of BPG were conducted in healthy, fit, young military recruits without ARF/RHD. BPG bioavailability, metabolism may differ in paediatric populations groups with ARF who have comorbidities and vary in Body Mass Index. This project seeks to determine the PK characteristics in a paediatric population currently receiving monthly injections of BPG while at the same time monitoring antibody immune responses to possible GAS infections. This is a prospective cohort study in a paediatric population of Wellington based children and teens (aged 5–21 years of predominantly Pasifika and Māori heritage) with a previous diagnosis of ARF and are receiving monthly BPG injections via community services. Participants will contribute finger prick blood samples over time for Dried Blood Spot assays designed to quantify penicillin G levels in the blood and measure streptococcal serology. Routine throat swab samples will also be collected with ASOT antibody levels monitored for GAS breakthrough infections. This is the first population PK study exploring use of BPG in Māori and Pacific children previously diagnosed with ARF.