Abstract

BackgroundDengue presents a wide clinical spectrum. Most patients recover following a self-limiting non-severe clinical course. A small proportion of patients progress to severe disease, mostly characterized by plasma leakage with or without hemorrhage. Early symptoms of severe dengue (SD) are similar to those of non-severe dengue fever (DF). Severe symptoms manifest after 3–5 days of fever, which can be life threatening due to lack of proper medications and inability to distinguish severe cases during the early stages. Early prediction of SD in patients with no warning signs who may later develop severe infection is very important for proper disease management to alleviate related complications and mortality. microRNA are small non-coding RNA molecules that regulate post-transcriptional gene expression. Due to the remarkable stability and the role of microRNA in gene expression, altered expression of microRNA was evaluated to explore clinically relevant prognostic markers of severe dengue.MethodsThe relative expression of microRNA hsa-let-7e (let-7e), hsa-miR-30b-5p (miR-30b), hsa-miR-30e-3p (miR-30e), hsa-miR-33a (miR-33a), and hsa-miR-150-5p (miR-150) and several putative target genes in peripheral blood cells (PBC) collected from 20 DF and 20 SD positive patients within 4 days from fever onset was evaluated by quantitative reverse transcription PCR (qRT-PCR).ResultsmiR-150 showed significant (P < 0.01) up regulation in PBC of SD patients compared to DF patients during the acute phase of infection. Expression of enhancer of zeste homolog 2 (EZH2) was significantly (P < 0.01) down regulated indicating that genes involved in epigenetic regulation are also differentially expressed in SD patients during the early stage of infection.ConclusionsDifferential expression of microRNA miR-150 and the putative target gene EZH2 may serve as reliable biomarkers of disease severity during early stages of dengue infection.

Highlights

  • IntroductionA small proportion of patients progress to severe disease, mostly characterized by plasma leakage with or without hemorrhage

  • Differential expression analysis of selected microRNA in dengue patients within 4 days from fever onset Expression of let-7e, miR-30b, miR-30e, miR-33a and miR-150 in peripheral blood cells (PBC) collected at admission, within 4 days from fever onset from patients confirmed to have presented with dengue fever (DF) and patients who later developed severe dengue (SD) based on clinical symptoms was analyzed

  • There were no statistically significant differences in median laboratory clinical parameters including platelet count, hematocrit level (HCT), Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) levels in patients who later developed SD compared with DF (Table 1)

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Summary

Introduction

A small proportion of patients progress to severe disease, mostly characterized by plasma leakage with or without hemorrhage. Symptoms of severe dengue (SD) are similar to those of non-severe dengue fever (DF). Severe symptoms manifest after 3–5 days of fever, which can be life threatening due to lack of proper medications and inability to distinguish severe cases during the early stages. Prediction of SD in patients with no warning signs who may later develop severe infection is very important for proper disease management to alleviate related complications and mortality. The warning signs include, abdominal pain or tenderness, persistent vomiting, clinical fluid accumulation, mucosal bleeding, lethargy, restlessness, liver enlargement > 2 cm, increase in hematocrit level (HCT) concurrent with rapid decrease in platelet count. Severe manifestations of dengue show similar symptoms during the early stages of infection. Inability to distinguish SD from DF during the early stages of infection makes this disease life threatening

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