The Translational Potential of Next-Generation Sequencing and Biological Mass Spectrometry in Patients with Central Nervous System Infections in Vietnam.

Nghiem, My Ngoc (2024). The Translational Potential of Next-Generation Sequencing and Biological Mass Spectrometry in Patients with Central Nervous System Infections in Vietnam. PhD thesis The Open University.

DOI: https://doi.org/10.21954/ou.ro.0001766e

Abstract

Central nervous system (CNS) infections cause significant mortality and morbidity worldwide. Novel diagnostic approaches are therefore urgently needed to improve patient outcomes. My study was conducted at a tertiary referral hospital for Southern Vietnam between September 2017 and September 2020, aiming at improving the diagnosis in adult patients with CNS infection syndromes using a combination of metagenomics- and proteomics-based approaches. I set out to study significant insights into the epidemiology, causes, clinical features, and outcomes of 581 patients. Despite extensive laboratory investigations, the causes were established in 58.7% of the study patients. Diverse infectious agents encompassing bacteria, viruses, fungi, and parasites were detected with Mycobacterium tuberculosis, Streptococcus suis, HSV and VZV as the major causes. My research also revealed for the first-time that anti-NMDAR encephalitis is a common cause of CNS infection syndromes, accounting for 21.3% of 221 patients with suspected encephalitis, and disability documented up to 12 months post-discharge. CNS infection syndromes in our setting are associated with high morbidity and mortality (2397/581, 68.3% and 29/581, 5.0%, respectively) and with overlapped clinical and laboratory findings. To address diagnostic challenges of CNS infection syndromes, I developed and prospectively evaluated a metagenomic pipeline for simultaneous detection of both bacterial and viral causes. The results emphasised that metagenomics could provide a complementary approach to improve pathogen identification alongside conventional diagnostic assays. Additionally, I evaluated the diagnostic performance of two novel CSF biomarkers, Lipocalin 2 (LCN2) and a disintegrin and metalloprotease like decysin (ADAMDEC1). The results showed that LCN2 outperformed existing CSF parameters (leukocytes, protein, lactate, and glucose) in discriminating bacterial meningitis from other causes. In contrast, ADAMDEC1 did not offer any extra diagnostic values as compared to current CSF biomarkers. Collectively, my findings open new research opportunities to improve the diagnosis of patients with CNS infections in Vietnam and other regions where pathogen exposure is prevalent.

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