Endothelial Nitric Oxide Pathways in the Pathophysiology of Dengue: A Prospective Observational Study

Sophie Yacoub, Phung Khanh Lam, Trieu Trung Huynh, Hong Hanh Nguyen Ho, Hoai Tam Dong Thi, Nguyen Van Thu, Le Thi Lien, Quyen Nguyen Than Ha, Duyen Huynh Thi Le, Juthathip Mongkolspaya, Abigail Culshaw, Tsin Wen Yeo, Heiman Wertheim, Cameron Simmons, Gavin Screaton, Bridget Wills

    Research output: Contribution to journalArticle

    Abstract

    Background: Dengue can cause increased vascular permeability that may lead to hypovolemic shock. Endothelial dysfunction may underlie this; however, the association of endothelial nitric oxide (NO) pathways with disease severity is unknown. 

    Methods: We performed a prospective observational study in 2 Vietnamese hospitals, assessing patients presenting early (<72 hours of fever) and patients hospitalized with warning signs or severe dengue. The reactive hyperemic index (RHI), which measures endothelium-dependent vasodilation and is a surrogate marker of endothelial function and NO bioavailability, was evaluated using peripheral artery tonometry (EndoPAT), and plasma levels of l-arginine, arginase-1, and asymmetric dimethylarginine were measured at serial time-points. The main outcome of interest was plasma leakage severity. 

    Results: Three hundred fourteen patients were enrolled; median age of the participants was 21(interquartile range, 13-30) years. No difference was found in the endothelial parameters between dengue and other febrile illness. Considering dengue patients, the RHI was significantly lower for patients with severe plasma leakage compared to those with no leakage (1.46 vs 2.00; P <.001), over acute time-points, apparent already in the early febrile phase (1.29 vs 1.75; P =.012). RHI correlated negatively with arginase-1 and positively with l-arginine (P =.001). 

    Conclusions: Endothelial dysfunction/NO bioavailability is associated with worse plasma leakage, occurs early in dengue illness and correlates with hypoargininemia and high arginase-1 levels.

    Original languageEnglish
    Pages (from-to)1453-1461
    Number of pages9
    JournalClinical Infectious Diseases
    Volume65
    Issue number9
    DOIs
    Publication statusPublished - 1 Nov 2017

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  • Cite this

    Yacoub, S., Lam, P. K., Huynh, T. T., Nguyen Ho, H. H., Dong Thi, H. T., Van Thu, N., Lien, L. T., Ha, Q. N. T., Le, D. H. T., Mongkolspaya, J., Culshaw, A., Yeo, T. W., Wertheim, H., Simmons, C., Screaton, G., & Wills, B. (2017). Endothelial Nitric Oxide Pathways in the Pathophysiology of Dengue: A Prospective Observational Study. Clinical Infectious Diseases, 65(9), 1453-1461. https://doi.org/10.1093/cid/cix567