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Bridget Wills - One of the best experts on this subject based on the ideXlab platform.

  • microvascular fluid exchange implications of the revised starling model for resuscitation of Dengue Shock Syndrome
    Frontiers of Medicine in China, 2020
    Co-Authors: Huynh Trung Trieu, Bridget Wills
    Abstract:

    Dengue is the most common mosquito-borne viral infection in the world. The most feared complication is a poorly understood vasculopathy that occurs in only a small minority of symptomatic individuals, especially children and young adults, but can result in potentially fatal Dengue Shock Syndrome (DSS). Based mainly on expert opinion, WHO management guidelines for DSS recommend prompt infusion of a crystalloid fluid bolus followed by a tapering crystalloid fluid regimen, supplemented if necessary by boluses of synthetic colloid solutions. However, following publication of a number of major trials undertaken in other, primarily adult, critical care scenarios, use of both synthetic colloid solutions and of fluid boluses for volume expansion have become controversial. Synthetic colloids tend to be used for severe DSS cases in order to boost intravascular oncotic pressure, based on the classic Starling hypothesis in which opposing hydrostatic and oncotic forces determine fluid flow across the microvascular barrier. However, the revised Starling model emphasizes the critical contribution of the endothelial glycocalyx layer (EGL), indicating that it is the effective oncotic pressure gradient across the EGL not endothelial cells per se that opposes filtration. Based on several novel concepts that are integral to the revised Starling model, we review the clinical features of DSS and discuss a number of implications that are relevant for fluid management. We also highlight the need for context-specific clinical trials that address crucially important questions around the management of DSS.

  • Skin dendritic cell and T cell activation associated with Dengue Shock Syndrome
    Scientific Reports, 2017
    Co-Authors: Huynh Thi Le Duyen, Bridget Wills, Daniela Cerny, Dinh The Trung, Jassia Pang, Sumathy Velumani, Cameron Simmons, Muzlifah Haniffa, Katja Fink
    Abstract:

    The pathogenesis of severe Dengue remains unclear, particularly the mechanisms underlying the plasma leakage that results in hypovolaemic Shock in a small proportion of individuals. Maximal leakage occurs several days after peak viraemia implicating immunological pathways. Skin is a highly vascular organ and also an important site of immune reactions with a high density of dendritic cells (DCs), macrophages and T cells. We obtained skin biopsies and contemporaneous blood samples from patients within 24 hours of onset of Dengue Shock Syndrome (DSS), and from healthy controls. We analyzed cell subsets by flow cytometry, and soluble mediators and antibodies by ELISA; the percentage of migratory CD1a^+ dermal DCs was significantly decreased in the DSS patients, and skin CD8^+ T cells were activated, but there was no accumulation of Dengue-specific antibodies. Inflammatory monocytic cells were not observed infiltrating the skin of DSS cases on whole-mount histology, although CD14^dim cells disappeared from blood.

  • Genome-wide association study identifies susceptibility loci for Dengue Shock Syndrome at MICB and PLCE1
    Nature Genetics, 2011
    Co-Authors: Chiea Chuen Khor, Bridget Wills, Jeremy Farrar, Tran Nguyen Bich Chau, Junxiong Pang, Sonia Davila, Hoang Truong Long, Rick T. H. Hong, Sarah Dunstan, Ta Van Tram
    Abstract:

    Hypovolemic Shock (Dengue Shock Syndrome (DSS)) is the most common life-threatening complication of Dengue. We conducted a genome-wide association study of 2,008 pediatric cases treated for DSS and 2,018 controls from Vietnam. Replication of the most significantly associated markers was carried out in an independent Vietnamese sample of 1,737 cases and 2,934 controls. SNPs at two loci showed genome-wide significant association with DSS. We identified a susceptibility locus at MICB (major histocompatibility complex (MHC) class I polypeptide-related sequence B), which was within the broad MHC region on chromosome 6 but outside the class I and class II HLA loci (rs3132468, P(meta) = 4.41 × 10(-11), per-allele odds ratio (OR) = 1.34 (95% confidence interval: 1.23-1.46)). We identified associated variants within PLCE1 (phospholipase C, epsilon 1) on chromosome 10 (rs3765524, P(meta) = 3.08 × 10(-10), per-allele OR = 0.80 (95% confidence interval: 0.75-0.86)). We identify two loci associated with susceptibility to DSS in people with Dengue, suggesting possible mechanisms for this severe complication of Dengue.

