title: Association of Microvascular Function and Endothelial Biomarkers With Clinical Outcome in Dengue: An Observational Study.
abstract: BACKGROUND
  The hallmark of severe dengue is increased microvascular permeability, but alterations in the microcirculation and their evolution over the course of dengue are unknown.
  
  
  METHODS
  We conducted a prospective observational study to evaluate the sublingual microcirculation using side-stream dark-field imaging in patients presenting early (<72 hours after fever onset) and patients hospitalized with warning signs or severe dengue in Vietnam. Clinical findings, microvascular function, global hemodynamics assessed with echocardiography, and serological markers of endothelial activation were determined at 4 time points.
  
  
  RESULTS
  A total of 165 patients were enrolled. No difference was found between the microcirculatory parameters comparing dengue with other febrile illnesses. The proportion of perfused vessels (PPV) and the mean flow index (MFI) were lower in patients with dengue with plasma than those without leakage (PPV, 88.1% vs 90.6% [P = .01]; MFI, 2.1 vs 2.4 [P = .007]), most markedly during the critical phase. PPV and MFI were correlated with the endothelial activation markers vascular cell adhesion molecule 1 (P < .001 for both) and angiopoietin 2 (P < .001 for both), negatively correlated.
  
  
  CONCLUSIONS
  Modest microcirculatory alterations occur in dengue, are associated with plasma leakage, and are correlate with molecules of endothelial activation, angiopoietin 2 and vascular cell adhesion molecule 1.
authors.affiliation: Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Programme, Ho Chi Minh City, Hanoi Department of Medicine, Imperial College London.
authors.forename: Sophie
authors.initials: S
authors.lastname: Yacoub
authors.affiliation: Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Programme, Ho Chi Minh City, Hanoi.
authors.forename: Phung Khanh
authors.initials: PK
authors.lastname: Lam
authors.affiliation: Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Programme, Ho Chi Minh City, Hanoi.
authors.forename: Le Hoang Mai
authors.initials: le HM
authors.lastname: Vu
authors.affiliation: National Hospital for Tropical Diseases, Hanoi, Vietnam.
authors.forename: Thi Lien
authors.initials: TL
authors.lastname: Le
authors.affiliation: National Hospital for Tropical Diseases, Hanoi, Vietnam.
authors.forename: Ngo Thanh
authors.initials: NT
authors.lastname: Ha
authors.affiliation: National Hospital for Tropical Diseases, Hanoi, Vietnam.
authors.forename: Tran Thi
authors.initials: TT
authors.lastname: Toan
authors.affiliation: Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Programme, Ho Chi Minh City, Hanoi.
authors.forename: Nguyen Thu
authors.initials: NT
authors.lastname: Van
authors.affiliation: Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Programme, Ho Chi Minh City, Hanoi.
authors.forename: Nguyen Than Ha
authors.initials: NT
authors.lastname: Quyen
authors.affiliation: Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Programme, Ho Chi Minh City, Hanoi.
authors.forename: Huynh Thi
authors.initials: HT
authors.lastname: Le Duyen
authors.affiliation: National Hospital for Tropical Diseases, Hanoi, Vietnam.
authors.forename: Nguyen
authors.initials: N
authors.lastname: Van Kinh
authors.affiliation: Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Programme, Ho Chi Minh City, Hanoi.
authors.forename: Annette
authors.initials: A
authors.lastname: Fox
authors.affiliation: Department of Medicine, Imperial College London.
authors.forename: Juthathip
authors.initials: J
authors.lastname: Mongkolspaya
authors.affiliation: Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Programme, Ho Chi Minh City, Hanoi.
authors.forename: Marcel
authors.initials: M
authors.lastname: Wolbers
authors.affiliation: Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Programme, Ho Chi Minh City, Hanoi Nuffield Department of Medicine, University of Oxford, United Kingdom.
authors.forename: Cameron Paul
authors.initials: CP
authors.lastname: Simmons
authors.affiliation: Department of Medicine, Imperial College London.
authors.forename: Gavin Robert
authors.initials: GR
authors.lastname: Screaton
authors.affiliation: Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Programme, Ho Chi Minh City, Hanoi Nuffield Department of Medicine, University of Oxford, United Kingdom.
authors.forename: Heiman
authors.initials: H
authors.lastname: Wertheim
authors.affiliation: Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Programme, Ho Chi Minh City, Hanoi Nuffield Department of Medicine, University of Oxford, United Kingdom.
authors.forename: Bridget
authors.initials: B
authors.lastname: Wills
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000032:analysis*; D001808:Blood Vessels / Q000000981:diagnostic imaging / Q000473:pathology*; D002199:Capillary Permeability; D002648:Child; D003715:Dengue / Q000000981:diagnostic imaging / Q000473:pathology*; D042783:Endothelial Cells / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D061848:Optical Imaging; D011446:Prospective Studies; D016896:Treatment Outcome; D014744:Vietnam; D055815:Young Adult
chemical_list: D015415:Biomarkers
keywords: Dengue; angiopoietin 2; microcirculation; sidestream dark field imaging; vascular cell adhesion molecule 1