title: Increased Serum Hyaluronic Acid and Heparan Sulfate in Dengue Fever: Association with Plasma Leakage and Disease Severity.
abstract: Plasma leakage is a major pathogenic mechanism of severe dengue, but the etiology remains unclear. The association between endothelial glycocalyx integrity and vascular permeability in older adults with dengue has not been evaluated. A prospective cohort study of adults with undifferentiated fever screened for dengue by RT-PCR or NS1 antigen testing was performed. Patients were assessed daily while symptomatic and at convalescence. Serum hyaluronic acid (HA), heparan sulfate (HS) and selected cytokines (TNF-α, IL-6, IL-10) were measured on enrollment and convalescence. Patients were diagnosed as dengue fever (DF, n = 30), dengue hemorrhagic fever (DHF, n = 20) and non-dengue (ND) febrile illness (n = 11). Acute HA and HS levels were significantly higher in all dengue patients compared to ND (p = 0.0033 and p = 0.0441 respectively), but not different between DF and DHF (p = 0.3426 and p = 0.9180 respectively). Enrolment HA inversely correlated with serum albumin, protein and platelets in all dengue and DHF (p < 0.05). HA and HS in all dengue patients decreased significantly at convalescence. Serum IL-10 was significantly associated with HA in all dengue patients (p = 0.002). Serum HA and HS levels were increased in adult dengue and HA was associated with markers of disease severity. Endothelial glycocalyx damage may have a role in vascular leakage in dengue.
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Queen Elizabeth Hospital, Hong Kong SAR.
authors.forename: Tommy Hing-Cheung
authors.initials: TH
authors.lastname: Tang
authors.affiliation: Department of Microbiology, Yong Loo Lin School of Medicine and Immunology programme, Life Sciences Institute, National University of Singapore, Singapore.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Alonso
authors.affiliation: Laboratory of Microbial Immunity, Singapore Immunology Network (SIgN), A*STAR, Singapore.
authors.forename: Lisa Fong-Poh
authors.initials: LF
authors.lastname: Ng
authors.affiliation: Communicable Disease Centre, Institute of Infectious Diseases and Epidemiology, Tan Tock Seng Hospital, Singapore.
authors.forename: Tun-Linn
authors.initials: TL
authors.lastname: Thein
authors.affiliation: Communicable Disease Centre, Institute of Infectious Diseases and Epidemiology, Tan Tock Seng Hospital, Singapore.|Saw Swee Hock School of Public Health, National University of Singapore, Singapore.
authors.forename: Vincent Jun-Xiong
authors.initials: VJ
authors.lastname: Pang
authors.affiliation: Communicable Disease Centre, Institute of Infectious Diseases and Epidemiology, Tan Tock Seng Hospital, Singapore.|Saw Swee Hock School of Public Health, National University of Singapore, Singapore.|Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Yee-Sin
authors.initials: YS
authors.lastname: Leo
authors.affiliation: Communicable Disease Centre, Institute of Infectious Diseases and Epidemiology, Tan Tock Seng Hospital, Singapore.|Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: David Chien-Boon
authors.initials: DC
authors.lastname: Lye
authors.affiliation: Communicable Disease Centre, Institute of Infectious Diseases and Epidemiology, Tan Tock Seng Hospital, Singapore.|Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore.
authors.forename: Tsin-Wen
authors.initials: TW
authors.lastname: Yeo
mesh_terms: D000208:Acute Disease; D000328:Adult; D015415:Biomarkers / Q000097:blood; D016207:Cytokines / Q000097:blood; D003715:Dengue / Q000097:blood* / Q000473:pathology*; D005260:Female; D006497:Heparan Sulfate / Q000097:blood*; D006801:Humans; D006820:Hyaluronic Acid / Q000097:blood*; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers; D016207:Cytokines; D006497:Heparan Sulfate; D006820:Hyaluronic Acid; D018836:Inflammation Mediators