Severe Dengue

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Gathsaurie Neelika Malavige - One of the best experts on this subject based on the ideXlab platform.

  • Serum IL-10 as a marker of Severe Dengue infection.
    BMC Infectious Diseases, 2013
    Co-Authors: Gathsaurie Neelika Malavige, Laksiri Gomes, Lukmall Alles, Thashi Chang, Maryam Salimi, Sachie Fernando, Kushan Dl Nanayakkara, Sd Jayaratne
    Abstract:

    Several studies have shown that serum IL-10, IFNγ and MIF are elevated in patients in Severe Dengue (SD) and could be used as potential biomarkers. We proceeded to determine if these cytokines could be used as biomarkers in a large cohort of adult Dengue patients with varying severity of Dengue infection. Serum IL-10 levels were determined in 259 of whom 40 had Severe Dengue infection. Serum IFNγ and IFNα levels were done in 78 and MIF levels were done in 65 patients with acute Dengue infection. Clinical features and laboratory investigations were undertaken during the febrile and critical phase. We found that serum IL-10 levels were significantly higher (p = 0.001) in patients with SD, when compared to those with non SD. Serum IL-10 levels significantly and inversely correlated with white cell counts (R = −0.23, p = 0.0002) and lymphocyte counts (R = −0.29, p 

  • serum il 10 as a marker of Severe Dengue infection
    BMC Infectious Diseases, 2013
    Co-Authors: Gathsaurie Neelika Malavige, Laksiri Gomes, Lukmall Alles, Thashi Chang, Maryam Salimi, Sachie Fernando, Kushan Dl Nanayakkara, Sd Jayaratne
    Abstract:

    Several studies have shown that serum IL-10, IFNγ and MIF are elevated in patients in Severe Dengue (SD) and could be used as potential biomarkers. We proceeded to determine if these cytokines could be used as biomarkers in a large cohort of adult Dengue patients with varying severity of Dengue infection. Serum IL-10 levels were determined in 259 of whom 40 had Severe Dengue infection. Serum IFNγ and IFNα levels were done in 78 and MIF levels were done in 65 patients with acute Dengue infection. Clinical features and laboratory investigations were undertaken during the febrile and critical phase. We found that serum IL-10 levels were significantly higher (p = 0.001) in patients with SD, when compared to those with non SD. Serum IL-10 levels significantly and inversely correlated with white cell counts (R = −0.23, p = 0.0002) and lymphocyte counts (R = −0.29, p < 0.0001) but significantly and positively correlated with aspartate tranaminase levels (R = 0.16, p = 0.01) and alanine transaminase levels (R = 0.22, p = 0.007). However, IL-10 levels did not have a good predictive value in discriminating those who were likely to develop SD (AUC = 0.66). Serum IFNγ levels were also significantly higher (p = 0.04) in patients with SD when compared to non SD. There was no difference (p = 0.34) in serum IFNα levels and serum MIF levels (p = 0.15) in patients with SD and non SD. Although serum IL-10 was significantly elevated in patients with SD it had a poor discriminatory value in identifying those with SD and non SD and therefore, is unsuitable to be used as a robust biomarker in this cohort.

Patricia Brasil - One of the best experts on this subject based on the ideXlab platform.

  • sensitivity and specificity of the world health organization Dengue classification schemes for Severe Dengue assessment in children in rio de janeiro
    PLOS ONE, 2014
    Co-Authors: Gleicy A Macedo, Michelle Luiza Gonin, Sheila Moura Pone, Oswaldo Goncalves Cruz, Flavio Fonseca Nobre, Patricia Brasil
    Abstract:

    Background:The clinical definition of Severe Dengue fever remains a challenge for researchers in hyperendemic areas like Brazil. The ability of the traditional (1997) as well as the revised (2009) World Health Organization (WHO) Dengue case classification schemes to detect Severe Dengue cases was evaluated in 267 children admitted to hospital with laboratory-confirmed Dengue. Principal Findings:Using the traditional scheme, 28.5% of patients could not be assigned to any category, while the revised scheme categorized all patients. Intensive therapeutic interventions were used as the reference standard to evaluate the ability of both the traditional and revised schemes to detect Severe Dengue cases. Analyses of the classified cases (n = 183) demonstrated that the revised scheme had better sensitivity (86.8%,P,0.001), while the traditional scheme had better specificity (93.4%,P,0.001) for the detection of Severe forms of Dengue. Conclusions/Significance:This improved sensitivity of the revised scheme allows for better case capture and increased ICU admission, which may aid pediatricians in avoiding deaths due to Severe Dengue among children, but, in turn, it may also result in the misclassification of the patients’ condition as Severe, reflected in the observed lower positive predictive value (61.6%, P,0.001) when compared with the traditional scheme (82.6%, P,0.001). The inclusion of unusual Dengue manifestations in the revised scheme has not shifted the emphasis from the most important aspects of Dengue disease and the major factors contributing to fatality in this study: shock with consequent organ dysfunction.

  • is pregnancy associated with Severe Dengue a review of data from the rio de janeiro surveillance information system
    PLOS Neglected Tropical Diseases, 2013
    Co-Authors: Carolina Romero Machado, Elizabeth S Machado, Roger Rohloff, Marina Azevedo, Dayse Pereira Campos, Robson Bruniera De Oliveira, Patricia Brasil
    Abstract:

    BACKGROUND: Dengue is a reportable disease in Brazil; however pregnancy has been included in the application form of the Brazilian notification information system only after 2006. To estimate the severity of maternal Dengue infection the available data that were compiled from January 2007 to December 2008 by the official surveillance information system of the city of Rio de Janeiro were reviewed. METHODS AND PRINCIPAL FINDINGS: During the study period 151604 cases of suspected Dengue infection were reported. Five hundred sixty-one women in their reproductive age (15-49 years) presented with Dengue infection; 99 (18.1%) pregnant and 447 (81.9%) non-pregnant women were analyzed. Dengue cases were categorized using the 1997 WHO classification system and DHF/DSS were considered Severe disease. The Mann-Whitney test was used to compare maternal age according to gestational period and severity of disease. A chi-square test was utilized to evaluate the differences in the proportion of Dengue severity between pregnant and non-pregnant women. Univariate analysis was performed to compare outcome variables (Severe Dengue and non-Severe Dengue) and explanatory variables (pregnancy gestational age and trimester) using the Wald test. A multivariate analysis was performed to assess the independence of statistically significant variables in the univariate analysis. A p-value<0.05 was considered statistically significant. A higher percentage of Severe Dengue infection among pregnant women was found p = 0.0001. Final analysis demonstrated that pregnant women are 3.4 times more prone to developing Severe Dengue (OR: 3.38; CI: 2.10-5.42). Mortality among pregnant women was superior to non-pregnant women. CONCLUSION: Pregnant women have an increased risk of developing Severe Dengue infection and dying of Dengue.

Sd Jayaratne - One of the best experts on this subject based on the ideXlab platform.

  • Serum IL-10 as a marker of Severe Dengue infection.
    BMC Infectious Diseases, 2013
    Co-Authors: Gathsaurie Neelika Malavige, Laksiri Gomes, Lukmall Alles, Thashi Chang, Maryam Salimi, Sachie Fernando, Kushan Dl Nanayakkara, Sd Jayaratne
    Abstract:

    Several studies have shown that serum IL-10, IFNγ and MIF are elevated in patients in Severe Dengue (SD) and could be used as potential biomarkers. We proceeded to determine if these cytokines could be used as biomarkers in a large cohort of adult Dengue patients with varying severity of Dengue infection. Serum IL-10 levels were determined in 259 of whom 40 had Severe Dengue infection. Serum IFNγ and IFNα levels were done in 78 and MIF levels were done in 65 patients with acute Dengue infection. Clinical features and laboratory investigations were undertaken during the febrile and critical phase. We found that serum IL-10 levels were significantly higher (p = 0.001) in patients with SD, when compared to those with non SD. Serum IL-10 levels significantly and inversely correlated with white cell counts (R = −0.23, p = 0.0002) and lymphocyte counts (R = −0.29, p 

  • serum il 10 as a marker of Severe Dengue infection
    BMC Infectious Diseases, 2013
    Co-Authors: Gathsaurie Neelika Malavige, Laksiri Gomes, Lukmall Alles, Thashi Chang, Maryam Salimi, Sachie Fernando, Kushan Dl Nanayakkara, Sd Jayaratne
    Abstract:

    Several studies have shown that serum IL-10, IFNγ and MIF are elevated in patients in Severe Dengue (SD) and could be used as potential biomarkers. We proceeded to determine if these cytokines could be used as biomarkers in a large cohort of adult Dengue patients with varying severity of Dengue infection. Serum IL-10 levels were determined in 259 of whom 40 had Severe Dengue infection. Serum IFNγ and IFNα levels were done in 78 and MIF levels were done in 65 patients with acute Dengue infection. Clinical features and laboratory investigations were undertaken during the febrile and critical phase. We found that serum IL-10 levels were significantly higher (p = 0.001) in patients with SD, when compared to those with non SD. Serum IL-10 levels significantly and inversely correlated with white cell counts (R = −0.23, p = 0.0002) and lymphocyte counts (R = −0.29, p < 0.0001) but significantly and positively correlated with aspartate tranaminase levels (R = 0.16, p = 0.01) and alanine transaminase levels (R = 0.22, p = 0.007). However, IL-10 levels did not have a good predictive value in discriminating those who were likely to develop SD (AUC = 0.66). Serum IFNγ levels were also significantly higher (p = 0.04) in patients with SD when compared to non SD. There was no difference (p = 0.34) in serum IFNα levels and serum MIF levels (p = 0.15) in patients with SD and non SD. Although serum IL-10 was significantly elevated in patients with SD it had a poor discriminatory value in identifying those with SD and non SD and therefore, is unsuitable to be used as a robust biomarker in this cohort.

