Urine-Based Assay Predicts Severe Dengue Risk Early

Dengue is among the most widespread mosquito-borne infections, yet early risk stratification can be difficult when symptoms overlap with other febrile illnesses. Only about 2% to 5% of patients develop severe disease characterized by bleeding, organ failure, or death, so targeted triage is essential. Clinicians commonly rely on seven World Health Organization warning signs, but subjective interpretation can lead to avoidable admissions. Researchers now describe a urine-based biomarker approach that estimates progression risk earlier in the illness.

Nanyang Technological University, Singapore (NTU Singapore), through its Lee Kong Chian School of Medicine (LKCMedicine), identified a non-invasive method that measures two inflammation-associated proteins in urine: neutrophil gelatinase-associated lipocalin (NGAL) and soluble urokinase plasminogen activator receptor (suPAR). According to the team, this is a first-of-its-kind test aimed at predicting the likelihood of severe dengue. The study is published in Open Forum Infectious Diseases.

The approach quantifies urinary NGAL and suPAR, both reported to be linked to severe dengue. Investigators found these analytes were significantly elevated in dengue patients compared with individuals without dengue, and their concentrations increased with disease severity. Importantly for clinical workflows, the biomarkers can be assessed before the onset of the critical phase, when complications typically emerge.

In the study, researchers measured NGAL and suPAR concentrations in urine from dengue patients and healthy individuals. When samples collected prior to the critical phase were analyzed, both biomarkers predicted the likelihood of severe dengue three to four times more accurately than warning signs alone. The findings suggest that combining objective urinary biomarkers with existing symptom-based criteria can improve risk assessment during patient evaluation.

The work involved LKCMedicine and co-authors from the National Center for Infectious Diseases in Singapore. The researchers note they are developing and validating an all-in-one assay that measures NGAL, suPAR, and dengue proteins in urine, with the goal of enabling monitoring outside the hospital setting.

"Our results indicate that measuring urinary NGAL and suPAR, in combination with dengue warning signs, can significantly reduce unnecessary hospital admissions without an increased risk of misdiagnosis of severe cases," said Dr. Andrew Teo, senior research fellow at LKCMedicine.

"This will help health care professionals identify if a patient is likely to develop life-threatening dengue before severe symptoms surface and provide better care, especially during dengue outbreaks," said Dr. Chia Po Ying, senior consultant and head of the Research Office at the National Center for Infectious Diseases in Singapore.

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