scholarly journals Role of NS1 antibodies in the pathogenesis of acute dengue infection

2018 ◽  
Author(s):  
Deshni Jayathilaka ◽  
Laksiri Gomes ◽  
Chandima Jeewandara ◽  
Geethal S.Bandara Jayarathna ◽  
Dhanushka Herath ◽  
...  
Keyword(s):  
Acute Infection ◽  
Dengue Infection ◽  
Hemorrhagic Fever ◽  
Therapeutic Benefit ◽  
Antibody Responses ◽  
Severe Dengue ◽  
Ns1 Protein ◽  
Serum Samples ◽  
Denv2 Infection

AbstractThe role of NS1-specific antibodies in the pathogenesis of dengue virus infection is of particular interest to the dengue field, yet remains poorly understood. We therefore investigated the immunoglobulin responses of patients with dengue fever (DF) and dengue hemorrhagic fever (DHF) to NS1. Antibody responses to recombinant-NS1 were assessed in serum samples obtained throughout illness of patients with acute secondary DENV1 and DENV2 infection by ELISA. NS1 antibody titres were significantly higher in patients with DHF compared to those with DF for both serotypes, during the critical phase of illness. Antibody responses were further assessed to NS1 peptides and showed that in both acute secondary DENV1 and DENV2 infection, the antibody repertoire of DF and DHF patients is directed towards distinct regions of the NS1 protein. Further experiments in healthy individuals, with either past severe dengue or past asymptomatic dengue infection revealed that individuals with past inapparent disease mounted antibody responses directed to the same NS1 epitope regions as those with mild acute infection (DF). Our results suggest that the specific epitope target of NS1-antibodies generated by patients could predict disease severity and be of potential therapeutic benefit in aiding vaccine and treatment design.

scholarly journals Increased frequencies of CD4+CD25high regulatory T cells in acute dengue infection

2007 ◽  
Vol 204 (5) ◽  
pp. 979-985 ◽  
Author(s):  
Kerstin Lühn ◽  
Cameron P. Simmons ◽  
Edward Moran ◽  
Nguyen Thi Phuong Dung ◽  
Tran Nguyen Bich Chau ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
Severe Disease ◽  
Acute Infection ◽  
Dengue Infection ◽  
Hemorrhagic Fever ◽  
Severe Dengue ◽  
Effector T Cell ◽  
Cell Effector

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 < 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.

scholarly journals Meta-analysis of biomarkers for severe dengue infections

PeerJ ◽  
2017 ◽  
Vol 5 ◽  
pp. e3589 ◽  
Author(s):  
Kuan-Meng Soo ◽  
Bahariah Khalid ◽  
Siew-Mooi Ching ◽  
Chau Ling Tham ◽  
Rusliza Basir ◽  
...  
Keyword(s):  
Secondary Infection ◽  
Meta Analysis ◽  
Acute Infection ◽  
Dengue Infection ◽  
Dengue Shock Syndrome ◽  
Hemorrhagic Fever ◽  
Severe Dengue ◽  
Future Research ◽  
Medical Subject Headings ◽  
Potential Biomarkers

