scholarly journals Increased Plasma Heparanase Activity and Endothelial Glycocalyx Degradation in Dengue Patients Is Associated With Plasma Leakage

2021 ◽  
Vol 12 ◽  
Author(s):  
Baranca Buijsers ◽  
Fadel Muhammad Garishah ◽  
Silvita Fitri Riswari ◽  
Rosalie M. van Ast ◽  
Setyo Gundi Pramudo ◽  
...  

BackgroundEndothelial hyper-permeability with plasma leakage and thrombocytopenia are predominant features of severe dengue virus infection. It is well established that heparanase, the endothelial glycocalyx degrading enzyme, plays a major role in various diseases with vascular leakage. It is yet to be elucidated whether heparanase activity plays a major role in dengue-associated plasma leakage. Moreover, the major source of heparanase secretion and activation in dengue remains elusive. Since a relatively high amount of heparanase is stored in platelets, we postulate that heparanase released by activated platelets contributes to the increased plasma heparanase activity during dengue virus infection.MethodsHeparanase activity (plasma and urine), and heparan sulfate and syndecan-1 (plasma levels) were measured in dengue patients with thrombocytopenia in acute phase (n=30), during course of disease (n=10) and in convalescent phase (n=25). Associations with clinical parameters and plasma leakage markers were explored. Platelets from healthy donors were stimulated with dengue non-structural protein-1, DENV2 virus and thrombin to evaluate heparanase release and activity ex vivo.ResultsHeparanase activity was elevated in acute dengue and normalized during convalescence. Similarly, glycocalyx components, such as heparan sulfate and syndecan-1, were increased in acute dengue and restored during convalescence. Increased heparanase activity correlated with the endothelial dysfunction markers heparan sulfate and syndecan-1, as well as clinical markers of plasma leakage such as ascites, hematocrit concentration and gall-bladder wall thickening. Notably, platelet number inversely correlated with heparanase activity. Ex vivo incubation of platelets with thrombin and live DENV2 virus, but not dengue virus-2-derived non-structural protein 1 induced heparanase release from platelets.ConclusionTaken together, our findings suggest that the increase of heparanase activity in dengue patients is associated with endothelial glycocalyx degradation and plasma leakage. Furthermore, thrombin or DENV2 activated platelets may be considered as a potential source of heparanase.

2021 ◽  
Vol 166 (5) ◽  
pp. 1439-1446 ◽  
Author(s):  
Selvin Noé Palacios-Rápalo ◽  
Luis Adrián De Jesús-González ◽  
José Manuel Reyes-Ruiz ◽  
Juan Fidel Osuna-Ramos ◽  
Carlos Noe Farfan-Morales ◽  
...  

Author(s):  
Arnaud Lecadieu ◽  
Laura Teysseyre ◽  
Kevin Larsen ◽  
Charles Vidal ◽  
Margot Caron ◽  
...  

Since 2018, a dengue epidemic has been ongoing in the French overseas department of Reunion Island, in the Indian Ocean, with more than 25,000 serologically confirmed cases. Currently, three dengue serotypes have been identified in Réunion Island (DENV-1, DENV-2, and DENV-3) progressing in the form of epidemic outbreaks. This arbovirus is mainly transmitted by mosquitoes of the genus Aedes and may be responsible for serious clinical forms. To date, very few cases of kidney transplant–related dengue virus infection have been described. Here we report the first case of severe dengue virus infection related to kidney transplantation from a patient previously infected with dengue. Testing for dengue fever with PCR search in donor’s urine may help complete the pretransplant assessment in areas where this disease occurs.


2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Yu-Wen Chien ◽  
Hsiang-Min Huang ◽  
Tzu-Chuan Ho ◽  
Fan-Chen Tseng ◽  
Nai-Ying Ko ◽  
...  

Author(s):  
Puneet Bhatt ◽  
Sasidharan Pillai Sabeena ◽  
Muralidhar Varma ◽  
Govindakarnavar Arunkumar

