title: TOWARDS IMPROVING THE MANAGEMENT OF ACUTE ENCEPHALITIS SYNDROME IN NEPAL
Creators: name: Rayamajhi, A
Publisher: name: University of Liverpool Repository
Year: 2017

description: Acute Encephalitis Syndrome (AES) is a group of clinical symptoms and signs, used by the World Health Organisation (WHO) and clinicians, to screen for acute encephalitis. Viruses are the most important cause of AES worldwide. Japanese encephalitis virus (JEV), which causes Japanese encephalitis (JE), accounts for approximately one-quarter of AES cases in Nepal. In the absence of definite treatments for JE and many other viral enecpahlitides, improvements in supportive management are vital. In my thesis, the predictors of bad outcome (neurological sequelae or death) among patients with AES and JE were investigated. The relationships between weight-for-age (WFA), hydration status, intravenous fluids and outcome were studied. In addition, a preliminary randomised double blind placebo controlled trial of intravenous immunoglobulin (IVIG), as a novel adjunctive treatment for JE, was conducted. Prolonged fever duration was identified to be a significant predictor of bad outcome in both AES and JE patients. Prolonged fever, low Glasgow coma score (GCS) and focal neurological deficit at hospital admission were significantly associated with bad outcome in AES patients. AES patients with focal neurological deficit were significantly more likely to have a final diagnosis of JE. JE patients presented with a significantly lower body weight and higher respiratory rate. They also presented with a trend for higher urea and potassium levels compared to other AES patients. These findings led me to investigate further whether children with JE were more likely to suffer from dehydration during acute illness. When children are grouped into different weight categories by WFA (Z score), low WFA can indicate dehydration or malnutrition. I found a significant association between frequency of bad outcome and low WFA among both AES and JE patients at hospital admission. To help distinguish dehydration and malnutrition in low WFA children, I then studied additional indicators of malnutrition and dehydration status, including midupper arm circumference, blood lactate levels and fluid status at admission and during hospital stay. I found AES patients suffering a bad outcome had significantly higher admission serum lactate levels, drunk a lower volume of oral fluids, and were more likely to be prescribed a restricted regimen of intravenous fluids. These results suggest AES patients with bad outcome were more likely to be dehydrated. The implications of my findings are that earlier hospital admission during the course of the illness and better in hospital administration of adequate and appropriate fluids may improve outcome among AES and JE patients. Since the majority of families self-refer to hospitals, provision of this simple message into the community, could help improve the lives of people living in high risk areas for JE, like Nepal. Improvement in the treatment of JE is necessary to improve the outcome of the disease in Nepal. Intravenous immunoglobulin, which contains anti-JE virus neutralising antibodies and has anti-inflammatory properties, may be a useful adjunctive treatment. In a preliminary Phase II study, I showed IVIG could be safely administered to JE patients, without any significant increase in drug related adverse events. JE patients treated with IVIG exhibited higher levels of neutralising antibodies and higher IL-4 and IL-6 cytokine levels compared with placebo (saline) treated patients. Although, there was no difference in clinical outcome, the data from this small pilot study suggests IVIG may be an appealing adjunctive treatment option for a phase III trial in the future.