My PhD research consists of a series of studies on the application of metagenomic next-generation sequencing (mNGS) to search for viral etiology in patients presenting with community-acquired sepsis or central nervous system (CNS) infections. I first developed a mNGS workflow for the sensitive detection of a broad range of viruses in clinical samples (Chapter 2). I then used this optimized method to search for viruses in 665 patients presenting with community-acquired sepsis of unknown origin enrolled in an observational study across Thailand and Vietnam in 2013-2015. While the mNGS analysis revealed significant insights into the epidemiology of sepsis in both countries, the analysis also led to the first detection of a recently discovered flavivirus - human pegivirus 2 (HPgV-2) - in a serum sample of a Vietnamese patient co-infected with HIV and HCV. This represents the first detection of HPgV-2 in Vietnam. Therefore, I conducted further research to unravel its epidemiology in Vietnam (Chapter 4). In Chapter 5, I used mNGS to analyze 204 cerebrospinal fluid (CSF) from patients with CNS infections of unknown origin enrolled from hospitals across central and southern Vietnam in 2012-2016. Enteroviruses were the most common viruses detected, especially in children and young adults. To inform future research directions, I conducted a pilot of 66 consecutive CSF samples collected from patients presenting with CNS infections admitted to the Hospital for Tropical Diseases in Ho Chi Minh City, Vietnam (Chapter 6). mNGS accurately detected a wide range of pathogens that were also detected by routine diagnostic methods, but also increased the diagnostic yield from 22.7% (15/66) to 34.8% (23/66) (Chapter 6). Finally, in Chapter 7, I provide an overview about my research findings, and propose some future directions based on the main findings obtained during my PhD research