Thomas Jaenisch - One of the best experts on this subject based on the ideXlab platform.

  • Severe Dengue categories as research endpoints-Results from a prospective observational study in hospitalised Dengue patients.
    PLOS Neglected Tropical Diseases, 2020
    Co-Authors: Kerstin Rosenberger, Neal Alexander, Eric Martinez, Carl-erik Dempfle, Thomas Junghanss, Bridget Wills, Thomas Jaenisch
    Abstract:

    Severe Dengue was perceived as one clinical disease entity until the WHO 2009 classification stratified it into Severe vascular leakage, Severe bleeding, and Severe organ dysfunction. The objectives of this study were to investigate the potential use of Severe Dengue categories as endpoints for intervention research. 271 patients with Severe Dengue among 1734 confirmed Dengue patients were followed prospectively in this hospital-based observational study in Latin America and Asia. We compared the distribution of Severe Dengue categories according to gender and age (below/above 15y), and determined the relative frequency and the overlap of Severe Dengue categories in the same patients. In a next step, we extended the analysis to candidate moderate severity categories, based on recently suggested definitions which were adapted for our purposes. Severe vascular leakage occurred in 244 (90%), Severe bleeding in 39 (14%), and Severe organ dysfunction in 28 (10%) of 271 Severe Dengue patients. A higher frequency of Severe leakage was seen in children or adolescents (

  • Severe Dengue categories as research endpoints results from a prospective observational study in hospitalised Dengue patients
    PLOS Neglected Tropical Diseases, 2020
    Co-Authors: Kerstin Rosenberger, Neal Alexander, Eric Martinez, Carl-erik Dempfle, Thomas Junghanss, Bridget Wills, Thomas Jaenisch
    Abstract:

    Severe Dengue was perceived as one clinical disease entity until the WHO 2009 classification stratified it into Severe vascular leakage, Severe bleeding, and Severe organ dysfunction. The objectives of this study were to investigate the potential use of Severe Dengue categories as endpoints for intervention research. 271 patients with Severe Dengue among 1734 confirmed Dengue patients were followed prospectively in this hospital-based observational study in Latin America and Asia. We compared the distribution of Severe Dengue categories according to gender and age (below/above 15y), and determined the relative frequency and the overlap of Severe Dengue categories in the same patients. In a next step, we extended the analysis to candidate moderate severity categories, based on recently suggested definitions which were adapted for our purposes. Severe vascular leakage occurred in 244 (90%), Severe bleeding in 39 (14%), and Severe organ dysfunction in 28 (10%) of 271 Severe Dengue patients. A higher frequency of Severe leakage was seen in children or adolescents (<15y) compared to adults. More than 80% of the Severe leakage cases, and 30–50% of the cases with Severe bleeding or Severe organ dysfunction, were defined as Severe on the basis of that feature alone. In 136 out of 213 patients with Severe leakage alone, neither moderate bleeding manifestation nor hepatic involvement was recorded. On the other hand, moderate leakage manifestations were detected in 4 out of 12 cases that were classified as Severe based on bleeding alone. A major proportion of Severe Dengue patients exhibited clinical manifestations of Severe vascular leakage only, which may constitute a useful endpoint for intervention research or pathophysiology studies. Severe bleeding and Severe organ manifestation were recorded less frequently and exhibited a higher degree of overlap with Severe leakage. Severe bleeding without leakage may be associated with individual predisposition or the presence of comorbidities. More detailed assessments are needed to explore this hypothesis. Candidate moderate disease endpoints were investigated and need to be further validated.

Eva Harris - One of the best experts on this subject based on the ideXlab platform.

