Early molecular markers predictive of dengue hemorrhagic fever

Abstract

The management of acute dengue patients during outbreaks is a challenging problem. Most of the dengue fever cases are benign, but some cases develop into a severe and possibly lethal vasculopathy, known as dengue hemorrhagic fever. Early symptoms of dengue and hemorrhagic fever are very similar. An early differential diagnosis is needed to predict which of these two clinical presentations is crucial to proper patient care and public health management. This study evaluates the predictive potential of specific mRNA expression markers of dengue hemorrhagic fever using quantitative real-time PCR assays. Six candidate "dengue hemorrhagic fever specific signature genes" were evaluated and all showed good correlation among their transcription levels at early days of infection and the later development of severe vasculopathy. The markers selected were able to indicate, at early stages of infection, the evolution of a dengue-infected patient to the severe form of the illness. Despite the fact that these results grant further validation studies, the panel of candidate prognostic markers obtained demonstrated the potential to be useful for clinical use in the form of a fast assay based in blood samples.

Potential biomarkers for the clinical prognosis of severe dengue

“…Coffey et al (2009) tested the extremely valuable identification of markers and candidate genes of dengue severity. Previously, we suggested that the measurement of several genes by qPCR in PBMC samples collected from dengue-infected patients during the acute phase of the disease could be useful for prognosis of DHF development (Calzavara-Silva et al 2009). Here, we reinforce the viability of using a panel of carefully selected genes to assess the likelihood of developing DHF.…”

“…In previous work (Calzavara-Silva et al 2009), we suggested that it is possible to define genes that are differentially expressed between DF and DHF patients during the onset of symptoms and, consequently, predict the propensity of a dengue patient to progress to the severe form of the disease. Here, we propose the use of five genes that may predict a propensity of a DENV-infected patient to develop the severe symptoms of dengue as a molecular tool to aid DHF clinical diagnosis.…”

A systematic review of molecular diagnostic methods for the detection of arboviruses in clinical specimens in Brazil and the importance of a differential diagnosis

“…In a patient who was infected with dengue, the markers could identify the evolution of the virus from the classical disease form to the hemorrhagic disease form. Despite the small sample (n = 16), these markers may be useful for the prognosis of the severe form of dengue and in a rapid assay with potential clinical use [43]. Moreover, among the studies that were included in this review, only Dos Santos et al, used the ELISA to capture the NS1 antigen in the acute phase of dengue [45].…”

Differential expression of NADPH oxidase-2 (Nox-2) and nuclear factor-erythroid 2-related factor 2 (Nrf2) transcripts in peripheral blood mononuclear cells isolated from dengue patients

“…The diagnosis generally made after the patients have presented with severe dengue symptoms. So a prognosis test which helps to distinguish the patients who are more prone to develop the disease severity could be able to safeguard by providing better medical attention [3,6](http://www.cdc.gov/dengue/clinicalLab/). Earlier we have reported that various biochemical oxidant-antioxidant markers in the circulation of dengue infected study subjects [16,23].…”