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 ◽  
...  

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.

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 < 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.


2021 ◽  
Vol 2021 ◽  
pp. 1-5
Author(s):  
Randula Ranawaka ◽  
Chamara Jayamanne ◽  
Kavinda Dayasiri ◽  
Dinuka Samaranayake ◽  
Udara Sandakelum ◽  
...  

Pathogenesis of dengue haemorrhagic fever is not fully understood, but it is thought that there is antibody enhancement during the secondary infection, which causes severe dengue haemorrhagic fever (DHF). Therefore, patients who have DHF should have a documented history of symptomatic dengue infection in the past. A retrospective descriptive-analytical study was conducted at the University Paediatric Unit at Lady Ridgeway Hospital for Children, Colombo, Sri Lanka. All children who had fulfilled the criteria for DHF admitted to the unit from April 2018 to September 2018 were recruited into the study. Relevant data were collected from bed head tickets. One hundred and eighty-four children were included in the final analysis. Thirty-three (17.9%) had a past history of documented symptomatic dengue infection, while 82.1% did not have a documented dengue infection. Twelve patients had dengue shock syndrome, and none of them had previously documented symptomatic dengue fever. Dextran was used in 96 patients in the critical phase. Twelve (42%) patients with past documented symptomatic dengue fever needed dextran while 84 (54.9%) patients without a documented past history of dengue fever needed dextran. In our clinical observation, we noticed that children with DHF mostly did not have a documented symptomatic prior dengue infection, while those with a documented symptomatic prior infection had a milder subsequent illness. In fact, the majority (82.1%) of patients with DHF did not have documented previous symptomatic dengue infection. It was also observed that the clinical course of subsequent dengue infection was less severe in patients with previously documented symptomatic dengue fever. This finding should be further evaluated in a larger scale study minimizing the all-confounding factors. This fact is more important in selecting recipients for vaccines against the dengue virus, which are supposed to produce immunity against the virus without causing the severe disease.


2018 ◽  
Author(s):  
Deshni Jayathilaka ◽  
Laksiri Gomes ◽  
Chandima Jeewandara ◽  
Geethal S.Bandara Jayarathna ◽  
Dhanushka Herath ◽  
...  

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.


2011 ◽  
Vol 51 (3) ◽  
pp. 157 ◽  
Author(s):  
Mulya Rahma Karyanti

Background Dengue hemorrhagic fever (DHF) is endemic to Indonesia and remains a public health problem, with its highest incidence in children. There have been few reports on the clinical, hematological and serological data in children \\lith dengue.Objective To assess the clinical and laboratory profiles of children \\lith dengue infection in Cipto Mangunkusumo Hospital, Jakarta, Indonesia.Methods Clinical, hematological and serological infonnation from children diagnosed v.ith dengue infection in Cipto Mangunkusumo Hospital were collected from 2007 to 2009.Results Of611 children admitted with dengue, 143 (23.4%) had dengue fever (DF), 252 (41.2%) had DHF grades I and II; and 216 (35.4%) had DHF grades III and IV. Of the 81 cases where dengue serotypes were identified, 12.3% were DENV1, 35.8% were DENV-2, 48.2% were DENV-3 and 3.7% were DENV-4. Mean age of subjects was 8.9 years (SD 4.4), and 48.4% of cases were boys. The mean length of fever before hospital admission was 4.2 days (SD 1.1) and mean length of stay in the hospital was 4 days (SD 2.7). Common symptoms observed were petechiae, hepatomegaly and epistaxis. Complications found mostly in those with dengue shock syndrome (DSS) were hematemesis (30 cases, 4.9% of all patients), encephalopathy (19 cases, 3.1 %) and melena (17 cases, 2.8%).Conclusion Signs and symptoms of fever, bleeding manifestations and thrombocytopenia were present in children 'With DF and DHF, while signs of increased vascular permeability were found only in those 'With DHF. Encephalopathy and gastrointestinal bleeding were found mostly in DSS cases. At admission, leukopenia was found in more DF patients than in DHF patients. Absence of leukopenia may be a sign of more severe dengue infection. 


2021 ◽  
Vol 10 (1) ◽  
pp. 49
Author(s):  
Annelin Kurniati ◽  
Ahmad Fandi ◽  
Mardhatillah Sariyanti ◽  
Ety Febrianti ◽  
Debie Rizqoh

Secondary infection with the dengue virus causes mild to severe manifestations. The distribution of dengue virus serotypes varies in various areas and can change over time. There are four dengue serotypes, namely DENV-1, DENV-2, DENV-3 and DENV-4. Objectives: To knew the distribution of virus serotypes in an area and determined the pathogenesis of the disease, which can cause severe manifestations in patients with secondary infections. Methods: The data taken is the severity of secondary infections and dengue serotypes. The literature search was performed on PMC and Cochrane. Search criteria were performed using keywords (secondary infection * OR secondary dengue infection *) AND (Dengue Virus * OR Dengue Infection * OR Dengue * OR DENV) AND (Serotype * OR Serogroup) AND (severe dengue * OR severity * OR severity of illness indexs * OR dengue fever * OR dengue haemorrhage fever * OR dengue shock syndrome * OR DF * OR DHF * OR DSS *) AND (Indonesia *). Results: Literature study search found 387 literature with five studies conducted the analysis. From the results of the analysis, it was found that secondary infections were more common in patients with recurrent dengue infection with serotype 2 (DENV-2), serotype 3 (DENV-3) and serotype 4 (DENV-4). Conclusion: Secondary infection of dengue virus serotype 2 (DENV-2) and serotype 3 (DENV-3) can cause severe dengue infection.Keywords:  Dengue Virus, Indonesia, Secondary Infection, Serotype, Severity


2016 ◽  
Vol 2016 ◽  
pp. 1-5 ◽  
Author(s):  
Nurhayati Lukman ◽  
Gustiani Salim ◽  
Herman Kosasih ◽  
Nugroho Harry Susanto ◽  
Ida Parwati ◽  
...  

