Combination of biological markers may improve triage and risk prediction in patients with dengue fever

Researchers have been able to identify a combination of biological markers in patients with dengue and predict whether they will develop moderate to severe disease, according to a study published today. eLife..

Biomarkers are used to identify a patient’s condition or risk of illness. Examples of biomarkers can include molecules or genes that are naturally occurring in blood vessels, inflammation, or other biological pathways. New discoveries may help develop biomarker panels for clinical use and improve triage and risk prediction in patients with dengue fever.

Dengue fever is the most common mosquito-borne viral disease affecting humans worldwide. In 2019, the World Health Organization identified dengue as one of the top 10 threats to global health, with infections in 129 countries and an estimated 3.9 billion people at risk.

Most symptomatic dengue infections are self-limited, but a few patients develop complications that usually occur about 4 to 6 days after the onset of symptoms. Therefore, many patients require regular evaluation to identify these complications. Accurate and early identification of such patients, especially within the first 3 days of illness, should provide adequate care. “

Vuong Nguyen Lam, Ho Chi Minh City, Vietnam, Lead Author, Researcher, PhD Student, Clinical Research Unit (OUCRU), Oxford University

The role of blood biomarkers in predicting severe outcomes has been investigated in other studies, but most often after disease progression or at admission. Many of these biomarkers are not clinically useful because the peak of the disease course is too late or the half-life is too short.

To address this, Vuong et al. Selected 10 candidate biomarkers from vascular, immune, and inflammatory pathways associated with the pathogenesis of dengue fever. These biomarkers were VCAM-1, SDC-1, Ang-2, IL-8, IP-10, IL-1RA, sCD163, sTREM-1, ferritin, and CRP. They were selected based on their potential to increase in the early stages of the disease.

The team then conducted the study using samples and clinical information from a large multilateral observational study called “Clinical Assessment of Dengue Fever and Identification of Risk Factors for Severe Diseases” (IDAMS study). Of the 2,694 tests identified in the IDAMS study, 38 and 266 were classified as severe and moderate dengue, respectively.

In the current study, researchers selected 281 cases in four countries: Vietnam, Cambodia, Malaysia and El Salvador. Blood samples from these participants were stored at the OUCRU Institute. For comparison, the team also selected 556 patients with simple dengue who shared similar geographic and demographic features.

They measured participants’ blood biomarkers at two different time points. One is the first 3 days of the illness and the other is after recovery (10-31 days after the onset of symptoms). They found that high levels of any of the 10 biomarkers during the first three days of the disease increased the risk of patients developing moderate to severe dengue.

They also identified a combination of six biomarkers most associated with serious illness in children and a combination of seven biomarkers most associated with serious illness in adults. “This highlights how the relationship between biomarkers and clinical outcomes differs between age groups,” says Vuong.

“Together, our findings should help develop a biomarker panel that will help improve future triage and early assessment of patients with dengue,” said senior author, OUCRU’s Head of Dengue Research Group. Sophie Yacoub concludes. “This helps improve individual patient management and health care assignments, which is a major public health benefit, especially in outbreak situations.”