scholarly journals Cytokine Signature of Dengue Patients at Different Severity of the Disease

2021 ◽  
Vol 22 (6) ◽  
pp. 2879
Author(s):  
Irwin Puc ◽  
Tzu-Chuan Ho ◽  
Ko-Lun Yen ◽  
Amrita Vats ◽  
Jih-Jin Tsai ◽  
...  
Keyword(s):  
Warning Signs ◽  
University Hospital ◽  
Severe Dengue ◽  
Warning Sign ◽  
Gm Csf ◽  
Clinical Presentations ◽  
Cytokine Levels ◽  
Profile Changes ◽  
Severity Of The Disease ◽  
Dengue With Warning Signs

Clinical presentations of dengue fever (DF) are diverse and non-specific, causing unpredictable progression and outcomes. Its progression and severity have been associated with cytokine levels alteration. In this study, dengue patients were classified into groups following the 2009 WHO dengue classification scheme to investigate the cytokine signature at different severity of the disease: dengue without warning sign symptoms (A); dengue with warning signs (B); severe dengue (C); other fever (OF) and healthy (Healthy). We analyzed 23 different cytokines simultaneously, namely IL-1b, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-17A, IL-33, CD14, CD54, CD62E, CD62L, CD62p, CD106, CD121b, CD154, CD178, GM-CSF, IFN-g, MIF, ST2 and TNF from patients admitted to National Cheng Kung University Hospital during the 2015 Taiwan dengue outbreak. Cytokines TNF, CD54, CD62E, CD62L, CD62P, GM-CSF, IL-1b, IL-2, IL-6, IL-8, IL-10, IL-12p70, IL-17A, INF-g and MIF were elevated while CD106, CD154, IL-4 and L-33 were decreased when compared to the control. IL-10 demonstrated to be a potential diagnostic marker for DF (H and A group; AUC = 0.944, H and OF group; AUC = 0.969). CD121b demonstrated to be predictive of the SD (A and B group; AUC = 0.744, B and C group; AUC = 0.775). Our results demonstrate the cytokine profile changes during the progression of dengue and highlight possible biomarkers for optimizing effective intervention strategies.

scholarly journals Inflammatory phenotyping predicts clinical outcome in COVID-19

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
H. Burke ◽  
◽  
A. Freeman ◽  
D. C. Cellura ◽  
B. L. Stuart ◽  
...  
Keyword(s):  
Adverse Outcome ◽  
Outcome Data ◽  
University Hospital ◽  
Clinical Parameters ◽  
Gm Csf ◽  
Poor Outcome ◽  
Hospitalised Patients ◽  
Cytokine Levels ◽  
Patients At Risk ◽  
Multiplex Cytokine

Abstract Background The COVID-19 pandemic has led to more than 760,000 deaths worldwide (correct as of 16th August 2020). Studies suggest a hyperinflammatory response is a major cause of disease severity and death. Identitfying COVID-19 patients with hyperinflammation may identify subgroups who could benefit from targeted immunomodulatory treatments. Analysis of cytokine levels at the point of diagnosis of SARS-CoV-2 infection can identify patients at risk of deterioration. Methods We used a multiplex cytokine assay to measure serum IL-6, IL-8, TNF, IL-1β, GM-CSF, IL-10, IL-33 and IFN-γ in 100 hospitalised patients with confirmed COVID-19 at admission to University Hospital Southampton (UK). Demographic, clinical and outcome data were collected for analysis. Results Age > 70 years was the strongest predictor of death (OR 28, 95% CI 5.94, 139.45). IL-6, IL-8, TNF, IL-1β and IL-33 were significantly associated with adverse outcome. Clinical parameters were predictive of poor outcome (AUROC 0.71), addition of a combined cytokine panel significantly improved the predictability (AUROC 0.85). In those ≤70 years, IL-33 and TNF were predictive of poor outcome (AUROC 0.83 and 0.84), addition of a combined cytokine panel demonstrated greater predictability of poor outcome than clinical parameters alone (AUROC 0.92 vs 0.77). Conclusions A combined cytokine panel improves the accuracy of the predictive value for adverse outcome beyond standard clinical data alone. Identification of specific cytokines may help to stratify patients towards trials of specific immunomodulatory treatments to improve outcomes in COVID-19.

scholarly journals Complement protein levels and MBL2 polymorphisms are associated with dengue and disease severity

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Ngo Truong Giang ◽  
Hoang van Tong ◽  
Do Quyet ◽  
Nghiem Xuan Hoan ◽  
Trinh Huu Nghia ◽  
...  
Keyword(s):  
Warning Signs ◽  
Severe Dengue ◽  
Healthy Controls ◽  
Complement Protein ◽  
Complement Proteins ◽  
Protein Levels ◽  
Study Population ◽  
Dengue With Warning Signs ◽  
The Complement System

