Abstract
BackgroundWe report the detailed development of biomarkers to predict the clinical outcome under dengue infection. Transcriptional signatures from purified peripheral blood mononuclear cells were derived from whole-genome gene-expression microarray data, validated by quantitative PCR and tested in independent samples.Methodology/Principal FindingsThe study was performed on patients of a well-characterized dengue cohort from Recife, Brazil. The samples analyzed were collected prospectively from acute febrile dengue patients who evolved with different degrees of disease severity: classic dengue fever or dengue hemorrhagic fever (DHF) samples were compared with similar samples from other non-dengue febrile illnesses. The DHF samples were collected 2–3 days before the presentation of the plasma leakage symptoms. Differentially-expressed genes were selected by univariate statistical tests as well as multivariate classification techniques. The results showed that at early stages of dengue infection, the genes involved in effector mechanisms of innate immune response presented a weaker activation on patients who later developed hemorrhagic fever, whereas the genes involved in apoptosis were expressed in higher levels.Conclusions/SignificanceSome of the gene expression signatures displayed estimated accuracy rates of more than 95%, indicating that expression profiling with these signatures may provide a useful means of DHF prognosis at early stages of infection.
Highlights
The dengue virus is a member of Flaviviridae family, genus flavivirus with four antigenically distinct serotypes (DENV-1 to DENV-4)
We can see that the samples fell into two major groups; the one on the right contains only non-dengue group of patients (ND) samples, and half (4) of the dengue fever (DF) samples, while the group on the left contains all the dengue hemorrhagic fever syndrome (DHF) samples, a couple of ND samples, and the other half of the DF samples
This agrees with intuition, since the two most different groups should be ND and DHF, with the DF samples forming an intermediary group
Summary
The dengue virus is a member of Flaviviridae family, genus flavivirus with four antigenically distinct serotypes (DENV-1 to DENV-4). At defervescence (after 4 to 7 days of the beginning of the symptoms), DHF patients start to present signs of circulatory disturbance [2], which makes medical management a major challenge in endemic areas. This is especially true during outbreaks when dengue cases typically over saturates the capacity of all medical points-of-care, and results in shortage on the capacity to attend the regular demand for medical assistance causing major disruptions on the public health systems. Transcriptional signatures from purified peripheral blood mononuclear cells were derived from whole-genome geneexpression microarray data, validated by quantitative PCR and tested in independent samples
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