Intro: Ninety-six million people are symptomatically infected with Dengue globally every year. Under the current standard-of-care, up to 20% of Dengue patients may be hospitalized, while only 500,000 develop Dengue Haemorrhagic Fever (DHF) and require hospitalization. This leads to unnecessary overwhelming of hospitals in tropical countries during large Dengue epidemics, especially when healthcare systems are grappling with large numbers of COVID-19 patients. Our research team set out to discover biomarkers to prognosticate Dengue patients, and augment the infectious disease clinician's decision-making process to hospitalize Dengue patients. Methods: Host biomarkers with concentrations significantly different between pooled serum samples of Dengue Fever (DF) patients and DHF patients were identified using protein array. The prognostication capabilities of selected biomarkers were then validated over 283 adult Dengue patients recruited from three Singapore tertiary hospitals, prior to the diagnosis of DHF. Findings: Three biomarkers (A2M, CMA1 and VEGFA) were identified that provide independent prognostication value from one another, and from clinical parameters commonly monitored in Dengue patients. The combination of all three biomarkers was able to identify from as early as Day 1 after the onset of fever, DF patients whose conditions will deteriorate into DHF. The biomarkers are robust and able to predict DHF well when trained on different AI/ML algorithms (logistic regression, support vector machine, decision tree, random forest, AdaBoost and gradient boosting). When stacked, prediction models based on the biomarkers were able to predict DHF with 97.3% sensitivity, 92.7% specificity, 66.7% PPV, 99.6% NPV and an AUC of 0.978. Conclusion: To the best of our knowledge, our panel of three biomarkers offers the highest accuracy in prognosticating Dengue to date. Further studies are required to validate the biomarkers in different geographical settings and pilot their implementation as part of the standard-of-care workflow for Dengue patients.
Full Text via ClinicalKey 
Full Text Finder