  • epidemiological factors associated with Dengue Shock Syndrome and mortality in hospitalized Dengue patients in ho chi minh city vietnam
    American Journal of Tropical Medicine and Hygiene, 2011
    Co-Authors: Katherine L Anders, Bridget Wills, Nguyen Van Vinh Chau, Jeremy Farrar, Nguyen Thanh Hung, Le Bich Lien, Tran Thi Thuy, Tran Tinh Hien, Nguyen Minh Nguyet, Cameron R Simmons
    Abstract:

    Understanding trends in Dengue disease burden and risk factors for severe disease can inform health service allocation, clinical management, and planning for vaccines and therapeutics. Dengue admissions at three tertiary hospitals in Ho Chi Minh City, Vietnam, increased between 1996 and 2009, peaking at 22,860 in 2008. Children aged 6-10 years had highest risk of Dengue Shock Syndrome (DSS); however, mortality was highest in younger children and decreased with increasing age (odds ratio [OR] = 0.52, 95% confidence interval [CI] = 0.36-0.75 in 6- to 10- year-old children and OR = 0.27, 95% CI = 0.16-0.44 in 11- to 15-year-old children compared with 1- to 5-year-old children). Males were overrepresented among Dengue cases; however, girls had higher risk of DSS (OR = 1.19, 95% CI = 1.14-1.24) and death (OR = 1.57, 95% CI = 1.14-2.17). Young children with Dengue had greatest risk of death and should be targeted in Dengue vaccine and drug trials. The increased risk of severe outcomes in girls warrants further attention in studies of pathogenesis, health-seeking behavior, and clinical care.

  • three commentaries on corticosteroids for treating Dengue Shock Syndrome with introduction by ebch editor
    Evidence-based Child Health: A Cochrane Review Journal, 2007
    Co-Authors: Joan L Robinson, Bridget Wills, Scott B Halstead, Joseph L Mathew
    Abstract:

    This is a commentary on a Cochrane review, published in this issue of EBCH, first published as: Panpanich R, Sornchai P, Kanjanaratanakorn K. Corticosteroids for treating Dengue Shock Syndrome. Cochrane Database of Systematic Reviews 2006, Issue 3. Art. No.: CD003488. DOI: 10.1002/14651858.CD003488.pub2. Further information for this Cochrane review is available in this issue of EBCH in the accompanying EBCH Summary and Characteristics and Key Findings Tables articles. Copyright © 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. The Cochrane Collaboration

Jeremy Farrar - One of the best experts on this subject based on the ideXlab platform.

  • clinical characteristics of Dengue Shock Syndrome in vietnamese children a 10 year prospective study in a single hospital
    Clinical Infectious Diseases, 2013
    Co-Authors: Phung Khanh Lam, Jeremy Farrar, Tran Vinh Diet, Dong Thi Hoai Tam, Cameron P Simmons, Cao Thi Tam, Nguyen Thi Hanh Tien, Nguyen Tan Thanh Kieu, Nguyen Thi Ngoc Nga, Phan Tu Qui
    Abstract:

