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BackgroundSevere dengue with severe plasma leakage (SD-SPL) is the most frequent of dengue severe form. Plasma biomarkers for early predictive diagnosis of SD-SPL are required in the primary clinics for the prevention of dengue death.MethodologyAmong 63 confirmed dengue pediatric patients recruited, hospital based longitudinal study detected six SD-SPL and ten dengue with warning sign (DWS). To identify the specific proteins increased or decreased in the SD-SPL plasma obtained 6–48 hours before the shock compared with the DWS, the isobaric tags for relative and absolute quantification (iTRAQ) technology was performed using four patients each group. Validation was undertaken in 6 SD-SPL and 10 DWS patients.Principal findingsNineteen plasma proteins exhibited significantly different relative concentrations (p<0.05), with five over-expressed and fourteen under-expressed in SD-SPL compared with DWS. The individual protein was classified to either blood coagulation, vascular regulation, cellular transport-related processes or immune response. The immunoblot quantification showed angiotensinogen and antithrombin III significantly increased in SD-SPL whole plasma of early stage compared with DWS subjects. Even using this small number of samples, antithrombin III predicted SD-SPL before shock occurrence with accuracy.ConclusionProteins identified here may serve as candidate predictive markers to diagnose SD-SPL for timely clinical management. Since the number of subjects are small, so further studies are needed to confirm all these biomarkers.

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Background: The protective or pathogenic role of T lymphocytes during the acute phase of dengue virus (DENV) infection has not been fully understood despite its importance in immunity and vaccine development. Objectives: This study aimed to clarify the kinetics of T lymphocyte subsets during the clinical course of acute dengue patients. Study design: In this hospital-based cohort study, 59 eligible Vietnamese dengue patients were recruited and admitted. They were investigated and monitored for T cell subsets and a panel of clinical and laboratory parameters every day until discharged and at post-discharge from the hospital. Results: We described for the first time the kinetics of T cell response during the clinical course of DENV infection. Severe cases showed significantly lower levels of effector CD8 + T cells compared to mild cases at day −1 (p = 0.017) and day 0 (p = 0.033) of defervescence. After defervescence, these cell counts in severe cases increased rapidly to equalize with the levels of mild cases. Our results also showed a decline in total CD4 + T, Th1, Th1/17 cells during febrile phase of dengue patients compared to normal controls or convalescent phase. On the other hand, Th2 cells increased during DENV infection until convalescent phase. Cytokines such as interferon-γ, IL-12p70, IL-5, IL-23, IL-17A showed tendency to decrease on day 0 and 1 compared with convalescence and only IL-5 showed significance indicating the production during acute phase was not systemic.

IntroductionDengue is a viral disease that spreads rapidly in the tropic and subtropic regions of the world and causes 22,000 deaths annually. In 2009, the World Health Organization (WHO) released a new classification of dengue infections, which divided them into three categories: dengue without warning sign (D), dengue with warning sign (DWS), and severe dengue (SD). However, researchers have been using different criteria to define persistent vomiting; therefore, we aimed to evaluate the ability of the number of vomiting times in early prediction of SD development among D/DWS patients.MethodA hospital-based cohort study was conducted in Ben Tre-south of Vietnam. We enrolled confirmed dengue patients with D and DWS at admission. The final classification was determined on the discharged day for every patient based on the classification of WHO 2009 without using vomiting symptom, using the receiver operating characteristic (ROC) curve to evaluate the ability of the number of vomiting times in early prediction of SD development among D/DWS patients.ResultThe prevalence of vomiting symptom was higher in SD group than D/DWS group (92 versus 46 %, p = 0.006), and the median of the number of vomiting times was higher in SD group than D/DWS group (2.5 versus 0, p = 0.001). To distinguish SD from D/DWS, the ROC curve of the number of vomiting episodes showed that the area under the curve was 0.77; with the cut point of two, the sensitivity and specificity were 92 and 52 %, respectively.DiscussionThe number of vomiting times could be a good clinical sign which can early predict SD from the group of D/DWS. We suggest the definition of persistent vomiting should be vomiting two times or more per day.