BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Authors: Manoj V Murhekar; P Kamaraj; Muthusamy Santhosh Kumar; Siraj Ahmed Khan; Ramesh Reddy Allam; Pradip Barde; Bhagirathi Dwibedi; Suman Kanungo; Uday Mohan; Suman Sundar Mohanty; Subarna Roy; Vivek Sagar; Deepali Savargaonkar; Babasaheb V Tandale; Roshan Kamal Topno; Gajanan Sapkal; C P Girish Kumar; R Sabarinathan; Velusamy Saravana Kumar; Sailaja Bitragunta; Gagandeep Singh Grover; P V M Lakshmi; Chandra Mauli Mishra; Provash Sadhukhan; Prakash Kumar Sahoo; S K Singh; Chander Prakash Yadav; Asha Bhagat; Rashi Srivastava; E Ramya Dinesh; T Karunakaran; C Govindhasamy; T Daniel Rajasekar; A Jeyakumar; A Suresh; D Augustine; P Ashok Kumar; Rajesh Kumar; Shanta Dutta; G S Toteja; Nivedita Gupta; Sanjay M Mehendale Journal: Lancet Glob Health Date: 2019-06-11 Impact factor: 26.763
Authors: Wai Mun Loke; Angelia Yee Chow; Karen Lam Mok Sing; Chung-Yung J Lee; Barry Halliwell; Erle C H Lim; Amy M L Quek; Eng Eong Ooi; Raymond C S Seet Journal: Virol J Date: 2013-10-30 Impact factor: 4.099
Authors: Chandima Jeewandara; Laksiri Gomes; N Wickramasinghe; Danuta Gutowska-Owsiak; Dominic Waithe; S A Paranavitane; N L A Shyamali; Graham S Ogg; Gathsaurie Neelika Malavige Journal: PLoS Negl Trop Dis Date: 2015-02-03