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.

scholarly journals A 23bp Indel Polymorphism in TLR2 Gene Enhances Inflammation and Disease Severity in Dengue

2017 ◽  
Author(s):  
A. Raj Kumar Patro ◽  
Sriprasad Mohanty ◽  
Aditya K. Panda ◽  
Birendra K. Prusty ◽  
Diwakar K. Singh ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Dengue Fever ◽  
Disease Severity ◽  
Warning Signs ◽  
Severe Dengue ◽  
Healthy Controls ◽  
Indel Polymorphism ◽  
Rt Pcr ◽  
Tlr2 Gene ◽  
Indel Mutation

AbstractBackgroundDengue is the most rapidly spreading viral disease transmitted by the bite of infectedAedesmosquitos. Pathogenesis of dengue is still unclear; although host genetic factors, immune responses and virus serotypes have been proposed to contribute to disease severity. The development of high-throughput methods have allowed to scale up capabilities of identifying the key markers of inflammation. Since NS1 protein of dengue virus has been reported to activate immune cells towards enhanced inflammation through TLR2, we examined the role of a polymorphism, a 23bp deletion in 5’UTR region of TLR2 gene in patients with dengue (with and without warning signs) and correlated with plasma levels of inflammatory mediators with disease severity and viral serotypes.MethodsEighty nine patients classified as per WHO 2009 criteria during dengue outbreak in Odisha, India in 2016 were included in the current study. Presence of dengue virus (DENV) was demonstrated by detecting NS1 antigen, IgM capture ELISA and serotypes in circulation were discriminated by type-specific RT-PCR and/or sequencing. Sixty-one confirmed dengue cases were typed for TLR2 indel polymorphism and compared with 485 disease free controls. Plasma samples were assayed for 41-plex cytokine/ chemokines using Luminex bead based immunoassay.ResultsPresence of 23bp deletion allele of TLR2 gene was significantly more in patients with severe dengue in comparison to dengue fever cases (p= 0.03; Odds ratio 4.05) although the frequency of insertion (Ins) allele of TLR2 was comparable in healthy controls and dengue cases (82.4 and 87.9 % respectively). Seventy-three (82%) samples were found to be positive by NS1/IgM capture ELISA/ RT-PCR. DENV-2 was predominant (58%) during the outbreak. Among the host inflammatory biomarkers 9 molecules were significantly altered in dengue patients when compared to healthy controls. The increased levels of IFN-γ, GM-CSF, IL-10, IL-1Rα and MIP-1β correlated significantly with severe dengue.ConclusionsThe frequency of 23bp Indel mutation of TLR2 was comparable between healthy controls and dengue fever (with and without warning signs), suggesting that this indel mutation does not contribute significantly to susceptibility/ resistance to dengue; however, del allele of TLR2 gene was significantly more associated in patients with severe dengue symptoms when compared to dengue fever cases.

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 Viral Dynamics and Real-Time RT-PCR Ct Values Correlation with Disease Severity in COVID-19

Diagnostics ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1091
Author(s):  
Ali A. Rabaan ◽  
Raghavendra Tirupathi ◽  
Anupam A Sule ◽  
Jehad Aldali ◽  
Abbas Al Mutair ◽  
...  
Keyword(s):  
Viral Load ◽  
Real Time ◽  
Disease Severity ◽  
False Negative ◽  
Influential Factors ◽  
Confirmatory Test ◽  
Acid Extraction ◽  
Rt Pcr ◽  
Viral Kinetics ◽  
Ct Value