Abstract The complement system may be crucial during dengue virus infection and progression to severe dengue. This study investigates the role of MBL2 genetic variants and levels of MBL in serum and complement proteins in Vietnamese dengue patients. MBL2 genotypes (− 550L/H, MBL2 codon 54), MBL2 diplotypes (XA/XO, YA/XO) and MBL2 haplotypes (LXPB, HXPA, XO) were associated with dengue in the study population. The levels of complement factors C2, C5, and C5a were higher in dengue and dengue with warning signs (DWS) patients compared to those in healthy controls, while factor D levels were decreased in dengue and DWS patients compared to the levels determined in healthy controls. C2 and C5a levels were associated with the levels of AST and ALT and with WBC counts. C9 levels were negatively correlated with ALT levels and WBC counts, and factor D levels were associated with AST and ALT levels and with platelet counts. In conclusions, MBL2 polymorphisms are associated with dengue in the Vietnamese study population. The levels of the complement proteins C2, C4b, C5, C5a, C9, factor D and factor I are modulated in dengue patients during the clinical course of dengue.

scholarly journals Cytokine Signature Associated with Disease Severity in Dengue

Viruses ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 34 ◽  
Author(s):  
A. Raj Kumar Patro ◽  
Sriprasad Mohanty ◽  
Birendra K. Prusty ◽  
Diwakar K. Singh ◽  
Sagar Gaikwad ◽  
...  
Keyword(s):  
Disease Severity ◽  
Viral Disease ◽  
Warning Signs ◽  
Severe Dengue ◽  
Rt Pcr ◽  
Capture Elisa ◽  
Gm Csf ◽  
Host Immune Responses ◽  
Luminex Assay ◽  
Ifn Γ

Dengue is the most rapidly spreading viral disease transmitted by the bite of infected Aedes mosquitos. The pathogenesis of dengue is still unclear; although host immune responses and virus serotypes have been proposed to contribute to disease severity. In this study, we examined the circulating dengue virus (DENV) and measured plasma levels of inflammatory mediators. Ninety-eight patients during a dengue outbreak in eastern India in 2016 were included in the study. The presence of DENV was demonstrated by detecting NS1 antigen; IgM capture ELISA and serotypes were discriminated by type-specific RT-PCR and/or sequencing. Plasma samples were assayed for 41-plex cytokine/chemokines using multiplex Luminex assay. Eighty-five (87%) samples were positive by NS1/IgM capture ELISA/RT-PCR. All four serotypes of DENV were detected in this outbreak, with DENV-2 as the predominant type, seen in 55% of cases. Mixed infections were seen in 39% of subjects. Among the host inflammatory biomarkers, GM-CSF, IFN-γ, IL-10, IL-15, IL-8, MCP-1, IL-6, MIP-1β, and TNF-α levels were significantly increased in dengue with and without warning signs, in severe dengue patients in comparison to healthy controls. Four cytokines IFN-γ, GM-CSF, IL-10, and MIP-1β correlated significantly with disease severity and could serve as potential predictor for disease severity. Information on the host biomarkers and the dengue serotype may help guide in optimizing effective intervention strategies.

Factors predicting the severity of dengue in patients with warning signs in Rio de Janeiro, Brazil (1986–2012)

2019 ◽  
Vol 113 (11) ◽  
pp. 670-677 ◽  
Author(s):  
Bianca De Santis Gonçalves ◽  
Rita Maria Ribeiro Nogueira ◽  
Ana Maria Bispo de Filippis ◽  
Marco Aurélio Pereira Horta
Keyword(s):  
Rio De Janeiro ◽  
Dengue Infection ◽  
Warning Signs ◽  
Severe Dengue ◽  
Enzyme Linked Immunosorbent Assay ◽  
Infection Status ◽  
Viral Loads ◽  
Dengue Virus Type 3 ◽  
Dengue With Warning Signs ◽  
Type 3

AbstractBackgroundSince 1981, >12 million cases of dengue have been reported in Brazil. Early prediction of severe dengue with no warning signs is crucial to avoid progression to severe dengue. Here we aimed to identify early markers of dengue severity and characterize dengue infection in patients in Rio de Janeiro.MethodsWe evaluated early severity markers, serotypes, infection status, number of days of illness and viral loads associated with dengue fever in patients from Rio de Janeiro, Brazil through an observational retrospective study (1986–2012). We compared dengue without warning signs and dengue with warning signs/severe dengue (DWWS/SD). Infection status was classified by enzyme-linked immunosorbent assay and viraemia was quantified by quantitative real-time reverse transcription polymerase chain reaction.ResultsThe presence of DWWS/ SD was significantly associated with younger age; patients 13–19 y of age had a significantly greater chance of presenting warning signs. Dengue virus type 3 (DENV3) was more likely to induce DWWS/SD, which was more frequent on days 4–5 of illness.ConclusionsDENV3, 4–5 d of illness and 13–19 y of age were early biomarkers of dengue severity. To our knowledge, this was the first study to analyse the characteristics of dengue severity in the state of Rio de Janeiro over 27 y of epidemics since the introduction of DENV.

