Urinary leukotrienes and histamine in patients with varying severity of acute dengue.

<h4>Background</h4>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 LTE4 and urinary histamine in...

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Main Authors: Tehani Silva, Chandima Jeewandara, Laksiri Gomes, Chathurika Gangani, Sameera D Mahapatuna, Thilagaraj Pathmanathan, Ananda Wijewickrama, Graham S Ogg, Gathsaurie Neelika Malavige
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2021-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0245926
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author Tehani Silva
Chandima Jeewandara
Laksiri Gomes
Chathurika Gangani
Sameera D Mahapatuna
Thilagaraj Pathmanathan
Ananda Wijewickrama
Graham S Ogg
Gathsaurie Neelika Malavige
author_facet Tehani Silva
Chandima Jeewandara
Laksiri Gomes
Chathurika Gangani
Sameera D Mahapatuna
Thilagaraj Pathmanathan
Ananda Wijewickrama
Graham S Ogg
Gathsaurie Neelika Malavige
author_sort Tehani Silva
collection DOAJ
description <h4>Background</h4>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 LTE4 and urinary histamine in patients with varying severity of acute dengue.<h4>Methods</h4>Urinary LTE4, histamine and creatinine were measured by a quantitative ELISA, in healthy individuals (n = 19), patients with dengue fever (DF = 72) and dengue haemorrhagic fever DHF (n = 48). The kinetics of LTE4 and histamine and diurnal variations were assessed in a subset of patients.<h4>Results</h4>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), which continued to rise in patients who developed DHF during the course of illness. However, LTE4 is unlikely to be a good biomarker as ROCs gave an AUC value of 0.67 (95% CI 0.57 and 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. Urinary histamine levels were significantly high in patients with acute dengue although no difference was observed between patients with DF and DHF and again did not associate with the viraemia. Interestingly, LTE4, histamine and the viral loads showed a marked diurnal variation in both patients with DF and DHF.<h4>Conclusions</h4>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.
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spelling doaj.art-79194b72ad4b4d948c396630420ae64c2022-12-21T17:23:58ZengPublic Library of Science (PLoS)PLoS ONE1932-62032021-01-01162e024592610.1371/journal.pone.0245926Urinary leukotrienes and histamine in patients with varying severity of acute dengue.Tehani SilvaChandima JeewandaraLaksiri GomesChathurika GanganiSameera D MahapatunaThilagaraj PathmanathanAnanda WijewickramaGraham S OggGathsaurie Neelika Malavige<h4>Background</h4>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 LTE4 and urinary histamine in patients with varying severity of acute dengue.<h4>Methods</h4>Urinary LTE4, histamine and creatinine were measured by a quantitative ELISA, in healthy individuals (n = 19), patients with dengue fever (DF = 72) and dengue haemorrhagic fever DHF (n = 48). The kinetics of LTE4 and histamine and diurnal variations were assessed in a subset of patients.<h4>Results</h4>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), which continued to rise in patients who developed DHF during the course of illness. However, LTE4 is unlikely to be a good biomarker as ROCs gave an AUC value of 0.67 (95% CI 0.57 and 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. Urinary histamine levels were significantly high in patients with acute dengue although no difference was observed between patients with DF and DHF and again did not associate with the viraemia. Interestingly, LTE4, histamine and the viral loads showed a marked diurnal variation in both patients with DF and DHF.<h4>Conclusions</h4>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.https://doi.org/10.1371/journal.pone.0245926
spellingShingle Tehani Silva
Chandima Jeewandara
Laksiri Gomes
Chathurika Gangani
Sameera D Mahapatuna
Thilagaraj Pathmanathan
Ananda Wijewickrama
Graham S Ogg
Gathsaurie Neelika Malavige
Urinary leukotrienes and histamine in patients with varying severity of acute dengue.
PLoS ONE
title Urinary leukotrienes and histamine in patients with varying severity of acute dengue.
title_full Urinary leukotrienes and histamine in patients with varying severity of acute dengue.
title_fullStr Urinary leukotrienes and histamine in patients with varying severity of acute dengue.
title_full_unstemmed Urinary leukotrienes and histamine in patients with varying severity of acute dengue.
title_short Urinary leukotrienes and histamine in patients with varying severity of acute dengue.
title_sort urinary leukotrienes and histamine in patients with varying severity of acute dengue
url https://doi.org/10.1371/journal.pone.0245926
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