Abstract
BackgroundGroup A Streptococcal (GAS) infections cause the autoimmune disease acute rheumatic fever (ARF), which can progress to chronic rheumatic heart disease (RHD). Treating pharyngitis caused by GAS with antibiotics is important in preventing ARF. However, it is difficult to distinguish these infections from GAS carriers. There is growing evidence for GAS skin infections as a cause of ARF. This study will identify the incidence of true GAS pharyngitis and serological responses to GAS skin infections. The effectiveness of antibiotics for these conditions will be explored, and modifiable risk factors. Serum antibody titres indicating the upper limits of normal (ULN for ASO/ADB antibodies) will be established alongside carriage rates in asymptomatic children.MethodsThis is a prospective disease incidence study, with an associated case-control study. The study population includes 1000 children (5–14 years) from Auckland, New Zealand, 800 of whom have visited their healthcare professional, resulting in a throat or skin swab for GAS, and 200 who are asymptomatic. The conditions of interest are GAS throat swab positive pharyngitis (n = 200); GAS carriage (n = 200); GAS negative throat swab (n = 200); GAS skin infections (n = 200); and asymptomatic controls (n = 200). All participants, except asymptomatic controls, will have acute and convalescent serological testing for ASO/ADB titres (collected < 9 days, and 2–4 weeks following symptom onset, respectively), alongside viral PCR from throat swabs. Asymptomatic controls will have ASO/ADB titres measured in one blood specimen and a throat swab for microbial culture. Caregivers of children will be interviewed using a questionnaire and any GAS isolates identified will be emm typed. The persistence of GAS antibodies will also be investigated.DiscussionFindings from this study will fill critical gaps in scientific knowledge to better understand the pathophysiology of ARF, improve clinical management of GAS infections, and design more effective ARF prevention programmes. In particular it will measure the incidence of true, serologically confirmed GAS pharyngitis; assess the immune response to GAS skin infections and its role as a cause of ARF; examine the effectiveness of oral antibiotics for treating GAS pharyngitis and carriage; and identify whether risk factors for GAS infections might provide intervention points for reducing ARF.
Highlights
Group A Streptococcal (GAS) infections cause the autoimmune disease acute rheumatic fever (ARF), which can progress to chronic rheumatic heart disease (RHD)
The analysis identified 285 eligible studies and reported that in clinical settings; approximately 10% of children swabbed with a sore throat had serologically-confirmed GAS pharyngitis, with this increasing to around 50–60% when the child was GAS culture-positive
The analysis reported a prevalence of 10.3% (6.6–15.7%) for serologicallyconfirmed GAS pharyngitis in children from high-income countries and an asymptomatic GAS carriage prevalence of 10.5% (8.4–12.9%)
Summary
Study design and population The study design is a prospective disease incidence study that has an associated case-control study. At the end of these analyses, this study will be able to identify, with a reasonable degree of certainty, whether the risk of GAS pharyngitis and GAS skin infection in New Zealand is associated with a number of important risk factors that are potentially modifiable: structural and functional household crowding and bed sharing; poor indoor environments (cold, damp, mould) and fuel poverty; tobacco smoke exposure; limited resources for personal hygiene (e.g. washing, teeth cleaning); poor access to health services, including pharyngitis and skin infection treatment; and poor oral health This analysis will begin by describing the distribution of detected viral pathogens across all the study populations of children presenting with sore throats (n = 600). Members of the research group are already providing advice to the Ministry of Health and Health Promotion Agency of aspects of the RFPP programme and are recognised opinion leaders in clinical aspects of ARF and RHD management
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