Factors Associated with Dengue Shock Syndrome: A Systematic Review and Meta-Analysis

Abstract

BackgroundThe 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 FindingsPubMed, 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.ConclusionsThe results improve our knowledge of the pathogenesis of DSS by identifying the association between the epidemiology, clinical signs, and biomarkers involved in DSS.

Clinical Presentation of Dengue by Serotype and Year of Epidemic in Martinique

“…13,15,21,22,26 The DENV-2 was recently found to be significantly associated with DSS in several countries. 27 However, all serotypes could lead to severe forms and death 1 ; among the deaths observed during the study period, one notes that half were attributed to cardiovascular-associated disease, diabetes, sickle cell disease, or nosocomial infections contracted in intensive care. The existence of a chronic disease that has been decompensated by viral infection increases the risk of death in dengue.…”

Serum lactate as predictor and diagnostic biomarker of plasma leakage in adult dengue patients

“…There are many studies assessing the factors associated with severe dengue or DSS. (24,25) The WHO proposed a list of warning signs, such as abdominal pain, persistent vomiting, mucosal bleed, and lethargy, for predicting severe dengue and the need for strict observation. However, a study by Thanachartwet et al found that the sensitivity and specificity of the 2009 WHO warning signs (except the presence of clinical fluid accumulation) were too low for identifying severe dengue at admission.…”

Mortalidad en pacientes con dengue en la epidemia 2012-2013

“…Estos resultados pueden explicarse por un cambio en el patrón de enfermedad que se caracteriza por hiperendemicidad, la circulación simultánea de varios serotipos del virus del dengue (DENV 1, DENV 2, DENV 3 y DENV 4) y la falta de conciencia de la población en cuanto a medidas de prevención o de formación del profesional de salud en el reconocimiento oportuno de las formas graves 3,37 . Es importante que cuanto antes se identifique un factor de riesgo de muerte, mayor es la posibilidad de introducir intervenciones terapéuticas adecuadas para evitar la misma, lo que impone la necesidad de conocerlos 44,45 . Los pacientes con infecciones secundarias por el virus del dengue tienen un mayor riesgo de desarrollar FHD/SSD 44,45,47 .…”