The clinical features, aetiology, and economic burden of paediatric encephalitis in southern Vietnam

Thesis

My PhD thesis consisted a body of novel work on the epidemiology, clinical features, outcome and illness costs of encephalitis in Vietnamese children. To address my research hypotheses, I based my analysis on 164 children with encephalitis recruited into an observational study conducted at a major children’s hospital in Southern Vietnam between March 2020 and December 2022. I applied a multidisciplinary approach to establish the possible infectious and non-infectious causes, and to estimate the illness costs of the disease. Accordingly, Chapter 1 and 2 provide an overview describing the background and methodologies. In Chapter 3, I demonstrate that N-Methyl-D-Aspartate Receptor (NMDAR)-antibody encephalitis has become a leading cause in Vietnamese children with encephalitis, surpassing Japanese encephalitis virus (JEV), the most common viral cause of infectious encephalitis. While there were considerable similarities in clinical presentations, in NMDAR-antibody encephalitis patients, psychiatric features, cognitive dysfunction, language changes, abnormal movements were predominantly documented. Additionally, patients with NMDAR-antibody encephalitis had a longer duration of hospital stay than JEV encephalitis patients. As a diverse range of pathogens can cause encephalitis, in Chapters 4 and 5, I applied an extensive diagnostic workup including PCR and metagenomic next generation sequencing (mNGS) to better identify infectious causes of encephalitis in 89 patients with clinically suspected infectious encephalitis. Collective findings in these two Chapters showed that the overall the diagnostic yield increased from 18/89 (20.2%) after routine diagnosis to 34/89 (38.2%) after extensive PCR testing, and to 36/89 (40.4%) after mNGS, representing a doubling in diagnoses. However, this still left ~60% of children with suspected infectious encephalitis having no cause identified. To inform health policy makers with evidence-based decisions on resource allocation for encephalitis research and management, Chapter 6 reports my comprehensive analysis to estimate the cost of illness attributed to encephalitis in Vietnamese children. The results showed that the illness costs were considerable and higher in more severe patients, patients with sequelae, and ventilated patients. Notably, I also found that, despite high health insurance coverage, encephalitis patients and families still incur significant costs. Of note, many of the children in my study suffered from JEV, a vaccine-preventable disease, indicating the potential of preventative public health measures to impact and reduce these cost outcomes. Finally, in Chapter 7, I provide a summary of my PhD findings and offer some associated future research directions.

Authors: Nguyen, H

• Alternative title: Paediatric encephalitis in Vietnam
• DOI: 10.5287/ora-da74mxabk
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford
• Language: Vietnamese, English
• Keywords: Vietnam; nmdar-antibody; JEV; health economics; encephalitis; children; metagenomic next-generation sequencing (mNGS); phylogenetics; polymerase chain reaction (PCR)
• Subjects: Economics; Emerging infectious diseases; Metagenomics; Microbiology; Autoimmune diseases; Infection; Neurology; Pediatrics