Combination of inflammatory and vascular markers in the febrile phase of dengue is associated with more severe outcomes.
Vuong NL., Lam PK., Ming DKY., Duyen HTL., Nguyen NM., Tam DTH., Duong Thi Hue K., Chau NV., Chanpheaktra N., Lum LCS., Pleités E., Simmons CP., Rosenberger KD., Jaenisch T., Bell D., Acestor N., Halleux C., Olliaro PL., Wills BA., Geskus R., Yacoub S.
Background: Early identification of severe dengue patients is important regarding patient management and resource allocation. We investigated the association of ten biomarkers (VCAM-1, SDC-1, Ang-2, IL-8, IP-10, IL-1RA, sCD163, sTREM-1, ferritin, CRP) with the development of severe/moderate dengue (S/MD). Methods: We performed a nested case-control study from a multi-country study. A total of 281 S/MD and 556 uncomplicated dengue cases were included. Results: On days 1-3 from symptom onset, higher levels of any biomarker increased the risk of developing S/MD. When assessing together, SDC-1 and IL-1RA were stable, while IP-10 changed the association from positive to negative; others showed weaker associations. The best combinations associated with S/MD comprised IL-1RA, Ang-2, IL-8, ferritin, IP-10, and SDC-1 for children, and SDC-1, IL-8, ferritin, sTREM-1, IL-1RA, IP-10, and sCD163 for adults. Conclusions: Our findings assist the development of biomarker panels for clinical use and could improve triage and risk prediction in dengue patients.