Endothelial dysfunction/reduced nitric oxide bioavailability is associated with worse plasma leakage in dengue patients and occurs early in the course of the disease. Endothelial dysfunction correlates with lower plasma l-arginine and higher arginase-1 levels.

Background: Dengue is the most common arboviral infection globally; a minority of patients develop shock due to profound plasma leak through a disrupted endothelial barrier. Understanding of the pathophysiology underlying plasma leak is incomplete, but emerging evidence indicates a key role for degradation of the endothelial glycocalyx. Conclusions: We present the first human in vivo evidence of glycocalyx disruption in dengue, with worse visual glycocalyx damage and higher plasma degradation products associated with more severe plasma leak.

Background Brainstem encephalitis is a serious complication of hand foot and mouth disease (HFMD) in children. Autonomic nervous system (ANS) dysregulation and hypertension may occur, sometimes progressing to cardiopulmonary failure and death. Vietnamese national guidelines recommend use of milrinone if ANS dysregulation with Stage 2 hypertension develops. We wished to investigate whether magnesium sulfate (MgSO 4 ) improved outcomes in children with HFMD if used earlier in the evolution of the ANS dysregulation (Stage 1 hypertension). Methods During a regional epidemic we conducted a randomized, double-blind, placebo-controlled trial of MgSO 4 in children with HFMD, ANS dysregulation and Stage 1 hypertension, at the Hospital for Tropical Diseases in Ho Chi Minh city. Study participants received an infusion of MgSO 4 or matched placebo for 72 h. We also reviewed data from non-trial HFMD patients in whom milrinone failed to control hypertension, some of whom received MgSO 4 as second line therapy. The primary outcome for both analyses was a composite of disease progression within 72 h - addition of milrinone (trial participants only), need for ventilation, shock, or death. Results Between June 2014 and September 2016, 14 and 12 participants received MgSO 4 or placebo respectively, before the trial was stopped due to futility. Among 45 non-trial cases with poorly controlled hypertension despite high-dose milrinone, 33 received MgSO 4 while 12 did not. There were no statistically significant differences in the composite outcome between the MgSO 4 and the placebo/control groups in either study (adjusted relative risk (95%CI) of [6/14 (43%) vs. 6/12 (50%)], 0.84 (0.37, 1.92), p = 0.682 in the trial and [1/33 (3%) vs. 2/12 (17%)], 0.16 (0.01, 1.79), p = 0.132 in the observational cohort). The incidence of adverse events was similar between the groups. Potentially toxic magnesium levels occurred very rarely with the infusion regime used. Conclusion Although we could not demonstrate efficacy in these studies, there were no safety signals associated with use of 30-50 mg/kg/hr. MgSO 4 in severe HFMD. Intermittent outbreaks of HFMD are likely to continue across the region, and an adequately powered trial is still needed to evaluate use of MgSO 4 in controlling hypertension in severe HFMD, potentially involving a higher dose regimen. Trial registration ClinicalTrials.gov Identifier: NCT01940250 (Registered 22 AUG 2013). Trial sponsor : University of Oxford Electronic supplementary material The online version of this artic...