    Dengue is the most important mosquito-borne viral disease affecting humans. Infection can be caused by any 1 of 4 Dengue viruses (DENV-1 to DENV-4), transmitted by Aedes mosquitoes [1]. Currently about 100 million clinically apparent cases are estimated to occur each year [2], resulting in approximately 20 000 deaths [3]. Infection with any serotype can cause a broad range of disease manifestations, from inapparent infection to severe and fatal disease [4]. The most notable complication is an unexplained vasculopathy that manifests as a transient increase in vascular permeability resulting in leakage of plasma from the circulation. Substantial plasma losses may occur, leading to the potentially fatal Dengue Shock Syndrome (DSS). Although adults do experience Shock, vascular leakage is generally more severe in young children [5], and in endemic areas DSS is seen primarily in the pediatric population. Thrombocytopenia and coagulation derangements also occur, and a variety of bleeding manifestations ranging from minor skin petechiae to major mucosal bleeding may be seen. Neither vaccines nor specific therapies are currently available; careful clinical observation and judicious use of intravenous fluid therapy, in particular urgent Shock resuscitation for DSS, are the foundations for successful management [6]. Many individuals with DSS respond to resuscitation with crystalloid solutions, but patients with profound or protracted Shock often require additional support with colloid solutions and are at risk of developing respiratory compromise due to ongoing plasma leakage. Mortality rates for DSS vary from 10% depending on the severity of the cases reported, the level of monitoring available, and the experience of the attending healthcare personnel [7–9]. Despite the increasing burden of Dengue globally, only a few small retrospective reports have described the clinical characteristics, management, or outcomes of DSS [8, 10, 11]. At the Hospital for Tropical Diseases (HTD) in Ho Chi Minh City, a prospective observational study aiming to enroll all children presenting with DSS was conducted from 1999 to 2009. Here we present data on >1700 cases collected during this 10-year period, providing the first comprehensive description of the clinical features of DSS in children.

  • Genome-wide association study identifies susceptibility loci for Dengue Shock Syndrome at MICB and PLCE1
    Nature Genetics, 2011
    Co-Authors: Chiea Chuen Khor, Bridget Wills, Jeremy Farrar, Tran Nguyen Bich Chau, Junxiong Pang, Sonia Davila, Hoang Truong Long, Rick T. H. Hong, Sarah Dunstan, Ta Van Tram
    Abstract:

    Hypovolemic Shock (Dengue Shock Syndrome (DSS)) is the most common life-threatening complication of Dengue. We conducted a genome-wide association study of 2,008 pediatric cases treated for DSS and 2,018 controls from Vietnam. Replication of the most significantly associated markers was carried out in an independent Vietnamese sample of 1,737 cases and 2,934 controls. SNPs at two loci showed genome-wide significant association with DSS. We identified a susceptibility locus at MICB (major histocompatibility complex (MHC) class I polypeptide-related sequence B), which was within the broad MHC region on chromosome 6 but outside the class I and class II HLA loci (rs3132468, P(meta) = 4.41 × 10(-11), per-allele odds ratio (OR) = 1.34 (95% confidence interval: 1.23-1.46)). We identified associated variants within PLCE1 (phospholipase C, epsilon 1) on chromosome 10 (rs3765524, P(meta) = 3.08 × 10(-10), per-allele OR = 0.80 (95% confidence interval: 0.75-0.86)). We identify two loci associated with susceptibility to DSS in people with Dengue, suggesting possible mechanisms for this severe complication of Dengue.

  • epidemiological factors associated with Dengue Shock Syndrome and mortality in hospitalized Dengue patients in ho chi minh city vietnam
    American Journal of Tropical Medicine and Hygiene, 2011
    Co-Authors: Katherine L Anders, Bridget Wills, Nguyen Van Vinh Chau, Jeremy Farrar, Nguyen Thanh Hung, Le Bich Lien, Tran Thi Thuy, Tran Tinh Hien, Nguyen Minh Nguyet, Cameron R Simmons
    Abstract:

    Understanding trends in Dengue disease burden and risk factors for severe disease can inform health service allocation, clinical management, and planning for vaccines and therapeutics. Dengue admissions at three tertiary hospitals in Ho Chi Minh City, Vietnam, increased between 1996 and 2009, peaking at 22,860 in 2008. Children aged 6-10 years had highest risk of Dengue Shock Syndrome (DSS); however, mortality was highest in younger children and decreased with increasing age (odds ratio [OR] = 0.52, 95% confidence interval [CI] = 0.36-0.75 in 6- to 10- year-old children and OR = 0.27, 95% CI = 0.16-0.44 in 11- to 15-year-old children compared with 1- to 5-year-old children). Males were overrepresented among Dengue cases; however, girls had higher risk of DSS (OR = 1.19, 95% CI = 1.14-1.24) and death (OR = 1.57, 95% CI = 1.14-2.17). Young children with Dengue had greatest risk of death and should be targeted in Dengue vaccine and drug trials. The increased risk of severe outcomes in girls warrants further attention in studies of pathogenesis, health-seeking behavior, and clinical care.

