The translational potential of mass spectrometry and next-generation sequencing in patients with central nervous system infections in Vietnam (360G-Wellcome-204904_Z_16_Z)

Central nervous system (CNS) infections are devastating conditions worldwide, especially in low- and middle-income counties (LMIC). Clinical outcomes are dependent upon the rapid identification of the causative agent and instituting effective antimicrobial therapy, although the causative agent is only identified in <50% of patients. Furthermore, Southeast Asia is highly susceptible to the emergence of novel and drug resistant pathogens. New diagnostic techniques are urgently required for rapid response to future outbreaks, and to improve patient outcomes. This Fellowship will focus on the translational potential of mass spectrometry and next-generation sequencing (NGS) in clinical diagnostics of CNS infections in Vietnam, and has three key goals: - To determine whether Mass spectrometry of cerebrospinal fluid (CSF) will identify protein/peptide signatures associated with different infectious aetiologies. - To determine whether NGS-based metagenomic analysis will identify a broad range of known/unknown pathogens in the CSF and improve upon current standard laboratory assays. - To determine whether NGS can provide rapid, whole genome sequence-based prediction of antimicrobial susceptibility for Mycobacterium tuberculosis and Streptococcus pneumoniae. I aim to provide proof-of-principle that CSF proteomics- and NGS-based methods can improve upon the diagnostic assays currently available in hospital settings, especially in LMIC, and thereby potentially improve patient outcomes.