Dengue viral infection in children: a perspective

2012 ◽  
Vol 97 (10) ◽  
pp. 907-912 ◽  
Author(s):  
S Balasubramanian ◽  
Bala Ramachandran ◽  
Sumanth Amperayani
Keyword(s):  
Viral Infection ◽  
Viral Infections ◽  
Early Recognition ◽  
Warning Signs ◽  
Severe Dengue ◽  
High Morbidity ◽  
Ns1 Antigen ◽  
Vector Borne ◽  
Immune Enhancement ◽  
Dengue With Warning Signs

Dengue is a vector-borne viral infection of global importance. Several pathogenetic mechanisms such as immune enhancement and selection pressure have been proposed and febrile, critical and recovery phases have been identified. A new classification proposed by WHO has recently been introduced where definitions have been changed to ‘probable dengue’, ‘dengue with warning signs’ and ‘severe dengue’. The majority of dengue viral infections are self-limiting, but complications have high morbidity and mortality. The diagnosis of dengue viral infection is essentially clinical, although confirmation requires laboratory tests including serology, NS1 antigen detection, PCR and viral cultures. There are no specific anti-dengue drugs and treatment is basically supportive and consists of early recognition of complications and appropriate fluid therapy. A number of candidate vaccines are under development.

scholarly journals Serum sodium level in dengue infected children: a retrospective study

2018 ◽  
Vol 5 (5) ◽  
pp. 1801
Author(s):  
Reshma Raj ◽  
Rashmi Alva
Keyword(s):  
Dengue Fever ◽  
Serum Sodium ◽  
Sodium Level ◽  
Serum Sodium Level ◽  
Tertiary Care ◽  
Clinical Manifestations ◽  
Warning Signs ◽  
Severe Dengue ◽  
Dengue With Warning Signs ◽  
Group B

Background: Dengue fever is one of the most common arbo virus mediated outbreaks, being reported from different parts of the world. Now as the outbreaks are hitting different geographic locations, different clinical manifestations are being reported recently. Aim of this study is to document the serum Sodium level in dengue infected children in a tertiary care centre.Methods: A total 128 cases of NS1 antigen, IgM positive or ELISA positive dengue patients were included in this observational study and analyzed.Results: The serum Sodium level in dengue varies according to the different groups. In group A (dengue with no warning signs) the serum Sodium level was normal, whereas in case of group B (dengue with warning signs), there was significant hyponatremia. In group C, severe dengue the serum Sodium was normalConclusions: Mild hyponatremia is a common electrolyte disturbance in patients with dengue with warning signs. Hence, the lower the serum Sodium levels the higher is the incidence of complications associated with dengue fever.

scholarly journals Immunophenotyping and transcriptional profiling of human plasmablasts in dengue.

2021 ◽  
Author(s):  
Charu Aggarwal ◽  
Keshav Saini ◽  
Elluri Seetharami Reddy ◽  
Mohit Singla ◽  
Kaustuv Nayak ◽  
...  
Keyword(s):  
Chemokine Receptors ◽  
Influenza Infection ◽  
Transcriptional Profiling ◽  
Dengue Infection ◽  
Warning Signs ◽  
Severe Dengue ◽  
Dengue Disease ◽  
Mucosal Tissues ◽  
Dengue With Warning Signs

Previous studies have shown that plasmablasts expand massively in dengue patients as compared to many other situations such as influenza infection or vaccination. However, a detailed understanding of the phenotypes and transcriptional features of these cells is lacking. Moreover, despite India having nearly a third of global dengue disease burden, there is virtually no information on plasmablasts responses in dengue patients from India. Here, we provide a detailed characterization of plasmablast responses from dengue confirmed febrile children in India. Immunophenotyping and RNA seq analysis showed that in addition to secreting dengue specific antibodies, these massively expanding cells expressed several adhesion molecules, chemokines and chemokine receptors that are involved in endothelial interactions, homing to skin or mucosal tissues including intestine. Surprisingly, we found that these cells also upregulated expression of several cytokine genes that are involved in angiogenesis, leukocyte extravasation and vascular permeability. These transcriptional features were qualitatively similar to plasmablasts from influenza vaccinees. Interestingly, the expansion of the plasmablasts in dengue patients was significantly lower in patients with primary dengue infection compared to those with secondary dengue. Moreover, within the primary dengue patients, their expansion was significantly lower in patients with mild dengue infection (DI) compared to patients with dengue with warning signs (DW) or severe dengue (SD). These results significantly improve our understanding of human plasmablast responses in dengue.