Real-time RT-PCR is considered the gold standard confirmatory test for coronavirus disease 2019 (COVID-19). However, many scientists disagree, and it is essential to understand that several factors and variables can cause a false-negative test. In this context, cycle threshold (Ct) values are being utilized to diagnose or predict SARS-CoV-2 infection. This practice has a significant clinical utility as Ct values can be correlated with the viral load. In addition, Ct values have a strong correlation with multiple haematological and biochemical markers. However, it is essential to consider that Ct values might be affected by pre-analytic, analytic, and post-analytical variables such as collection technique, specimen type, sampling time, viral kinetics, transport and storage conditions, nucleic acid extraction, viral RNA load, primer designing, real-time PCR efficiency, and Ct value determination method. Therefore, understanding the interpretation of Ct values and other influential factors could play a crucial role in interpreting viral load and disease severity. In several clinical studies consisting of small or large sample sizes, several discrepancies exist regarding a significant positive correlation between the Ct value and disease severity in COVID-19. In this context, a revised review of the literature has been conducted to fill the knowledge gaps regarding the correlations between Ct values and severity/fatality rates of patients with COVID-19. Various databases such as PubMed, Science Direct, Medline, Scopus, and Google Scholar were searched up to April 2021 by using keywords including “RT-PCR or viral load”, “SARS-CoV-2 and RT-PCR”, “Ct value and viral load”, “Ct value or COVID-19”. Research articles were extracted and selected independently by the authors and included in the present review based on their relevance to the study. The current narrative review explores the correlation of Ct values with mortality, disease progression, severity, and infectivity. We also discuss the factors that can affect these values, such as collection technique, type of swab, sampling method, etc.

scholarly journals Increased levels of pentraxins protein and cytokines bear good association in patients with severe dengue infection

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Goutam Patra ◽  
Bibhuti Saha ◽  
Sumi Mukhopadhyay
Keyword(s):  
Dengue Infection ◽  
Clinical Manifestations ◽  
Blood Parameters ◽  
Warning Signs ◽  
Severe Dengue ◽  
Disease Manifestation ◽  
Mild Disease ◽  
Tnf Α ◽  
The Status ◽  
The Tropics

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.

Adjuvant properties of IFN-γ and GM-CSF in the scFv6.C4 DNA vaccine against CEA-expressing tumors

Gene Therapy ◽  
2021 ◽  
Author(s):  
Bianca Ferrarini Zanetti ◽  
Camila Pontes Ferreira ◽  
José Ronnie Carvalho Vasconcelos ◽  
Sang Won Han
Keyword(s):  
Dna Vaccine ◽  
Gm Csf ◽  
Ifn Γ

scholarly journals JAK2 Phosphorylation Signals and Their Associated Cytokines Involved in Chronic Rhinosinusitis with Nasal Polyps and Correlated with Disease Severity

Biomolecules ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1059
Author(s):  
Yu-Tsai Lin ◽  
Wei-Chih Chen ◽  
Ming-Hsien Tsai ◽  
Jing-Ying Chen ◽  
Chih-Yen Chien ◽  
...  
Keyword(s):  
Chronic Rhinosinusitis ◽  
Disease Severity ◽  
Nasal Polyps ◽  
Inflammatory Diseases ◽  
Janus Kinase ◽  
Sinus Surgery ◽  
Control Group ◽  
Jak2 Inhibitor ◽  
Ifn Γ ◽  
Snot 22

Janus kinase 2 (JAK2) is a member of the JAK family that transduces cytokine-mediated signals via the JAKs/STATs (signal transducer and activator of transcription proteins) pathway, which plays an important role in many inflammatory diseases. This study investigates the association of p-JAK2 and JAK2-associated cytokines from nasal polyp (NP) tissue with disease severity, and evaluates the p-JAK2-mediated STATs in chronic rhinosinusitis (CRS) with NP. Sixty-one CRSwNP patients with nasal polyps undergoing endoscopic sinus surgery were enrolled, while the turbinate tissues from 26 nasal obstruction patients were examined as the control group. Elevated levels of p-JAK2 were detected in CRSwNP, and significantly correlated with scores of disease severity (LMK-CT, TPS, and SNOT-22). Expressions of the JAK2-associated cytokines, such as IL-5, IL-6, IL-13, G-CSF, and IFN-γ were significantly higher in CRSwNP than in the controls, while the levels of IL-5, IL-6, IL-13, or G-CSF had positive correlation with scores of disease severity. Moreover, markedly increased expression of p-STAT3 in CRSwNP was observed relative to the control. Taken together, these data showed that the JAK2-associated cytokines including IL-6 and G-CSF may stimulate JAK2 phosphorylation to activate p-STAT3, indicating an association with disease severity and supporting its development of JAK2 inhibitor as a potential therapeutic agent for CRS.

