Soluble tumour necrosis factor receptor 1 predicts hospitalization in children and young adults with dengue virus infection in the Philippines

Abstract

Background

Dengue fever is a common cause of acute febrile illness in the tropics and requires hospitalization for intravenous (IV) fluid therapy in a minority of patients. Predicting which patients will progress to severe disease is challenging. Soluble tumour necrosis factor receptor 1 (sTNFR1) is associated with severe dengue and may have prognostic value.

Methods

Prospective cohort study of outpatients in the Philippines with dengue fever, confirmed by NS1 antigenemia or IgM seropositivity. sTNFR1 was measured at presentation and patients were followed for 14–21 days for hospitalization (primary outcome), duration of stay, IV fluid resuscitation, hemoconcentration, and thrombocytopenia (secondary outcomes).

Results

244 patients (median age 9 years, 40 % female, 26 % uncomplicated dengue, 73 % dengue with warning signs, 0.82 % severe dengue) were included. The median sTNFR1 plasma concentration was 3000pg/mL (IQR 2400–3700) at clinic presentation, decreasing to 1800 (IQR 1600–2100) after recovery. 181 patients (74 %) required hospitalization. Plasma sTNFR1 concentration > 2800 pg/mL, measured at clinic presentation, was associated with subsequent hospitalization (relative risk 1.5, 95 %CI 1.2–1.7, p < 0.0001). Elevated sTNFR1 was also associated with longer duration of stay, IV fluid requirement, hemoconcentration, and thrombocytopenia. sTNFR1 was also associated with a marker of systemic inflammation (procalcitonin), and circulating markers of endothelial activation (Ang2, sTie-2, sVCAM-1, and endoglin).

Conclusion

Elevated sTNFR1 is predictive of subsequent hospitalization among outpatients with DENV infection. It shows promise as a marker that could guide triage to reduce the large healthcare burden of dengue in resource-constrained settings.