scholarly journals Comparing the 2009 and 1997 World Health Organization dengue case classifications in a large cohort of South Asian patients

2020 ◽  
Vol 14 (07) ◽  
pp. 781-787 ◽  
Author(s):  
Umesh Jayarajah ◽  
Upul Dissanayake ◽  
Visula Abeysuriya ◽  
Pradeep K De Silva ◽  
Priyankara Jayawardena ◽  
...  
Keyword(s):  
World Health Organisation ◽  
Warning Signs ◽  
World Health ◽  
Severe Dengue ◽  
Dengue Case ◽  
Dengue Disease ◽  
Asian Patients ◽  
Resource Limited ◽  
Dengue With Warning Signs ◽  
Health Organization

Introduction: Due to the shortcomings in the 1997-World Health Organisation (WHO) dengue case classification (DCC), a revised classification was proposed in 2009. This study was aimed to assess the clinical usefulness of the two classifications during a large dengue epidemic. Methodology: Clinical data of dengue patients admitted to selected units at National Hospital of Sri Lanka, Panadura Base Hospital and Nawaloka Hospital Colombo between June and August 2017 were collected prospectively. Cases were classified using the 1997 and 2009 WHO DCCs. Results: 1,878 patients [adult = 1,573 (83.8%)] were studied. Based on 1997-WHO-DCC-DF (Dengue Fever): 1,316 (70.1%), DHF (Dengue Haemorrhagic Fever) -1: 468 (24.9%), DHF-2: 86 (4.6%) and DHF-3: 8 (0.4%). Based on 2009-WHO-DCC–Dengue with warning signs (WS): 1647 (87.7%), Dengue without WS: 231 (12.3%) and severe dengue (SD): 41 (2.18%). A total of 1,088 (82.7%) DF and 559 (99.5%) DHF patients developed WS. Of those without WS, 228 (17.3%) were DF patients and 3 (0.5%) were DHF patients. Three (0.23%) DF and 38 (6.76%) DHF patients had SD. All SD patients had WS. The level of agreement between the two systems of classification was poor (Kappa = - 0.035, p < 0.001). Conclusions: The 2009-WHO-DCC was more useful than 1997-WHO-DCC in predicting dengue disease severity as few DF patients also had SD. Furthermore, the presence of WS identified patients with SD. However, the 2009-WHO-DCC may not suit the resource limited countries as WS are non-specific, and lack of diagnostic tests can result in case overload.

scholarly journals Serum ionic calcium levels and hypocalcemia in dengue fever in children and its correlation with its severity: case control study

2019 ◽  
Vol 6 (3) ◽  
pp. 1289
Author(s):  
V. G. Manjunath ◽  
Sruthi Balla ◽  
Jagadish Kumar
Keyword(s):  
Dengue Fever ◽  
Case Control Study ◽  
Case Control ◽  
Warning Signs ◽  
Severe Dengue ◽  
Case Group ◽  
Major Health Problem ◽  
Ionic Calcium ◽  
Dengue With Warning Signs ◽  
Control Study

Background: Dengue fever (DF) is a major health problem, 90% of dengue hemorrhagic fever (DHF) occurring in children <5 years and mortality of 2.5%. Abnormalities like metabolic acidosis, hyponatremia and hypocalcemia can occur in severe dengue especially in dengue shock patients. Alterations in calcium homeostasis, may play a role in the pathogenesis of dengue shock. Objectives is to evaluate serum ionic calcium (Ca2+) levels in children aged 1-18yrs with dengue fever and correlate it with severity and outcomeMethods: The study was prospective hospital based case-control study. Case group had 75 children with dengue fever with equal number of controls. Cases were classified according to WHO classification. Serum Ca2+ levels were estimated within 24 hours of admission.Results: Majority of children with dengue were in the age-group of 6-15 years (71.4%). Out of 75 cases,16% were dengue without warning signs, 54.7% dengue with warning signs and 29.3% were severe dengue cases. Mean Ca2+ level (in mmol/l) was 1.2009 (±0.09) among controls and 1.0911 (±0.10) in dengue cases (p=0.0001). Mean Ca2+ level in dengue without warning signs was 1.0950 mmol/l, dengue with warning signs was 1.1088 mmol/l and severe dengue was 1.0559 mmol/l. Mean Ca2+ level in severe dengue was significantly lower compared to dengue with warning signs (p=0.04). Hypocalcemia was seen in 56% of dengue cases but only 14% among controls. Seven children with severe dengue who died had hypocalemia.Conclusions: Hypocalcemia is common in dengue fever. Lower levels of ionic calcium correlate with severity of dengue illness and may be considered as a prognostic indicator of poor outcome.

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