High Levels of Serum Hyaluronan Predicts Severe Dengue Infection and Perturbs Vascular Integrity

2019 ◽  
Author(s):  
Chun-Yu Lin ◽  
Constantinos Kolliopoulos ◽  
Chung-Hao Huang ◽  
Jyrki Tenhunen ◽  
Carl-Henrik Heldin ◽  
...  
2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Goutam Patra ◽  
Bibhuti Saha ◽  
Sumi Mukhopadhyay

AbstractDengue is an arboviral infection with high rates of morbidity and mortality throughout the tropics and sub-tropics. This work studied the status of pentraxin (CRP/SAP) protein, ferritin, TNF-α and IL-1β levels in Dengue patients of different pathophysiological manifestations. Accordingly, clinically confirmed Dengue cases (n = 97) were enrolled and subsequently blood parameters were studied by Haematology cell counter and Biochemistry Autoanalyser. CRP, SAP, ferritin, TNF-α and IL-1β ELISA were done in all the samples by using standard ELISA kits. Statistical Analysis was done in all the experiments. The levels of CRP (p < 0.0001), SAP (p < 0.0001), ferritin (p < 0.0001), TNF-α (p < 0.0001) and IL-1β (p < 0.0001) were high in patients with Severe Dengue as compared to Dengue without warning signs. High levels of SGOT, SGPT and decreased platelet counts were found in severe patients as compared to Healthy donor. CRP/SAP as well as TNF-α/IL-1β were independently associated with both dengue severity and overall disease manifestation. Statistically significant increased CRP, SAP, ferritin, TNF-α and IL-1β titres were correlated in patients with severe clinical manifestations as compared to mild disease forms of dengue. Elevated levels of pentraxin, TNF-α/IL-1β in blood during dengue infection could act as an early predictor in Severe Dengue infection.


Viruses ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1540
Author(s):  
Beatriz Sierra ◽  
Ana Cristina Magalhães ◽  
Daniel Soares ◽  
Bruno Cavadas ◽  
Ana B. Perez ◽  
...  

Transcriptomics, proteomics and pathogen-host interactomics data are being explored for the in silico–informed selection of drugs, prior to their functional evaluation. The effectiveness of this kind of strategy has been put to the test in the current COVID-19 pandemic, and it has been paying off, leading to a few drugs being rapidly repurposed as treatment against SARS-CoV-2 infection. Several neglected tropical diseases, for which treatment remains unavailable, would benefit from informed in silico investigations of drugs, as performed in this work for Dengue fever disease. We analyzed transcriptomic data in the key tissues of liver, spleen and blood profiles and verified that despite transcriptomic differences due to tissue specialization, the common mechanisms of action, “Adrenergic receptor antagonist”, “ATPase inhibitor”, “NF-kB pathway inhibitor” and “Serotonin receptor antagonist”, were identified as druggable (e.g., oxprenolol, digoxin, auranofin and palonosetron, respectively) to oppose the effects of severe Dengue infection in these tissues. These are good candidates for future functional evaluation and clinical trials.


Author(s):  
Velammal Petchiappan ◽  
Thaha Mohammed Hussain ◽  
Saravanan Thangavelu

Background: Dengue infection is a major public health threat; early recognition is crucial to improve the survival in severe dengue. Although there are various biomarkers to predict the severity of dengue, they are not routinely used in clinical practice for prognostication. We analyzed whether serum ferritin can be used to predict the severity at an earlier stage.Methods: A hospital based prospective observational study was done involving 119 dengue cases diagnosed by positive NS1 antigen or dengue specific serology (capture ELISA). Serum ferritin was measured in all at the time of diagnosis. Clinical and platelet count monitoring was done daily; classified as severe and non-severe according to 2009 WHO criteria.Results: Out of 119, 5 developed severe dengue; patients with severe dengue had significantly lower median platelet count (p<0.0001); higher ferritin levels (p=0.03) and hospital stay (p<0.0001) than non-severe group. Age had a significant negative co-relation with platelet count (r= -0.427; p<0.0001); positive correlation with ferritin levels (r=0.16; p=0.08) and hospital stay (r= 0.26; p=0.004) indicating that elderly subjects are at risk of severe disease. Serum ferritin levels negatively correlated with the platelet count (r= -0.51 p<0.001). High ferritin levels in severe cases are noted from day 4 of clinical illness.Conclusions: Elevated serum ferritin levels can be used as a potential early prognostic marker to predict the severity of dengue infection in clinical practice.


