The Use of Biomarkers in Predicting Dengue Outcome

Study Overview
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Brief Summary
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The burden of dengue infection has increased due to the current non-specific classification. A pilot study was conducted to evaluate the five of the biomarkers: neopterin, vascular endothelial growth factor (VEGF), thrombomodulin, Vascular Cell Adhesion Molecule 1 (VCAM-1) and pentraxin 3 (PTX-3). VEGF and PTX-3 was the only two potential biomarkers in differentiating severe dengue from non-severe dengue cases. The analysis between severe dengue and non-severe dengue cases indicated that only VEGF was able to discriminate the two categories. Though VCAM-1 and PTX-3 were not statistically significant, the p-values were at the margin of the pre-determined p-value of less than 0.05. Hence, this study aims to evaluate VEGF and PTX-3 levels in differentiating severe dengue from non-severe dengue cases. The secondary objective is to evaluate the correlation of VEGF and PTX-3 levels with full blood count (platelet, white blood cell count and haematocrit) and liver function test (alanine aminotransferase and aspartate).

Detailed Description
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The burden of dengue infection has increased due to the current non-specific classification. A pilot study was conducted to evaluate the five of the biomarkers: neopterin, vascular endothelial growth factor (VEGF), thrombomodulin, Vascular Cell Adhesion Molecule 1 (VCAM-1) and pentraxin 3 (PTX-3). VEGF and PTX-3 was the only two potential biomarkers in differentiating severe dengue from non-severe dengue cases. The analysis between severe dengue and non-severe dengue cases indicated that only VEGF was able to discriminate the two categories. Though VCAM-1 and PTX-3 were not statistically significant, the p-values were at the margin of the pre-determined p-value of less than 0.05. Hence, this study aims to evaluate VEGF and PTX-3 levels in differentiating severe dengue from non-severe dengue cases. The secondary objective is to evaluate the correlation of VEGF and PTX-3 levels with full blood count (platelet, white blood cell count and haematocrit) and liver function test (alanine aminotransferase and aspartate). This is a prospective cohort study in which the patient will be followed up from the day of presentation to the attending practitioner until the patient is discharged. The blood samples will be obtained daily during the follow-up. The demography and clinical final diagnosis will be obtained from the medical record of the patient. This study will aid triaging of dengue cases thereby reducing the need of unnecessary admission and better focused management to those might develop complication of dengue infection. This in turn reduces the workload and cost of the treating the dengue infection.

Official Title
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The Use of Biomarkers in Predicting Dengue Outcome

Conditions
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Dengue

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants who are age 15 or more. Participants must be recruited within the first three days of fever. Positive dengue by NS1Ag. Confirmed later on by paired dengue IgM/IgG. Final diagnosis of severe dengue or non-severe dengue. Exclusion Criteria: Participants who are less than 15 years old. Pregnant mothers. Participants should not have autoimmune disorder, haematological disorder, cancer, cardiovascular disease, on long term warfarin and aspirin. Participants who have been previously treated with dengue infection (secondary dengue infection will be excluded by dengue IgM/IgG).

Ages Eligible for Study
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Minimum Age: 15 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sensitivity (%) of biomarkers (PTX3 and VEGF) | The measures will be analysed using Receiver Operating Characteristics (ROC) during the first 4 days of illness to predict the outcome of dengue infection (severe dengue versus non-severe dengue. Both univariate and multivariate analysis will be performed to identify and control for confounding factors. | upon study completion, 3 years | 
| Specificity (%) of biomarkers (PTX3 and VEGF) | The measures will be analysed using Receiver Operating Characteristics (ROC) during the first 4 days of illness to predict the outcome of dengue infection (severe dengue versus non-severe dengue. Both univariate and multivariate analysis will be performed to identify and control for confounding factors. | upon study completion, 3 years | 
| Positive predictive value (%) of biomarkers (PTX3 and VEGF) | The measures will be analysed using Receiver Operating Characteristics (ROC) during the first 4 days of illness to predict the outcome of dengue infection (severe dengue versus non-severe dengue. Both univariate and multivariate analysis will be performed to identify and control for confounding factors. | upon study completion, 3 years | 
| Negative predictive value (%) of biomarkers (PTX3 and VEGF) | The measures will be analysed using Receiver Operating Characteristics (ROC) during the first 4 days of illness to predict the outcome of dengue infection (severe dengue versus non-severe dengue. Both univariate and multivariate analysis will be performed to identify and control for confounding factors. | upon study completion, 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation of routine blood parameters with PTX 3 and VEGF. | Pearson's/Spearmann correlation routine blood parameters (ALT, AST, PLT count, HCT and WBC count) with the biomarkers to identify possible prognostic value. | upon study completion, 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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dengue, Pentraxin 3, Vascular Endothelial Growth Factor