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Understanding Group A Streptococcus (GAS) pharyngitis and skin infections as causes of rheumatic fever

Background

The drive for this research is to fill critical gaps in scientific knowledge that are needed to support New Zealand’s Rheumatic Fever Prevention Programme. It will also add to our understanding of the pathophysiology of acute rheumatic fever (ARF).

ARF is an autoimmune disease that may follow untreated GAS pharyngitis and untreated GAS skin infections, in susceptible children. Disease manifestations include inflammation in the joints, heart, central nervous system and skin. In an estimated 60% of cases, carditis progresses to chronic rheumatic heart disease (RHD) with permanent heart valve damage. Unless treated with intramuscular injections of benzathine penicillin G every 28 days, ARF patients are likely to suffer worsening cardiac damage and an increasing chance of early death.

ARF is now rarely seen in high-income countries, with the exception of New Zealand and Australia. There are large and widening ethnic disparities in ARF rates in New Zealand. ARF incidence peaks in children aged 4-15 years. The rate of new cases of ARF notified in 2016 for Maori 5-to-12-year-olds was 23.4 per 100,000 and for Pacific 5-to-12-year-olds was 62.9 per 100,000, many times higher than the rates for European/Others.

A major challenge for treating GAS pharyngitis, or mounting interventions amongst populations at high-risk of developing ARF, is that significant numbers of children naturally carry GAS in their throats without evidence of infection or any autoimmune sequelae. This study will serologically confirm GAS pharyngitis to differentiate between children with true pharyngitis, who are considered at risk of progressing to ARF, from those that are GAS carriers. The study will also investigate the role of GAS skin infections and potential risk factors associated with GAS pharyngitis and skin infections.

Aims

  1. Determine the incidence and distribution of GAS pharyngitis (serologically confirmed) amongst children presenting with a sore throat.
  2. Determine the incidence of GAS positive skin infections amongst children presenting with a skin infection and the serological response to these infections.
  3. Compare the GAS emm types associated with Gas pharyngitis and skin infections to those associated with the GAS carrier date, ARF and well controls.
  4. Identify epidemiological risk factors for GAS pharyngitis and skin infections and assess their potential as modifiable risk factors for these infections and ARF.
  5. Assess the contribution of viral infection to presumed GAS pharyngitis seen in primary care.
  6. Measure the effectiveness of antibiotic treatment on pharyngeal GAS carriage compared with pharyngitis.
  7. Measure the persistence of GAS antibodies (and potentially GAS colonisation) six months following the initial sampling.
  8. To determine age-specific upper level of normal (ULN) values of ASO and ADB titers in children.
  9. To establish carriage rates of GAS in asymptomatic children.

Design

The project is a prospective disease incidence study, with an associated case-control study. The study population will include 1,000 school aged (5-14-years) children in Auckland, 600 of whom have had a throat swab collected for investigation of presumed GAS pharyngitis. It will include a further 200 children (5-14-years) from Auckland with GAS positive skin infections and 200 Auckland children (5-15 years) who are asymptomatic.

Investigators

Funding

This is a Health Research Council (HRC) funded project (Reference 16/005).

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