Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pntd.0006217
Title: Serum metabolome changes in adult patients with severe dengue in the critical and recovery phases of dengue infection
Authors: Cui L.
Pang J. 
Lee Y.H. 
Ooi E.E. 
Ong C.N. 
Leo Y.S. 
Tannenbaum S.R.
Keywords: 2 octenoylcarnitine
3 hydroxyoctanoyl carnitine
acylcarnitine
amino acid derivative
glycocholic acid
glycoursodeoxycholic acid
hypoxanthine
phenylalanine
purine
purine derivative
unclassified drug
uric acid
uridine
adult
Article
clinical article
convalescence
critical phase
dengue
dengue hemorrhagic fever
disease course
hematological parameters
human
liquid chromatography-mass spectrometry
liver injury
mass spectrometry
metabolome
metabolomics
oxidative stress
recovery phase
serology
severe dengue
virology
chemistry
pathology
serum
severe dengue
Adult
Humans
Mass Spectrometry
Metabolome
Serum
Severe Dengue
Issue Date: 2018
Citation: Cui L., Pang J., Lee Y.H., Ooi E.E., Ong C.N., Leo Y.S., Tannenbaum S.R. (2018). Serum metabolome changes in adult patients with severe dengue in the critical and recovery phases of dengue infection. PLoS Neglected Tropical Diseases 12 (1) : e0006217. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pntd.0006217
Abstract: Dengue virus (DENV) is the most prevalent arbovirus leading to an estimated 100 million symptomatic dengue infections every year. DENV can cause a spectrum of clinical manifestations, ranging from mild dengue fever (DF) to more life threatening forms such as dengue hemorrhagic fever (DHF). The clinical symptoms of DHF become evident typically at the critical phase of infection (5?7 days after onset of fever), yet the mechanisms that trigger transition from DF to DHF are not well understood. We performed a mass spectrometry-based metabolomic profiling of sera from adult DF and DHF patients at the critical and recovery phases of infection. There were 29 differentially expressed metabolites identified between DF and DHF at the critical phase. These include bile acids, purines, acylcarnitines, phospholipids, and amino acids. Bile acids were observed up to 5 fold higher levels among DHF compared to DF patients and were significantly correlated to the higher levels of aspartate transaminase (AST) and alanine transaminase (ALT), suggestive of liver injury among DHF. Uric acid, the most abundant antioxidant in the blood, was observed to be 1.5 fold lower among DHF compared to DF patients. This could result in decreased capacity of endogenous antioxidant defense and elevated oxidative stress among DHF patients. In the recovery phase, the levels of eight metabolites were still significantly higher or lower among DHF patients, including chenodeoxyglycocholic acid, one of the bile acids observed at the critical phase. This indicates potential prolonged adverse impact on the liver due to DENV infection in DHF patients. Our study identified altered metabolic pathways linked to DHF in the critical and recovery phases of dengue infection and provided insights into the different host and DENV interactions between DF and DHF. The results advance our understanding on the mechanisms of DHF pathogenesis, alluding to possible novel therapeutic targets to dengue management. ? 2018 Cui et al.
Source Title: PLoS Neglected Tropical Diseases
URI: https://scholarbank.nus.edu.sg/handle/10635/161887
ISSN: 19352727
DOI: 10.1371/journal.pntd.0006217
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