Novel bacterial biomarkers in the early diagnosis of paediatric sepsis Sarah Hopkinson Jonathan Benger Simon Jackson

Emergency Care Research Early diagnostic cardiac biomarkers Critical care therapies and airway Ambulance design/pre-hospital care Service delivery and professional role Pain control in emergency care Alcohol and drugs Early diagnostic biomarkers in sepsis

The problem Fever is one of the most common reasons for presentation to a children’s ED Fever is the leading cause of admission to a children’s ward Most children aged 0-5 years with fever have a self-limiting viral infection, but up to 1% have a bacterial infection 20% of all deaths in children occur as a result of infection (190 deaths per annum)

The problem Early treatment in bacterial infection works The key challenge is to distinguish the minority of children in the early stages of bacterial infection from the majority with a virus The deficiencies of the current approach are widely acknowledged, even by NICE Errors in diagnosis continue to be made

The potential solution! As the pathogenesis of sepsis has become more clearly understood there is the possibility of identifying a reliable marker of bacterial infection There are a multitude of potential markers, but nothing has yet demonstrated sufficient diagnostic accuracy

The biomarkers 1. Lipopolysaccharide (LPS): a bacterial cell wall component. There has been no previous study of LPS as a biomarker of bacterial infection in children, but studies of LPS-binding protein have been promising 2. Lipoteichoic acid (LTA): a heat-stable component of the cell membrane and wall of most gram-positive bacteria. There has been little research involving LTA to date

The MRC Application to MRC biomarkers call, June 2008 Multidisciplinary team: two universities and three paediatric Emergency Departments £818,000 total Strong reviews, but not funded

The CEM Application to CEM for pilot study, June 2008 Local study: UWE and Bristol Children’s Hospital £5,000 in total Successful application (x2!)

Study design (1) Prospective cohort study of 100 febrile children aged 1 month to 5 years presenting to BRHC Parents of consecutive children requiring blood testing as a component of their routine clinical care will be asked to give an additional 2 mls of blood, which will be subsequently analysed The primary outcome will be the presence or absence of significant bacterial infection, defined using a composite gold standard

Study design (2) Secondary outcomes will be initial disposition from the ED, the type of infection, causative organism and clinical outcome Data analysis will determine the diagnostic properties of these novel biomarkers with 95% confidence intervals, to guide further research Research governance and approvals are now being arranged Aim to commence recruitment in April

Future plans We hope that one of these markers, or a combination of the two, will assist in the diagnosis of children with fever, and improve clinical decision-making We also hope to proceed to a larger study that will validate the use of these markers in routine practice Current HTA call for diagnostic technologies