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Background:  Dengue virus infection typically causes mild dengue fever, but, in severe cases, life-threatening dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) occur. The pathophysiological hallmark of DHF and DSS is plasma leakage that leads to enhanced vascular permeability, likely due to a cytokine storm., Methods:  Ninety patients with dengue during 2010-2012 in Singapore were prospectively recruited and stratified according to their disease phase, primary and secondary infection status, and disease severity, measured by plasma leakage. Clinical parameters were recorded throughout the disease progression. The levels of various immune mediators were quantified using comprehensive multiplex microbead-based immunoassays for 46 immune mediators., Results:  Associations between clinical parameters and immune mediators were analyzed using various statistical methods. Potential immune markers, including interleukin 1 receptor antagonist, interferon γ-inducible protein 10, hepatocyte growth factor, soluble p75 tumor necrosis factor α receptor, vascular cell adhesion molecule 1, and matrix metalloproteinase 2, were significantly associated with significant plasma leakage. Secondary dengue virus infections were also shown to influence disease outcome in terms of disease severity., Conclusions:  This study identified several key markers for exacerbated dengue pathogenesis, notably plasma leakage. This will allow a better understanding of the molecular mechanisms of DHF and DSS in patients with dengue., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

Background: Previously, most dengue cases in Singapore were hospitalized despite low incidence of dengue hemorrhagic fever (DHF) or death. To minimize hospitalization, the Communicable Disease Centre at Tan Tock Seng Hospital (TTSH) in Singapore implemented new admission criteria which included clinical, laboratory, and DHF predictive parameters in 2007., Method: All laboratory-confirmed dengue patients seen at TTSH during 2006-2008 were retrospectively reviewed for clinical data. Disease outcome and clinical parameters were compared over the 3 years., Results: There was a 33.0% mean decrease in inpatients after the new criteria were implemented compared with the period before (p < 0.001). The proportion of inpatients with DHF increased significantly from 31.7% in 2006 to 34.4% in 2008 (p = 0.008); 68 DHF cases were managed safely on an outpatient basis after compared with none before implementation. DHF inpatients had more serious signs such as clinical fluid accumulation (15.5% vs 2.9% of outpatients), while most DHF outpatients had hypoproteinemia (92.7% vs 81.3% of inpatients). The eight intensive care unit admissions and five deaths during this time period all occurred among inpatients. The new criteria resulted in a median cost saving of US$1.4 million to patients in 2008., Conclusion: The new dengue admission criteria were effective in sustainably reducing length of hospitalization, yielding considerable cost savings. A minority of DHF patients with mild symptoms recovered uneventfully through outpatient management.