  • antibody dependent enhancement of Severe Dengue disease in humans
    Science, 2017
    Co-Authors: Leah C. Katzelnick, Juan Carlos Mercado, Lionel Gresh, Guillermina Kuan, Angel Balmaseda, Aubree Gordon, Elizabeth M Halloran, Eva Harris
    Abstract:

    For Dengue viruses 1 to 4 (DENV1-4), a specific range of antibody titer has been shown to enhance viral replication in vitro and Severe disease in animal models. Although suspected, such antibody-dependent enhancement of Severe disease has not been shown to occur in humans. Using multiple statistical approaches to study a long-term pediatric cohort in Nicaragua, we show that risk of Severe Dengue disease is highest within a narrow range of preexisting anti-DENV antibody titers. By contrast, we observe protection from all symptomatic Dengue disease at high antibody titers. Thus, immune correlates of Severe Dengue must be evaluated separately from correlates of protection against symptomatic disease. These results have implications for studies of Dengue pathogenesis and for vaccine development, because enhancement, not just lack of protection, is of concern.

  • Antibody-dependent enhancement of Severe Dengue disease in humans
    Science, 2017
    Co-Authors: Leah C. Katzelnick, Juan Carlos Mercado, Lionel Gresh, Guillermina Kuan, Angel Balmaseda, Aubree Gordon, M. Elizabeth Halloran, Eva Harris
    Abstract:

    © 2017, American Association for the Advancement of Science. All rights reserved. For Dengue viruses 1 to 4 (DENV1-4), a specific range of antibody titer has been shown to enhance viral replication in vitro and Severe disease in animal models. Although suspected, such antibody-dependent enhancement of Severe disease has not been shown to occur in humans. Using multiple statistical approaches to study a long-term pediatric cohort in Nicaragua, we show that risk of Severe Dengue disease is highest within a narrow range of preexisting anti-DENV antibody titers. By contrast, we observe protection from all symptomatic Dengue disease at high antibody titers. Thus, immune correlates of Severe Dengue must be evaluated separately from correlates of protection against symptomatic disease. These results have implications for studies of Dengue pathogenesis and for vaccine development, because enhancement, not just lack of protection, is of concern.

  • lower low density lipoprotein cholesterol levels are associated with Severe Dengue outcome
    PLOS Neglected Tropical Diseases, 2015
    Co-Authors: Hope H Biswas, Angel Balmaseda, Aubree Gordon, Andrea Nunez, Maria Angeles Perez, Eva Harris
    Abstract:

    Dengue virus (DENV) is a flavivirus of worldwide importance, with approximately 4 billion people across 128 countries at risk of infection, and up to 390 million infections and 96 million clinically apparent cases estimated annually. Previous in vitro studies have shown that lipids and lipoproteins play a role in modifying virus infectivity. However, the relationship between development of Severe Dengue and total cholesterol, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C), respectively, is unclear. We analyzed data from 789 laboratory-confirmed Dengue cases and 447 other febrile illnesses (OFI) in a prospective pediatric hospital-based study in Managua, Nicaragua between August 2005 and January 2013, using three different classifications of Dengue severity: World Health Organization (WHO) 1997, WHO 2009, and standardized intervention categories. Total serum cholesterol and LDL-C levels decreased over the course of illness and were generally lower with increasing Dengue severity, regardless of classification scheme. Greater decreases in LDL-C than HDL-C were observed among Dengue-positive patients compared to patients with OFI and among Severe Dengue compared to mild Dengue cases. Furthermore, daily cholesterol levels declined with daily albumin blood levels. To examine the effect of cholesterol at presentation on subsequent risk of development of Severe Dengue, relative risks and 95% confidence intervals were calculated using multivariable modified Poisson models. We found that lower total serum cholesterol and LDL-C levels at presentation were associated with subsequent risk of developing Dengue hemorrhagic fever/Dengue shock syndrome using the WHO 1997 Dengue severity classification, and thus that the reduction in LDL-C is likely driving the decreases observed in total serum cholesterol levels among Dengue-positive patients. Our results suggest that cholesterol blood levels are important correlates of Dengue pathophysiology and should be explored as part of a prognostic biomarker panel for Severe Dengue.

  • ultrasound measurement of gallbladder wall thickening as a diagnostic test and prognostic indicator for Severe Dengue in pediatric patients
    Pediatric Infectious Disease Journal, 2007
    Co-Authors: James A Colbert, Aubree Gordon, Rigoberto Roxelin, Sheyla Silva, Javier Silva, Crisanta Rocha, Eva Harris
    Abstract:

    : Gallbladder wall thickening measured by ultrasound was significantly associated with Severe Dengue, as well as with hallmark features of thrombocytopenia and elevated hematocrit/hemoconcentration, in children with suspected Dengue in Nicaragua. We demonstrate that gallbladder wall thickening serves as a clinically relevant diagnostic test and prognostic indicator of Severe Dengue in pediatric populations.