Tehani Silva

and 7 more

Vascular leak is a hallmark of severe dengue, and high leukotriene levels have been observed in dengue mouse models, suggesting a role in disease pathogenesis. We sought to explore their role in acute dengue, by assessing levels of urinary leukotriene (LTE4) and histamine in patients with varying severity of acute dengue. Urinary LTE4, histamine and creatinine were measured by a quantitative ELISA, in mid-morning urine samples collected from healthy individuals (n= 19) and patients with dengue fever (DF= 72) and dengue haemorrhagic fever (DHF= 48). The kinetics of LTE4 and histamine and diurnal variations were assessed in a subset of patients. Urinary LTE4 levels were significantly higher (p=0.004) in patients who proceed to develop DHF when compared to patients with DF during early illness (≤ 4 days) and during the critical phase (p=0.02). However, LTE4 was not a good predictive marker of DHF as ROCs gave an AUC value of 0.67 (95% CI 0.57 to 0.76), which was nevertheless significant (p=0.002). Urinary LTE4 levels did not associate with the degree of viraemia, infecting virus serotype and was not different in those with primary vs secondary dengue. LTE4, histamine and the viral loads showed a marked diurnal variation in both patients with DF and DHF. Our data suggest that LTE4 could play a role in disease pathogenesis and since there are safe and effective cysteinyl leukotriene receptor blockers, it would be important to assess their efficacy in reducing dengue disease severity.