scholarly journals Granulocyte-Macrophage Colony-Stimulating Factor-Deficient Mice Have Impaired Resistance to Blood-Stage Malaria

2001 ◽  
Vol 69 (1) ◽  
pp. 129-136 ◽  
Author(s):  
Julie Riopel ◽  
MiFong Tam ◽  
Karkada Mohan ◽  
Michael W. Marino ◽  
Mary M. Stevenson
Keyword(s):  
Blood Stage ◽  
Colony Stimulating Factor ◽  
Necrosis Factor Alpha ◽  
Gm Csf ◽  
Tnf Α ◽  
Macrophage Colony Stimulating Factor ◽  
Ifn Γ ◽  
Macrophage Colony ◽  
Stimulating Factor ◽  
Blood Stage Malaria

ABSTRACT The contribution of granulocyte-macrophage colony-stimulating factor (GM-CSF), a hematopoietic and immunoregulatory cytokine, to resistance to blood-stage malaria was investigated by infecting GM-CSF-deficient (knockout [KO]) mice with Plasmodium chabaudi AS. KO mice were more susceptible to infection than wild-type (WT) mice, as evidenced by higher peak parasitemia, recurrent recrudescent parasitemia, and high mortality. P. chabaudiAS-infected KO mice had impaired splenomegaly and lower leukocytosis but equivalent levels of anemia compared to infected WT mice. Both bone marrow and splenic erythropoiesis were normal in infected KO mice. However, granulocyte-macrophage colony formation was significantly decreased in these tissues of uninfected and infected KO mice, and the numbers of macrophages in the spleen and peritoneal cavity were significantly lower than in infected WT mice. Serum levels of gamma interferon (IFN-γ) were found to be significantly higher in uninfected KO mice, and the level of this cytokine was not increased during infection. In contrast, IFN-γ levels were significantly above normal levels in infected WT mice. During infection, tumor necrosis factor alpha (TNF-α) levels were significantly increased in KO mice and were significantly higher than TNF-α levels in infected WT mice. Our results indicate that GM-CSF contributes to resistance to P. chabaudi AS infection and that it is involved in the development of splenomegaly, leukocytosis, and granulocyte-macrophage hematopoiesis. GM-CSF may also regulate IFN-γ and TNF-α production and activity in response to infection. The abnormal responses seen in infected KO mice may be due to the lack of GM-CSF during development, to the lack of GM-CSF in the infected mature mice, or to both.

scholarly journals Patterns of Gall Bladder Wall Thickening in Dengue Fever: A Mirror of the Severity of Disease

2017 ◽  
Vol 03 (02) ◽  
pp. E76-E81 ◽  
Author(s):  
Jitendra Parmar ◽  
Chander Mohan ◽  
Maulik Vora
Keyword(s):  
Gall Bladder ◽  
Dengue Fever ◽  
Bladder Wall ◽  
Warning Signs ◽  
Severe Dengue ◽  
Wall Thickening ◽  
Severity Of Disease ◽  
Gall Bladder Wall ◽  
Track Pattern ◽  
Honeycomb Pattern

Abstract Background Dengue fever is a major public health problem with an increased incidence in recent years. Gall bladder wall thickening has been reported as one of the most common findings in dengue fever. There is a paucity of literature regarding the various patterns of gall bladder wall thickening in dengue fever and their significance in predicting the severity of disease. Methodology and Significant Findings Out of 93 seropositive patients included in the study, 54 patients with dengue fever had gall bladder wall thickening. 4 patterns of gall bladder wall thickening are demonstrated in this study. A uniform echogenic pattern in 20 patients, striated or tram track pattern in 11 patients, an asymmetric pattern in 2 patients and a honeycombing pattern in 21 patients. The range of patterns of wall thickening included normal wall thickening or uniform echogenic wall thickening in DF without warning signs, a striated or tram track pattern, and a honeycomb pattern in severe DF. Serial ultrasound done on consecutive alternate days revealed a change in the pattern of gall bladder wall thickening according to the severity of disease. Conclusion The present study revealed 4 distinct patterns of gall bladder wall thickening. The uniform echogenic pattern was found to be more prevalent in dengue fever without warning signs, while the honeycomb pattern was found to be more prevalent in severe dengue fever. A change in the pattern of gall bladder wall thickening on subsequent serial ultrasound can predict the severity of the disease.

