Abstract
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. 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. 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). Endothelial dysfunction/NO bioavailability is associated with worse plasma leakage, occurs early in dengue illness and correlates with hypoargininemia and high arginase-1 levels.
Highlights
Dengue can cause increased vascular permeability that may lead to hypovolemic shock
Endothelial dysfunction/nitric oxide (NO) bioavailability is associated with worse plasma leakage, occurs early in dengue illness and correlates with hypoargininemia and high arginase-1 levels
Dengue can present with a broad spectrum of clinical phenotypes, the defining feature of severe disease is altered vascular permeability resulting in a unique plasma leakage syndrome, which can progress to hypovolemic shock, known as dengue shock syndrome (DSS)
Summary
We performed a prospective observational study in 2 Vietnamese hospitals, assessing patients presenting early (3 years of age with a clinical diagnosis of possible dengue were eligible for enrollment into 1 of 2 study arms. Participants presenting within 72 hours of fever onset could be enrolled if no obvious alternative cause for the fever was apparent clinically [14]. Any individual admitted to NHTD or HTD with suspected dengue with warning signs or with severe dengue was eligible [15]. All patients were reviewed daily until fully recovered or for up to 6 days from enrollment, and at a follow-up visit 14 days later
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