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Title: The epidemiology of and risk factors for central nervous system infections in Vietnam
Author: Brindle, Hannah
ISNI:       0000 0005 0288 1486
Awarding Body: University of Liverpool
Current Institution: University of Liverpool
Date of Award: 2020
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In Vietnam, central nervous system (CNS) infections due to acute encephalitis syndrome (AES) and meningitis are caused by multiple aetiologies. Despite implementation of vaccination, the most common cause in children is Japanese encephalitis virus (JEV), and in adults, Streptococcus suis. In at least half of the cases, the cause is unknown however, there are peaks in incidence of acute encephalitis syndrome (AES) in the summer months in northern Vietnam. This thesis is composed of four results chapters with the following main objectives: 1) to understand the spatio-temporal distribution and risk factors of CNS infections in Vietnam; 2) to assess the feasibility and acceptability of conducting a case control study which aims to determine the risk factors for CNS infections; 3) to evaluate human movement and contact patterns in relation to risk factors for CNS infections and 4) to determine whether there are associations between the seroprevalence of JEV in pigs and incidence of AES and Japanese encephalitis (JE) in humans. The first results chapter uses monthly national surveillance data of the incidence of AES and meningitis at the provincial level from 1998 to 2016. The incidence of AES was highest in provinces bordering Lao PDR and seasonal patterns corresponded closely with those of JE. Negative binomial Integrated Nested Laplace Approximation (INLA) multivariate models showed a positive correlation of the number of cases of AES and meningitis with temperature and absolute humidity, and AES with the Normalised Difference Vegetation Index (NDVI) at a lag of one month. This might suggest that many cases of CNS infections are due to vector-borne diseases. In the second results chapter, many of the participants with AES had a bacterial meningitis due to the poor specificity of the case definition for AES, the predominantly adult patient population and the season of recruitment. The recruitment of matched controls who were relatives of hospital in-patients was also insufficient. Therefore, adaptations to the methods would be required for a future, larger case control study to evaluate risk factors for AES. The third results chapter showed that it was feasible to determine human movement patterns using global positioning system (GPS) tracking devices and contact patterns using diaries over the period of a year. Urban adults travelled the most and all participants spent the most time in areas of medium to high NDVI. Contact patterns occurred most frequently between children and adults. These findings may have implications for the transmission dynamics of pathogens causing CNS infections with larger studies recommended. The final results chapter showed that nearly two-third of pigs were seropositive to JEV at slaughter however, the specificity of the complement enzyme-linked immunosorbent assay (cELISA) was 57.4%. Multivariate analysis showed no evidence of an association between incidence of human JE and AES and seroprevalence of JEV in pigs. However, human-pig studies at the individual level are needed to determine whether this absence of risk is true. There is evidence that many CNS infections may be due to undiagnosed JE however, this requires further investigation before any changes to public health policy are made.
Supervisor: Not available Sponsor: Wellcome Trust
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral