P.Y.CHIA1, A.TEO2, T.W.YEO2
Tan Tock Seng Hospital1, Nanyang Technological University2
Dengue is the most important arthropod-borne virus in Southeast Asia. The main pathogenic mechanism is increased vascular permeability, leading to shock and organ dysfunction. The endothelial glycocalyx carpets the luminal surface of endothelial cells in blood vessels and regulates vascular permeability. This glycocalyx is susceptible to degradation by mediators released from innate immune cells. We hypothesized that glycocalyx thickness decreases and neutrophil mediators increases with increased dengue severity.
We measured glycocalyx thickness, glycocalyx breakdown products, neutrophil mediators and haematocrit change prospectively in 148 adult dengue patients and 30 controls. In dengue patients, measurements were done at febrile, critical and recovery phases, and severity was classified using World Health Organization 2009 criteria. Glycocalyx thickness was assessed in sublingual capillaries by measuring perfused boundary region in vessels 5-25 µm (PBR5) in diameter using a sidestream darkfield microscope camera. Syndecan-1, a glycocalyx proteoglycan, and neutrophil mediators (elastase and myeloperoxidase) were measured using ELISA.
In febrile and critical phases, PBR5 and syndecan-1 were significantly higher in patients with severe dengue, compared to dengue with warning signs, dengue fever and controls. Haematocrit change (P<0.001), myeloperoxidase levels (P<0.001) and elastase levels (P=0.04) were also significantly increased with increased disease severity. Only in the critical phase, haematocrit change was correlated with PBR5 (R=0.27; P=0.003) and myeloperoxidase levels (R=0.30, P=0.012).
Severe disease and increased vascular permeability in adult dengue is associated with decreased glycocalyx thickness and increased neutrophil myeloperoxidase levels. Therapies which augment glycocalyx thickness and decrease myeloperoxidase levels have potential as adjunctive therapies in dengue management.