  • comparison of three fluid solutions for resuscitation in Dengue Shock Syndrome
    The New England Journal of Medicine, 2005
    Co-Authors: Bridget Wills, Nguyen Minh Dung, Ha Thi Loan, Tran Thi Thuy, Le T T Minh, Tran Vinh Diet, Nguyen Van Vinh Chau, Kasia Stepniewska, Nicholas J White, Jeremy Farrar
    Abstract:

    Background Dengue Shock Syndrome is characterized by severe vascular leakage and disordered hemostasis and progresses to death in 1 to 5 percent of cases. Although volume replacement is recognized as the critical therapeutic intervention, World Health Organization management guidelines remain empirical rather than evidence-based. Methods We performed a double-blind, randomized comparison of three fluids for initial resuscitation of Vietnamese children with Dengue Shock Syndrome. We randomly assigned 383 children with moderately severe Shock to receive Ringer's lactate, 6 percent dextran 70 (a colloid), or 6 percent hydroxyethyl starch (a colloid) and 129 children with severe Shock to receive one of the colloids. The primary outcome measure was requirement for rescue colloid at any time after administration of the study fluid. Results Only one patient died (<0.2 percent mortality). The primary outcome measure — requirement for rescue colloid — was similar for the different fluids in the two severity groups...

  • size and charge characteristics of the protein leak in Dengue Shock Syndrome
    The Journal of Infectious Diseases, 2004
    Co-Authors: Bridget Wills, Emmanuelle E Oragui, Nguyen Minh Dung, Ha Thi Loan, Nguyen Van Vinh Chau, Jeremy Farrar, Michael Levin
    Abstract:

    Background. The mechanism underlying the transient vascular leak Syndrome of Dengue hemorrhagic fever (DHF) is unknown. We aimed to determine whether molecular size and charge selectivity, which help restrict plasma proteins within the intravascular space, are altered in patients with DHF and whether a disturbance of the anionic glycosaminoglycan (GAG) layer on the luminal endothelial surface contributes to disease pathogenesis Methods. We measured serial plasma levels and fractional clearances of proteins with different size and charge characteristics in 48 children with Dengue Shock Syndrome (DSS) and urinary excretion profiles of heparan sulfate, chondroitin-4-sulfate, and chondroitin-6-sulfate in affected children and healthy control subjects. Results. Compared with convalescent values, acute plasma concentrations of all proteins were reduced, with increased fractional clearances. Smaller proteins were more affected than larger molecules. Albumin, which is normally protected from leakage by its strong negative charge, demonstrated a clearance pattern similar to that of transferrin, a neutral molecule of similar size. Urinary heparan sulfate excretion was significantly increased in children with DSS. Conclusions. The endothelial size-dependent sieving mechanism for plasma proteins is at least partially retained, whereas selective restriction based on negative charge is impaired. The increased heparan sulfate excretion suggests a role for GAGs in the pathogenesis of the vascular leak.

Tran Thi Thuy - One of the best experts on this subject based on the ideXlab platform.

  • alpha tryptase allele of tryptase 1 tpsab1 gene associated with Dengue hemorrhagic fever dhf and Dengue Shock Syndrome dss in vietnam and philippines
    Human Immunology, 2015
    Co-Authors: Clara Vasquez Velasquez, Vu Thi Que Huong, Tran Thi Thuy, Nguyen Tien Huy, Nguyen Thi Phuong Lan, Arthur Dessi Roman, Edelwisa S Mercado, Fe Espino, Ma Lucila M Perez, Vo Dinh Tham
    Abstract:

    We previously reported, significantly higher levels of Chymase and Tryptase in early stage plasma of DSS patients prior to the occurrence of Shock suggesting a possible role of mast cells in Dengue pathogenesis. To further investigate, we analyzed CMA1 promoter SNP (rs1800875) and TPSAB1 gene alleles, which encode the Human Chymase and α- and β- tryptase 1 enzymes respectively, for susceptibility to Dengue Hemorrhagic Fever (DHF) and Dengue Shock Syndrome (DSS) in patients from hospitals in Vietnam (Ho Chi Minh City and Vinh Long) and the Philippines. While the CMA1 promoter SNP (rs1800875) was not associated with DHF/DSS, the homozygous form of α-tryptase allele was associated with DSS patients in Vinh Long and the Philippines (OR=3.52, p<0.0001; OR=3.37, p<0.0001, respectively) and with DHF in Ho Chi Minh City (OR=2.54, p=0.0084). Also, a statistically significant association was observed when DHF and DSS were combined in Vinh Long (OR=1.5, p=0.034) and the Philippines (OR=2.36, p=0.0004); in Ho Chi Minh City when DHF and DSS were combine an association was observed, but it was not statistically significant (OR=1.5, p=0.0505). Therefore, the α-tryptase might have a possible effect on the susceptibility to severe form of Dengue infection.

  • association of mast cell derived vegf and proteases in Dengue Shock Syndrome
    PLOS Neglected Tropical Diseases, 2012
    Co-Authors: Takahisa Furuta, Vu Thi Que Huong, Tran Thi Thuy, Nguyen Tien Huy, Lyre Anni Murao, Nguyen Thi Phuong Lan, Vo Dinh Tham, Cao Thi Phi Nga, Yasukazu Ohmoto, Mihoko Kikuchi
    Abstract:

    Background Recent in-vitro studies have suggested that mast cells are involved in Dengue virus infection. To clarify the role of mast cells in the development of clinical Dengue fever, we compared the plasma levels of several mast cell-derived mediators (vascular endothelial cell growth factor [VEGF], soluble VEGF receptors [sVEGFRs], tryptase, and chymase) and -related cytokines (IL-4, -9, and -17) between patients with differing severity of Dengue fever and healthy controls. Methodology/Principal Findings The study was performed at Children's Hospital No. 2, Ho Chi Minh City, and Vinh Long Province Hospital, Vietnam from 2002 to 2005. Study patients included 103 with Dengue fever (DF), Dengue hemorrhagic fever (DHF), and Dengue Shock Syndrome (DSS), as diagnosed by the World Health Organization criteria. There were 189 healthy subjects, and 19 febrile illness patients of the same Kinh ethnicity. The levels of mast cell-derived mediators and -related cytokines in plasma were measured by ELISA. VEGF and sVEGFR-1 levels were significantly increased in DHF and DSS compared with those of DF and controls, whereas sVEGFR-2 levels were significantly decreased in DHF and DSS. Significant increases in tryptase and chymase levels, which were accompanied by high IL-9 and -17 concentrations, were detected in DHF and DSS patients. By day 4 of admission, VEGF, sVEGFRs, and proteases levels had returned to similar levels as DF and controls. In-vitro VEGF production by mast cells was examined in KU812 and HMC-1 cells, and was found to be highest when the cells were inoculated with Dengue virus and human Dengue virus-immune serum in the presence of IL-9. Conclusions As mast cells are an important source of VEGF, tryptase, and chymase, our findings suggest that mast cell activation and mast cell-derived mediators participate in the development of DHF. The two proteases, particularly chymase, might serve as good predictive markers of Dengue disease severity.

