Biological Markers Associated with Severe Dengue Identified

In 2019, the World Health Organization identified dengue as one of the top 10 threats to global health, with transmission occurring in 129 countries and an estimated 3.9 billion people being at risk.

Biomarkers are used to identify the state or risk of a disease in patients. Examples of biomarkers can include naturally occurring molecules or genes in the vascular, inflammatory or other biological pathways. New findings could aid the development of biomarker panels for clinical use and help improve triage and risk prediction in patients with dengue.

A large team of international scientists led by the Oxford University Clinical Research Unit (OUCRU, Ho Chi Minh City, Viet Nam) conducted a study using samples and clinical information from a large multi-country observational study. Of the 2,694 laboratory-confirmed dengue cases included in the study, 38 and 266 cases were classified as severe and moderate dengue, respectively. The team selected 281 cases in four countries, Vietnam, Cambodia, Malaysia and El Salvador, as the blood samples from these participants were stored at the OUCRU laboratory. For comparison, the team also selected 556 patients with uncomplicated dengue who shared similar geographies and demographic characteristics.

The biomarkers were measured at two time points: at enrollment (illness day 1-3) and after recovery (day 10-31 post-symptom onset), if available. Eight biomarkers: VCAM-1, SDC-1, Ang-2, IL-8, IP-10, IL-1RA, sCD163, sTREM-1, were combined in a premixed magnetic bead panel (R&D Systems, Minneapolis, MN, USA). C-reactive protein (CRP) was measured using a separate commercial magnetic bead panel (EMD Millipore Corporation, Burlington, MA, USA). These panels were analyzed using the Luminex²⁰⁰ analyzer with the Luminex calibration (Austin, TX, USA). Ferritin was measured using the Human Ferritin ELISA kit (Arigo Biolaboratories, Hsinchu City, Taiwan, ROC).

The investigators reported that on days 1-3 from symptom onset, higher levels of any biomarker increased the risk of developing severe and moderate dengue (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. They found that, during the first three days of illness, higher levels of any of the 10 biomarkers increased a patient's risk of developing moderate to severe dengue.

Sophie Yacoub, PhD, a Consultant Physician and a senior author of the study, said, “Together, our findings should assist the development of biomarker panels to help improve future triage and early assessment of dengue patients. This would help improve individual patient management and healthcare allocation, which would be of major public health benefit especially in outbreak settings.”

The authors concluded that higher levels of the ten biomarkers (VCAM-1, SDC-1, Ang-2, IL-8, IP-10, IL-1RA, sCD163, sTREM-1, ferritin, and CRP), when considered individually, are associated with increased risk of adverse clinical outcomes in both children and adults with dengue. The study was published on June 22, 2021 in the journal eLife.

Related Links:
Oxford University Clinical Research Unit
R&D Systems
EMD Millipore Corporation
Luminex Corporation
Arigo Biolaboratories