Early individualized risk prediction using clinical data for children during the febrile phase of dengue in outpatient settings in Vietnam and Thailand

Dengue severity prediction models are usually developed using hospitalized patient data, but triage and hospital admission are mainly evaluated in outpatient settings. This study developed models using clinical and laboratory data from patients in outpatient settings during the febrile phase. Data from two cohort studies in Vietnam and Thailand were used to develop and validate six models: logistic regression with warning signs, Lasso-selected logistic regression, random forest, extreme gradient boosted classification, support vector machine, and artificial neural network. Models predicted dengue shock syndrome (DSS) as the primary endpoint and moderate plasma leakage and/or DSS as the secondary endpoint. We assessed model performance, discrimination, and calibration, using sensitivity, specificity, accuracy, Brier score, AUROC, CITL, calibration slope, calibration plots, and decision curve analysis. The optimal model was the Lasso-selected logistic regression for predicting DSS and the combined endpoint of moderate plasma leakage and/or DSS (Brier score: 0.044 [95% CI 0.043, 0.044] and 0.104 [95% CI 0.104, 0.105]; AUROC: 0.789 [95% CI 0.787, 0.791] and 0.741 [95% CI 0.740, 0.742]). We identified hematocrit, platelet count, lymphocyte count, and aspartate aminotransferase as predictors for DSS, and abdominal pain or tenderness, vomiting, mucosal bleeding, white blood cell count, lymphocyte count, platelet count, aspartate aminotransferase, and serum albumin as predictors for the secondary endpoint. Logistic regression and machine learning models using clinical and laboratory data during the febrile phase can support early prediction of severe disease in outpatient settings. Integrating risk prediction models into a decision support system could improve triage and optimize healthcare and resource allocation in endemic and resource-limited areas.