2018 ◽  
Vol 5 (6) ◽  
pp. 2265 ◽  
Author(s):  
Senthil Kumar K. ◽  
Rajendran N. K. ◽  
Ajith Brabhukumar C.

Background: In India, dengue epidemics are becoming more frequent (WHO, 2008). The majority of dengue viral infections are self-limiting, but complications may cause high morbidity and mortality. The objective of this study is to assess the clinical profile of the dengue infection in children less than 15 years of age and to evaluate the outcomes of dengue fever from March 2017 to July 2017 at the Pediatric Department of Karuna Medical College, the tertiary care hospital in Palakkad.Methods: In this retrospective study, medical records were reviewed and analyzed. Patients with suspected dengue infection were classified further into 2 groups, Dengue fever (probable dengue, dengue with warning signs) and ‘Severe Dengue’ (dengue hemorrhagic fever and/or dengue shock syndrome (DHF/DSS) according to WHO.Results: A total of 77 cases were classified into 67 (87%) non-severe and 10 (13%) severe dengue cases. The most common age of presentation was above 10 yrs. The mean age of admission was 8.9 yrs. The most common presenting symptom was fever seen in 93% followed by vomiting in 68%. Elevation in Aspartate transaminase (SGOT) and thrombocytopenia were found in 32.4 %.Conclusions: High grade fever, vomiting, abdominal pain and skin rash with normal or low platelet count were the presenting features. Early diagnosis, monitoring and prompt supportive management can reduce mortality.


2021 ◽  
Vol 8 (4) ◽  
pp. 706
Author(s):  
Srividya G. M. ◽  
Poornima Lakshmi

Background: The study was hepatic dysfunction in childhood dengue infection and to study clinical co-relation like severity, clinical features, and outcome.Methods: Dengue sero positive patients of 100 were admitted during the study period and examined for hepatomegaly and jaundice and subjected to complete blood count, liver function tests, ultrasound abdomen, PT, APTT, HBsAg, HCV, Widal and analysed.Results: All patients presented with fever, most commonly occurred in age group of 5 to 7 years, hepatomegaly was the commonest clinical sign seen, thrombocytopenia was seen in 88% of cases, serum total bilirubin was raised in 10% of subjects with severe dengue infection. Serum SGOT was raised in 74 % of patients with dengue. When compared between the groups, rise in SGOT occurred in 74% of patients with probable dengue, 98% with warning signs and 100% in severe dengue. SGPT was raised in 58% of patients with dengue infection. When compared between the groups, rise in SGPT occurred in 42% of patients with probable dengue, 66% with warning signs and 81% in severe dengue. SGPT was raised in 28% of patients with dengue infection. When compared between the groups, rise in SGOT occurred in 9.5% of patients with probable dengue, 32% with warning signs and 82% in severe dengue. Prothrombin time was raised in 11% of patients. When compared between the groups, rise in PT occurred in 6.4% with warning signs and 72% in severe dengue. When compared between the groups, rise in APTT occurred in 6.4% of patients with warning signs and 72% in severe dengue. When compared between the groups fall in serum protein occurred in 12.7% with warning signs and 54.5% in severe dengue. 2 cases of severe dengue expired, in which the enzyme levels were highly elevated.Conclusions: Significant rise of liver enzymes helps in recognition of severe forms of dengue infection. As hepatic dysfunction in dengue is transient and reversible, early identification of the same should help to reduce life threatening complications. This can help to reduce the morbidity and mortality due to dengue infection.al population.  