  • epidemiological factors associated with Dengue Shock Syndrome and mortality in hospitalized Dengue patients in ho chi minh city vietnam
    American Journal of Tropical Medicine and Hygiene, 2011
    Co-Authors: Katherine L Anders, Bridget Wills, Nguyen Van Vinh Chau, Jeremy Farrar, Nguyen Thanh Hung, Le Bich Lien, Tran Thi Thuy, Tran Tinh Hien, Nguyen Minh Nguyet, Cameron R Simmons
    Abstract:

    Understanding trends in Dengue disease burden and risk factors for severe disease can inform health service allocation, clinical management, and planning for vaccines and therapeutics. Dengue admissions at three tertiary hospitals in Ho Chi Minh City, Vietnam, increased between 1996 and 2009, peaking at 22,860 in 2008. Children aged 6-10 years had highest risk of Dengue Shock Syndrome (DSS); however, mortality was highest in younger children and decreased with increasing age (odds ratio [OR] = 0.52, 95% confidence interval [CI] = 0.36-0.75 in 6- to 10- year-old children and OR = 0.27, 95% CI = 0.16-0.44 in 11- to 15-year-old children compared with 1- to 5-year-old children). Males were overrepresented among Dengue cases; however, girls had higher risk of DSS (OR = 1.19, 95% CI = 1.14-1.24) and death (OR = 1.57, 95% CI = 1.14-2.17). Young children with Dengue had greatest risk of death and should be targeted in Dengue vaccine and drug trials. The increased risk of severe outcomes in girls warrants further attention in studies of pathogenesis, health-seeking behavior, and clinical care.

  • comparison of three fluid solutions for resuscitation in Dengue Shock Syndrome
    The New England Journal of Medicine, 2005
    Co-Authors: Bridget Wills, Nguyen Minh Dung, Ha Thi Loan, Tran Thi Thuy, Le T T Minh, Tran Vinh Diet, Nguyen Van Vinh Chau, Kasia Stepniewska, Nicholas J White, Jeremy Farrar
    Abstract:

    Background Dengue Shock Syndrome is characterized by severe vascular leakage and disordered hemostasis and progresses to death in 1 to 5 percent of cases. Although volume replacement is recognized as the critical therapeutic intervention, World Health Organization management guidelines remain empirical rather than evidence-based. Methods We performed a double-blind, randomized comparison of three fluids for initial resuscitation of Vietnamese children with Dengue Shock Syndrome. We randomly assigned 383 children with moderately severe Shock to receive Ringer's lactate, 6 percent dextran 70 (a colloid), or 6 percent hydroxyethyl starch (a colloid) and 129 children with severe Shock to receive one of the colloids. The primary outcome measure was requirement for rescue colloid at any time after administration of the study fluid. Results Only one patient died (<0.2 percent mortality). The primary outcome measure — requirement for rescue colloid — was similar for the different fluids in the two severity groups...

Tran Tinh Hien - One of the best experts on this subject based on the ideXlab platform.

  • factors associated with Dengue Shock Syndrome a systematic review and meta analysis
    PLOS Neglected Tropical Diseases, 2013
    Co-Authors: Nguyen Tien Huy, Tran Tinh Hien, Tran Van Giang, Dinh Ha Duy Thuy, Mihoko Kikuchi, Javier Zamora, Kenji Hirayama
    Abstract:

    Background The pathogenesis of Dengue Shock Syndrome (DSS, grade 3 and 4) is not yet completely understood. Several factors are reportedly associated with DSS, a more severe form of Dengue infection that reportedly causes 50 times higher mortality compared to that of Dengue patients without DSS. However, the results from these reports remain inconclusive. To better understand the epidemiology, clinical manifestation, and pathogenesis of DSS for development of new therapy, we systematically reviewed and performed a meta-analysis of relevant studies that reported factors in both DSS and Dengue hemorrhagic fever (DHF, grade 1 and 2) patients. Methods and Findings PubMed, EMBASE, Scopus, Google Scholar, Dengue Bulletin, Cochrane Library, Virtual Health Library, and a manual search of reference lists of articles published before September 2010 were used to retrieve relevant studies. A meta-analysis using fixed- or random-effects models was used to calculate pooled odds ratios (OR) or event rate with corresponding 95% confidence intervals. Assessment of heterogeneity and publication bias, meta-regression analysis, subgroup analysis, sensitivity analysis, and analysis of factor-specific relationships were further performed. There were 198 studies constituting 203 data sets that met our eligibility criteria. Our meta-regression analysis showed a sustained reduction of DSS/Dengue hemorrhagic fever (DHF) ratio over a period of 40 years in Southeast Asia, especially in Thailand. The meta-analysis revealed that age, female sex, neurological signs, nausea/vomiting, abdominal pain, gastrointestinal bleeding, hemoconcentration, ascites, pleural effusion, hypoalbuminemia, hypoproteinemia, hepatomegaly, levels of alanine transaminase and aspartate transaminase, thrombocytopenia, prothrombin time, activated partial thromboplastin time, fibrinogen level, primary/secondary infection, and Dengue virus serotype-2 were significantly associated with DSS when pooling all original relevant studies. Conclusions The results improve our knowledge of the pathogenesis of DSS by identifying the association between the epidemiology, clinical signs, and biomarkers involved in DSS.

