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Abstract
BackgroundAlthough increased capillary permeability is the major clinical feature associated with severe dengue infections the mechanisms underlying this phenomenon remain unclear. Dextran clearance methodology has been used to investigate the molecular sieving properties of the microvasculature in clinical situations associated with altered permeability, including during pregnancy and in various renal disorders. In order to better understand the characteristics of the vascular leak associated with dengue we undertook formal dextran clearance studies in Vietnamese dengue patients and healthy volunteers.Methodology/Principal FindingsWe carried out serial clearance studies in 15 young adult males with acute dengue and evidence of vascular leakage a) during the phase of maximal leakage and b) one and three months later, as well as in 16 healthy control subjects. Interestingly we found no difference in the clearance profiles of neutral dextran solutions among the dengue patients at any time-point or in comparison to the healthy volunteers.Conclusions/SignificanceThe surface glycocalyx layer, a fibre-matrix of proteoglycans, glycosaminoglycans, and plasma proteins, forms a complex with the underlying endothelial cells to regulate plasma volume within circumscribed limits. It is likely that during dengue infections loss of plasma proteins from this layer alters the permeability characteristics of the complex; physical and/or electrostatic interactions between the dextran molecules and the glycocalyx structure may temporarily restore normal function, rendering the technique unsuitable for assessing permeability in these patients. The implications for resuscitation of patients with dengue shock syndrome (DSS) are potentially important. It is possible that continuous low-dose infusions of dextran may help to stabilize the permeability barrier in patients with profound or refractory shock, reducing the need for repeated boluses, limiting the total colloid volume required. Formal clinical studies should help to assess this strategy as an alternative to conventional fluid resuscitation for severe DSS.
Highlights
Dengue infection is increasingly being recognised as a major burden on global health [1]
We performed carbohydrate clearance studies in 15 Vietnamese adult males with dengue and plasma leakage, comparing results obtained during the acute illness with recovery values, and results from a group of healthy volunteers
This means that the technique is unsuitable for investigating leakage in dengue patients, the implications for management of patients with severe leakage resulting in shock are potentially important
Summary
Dengue infection is increasingly being recognised as a major burden on global health [1]. Infection with any of the four viral serotypes may result in asymptomatic infection, or cause a variety of disease manifestations ranging from non-specific fever to a severe syndrome characterised by increased vascular permeability, deranged haemostasis and thrombocytopenia [2]. Despite the fact that vascular leakage is the pathognomonic feature of severe dengue, little is known of the mechanisms underlying the change in permeability. The prevailing view is that dengue infection triggers an immunopathogenic cascade that alters microvascular structure or function in some as yet undefined way, resulting in a transient, spontaneously-reversible increase in permeability [3]. Increased capillary permeability is the major clinical feature associated with severe dengue infections the mechanisms underlying this phenomenon remain unclear. Dextran clearance methodology has been used to investigate the molecular sieving properties of the microvasculature in clinical situations associated with altered permeability, including during pregnancy and in various renal disorders. In order to better understand the characteristics of the vascular leak associated with dengue we undertook formal dextran clearance studies in Vietnamese dengue patients and healthy volunteers
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