Neuroglial biomarkers for the identification of patients with infectious encephalitis and implications for pathogen detection and discovery

The cause of encephalitis, remains unknown in 39 – 60% of cases, despite the advances in routine pathogen and antibody tests. Early and accurate distinction between infectious and autoantibody aetiologies is vital for urgent appropriate antimicrobial or anti-inflammatory treatment which saves lives and reduces neurological injury in survivors. Neuroglial injury biomarkers detectable in blood represent a potential rapid non-invasive, low- cost test to differentiate between likely infectious and autoimmune cases; and have demonstrated encouraging discriminatory capacity in my pilot data; GFAP had predicted diagnostics sensitivity of 91% and specificity of 81%. However, their utility and relevance for pathogen discovery in cases with encephalitis of unknown aetiology is not explored. This proposal will: (i) Measure neuroglial injury biomarkers in patients with encephalitis to develop and validate prediction models incorporating clinical and immunological parameters. (ii) Apply these models in patients with encephalitis of unknown aetiology, to stratify them into 'unlikely', 'possible', or 'probable' infection and (iii) use metagenomic deep sequencing to identify any pathogens. (iv) Take training and career development courses to accelerate my transition to research independence. These activities will determine the diagnostics potential of neuroglial injury biomarkers, identify novel pathogens of encephalitis, and strengthen my skills in sequencing and bioinformatics.