Secondary dengue infection by heterotypic serotypes is associated with severe manifestations of disease, that is, dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). The World Health Organization (WHO) has recommended criteria based on the hemagglutination inhibition (HI) test to distinguish between primary and secondary dengue infections. Since the HI test has practical limitations and disadvantages, we evaluated the accuracy of WHO HI criteria and compared it with criteria based on an IgG enzyme-linked immunosorbent assay (ELISA) using a plaque reduction neutralization test (PRNT) as the gold standard. Both WHO HI criteria and IgG ELISA criteria performed strongly (16/16) in determining primary infection. However, to determine secondary infection, the IgG ELISA criteria performed better (72/73) compared to the WHO HI criteria (23/73).


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.


2015 ◽  
Vol 55 (2) ◽  
pp. 87
Author(s):  
Ni Made Adi Purnami ◽  
Mohammad Juffrie ◽  
Made Gde Dwi Lingga Utama

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.


2013 ◽  
Vol 53 (4) ◽  
pp. 187 ◽  
Author(s):  
Maria Mahdalena Tri Widiyati ◽  
Ida Safitri Laksanawati ◽  
Endy Paryanto Prawirohartono

Background Dengue hemorrhagic fever (DHF) leads to highmorbidity and mortality if not be treated properly and promptly.Obesity may play a role in the progression ofDHF to dengue shocksyndrome (DSS) and could be a prognostic factor.Objective To evaluate childhood obesity as a prognostic factorfor DSS.Methods We reviewed medical records of patients with DHFand DSS admitted to Department of Child Health, Dr. SardjitoHospital, Yogyakarta between June 2008 and February 2011.Subjects were aged less than 18 years and fulfilled WHO criteria(1997) for DHF or DSS. The exclusion criteria were the denguefever, a milder form of disease, or other viral infections. Riskfactors for DSS were analyzed by logistic regression analysis.Results Of342 patients who met the inclusion criteria, there were116 DSS patients (33 .9%) as the case group and 226 DHF patients(66.1%) as the control group. Univariate analysis revealed thatrisk factors for DSS were obesity (OR= 1.88; 95%CI 1.01 to3.5 l) ,secondary infection type (OR=0.82; 95%CI 0.41 to 1.63), plasmaleakage with hematocrit increase> 25% (OR=3.42; 95%CI 2.06to 5.65), platelet count < 20,000/μL (OR= l.95; 95%CI 1.20 to3 .16), and inadequate fluid management from prior hospitalization(OR=9.ll; 95% CI 1.13 to 73.66). By multivariate analysis,plasma leakage with hematocrit increase > 25% was associatedwith DSS (OR=2.5 l; 95%CI 1.12 to 5.59), while obesity was notassociated with DSS (OR= l.03; 95%CI 0.32 to3.3 1).Conclusion Obesity is not a risk factor for DSS, while plasmaleakage with hematocrit increase > 25% is associated with DSS.


2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Anish Laul ◽  
Poonam Laul ◽  
Vamsi Merugumala ◽  
Ravi Pathak ◽  
Urvashi Miglani ◽  
...  

Introduction.Dengue fever is an arboviral disease, which is transmitted by mosquito vector and presents as varied clinical spectrum of dengue fever (DF), dengue hemorrhagic fever (DHF), dengue shock syndrome (DSS), and expanded dengue syndrome (EDS) with atypical presentations, thus posing a diagnostic dilemma. Unless we are aware of these presentations, diagnosis as well as early initiation of treatment becomes difficult. We studied the various clinical presentations of dengue infection during an outbreak of disease in 2015.Materials and Methods. A total of 115 confirmed cases of dengue infection from Department of Medicine of Deen Dayal Upadhyay Hospital, New Delhi, were enrolled in this observational study.Results.The common signs and symptoms of dengue infection were fever, headache, body ache, backache, retro-orbital pain, bleeding manifestations, and rash in 100%, 87%, 86%, 58%, 41%, 21%, and 21%, respectively. Nonspecific or warning signs and symptoms included vomiting, weakness, abdominal pain, breathlessness, vertigo, sweating, and syncope. Other possible signs and symptoms of coinfections, comorbidities, or complications included diarrhea, sore throat, and neurological manifestations. There were seven patients with coinfections and four with comorbidities. The final diagnosis of these patients was DF (73%), DHF (16.5%), DSS (1.7%), and EDS (4.3%). Among EDS patients, the atypical presentations included encephalopathy, lateral rectus nerve palsy, acalculous cholecystitis, and myocarditis. Four patients required ICU care and there was no death in this study.Conclusion. Knowledge of atypical presentations is a must for early diagnosis and timely intervention to prevent life-threatening complications.


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