Association of microvascular function and endothelial biomarkers with clinical outcome in dengue: An observational study

Sophie Yacoub, Phung Khanh Lam, Le Hoang Mai Vu, Thi Lien Le, Ngo Thanh Ha, Tran Thi Toan, Nguyen Thu Van, Nguyen Than Ha Quyen, Huynh Thi Le Duyen, Nguyen Van Kinh, Annette Fox, Juthathip Mongkolspaya, Marcel Wolbers, Cameron P. Simmons, Gavin Robert Screaton, Heiman Wertheim, Bridget Wills

Research output: Contribution to journalArticleResearchpeer-review

36 Citations (Scopus)


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 darkfield 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.

Original languageEnglish
Pages (from-to)697-706
Number of pages10
JournalThe Journal of Infectious Diseases
Issue number5
Publication statusPublished - 1 Sept 2016
Externally publishedYes


  • Angiopoietin 2
  • Dengue
  • Microcirculation
  • Sidestream dark field imaging
  • Vascular cell adhesion molecule 1

Cite this