BackgroundDengue viral infection is an acute infection that has the potential to have severe complications as its major sequela. Currently, there is no routine laboratory biomarker with which to predict the severity of dengue infection or monitor the effectiveness of standard management. Hence, this meta-analysis compared biomarker levels between dengue fever (DF) and severe dengue infections (SDI) to identify potential biomarkers for SDI.MethodsData concerning levels of cytokines, chemokines, and other potential biomarkers of DF, dengue hemorrhagic fever, dengue shock syndrome, and severe dengue were obtained for patients of all ages and populations using the Scopus, PubMed, and Ovid search engines. The keywords “(IL1* or IL-1*) AND (dengue*)” were used and the same process was repeated for other potential biomarkers, according to Medical Subject Headings terms suggested by PubMed and Ovid. Meta-analysis of the mean difference in plasma or serum level of biomarkers between DF and SDI patients was performed, separated by different periods of time (days) since fever onset. Subgroup analyses comparing biomarker levels of healthy plasma and sera controls, biomarker levels of primary and secondary infection samples were also performed, as well as analyses of different levels of severity and biomarker levels upon infection by different dengue serotypes.ResultsFifty-six studies of 53 biomarkers from 3,739 dengue cases (2,021 DF and 1,728 SDI) were included in this meta-analysis. Results showed that RANTES, IL-7, IL-8, IL-10, IL-18, TGF-b, and VEGFR2 levels were significantly different between DF and SDI. IL-8, IL-10, and IL-18 levels increased during SDI (95% CI, 18.1–253.2 pg/mL, 3–13 studies,n = 177–1,909,I2 = 98.86%–99.75%). In contrast, RANTES, IL-7, TGF-b, and VEGFR2 showed a decrease in levels during SDI (95% CI, −3238.7 to −3.2 pg/mL, 1–3 studies,n = 95–418,I2 = 97.59%–99.99%). Levels of these biomarkers were also found to correlate with the severity of the dengue infection, in comparison to healthy controls. Furthermore, the results showed that IL-7, IL-8, IL-10, TGF-b, and VEGFR2 display peak differences between DF and SDI during or before the critical phase (day 4–5) of SDI.DiscussionThis meta-analysis suggests that IL-7, IL-8, IL-10, TGF-b, and VEGFR2 may be used as potential early laboratory biomarkers in the diagnosis of SDI. This can be used to predict the severity of dengue infection and to monitor the effectiveness of treatment. Nevertheless, methodological and reporting limitations must be overcome in future research to minimize variables that affect the results and to confirm the findings.

scholarly journals Clinical profile of dengue fever in children: analysis of 2017 outbreak from Central Kerala, India

2018 ◽  
Vol 5 (6) ◽  
pp. 2265 ◽  
Author(s):  
Senthil Kumar K. ◽  
Rajendran N. K. ◽  
Ajith Brabhukumar C.
Keyword(s):  
Dengue Fever ◽  
Dengue Infection ◽  
Tertiary Care ◽  
Hemorrhagic Fever ◽  
Warning Signs ◽  
Clinical Profile ◽  
Severe Dengue ◽  
High Morbidity ◽  
Care Hospital ◽  
High Grade Fever

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.

The association of lipopolysaccharide and inflammatory markers with severe dengue infection

2019 ◽  
Author(s):  
N.L Ajantha Shyamali ◽  
Sameera D. Mahaputuna ◽  
Laksiri Gomes ◽  
Ananda Wijewickrama ◽  
Graham Ogg ◽  
...  
Keyword(s):  
Inflammatory Markers ◽  
Metabolic Diseases ◽  
Dengue Infection ◽  
Severe Dengue ◽  
Atopic Diseases ◽  
Disease Pathogenesis ◽  
Critical Phase ◽  
Plasma Leakage ◽  
Detectable Serum

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.

scholarly journals Quantitative NS1 antigen and the severity of dengue virus infections

2015 ◽  
Vol 55 (2) ◽  
pp. 87
Author(s):  
Ni Made Adi Purnami ◽  
Mohammad Juffrie ◽  
Made Gde Dwi Lingga Utama
Keyword(s):  
Clinical Course ◽  
Nonstructural Protein ◽  
Dengue Infection ◽  
Hemorrhagic Fever ◽  
Cross Sectional Study ◽  
Severe Dengue ◽  
Virus Infections ◽  
Cross Sectional ◽  
Nonstructural Protein 1 ◽  
Spearman Test

Background Dengue infection is one of the main cause ofmorbidity and mortality in children in Indonesia. Since it is knownthat earlier treatment and supportive therapies can decreased casefatality rate from dengue hemorrhagic fever (DHF), identificationof children who have risks to develop to DHF must be quicklyidentified, mainly in areas of endemic.Objective To find a correlation between increased quantitativesecreted nonstructural protein-1 (sNS1) with clinical course ofsevere dengue infections.Methods This was a cross-sectional study conducted on childrenwith dengue infections in Tropical Infections Division of ChildHealth Department, Sanglah Hospital, Denpasar. Detection ofthe dengue antigen was made by examining sNS1 quantitativeimmuno-assay. Analysis correlation of Spearman test was used tolook the relationship between increased quantitative sNS1 withclinical course of severe dengue infections.Results There was a positive relationship between quantitativesNS1 and clinical course of severe dengue infections with a valueof r = 0.903, P=0.001. Increased sNS1 level had a positivecorrelation with more severe dengue infections.Conclusions Quantitative sNS1 titer has a strong positivecorrelation with clinical course of severe dengue infections.

