Factors that influence the severity of Dengue infection
File(s)
Author(s)
Kraivong, Romchat
Type
Thesis
Abstract
Dengue disease is a mosquito-borne condition that has become a major public health concern. Dengue severity can be classified into mild Dengue fever (DF) and severe Dengue or Dengue hemorrhagic fever (DHF). Genetic polymorphisms and variations in the host immune response are believed to contribute to different degrees to the disease progression. In this study, factors that have an influence on Dengue infection were identified. Genetic variants in the complement system, of which the degree of activation increases with Dengue severity, were identified. There was no association between the disease and complement genetic variants (complement factor H [CFH] rs3753394, CFH rs1061170, CFH rs800292, complement factor B (FB) rs12614/rs641153 and complement C3 rs2230199) in Thai cohorts. By contrast, with
multiplex bead immunoassay, numerous biological markers measured in the plasma of
Dengue patients were shown to increase the risk of Dengue severity. Up-regulation of plasma matrix metalloproteinase 3 (MMP-3) was shown to be associated with the risk of developing DHF even though recombinant MMP-3 (rMMP-3) did not affect endothelial permeability in vitro. Finally, an early predictive model to predict DHF was examined by using binary logistic regression. Low platelet cell count and high plasma levels of Monocyte chemotactic protein 2 (MCP2) were identified as early indicators. Sensitivity, specificity, and accuracy of the test were 73.17%, 83.13% and 82%, respectively. These data might be useful in the development of therapeutic agents and predictive markers for Dengue infection.
multiplex bead immunoassay, numerous biological markers measured in the plasma of
Dengue patients were shown to increase the risk of Dengue severity. Up-regulation of plasma matrix metalloproteinase 3 (MMP-3) was shown to be associated with the risk of developing DHF even though recombinant MMP-3 (rMMP-3) did not affect endothelial permeability in vitro. Finally, an early predictive model to predict DHF was examined by using binary logistic regression. Low platelet cell count and high plasma levels of Monocyte chemotactic protein 2 (MCP2) were identified as early indicators. Sensitivity, specificity, and accuracy of the test were 73.17%, 83.13% and 82%, respectively. These data might be useful in the development of therapeutic agents and predictive markers for Dengue infection.
Version
Open Access
Date Issued
2015-02
Date Awarded
2015-08
Copyright Statement
Attribution NoDerivatives 4.0 International Licence (CC BY-ND)
Advisor
Mongkolsapaya, Juthathip
Screaton, Gavin R
Pickering, Matthew C
Sponsor
Thailand
Publisher Department
Department of Medicine
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)