Risk and predictive factors for severe dengue infection: A systematic review and meta-analysis

Abstract

Background Dengue is a major public health issue worldwide and severe dengue (SD) is life threatening. It is critical to triage patients with dengue infection in the early stage. However, there is limited knowledge on early indicators of SD. The objective of this study is to identify risk factors for the prognosis of SD and try to find out some potential predictive factors for SD from dengue fever (DF) in the early of infection. Methods The PubMed, Cochrane Library and Web of Science databases were searched for relevant studies from June 1999 to December 2020. The pooled odds ratio (OR) or standardized mean difference (SMD) with 95% confidence intervals (CI) of identified factors was calculated using a fixed or random effect model in the meta-analysis. Tests for heterogeneity, publication bias, subgroup analyses, meta-regression, and a sensitivity analysis were further performed. Findings A total of 6,848 candidate articles were retrieved, 87 studies with 35,184 DF and 8,173 SD cases met the eligibility criteria. A total of 64 factors were identified, including population and virus characteristics, clinical symptoms and signs, laboratory biomarkers, cytokines, and chemokines; of these factors, 34 were found to be significantly different between DF and SD, while the other 30 factors were not significantly different between the two groups after pooling the data from the relevant studies. Additionally, 9 factors were positive associated with SD within 7 days after illness when the timing subgroup analysis were performed. Conclusions Practical factors and biomarkers for the identification of SD were established, which will be helpful for a prompt diagnosis and early effective treatment for those at greatest risk. These outcomes also enhance our knowledge of the clinical manifestations and pathogenesis of SD.

Changing epidemiology of dengue fever in children in South America

“…These severe categories appear to affect children and adults differently [17]; thus, severe vascular leakage is typically observed more frequently in children, and severe bleeding more frequently in adults. Secondary dengue infections by different serotypes have been shown to be an important risk factor for severe dengue as well warning signs and DENV-2 infection [18 ▪ ]. Dengue [3,19] should be suspected when a high fever (40 °C/104°F) is accompanied by two of the following symptoms during the febrile phase (2–7 days): severe headache, pain behind the eyes, muscle and join pains, nausea, vomiting, and rash.…”

Is new dengue vaccine efficacy data a relief or cause for concern?

“…A vaccine which does not increase the recipient’s risk of dengue and can reduce the risk of disease caused by even some of the DENV types would still deliver an overall public health net benefit. This is especially true for DENV types more commonly associated with disease (DENV-1, -2) and more severe clinical outcomes (DENV-2) 11 , 100 .…”

Management of Dengue: An Updated Review

“…Several biomarkers like red blood cell micro-particles, serum chymase levels and matrix metalloproteinases (MMP-2 and MMP-9) have been shown to predict this distinction [ 16 , 27 , 28 ]. Clinical features observed to have a positive association with severe dengue include lethargy, persistent vomiting, abdominal pain, diarrhea, hepatomegaly, severe bleeding, pleural effusion, and ascites [ 29 ]. Significantly high ALT and AST, hypoproteinemia, hypoalbuminemia, proteinuria, and elevated creatine kinase (CK), lactate dehydrogenase (LDH) and blood urea nitrogen (BUN) have been seen to be positively associated with severe dengue [ 29 ].…”

“…Clinical features observed to have a positive association with severe dengue include lethargy, persistent vomiting, abdominal pain, diarrhea, hepatomegaly, severe bleeding, pleural effusion, and ascites [ 29 ]. Significantly high ALT and AST, hypoproteinemia, hypoalbuminemia, proteinuria, and elevated creatine kinase (CK), lactate dehydrogenase (LDH) and blood urea nitrogen (BUN) have been seen to be positively associated with severe dengue [ 29 ]. Cytokines interleukin (IL)-10, IL-8, sVCAM-1, and IP-10 have also been shown to be positively associated with severity [ 29 ].…”

“…Significantly high ALT and AST, hypoproteinemia, hypoalbuminemia, proteinuria, and elevated creatine kinase (CK), lactate dehydrogenase (LDH) and blood urea nitrogen (BUN) have been seen to be positively associated with severe dengue [ 29 ]. Cytokines interleukin (IL)-10, IL-8, sVCAM-1, and IP-10 have also been shown to be positively associated with severity [ 29 ].…”