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Title: Human enterovirus 71 infection in Sarawak, Malaysia
Author: Ooi, Mong How
ISNI:       0000 0004 2732 3926
Awarding Body: University of Liverpool
Current Institution: University of Liverpool
Date of Award: 2011
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Introduction: Hand, foot and mouth disease (HFMD) is a childhood exanthema caused by enteroviruses, such as coxsackie virus A (CV A) 16. However since 1997 large epidemics ofHFMD caused by human enterovirus (EV) 71 and associated with severe and sometimes fatal neurological complications have occurred across Asia. Aims: To examine: (i) the diagnostic approach for detection ofEV71, (ii) the clinical and molecular epidemiology of the virus in Sarawak, (iii) the clinical predictors for neurological involvement, and (iv) the viral determinants for clinical phenotype of EV71 infection. Methods: A prospective study was set up to examine children with HFMD presenting to Sibu Hospital, Sarawak, Malaysia between January 2000 and December 2006. Detailed history and clinical examination was performed and recorded on standardised forms. Throat and rectal swabs, and swabs from skin vesicles and mouth ulcers, if present, were taken from every patient. Lumbar puncture was performed in patients with suspected neurological involvement. Virus isolation and RT-PCR for enteroviruses were performed on all specimens. Isolated enteroviruses were typed by nucleotide sequencing of VP 1 and VP4 genes and genogrouped by pbylogenetic analysis. Results: Throat and vesicle swabs were the most useful samples for detection of EV71. Using virus culture results as the reference, an EV71-specific assay originally developed for molecular typing ofEV71 clinical isolates had a sensitivity of76.9% (258/337), specificity of 82.6% (133/161), positive predictive value of90.2% (259/287) and negative predictive value of63.0% (l33/211) when evaluated with 337 EV71-positive, 161 non-EV71 culture-positive clinical specimens. Epidemics of EV71-associated HFMD occurred every 3 years in Sarawak, and were caused by genogroups B4 and B5, and Cl. The genogroups of EV71 differ in their risk of causing neurological disease and family clusters. Total duration of fever 23 days, peak temperature 238SC and history oflethargy were identified and validated as independent risk factors for neurological involvement. EV71-positive children were more likely to have neurological disease when compared to CVAl6-positive children. Discussion: EV71 has become a major public health problem in Asia and may continue to spread globally. The transmission dynamic of the virus is poorly understood. The public health intervention measure to date has been empirical and generic, but they have considerable socioeconomic implication. There is neither specific antiviral nor vaccine for EV71. Intravenous immunoglobulin is now used presumptively for severe EV71 infection in many Asian countries, although there are little data on its efficacy. Early diagnosis of neurological involvement may help reduce the mortality. A better understanding on diagnosis and management of this neurological infectious disease can help public health doctors and clinicians manage the epidemic caused by the virus when it spread to a new territory.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral