NHS Research Time Award

Under the supervision of Dr Waterfield, Vice Chair of PERUKI, I would develop a study to investigate the use of point-of-care viral testing for febrile young infants. This would be hosted at the University Hospital of Wales, Cardiff. The over-arching aim is to determine if point-of-care viral testing can be used to help identify a lower risk cohort of infants suitable for earlier de-escalation in care and earlier discharge home.

Year 1:

• Undertake, and publish, a literature review on the use of point-of-care viral tests for the assessment of febrile infants.
• Perform a multicentre survey of the PERUKI and GAPR-UK networks to explore the feasibility of a UK and Ireland trial led from Wales.

Year 2:

Form a Cardiff based PPIE group to co-design a study to investigate how point-of-care viral testing can be utilised to identify a lower risk cohort of infants suitable for earlier discharge. The expressed local support of the Cedar Health Technology Research Centre would be a significant enabler.

• Engage with key stakeholders including PERUKI, GARUKI and the Cardiff CTU to develop a research question and outline proposal.

Year 3:

• Submit a NIHR HTA grant application for a UK wide study to investigate if point-of-care viral testing can be used to identify a lower risk cohort of febrile infants.

Background

Infants under 3 months of age are at high risk of serious bacterial infections (SBI) including bacteremia and meningitis. Unlike older children, infants regularly have non-specific features despite having a SBI, with history and physical examination alone insufficient to detect all cases of SBI. The majority of children in this age group still have self-limiting illness, typically viral, making risk assessment challenging for clinicians.

The ideal approach to the management of febrile infants is unclear, as exemplified by the contrasting approaches advocated by the National Institute for Health and Care Excellence (NICE). The NICE guideline NG51 “Sepsis: recognition, diagnosis and early management” advises that all febrile infants (<3 months) receive parenteral antibiotics immediately whereas NICE guideline NG143 “Fever in under 5s: assessment and initial management” suggests a tailored approach based on clinical assessment and laboratory testing. These UK clinical decision aids (CDAs) were validated through the PERUKI network. All were found to have high sensitivity but poor specificity with none able to reliably identify a low risk population.

Internationally several other CDAs exist that aim to identify febrile infants at low risk of SBI that can be safely managed in a community setting without parenteral antibiotics. Recent validation of these reported greater specificity and negative predictive values (NPV) with an ability to identify over 45% of febrile infants considered to be low risk.

All of the CDAs make use of a range of clinical tests including urinalysis and blood biomarkers. None of these in isolation are diagnostic for SBI and identification of low-risk febrile infants. The role of PCT in the population of the UK and Ireland is currently under investigation within the Febrile Infant Diagnosis and Outcome study (FIDO) led by Dr Waterfield and for which I am PI at the University Hospital of Wales.

None of the CDAs include diagnosis of viral infection to aid risk stratification.

COVID-19 has resulted in widespread availability of point of care testing for respiratory viruses. This opens the possibility for these results to be incorporated into CDAs, improving specificity.

This may influence patient care by identifying a lower risk cohort who could safely benefit from fewer painful procedures (such as lumbar puncture), short courses of parenteral antibiotics and earlier discharge home. This could result in reduced costs, reduced hospital stays and better antimicrobial stewardship.