  • epidemiological factors associated with Dengue Shock Syndrome and mortality in hospitalized Dengue patients in ho chi minh city vietnam
    American Journal of Tropical Medicine and Hygiene, 2011
    Co-Authors: Katherine L Anders, Bridget Wills, Nguyen Van Vinh Chau, Jeremy Farrar, Nguyen Thanh Hung, Le Bich Lien, Tran Thi Thuy, Tran Tinh Hien, Nguyen Minh Nguyet, Cameron R Simmons
    Abstract:

    Understanding trends in Dengue disease burden and risk factors for severe disease can inform health service allocation, clinical management, and planning for vaccines and therapeutics. Dengue admissions at three tertiary hospitals in Ho Chi Minh City, Vietnam, increased between 1996 and 2009, peaking at 22,860 in 2008. Children aged 6-10 years had highest risk of Dengue Shock Syndrome (DSS); however, mortality was highest in younger children and decreased with increasing age (odds ratio [OR] = 0.52, 95% confidence interval [CI] = 0.36-0.75 in 6- to 10- year-old children and OR = 0.27, 95% CI = 0.16-0.44 in 11- to 15-year-old children compared with 1- to 5-year-old children). Males were overrepresented among Dengue cases; however, girls had higher risk of DSS (OR = 1.19, 95% CI = 1.14-1.24) and death (OR = 1.57, 95% CI = 1.14-2.17). Young children with Dengue had greatest risk of death and should be targeted in Dengue vaccine and drug trials. The increased risk of severe outcomes in girls warrants further attention in studies of pathogenesis, health-seeking behavior, and clinical care.

  • fluid replacement in Dengue Shock Syndrome a randomized double blind comparison of four intravenous fluid regimens
    Clinical Infectious Diseases, 1999
    Co-Authors: Nguyen Minh Dung, Tran Vinh Diet, N P J Day, Dong Thi Hoai Tam, Huynh Thi Loan, H T T Chau, L N Minh, D B Bethell, Rachel Kneen, Tran Tinh Hien
    Abstract:

    Dengue hemorrhagic fever and Dengue Shock Syndrome (DSS) are major causes of childhood morbidity and mortality in many tropical countries. Increased intravascular permeability leading to Shock is the cardinal feature of DSS. Fluid resuscitation to counteract massive plasma leakage is the mainstay of treatment. A double-blind, randomized trial comparing four intravenous-fluid regimens for acute resuscitation of 50 children with DSS was conducted. Colloids (dextran 70 or the protein digest gelafundin 35,000) restored cardiac index and blood pressure and normalized hematocrit more rapidly than crystalloids (Ringer's lactate or 0.9%-weight/volume saline). Dextran 70 provided the most rapid normalization of the hematocrit and restoration of the cardiac index, without adverse effects, and may be the preferred solution for acute resuscitation in DSS. Further large-scale double-blind trials are required to provide an evidence-based approach to the management of DSS.

Maria G Guzman - One of the best experts on this subject based on the ideXlab platform.