2007 ◽  
Vol 204 (5) ◽  
pp. 979-985 ◽  
Author(s):  
Kerstin Lühn ◽  
Cameron P. Simmons ◽  
Edward Moran ◽  
Nguyen Thi Phuong Dung ◽  
Tran Nguyen Bich Chau ◽  
...  

Dengue virus infection is an increasingly important tropical disease, causing 100 million cases each year. Symptoms range from mild febrile illness to severe hemorrhagic fever. The pathogenesis is incompletely understood, but immunopathology is thought to play a part, with antibody-dependent enhancement and massive immune activation of T cells and monocytes/macrophages leading to a disproportionate production of proinflammatory cytokines. We sought to investigate whether a defective population of regulatory T cells (T reg cells) could be contributing to immunopathology in severe dengue disease. CD4+CD25highFoxP3+ T reg cells of patients with acute dengue infection of different severities showed a conventional phenotype. Unexpectedly, their capacity to suppress T cell proliferation and to secrete interleukin-10 was not altered. Moreover, T reg cells suppressed the production of vasoactive cytokines after dengue-specific stimulation. Furthermore, T reg cell frequencies and also T reg cell/effector T cell ratios were increased in patients with acute infection. A strong indication that a relative rise of T reg cell/effector T cell ratios is beneficial for disease outcome comes from patients with mild disease in which this ratio is significantly increased (P &lt; 0.0001) in contrast to severe cases (P = 0.2145). We conclude that although T reg cells expand and function normally in acute dengue infection, their relative frequencies are insufficient to control the immunopathology of severe disease.


2018 ◽  
Vol 2018 ◽  
pp. 1-18 ◽  
Author(s):  
S. D. Perera ◽  
S. S. N. Perera

Dengue virus is a mosquito borne Flavivirus and the most prevalent arbovirus in tropical and subtropical regions around the world. The incidence of dengue has increased drastically over the last few years at an alarming rate. The clinical manifestation of dengue ranges from asymptomatic infection to severe dengue. Even though the viral kinetics of dengue infection is lacking, innate immune response and humoral immune response are thought to play a major role in controlling the virus count. Here, we developed a computer simulation mathematical model including both innate and adaptive immune responses to study the within-host dynamics of dengue virus infection. A sensitivity analysis was carried out to identify key parameters that would contribute towards severe dengue. A detailed stability analysis was carried out to identify relevant range of parameters that contributes to different outcomes of the infection. This study provides a qualitative understanding of the biological factors that can explain the viral kinetics during a dengue infection.


2019 ◽  
Author(s):  
N.L Ajantha Shyamali ◽  
Sameera D. Mahaputuna ◽  
Laksiri Gomes ◽  
Ananda Wijewickrama ◽  
Graham Ogg ◽  
...  

