Summary
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.