  • secondary infection as a risk factor for Dengue hemorrhagic fever Dengue Shock Syndrome an historical perspective and role of antibody dependent enhancement of infection
    Archives of Virology, 2013
    Co-Authors: Maria G Guzman, Mayling Alvarez, Scott B Halstead
    Abstract:

    Today, Dengue viruses are the most prevalent arthropod-borne viruses in the world. Since the 1960s, numerous reports have identified a second heterologous Dengue virus (DENV) infection as a principal risk factor for severe Dengue disease (Dengue hemorrhagic fever/Dengue Shock Syndrome, DHF/DSS). Modifiers of Dengue disease response include the specific sequence of two DENV infections, the interval between infections, and contributions from the human host, such as age, ethnicity, chronic illnesses and genetic background. Antibody-dependent enhancement (ADE) of Dengue virus infection has been proposed as the early mechanism underlying DHF/DSS. Dengue cross-reactive antibodies raised following a first Dengue infection combine with a second infecting virus to form infectious immune complexes that enter Fc-receptor-bearing cells. This results in an increased number of infected cells and increased viral output per cell. At the late illness stage, high levels of cytokines, possibly the result of T cell elimination of infected cells, result in vascular permeability, leading to Shock and death. This review is focused on the etiological role of secondary infections (SI) and mechanisms of ADE.

  • apoptosis in tissues from fatal Dengue Shock Syndrome
    Journal of Clinical Virology, 2007
    Co-Authors: Daniel Limonta, Virginia Capo, Griselda Torres, Ana B Perez, Maria G Guzman
    Abstract:

    Abstract Background Apoptosis, or programmed cell death, has been implicated in Dengue hemorrhagic fever/Dengue Shock Syndrome (DHF/DSS) pathogenesis. Objectives To determine the in vivo apoptosis contribution to the pathogenesis of fatal DHF/DSS during a Cuban Dengue epidemic. Study design We detected apoptosis by the TdT-mediated dUTP Nick-End Labeling (TUNEL) technique and Dengue virus (DENV) antigens by an immunohistochemical assay in different tissues from six individuals who died of DHF/DSS during the Santiago de Cuba DENV-2 epidemic in 1997. Results DENV antigens were immunolocalized mainly in hepatocytes. Apoptotic cells were found in five of the six cases studied. Apoptosis was demonstrated in liver, brain, intestinal and lung tissues. Severe brain hypoxia and ischemia in the studied subjects during DHF/DSS probably might induce apoptosis in cerebral cells. Apoptotic microvascular endothelial cells (ECs) in pulmonary and intestinal tissues, a finding only previously reported in vitro, are likely related to vascular plasma leakage manifested by the individuals. Conclusions Apoptosis was demonstrated in cerebral cells, white blood cells, intestinal and pulmonary microvascular ECs from Cuban fatal cases of DHF/DSS. As far as we know, these findings have not been previously reported in DHF/DSS. Our results indicate there is very likely an in vivo contribution of apoptosis to the pathophysiological mechanisms of DHF/DSS.

  • of cascades and perfect storms the immunopathogenesis of Dengue haemorrhagic fever Dengue Shock Syndrome dhf dss
    Immunology and Cell Biology, 2007
    Co-Authors: Tikki Pang, Mary Jane Cardosa, Maria G Guzman
    Abstract:

    The past four decades has witnessed a consolidation of the original observations made in the 1970s that Dengue haemorrhagic fever (DHF) and Dengue Shock Syndrome (DSS) have an immunological basis. Following reinfection with a Dengue virus of different serotype, severe disease is linked to high levels of antibody-enhanced viral replication early in illness which is followed by a cascade of memory T-cell activation and a 'storm' of inflammatory cytokines and other chemical mediators. These compounds are released mainly from T cells, monocytes/macrophages and endothelial cells, and ultimately cause an increase in vascular permeability. The consolidation of the evidence has been largely due to several important prospective sero-epidemiological studies in areas endemic for DHF/DSS, which have shown that risk of severe disease is significantly higher in secondary Dengue infections. These advances have underscored the fact that DHF/DSS pathogenesis is a complex, multifactorial process involving cocirculation of various Dengue virus serotypes and the interplay of host and viral factors that influence disease severity. The continued search to define risk factors in susceptible populations must be combined with the new techniques of molecular virology and innovative approaches in vaccine design to achieve the ultimate objective of developing a safe and effective vaccine.