Abstract Background Although serum lipopolysaccharide (LPS) was shown to associate with development of severe dengue, the reasons for high LPS and its subsequent involvement in disease pathogenesis are not known. Methods: We assessed LPS, lipopolysaccharide binding protein (LBP), CRP, IL-18, procalcitonin in patients with acute dengue fever (DF=129) and dengue haemorrhagic fever (DHF=64) and correlated these observations with the presence of comorbid illnesses, concurrent bacteraemia and clinical disease severity. Results: LPS levels were significantly (p=0.01) higher in patients with DHF, compared to those with DF. 45 (70%) of those with DHF and 63 (49%) of those with DF had detectable LPS and therefore, presence of LPS was significantly associated with DHF (p=0.005, OR=2.48, 95% CI: 1.29 to 4.64). Those with metabolic diseases, 22/29 (75.9%) and those with atopic diseases 17/22 (77.3%) were significantly more likely to have detectable LPS (p=0.025, OR=2.9, 95% CI- 1.17 to 7.59) and (p=0.039, OR=3.06, 95% CI-1.07 to 7.81) respectively, than others. LPS, LBP and CRP levels were high at the febrile phase, before onset of plasma leakage and reduced towards to the critical phase. The CRP levels were significantly higher (p=0.03) in early illness (≤3 days of illness) in those who progressed to develop DHF when compared to those who developed DF. Those who had detectable serum LPS also had a significantly higher CRP (p=0.01). Although there was no difference in procalcitonin (PCT) levels in patients with DF and DHF, the PCT levels were significantly higher in those who had detectable serum LPS (p=0.02). Conclusions: LPS levels were higher in patients with DHF and associated with high levels of other inflammatory markers. Since LPS levels were highest during early infection and were significantly more likely to be present in those with comorbid illnesses, the possible role of LPS in disease pathogenesis, should be further investigated.


2019 ◽  
Vol 2019 ◽  
pp. 1-6 ◽  
Author(s):  
Bui Vu Huy ◽  
Le Nguyen Minh Hoa ◽  
Dang Thi Thuy ◽  
Nguyen Van Kinh ◽  
Ta Thi Dieu Ngan ◽  
...  

Purpose. The clinical features and laboratory results of dengue-infected adult patients admitted to the hospital during the 2017 outbreak were analyzed in this study. Method. This is a cross-sectional study. 2922 patients aged 18 years or more with dengue fever in National Hospital for Tropical Diseases (NHTD) in the North and Hospital for Tropical Disease (HTD) in the South of Vietnam were recruited in this study. Result. Patients were admitted in the hospital around the year and concentrated from August to December, in 53/63 (84.0%) provinces in Vietnam, and patients in all ages were affected. The number of patients with dengue fever was 1675 (57.3%), dengue with warning signs 914 (31.3%), and severe dengue 333 (11.4%), respectively. Among patients with severe dengue, severe plasma leakage and dengue shock account for 238 (8.1%), severe organ impairment 73 (2.5%), and severe bleeding 22 (0.75%). The rate of mortality was 0.8%, and the outcome of dengue patients is worse in the elderly and people with underlying diseases. Conclusion. The 2017 dengue outbreak occurred in a larger scale than in the previous years in terms of time, location, and number of patients. More elderly patients were infected by dengue in this outbreak, and this may contribute to the mortality rate. Clinical manifestations of dengue patients in Southern Vietnam are more typical than the northern, but the rate of severe dengue is not different. The mortality risk and underlying conditions associated with dengue-infected elderly patients are worthy of further investigations in the future.


2019 ◽  
Vol 2019 ◽  
pp. 1-7
Author(s):  
Kevin John John ◽  
Karthik Gunasekaran ◽  
John Davis Prasad ◽  
Divya Mathew ◽  
Sohini Das ◽  
...  

We conducted a retrospective observational study to describe the clinical profile and outcomes of patients admitted with a diagnosis of dengue fever in a tertiary hospital in South India. A total of 159 patients admitted from April 2014 to October 2018 were included in the study. Vomiting (70.4%), myalgia (60.4%), headache (42.1%), abdominal pain (38.4%), bleeding (38%), and rash (37.1%) were the most common symptoms at presentation. The mean duration of hospital stay was 4.9 days (SD ± 2.4), and the median cost was INR 19,708 ($285) (IQR INR 12,968–32,056 ($188–$305)). Major bleeding was associated with elevated SGOT and SGPT, severe dengue, and secondary dengue. Mortality was associated with elderly age; elevated total leukocyte count, serum bilirubin, serum creatinine, SGOT, and SGPT; and high SOFA score. In view of these observations, we recommend stratifying patients according to the WHO classification of dengue and avoiding the use of thrombocytopenia as a single marker of the severity of the illness.


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