scholarly journals Monoclonal antibody-based capture ELISA in the diagnosis of previous dengue infection

2019 ◽  
Vol 16 (1) ◽  
Author(s):  
Chukiat Sirivichayakul ◽  
Kriengsak Limkittikul ◽  
Pornthep Chanthavanich ◽  
Sutee Yoksan ◽  
Anuttarasakdi Ratchatatat ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Neutralization Test ◽  
Dengue Infection ◽  
Severe Dengue ◽  
Enzyme Linked Immunosorbent Assay ◽  
Dengue Vaccine ◽  
Serum Samples ◽  
Specific Immunoglobulin ◽  
Study Population ◽  
Dengue Prevention

Abstract Background Dengue is an important mosquito-borne disease. There is currently only one licensed vaccine for dengue prevention. The vaccine provides higher efficacy in pre-vaccination dengue-seropositive persons but a higher risk of subsequent more severe dengue in dengue-seronegative persons. It is recommended that the dengue vaccine may be given in dengue-seropositive individuals or as mass vaccination without individual pre-vaccination screening in areas where the dengue seroprevalence is > 80% in children aged 9 years. We evaluated a dengue specific immunoglobulin G monoclonal antibody-based capture enzyme-linked immunosorbent assay (MAb-ELISA) in the diagnosis of previous dengue infection using serum samples from the cohort study in Ratchaburi Province, Thailand. Methods The MAb-ELISA was compared to 70% plaque reduction neutralization test (PRNT70) in 453 serum samples from children aged 3–11 years in Ratchaburi Province, Thailand. Results The sensitivity and specificity of MAb-ELISA at the positive to negative (P/N) ratio cut-off level of > 3 were both 0.91 in the diagnosis of previous dengue infection, compared to PRNT70. The false positivity was mainly in Japanese encephalitis (JE) seropositive subjects. Conclusions This research provides evidence that MAb-ELISA is useful for dengue seroprevalence study and dengue pre-vaccination screening. JE seropositivity was the major cause of false positive result in the study population.

Desialylation of Plasma Proteins in Severe Dengue Infection: Possible Role of Oxidative Stress

2008 ◽  
Vol 79 (3) ◽  
pp. 372-377 ◽  
Author(s):  
Soundravally Rajendiran ◽  
Selvaraj Nambiar ◽  
Hoti Sugeerappa Lakshamanappa ◽  
Bobby Zachariah
Keyword(s):  
Oxidative Stress ◽  
Plasma Proteins ◽  
Dengue Infection ◽  
Severe Dengue

scholarly journals Clinico-epidemiological study of dengue fever in Ajmer region

2019 ◽  
Vol 6 (5) ◽  
pp. 2046
Author(s):  
Dharmendra Rawat ◽  
Kanwar Singh ◽  
Pukhraj Garg
Keyword(s):  
Dengue Fever ◽  
Case Fatality Rate ◽  
Wide Spectrum ◽  
Dengue Infection ◽  
Case Fatality ◽  
Hemorrhagic Fever ◽  
Severe Dengue ◽  
Common Disease ◽  
Hemorrhagic Disease ◽  
Fatality Rate

Background: Dengue infection is a major challenge to public health, especially in South-East Asia. It present with a diverse clinical spectrum. Estimates suggest that annually over 50 million cases of dengue hemorrhagic fever (DHF) occur in Asian countries with a case fatality rate of less than 5%. Of those with DHF, at least 90% are children younger than 15 years old. In humans, dengue infection causes a spectrum of illness ranging from relatively mild, non-specific viral syndrome known as Dengue fever (DF) to severe hemorrhagic disease and death. Definitive early Dengue diagnosis requires laboratory tests and those suitable for use at this stage of illness are either costly, such as RT-PCR for Dengue; not sufficiently rapid, such as virus isolation. Currently test available are NS1 antigen detection and ELISA for dengue, IgM and IgG antibodies. Objective of this study is to study clinico-epidemiological and haematological features of Dengue infection.Methods: Prospective observational study involving initial 100 registered cases who were serologically confirmed dengue infection for a period of one year.Results: DF, DHF and DSS were found in 41%, 53% and 6% patients respectively. Most common presenting complaint and bleeding manifestation were fever and petechiae. Uncommonly altered sensorium and icterus were found in severe dengue infection. 6% patients had coagulopathy, 37 patients had hepatic involvement and 2 patients had deranged renal function who had DSS. Fever was present in (100%) cases of DF, DHF and DSS. 26% patients had their platelet count <50000/mm3.Conclusions: Dengue is a common disease in the India with wide spectrum of clinical presentations, affecting 5-15 years age group children commonly. It is one of the dreaded fevers but early diagnosis and management according to recent WHO guidelines can decrease case fatality rate significantly.

