PREDICTION OF DENGUE COMPLICATIONS: INFLAMMATORY AND HEMATOLOGICAL BIOMARKERS

Abstract

Objective: To identify prognostic evidence regarding inflammatory and hematological biomarkers measured prior to the onset of dengue complications. Methods: This systematic review included primary prognostic studies published between 2021 and 2026, guided by the PICOTS framework and relevant components of the PRISMA 2020 statement. A total of 29 records were identified through an initial literature search and supplementary identification across the PubMed/MEDLINE, SciELO, and LILACS databases. Eligible studies included longitudinal or cohort designs in which biomarkers were measured prior to the clinical outcomes. Critical appraisal was conducted using validity and applicability domains consistent with the QUIPS and PROBAST+AI tools. Outcomes—specifically severe dengue, moderate/severe dengue, and plasma leakage—were synthesized separately; no meta-analysis was performed due to heterogeneity and population overlap. Results: Following the removal of one duplicate and the application of eligibility criteria, five publications representing four independent study populations were included in the synthesis. Among 338 patients who were initially non-severe, chymase levels yielded an AUROC of 0.835 for the subsequent development of severe dengue (26 events). In a cohort of 99 adults, febrile-phase suPAR levels showed an AUROC of 0.82 for severe dengue. Ferritin levels measured on days 3–4 yielded an AUC of 0.78 for plasma leakage—an outcome distinct from severe dengue—in 209 participants. In the IDAMS cohort, hematological and clinical models achieved an AUC of approximately 0.68 at baseline, increasing to 0.73–0.85 following daily updates for the prediction of moderate/severe dengue; another publication from the same cohort evaluated inflammatory and endothelial biomarker panels. Conclusion: While biomarkers may complement clinical monitoring, the heterogeneity of outcomes and limited external validation preclude the recommendation of universal cutoff values.