Study protocol: The clinical features, epidemiology, and causes of paediatric encephalitis in southern Vietnam

Encephalitis is a major cause of morbidity and mortality worldwide. The clinical syndrome of encephalitis consists of altered mental status, seizures, neurologic signs, and is often accompanied by fever, headache, nausea, and vomiting. The encephalitis in children has been known that more common than in adult, with the incidence rate of infants was 3.9 times higher than that of people 20-44 years of age. The reported incidence of hospitalization attributed to paediatric encephalitis ranged from 3 to 13 admissions per 100,000 children per year with the overall mortality ranging from 0 to 7%. There are however more than 100 pathogens that can cause encephalitis and accurate diagnosis is challenging. Over 50% of patients with encephalitis are left undiagnosed despite extensive laboratory investigations. Furthermore, recent studies in high-income settings have suggested autoimmune encephalitis has now surpassed infectious aetiologies, mainly due to increased awareness and diagnostic capacity, which further challenges routine diagnosis and clinical management, especially in developing countries. There are limited contemporary data on the causes of encephalitis in children in Vietnam. Improving our knowledge of the causative agents of encephalitis in this resource-constrained setting remains critical to informing case management, resource distribution and vaccination strategy. Therefore, we conduct a prospective observational study to characterise the clinical, microbiological, and epidemiological features of encephalitis in a major children's hospital in southern Vietnam. Admission clinical samples will be collected alongside meta clinical data and from each study participants. A combination of classical assays (serology and PCR) and metagenomic next-generation sequencing will used to identify the causative agents. Undiagnosed patients with clinical presentations compatible with autoimmune encephalitis will then be tested for common forms of the disease. Finally, using direct- and indirect costs, we will estimate the economic burden of hospitalization and seven days post hospital discharge of paediatric encephalitis in our setting.