scholarly journals Seroprevalence of Dengue Infection in a Tertiary Care Hospital in Assam

2018 ◽  
Vol 7 (1) ◽  
pp. 1582 ◽  
Author(s):  
Liza Goswami ◽  
Chowdhury Runumi ◽  
Elmy S. Rasul
Keyword(s):  
Dengue Infection ◽  
Tertiary Care ◽  
Age Groups ◽  
Hemorrhagic Fever ◽  
Health Concern ◽  
Care Hospital ◽  
Serum Samples ◽  
Igm Antibody ◽  
Ns1 Antigen ◽  
Antibody Elisa

<p><strong>Background:</strong> Dengue fever (DF) and dengue hemorrhagic fever (DHF) are important arthropod borne viral diseases. Dengue in India has dramatically expanded over the last few decades, with rapidly changing epidemiology. Dengue is emerging as major public health concern in northeast India and spreading with increased morbidity.</p><p><strong>Objective:</strong>This study was carried out to determine the seroprevalence of Dengue infection among patients attending in Fakhruddin Ali Ahmed Medical College and Hospital, Barpeta, Assam during the period 2013-2016.</p><p><strong>Methods:</strong> A retrospective study was done from the year 2013 to 2016. A total of 340 serum samples received in the department of microbiology FAAMCH, were tested for the confirmation of suspected cases of dengue. Dengue NS1 antigen and Dengue IgM antibody ELISA tests were performed for the confirmation of dengue cases. We estimated the incidence by applying age, sex and season adjusted dengue positivity.</p><p><strong>Results:</strong> Out of 340 samples tested, 68 were positive either by NS1 antigen or for IgM antibody ELISA tests. These comprised all age groups of both sexes with higher incidence of cases in young males aged 26– 60 years.</p><p><strong>Conclusion:</strong> From this study, it is apparent that dengue surveillance and control should be enhanced by wider use of laboratory testing to confirm dengue as a cause of fever of unknown origin, especially during the local dengue transmission season.</p>

scholarly journals Relationship between Family Mobility and the Incidence of Dengue Hemorrhagic Fever at Sleman Regency, Yogyakarta, Indonesia

2019 ◽  
Vol 15 (2) ◽  
pp. 127
Author(s):  
Tri Wulandari Kesetyaningsih ◽  
Dimas Pradana Putra ◽  
Farizki Muhammad Muhammad
Keyword(s):  
Risk Factor ◽  
Dengue Hemorrhagic Fever ◽  
Dengue Infection ◽  
Family Members ◽  
Public Health Problem ◽  
Hemorrhagic Fever ◽  
Control Group ◽  
Case Group ◽  
Family Mobility

Abstract: Dengue hemorrhagic fever is a public health problem in the world. Transmission of dengue through Aedes mosquito, so that the incidence is locally limited to the distance of flying. A role of mobility towards dengue spreading have not been consistent. This study aims to provide information about the role of family members’ mobility in dengue incidence by using observational study with case control design. Case group are families whose members have suffered from dengue in 2014-2016 and control groups are their neighbors. There were 114 people for case and 116 for control group which is divided into two locations namely Sleman and gamping. Data on DHF patients and their addresses were obtained from Health Office, and mobility obtained through questionnaires then analyzed using chi square to determine the role of mobility in DHF incidence. The results show that there is no significance relationship between family mobility and the incidence of DHF. In Gamping, P high - low is 0.307 and P moderate - low is 0.523. In Sleman, P high - low is 0.685 and P moderate - low is 0.438. It was concluded that the mobility of family members was not a risk factor for dengue infection. Keywords: family mobility, DHF incidence, risk factor

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