scholarly journals Imunocompetent Mice Model for Dengue Virus Infection

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Denise Gonçalves ◽  
Rafael de Queiroz Prado ◽  
Eric Almeida Xavier ◽  
Natália Cristina de Oliveira ◽  
Paulo Marcos da Matta Guedes ◽  
...  
Keyword(s):  
Animal Model ◽  
Virus Infection ◽  
Dengue Virus ◽  
Viral Disease ◽  
Mice Model ◽  
Rt Pcr ◽  
Dengue Virus Infection ◽  
Dengue Disease ◽  
The Family ◽  
The World

Dengue fever is a noncontagious infectious disease caused by dengue virus (DENV). DENV belongs to the familyFlaviviridae, genusFlavivirus, and is classified into four antigenically distinct serotypes: DENV-1, DENV-2, DENV-3, and DENV-4. The number of nations and people affected has increased steadily and today is considered the most widely spread arbovirus (arthropod-borne viral disease) in the world. The absence of an appropriate animal model for studying the disease has hindered the understanding of dengue pathogenesis. In our study, we have found that immunocompetent C57BL/6 mice infected intraperitoneally with DENV-1 presented some signs of dengue disease such as thrombocytopenia, spleen hemorrhage, liver damage, and increase in production of IFNγand TNFαcytokines. Moreover, the animals became viremic and the virus was detected in several organs by real-time RT-PCR. Thus, this animal model could be used to study mechanism of dengue virus infection, to test antiviral drugs, as well as to evaluate candidate vaccines.

Severity and costs associated with hospitalization for dengue in public and private hospitals of Surat city, Gujarat, India, 2017–2018

2019 ◽  
Vol 113 (11) ◽  
pp. 661-669 ◽  
Author(s):  
Viral R Bajwala ◽  
Denny John ◽  
T Daniel Rajasekar ◽  
Manoj V Murhekar
Keyword(s):  
Urban Areas ◽  
Tertiary Care ◽  
Public Health Problem ◽  
Warning Signs ◽  
World Health ◽  
Severe Dengue ◽  
Major Public Health Problem ◽  
Private Hospitals ◽  
Government Hospitals ◽  
The Cost

Abstract Background Dengue is major public health problem in India, especially in urban areas. We conducted a study to estimate the severity and costs of treatment among hospitalized dengue patients in Surat city, Gujarat, India. Methods We reviewed the medical records of dengue patients hospitalized in five tertiary care facilities (private [n=2], semi-government [n=2] and government [n=1]) between April 2017 and March 2018. We used the World Health Organization 2009 classification to classify the severity of dengue. A resource utilization approach was used to estimate the cost of illness in US dollars (US$) (inflation adjusted to 2018) from a quasi-societal perspective (excluding non-medical cost) for dengue hospitalization. Results Of the 732 hospitalized dengue patients, 44.7% had no warning symptoms, 39.5% had warning signs and 15.8% had severe dengue. The mean cost of hospitalization was US$86.9±170.7. The cost of hospitalization was 28.8 times higher in private hospitals compared with government hospitals. Consultant charges in private hospitals, laboratory investigations in semi-government hospitals and registration with admission charges in government hospitals accounted for 27.3%, 39.4% and 53% of the direct cost in these facilities, respectively. Conclusions A better triage system for hospitalization, subsidizing costs in the public sector and cost capping in the private sector can help to reduce the cost of hospitalization due to dengue so as to ensure affordability for larger portion of the society for universal health coverage.

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