AbstractThe pathogenesis of dengue virus infection is attributed to complex interplay between virus, host genes and host immune response. Host factors such as antibody-dependent enhancement (ADE), memory cross-reactive T cells, anti-DENV NS1 antibodies, autoimmunity as well as genetic factors are major determinants of disease susceptibility. NS1 protein and anti-DENV NS1 antibodies were believed to be responsible for pathogenesis of severe dengue. The cytokine response of cross-reactive CD4+ T cells might be altered by the sequential infection with different DENV serotypes, leading to further elevation of pro-inflammatory cytokines contributing a detrimental immune response. Fcγ receptor-mediated antibody-dependent enhancement (ADE) results in release of cytokines from immune cells leading to vascular endothelial cell dysfunction and increased vascular permeability. Genomic variation of dengue virus and subgenomic flavivirus RNA (sfRNA) suppressing host immune response are viral determinants of disease severity. Dengue infection can lead to the generation of autoantibodies against DENV NS1antigen, DENV prM, and E proteins, which can cross-react with several self-antigens such as plasminogen, integrin, and platelet cells. Apart from viral factors, several host genetic factors and gene polymorphisms also have a role to play in pathogenesis of DENV infection. This review article highlights the various factors responsible for the pathogenesis of dengue and also highlights the recent advances in the field related to biomarkers which can be used in future for predicting severe disease outcome.


2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S651-S652
Author(s):  
Fernando Rosso ◽  
Ana M Sanz ◽  
Luis Gabriel Parra-Lara ◽  
Pablo A Moncada ◽  
Juan D Vélez ◽  
...  

Abstract Background Dengue fever is the most prevalent arbovirus among humans, its incidence has increased since the re-emergence, and Colombia is a hyperendemic country for this infection. The number of solid-organ transplant (SOT) recipients, at risk of acquiring dengue virus infection, is constantly increasing, and there are few data regarding the clinical course and outcomes of dengue infection among this population. The aim of this study was to describe dengue virus infection in SOT recipients in Cali, Colombia. Methods We present a case series of SOT recipients with dengue virus infection, diagnosed by World Health Organization criteria and a positive NS1 and/or IgM dengue antibodies, which were attended at the FVL from 2001 to 2018. Furthermore, we performed a literature review regarding dengue infection in SOT recipients. Results A total of 20 patients were included: 17 kidney and 3 liver recipients. The median age was 50.5 years (IQR = 31–63.5), 65% were female. The median time from transplant to dengue was 27.6 months (IQR = 3.82–59.12), and 3 patients had the infection in the first month after the transplant. The most common symptoms were fever (95%), myalgia, headache, and abdominal pain. Warning signs were present in 75% of patients, thrombocytopenia and hemorrhagic manifestations were present in 30% and 15%, respectively. 35% of patients were classified as severe dengue, and 45% were managed at the intensive care unit. Regarding laboratory findings, six patients had transaminases elevation more than three times the upper limit and 7 had serum creatinine elevation, which returned to normal levels. All patients were discharged and none of them had alterations in the graft function. To date, there are approximately 180 reported cases of dengue in SOT recipients (Table 2). Conclusion Dengue represents a threat among SOT recipients. Unlike other reports, all patients in this series had a full recovery after the infection, suggesting that timely and effective management of patients and the access to high complexity services could prevent fatal cases. Disclosures All authors: No reported disclosures.


2007 ◽  
Vol 195 (8) ◽  
pp. 1081-1083 ◽  
Author(s):  
Annelies Wilder‐Smith ◽  
Paul Ananth Tambyah

2020 ◽  
Vol 7 (5) ◽  
pp. 814
Author(s):  
Thyagaraj . ◽  
Sreedevi T.

Background: Dengue viruses are flavivirus, which include four serotypes 1, 2, 3 and 4. Clinical expression of dengue virus infection vary from asymptomatic infection to severe dengue with shock. It is the most rapidly spreading vector borne disease in the world. An estimated 50 million dengue infections occur annually and approximately 2.5 billion people live in dengue endemic countries. The objective of this study was to predict the severity of Dengue illness by correlating the serum albumin levels.Methods: An observational cross-sectional study done on patients admitted in Basaveshwara Medical College and Research Institute, Chitradurga, Karnataka, a tertiary care Hospital. Patients with Dengue NS1 Ag or IgM positive are included in the study after meeting inclusion and exclusion criteria. Complete Blood count, serum albumin levels are estimated at the time of admission.Results: Study enrolled 100 patients with confirmed Dengue virus infection who were admitted to the hospital between July 2017 and December 2018. Serum samples taken within 24 hours of admission was used for biochemical tests. Out of 100 patients, 24 developed Severe Dengue. Cases of Severe Dengue had low levels of serum albumin. Multivariate analysis showed that early alterations of albumin i.e. out of 24 patients who developed severe dengue, 21 patients i.e. 92.7% had low albumin of <3gm/dlConclusions: Early changes in biochemical parameter, serum albumin can predict Severe Dengue in patients with Dengue febrile illness.


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