Li Vanesse, Mishra Hridesh, Ngai Michelle, Crowley Valerie M, Tran Vanessa, Painaga Maria Salome Siose, Gaite James Yared, Hamilton Patrick, Conroy Andrea L, Kain Kevin C, Hawkes Michael T
Department of Pediatrics, University of British Columbia, Vancouver, Canada.
SAR Laboratories, Sandra Rotman Centre for Global Health, University Health Network-Toronto General Hospital Research Institute, Toronto, Canada.
Cytokine. 2025 Jun;190:156911. doi: 10.1016/j.cyto.2025.156911. Epub 2025 Mar 12.
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.
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).
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).
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.
登革热是热带地区急性发热性疾病的常见病因，少数患者需要住院接受静脉输液治疗。预测哪些患者会发展为重症疾病具有挑战性。可溶性肿瘤坏死因子受体1（sTNFR1）与重症登革热相关，可能具有预后价值。
对菲律宾门诊登革热患者进行前瞻性队列研究，通过NS1抗原血症或IgM血清学阳性确诊。在就诊时测量sTNFR1，并对患者进行14至21天的随访，观察住院情况（主要结局）、住院时间、静脉补液复苏、血液浓缩和血小板减少情况（次要结局）。
纳入244例患者（中位年龄9岁，40%为女性，26%为非重症登革热，73%为有警示体征的登革热，0.82%为重症登革热）。就诊时sTNFR1血浆浓度中位数为3000pg/mL（四分位间距2400 - 3700），恢复后降至1800（四分位间距1600 - 2100）。181例患者（74%）需要住院治疗。就诊时测得的血浆sTNFR1浓度>2800 pg/mL与随后住院相关（相对风险1.5，95%置信区间1.2 - 1.7，p<0.0001）。sTNFR1升高还与住院时间延长、静脉补液需求、血液浓缩和血小板减少相关。sTNFR1还与全身炎症标志物（降钙素原）以及内皮激活的循环标志物（血管生成素2、可溶性酪氨酸激酶2、可溶性血管细胞黏附分子1和内皮糖蛋白）相关。
sTNFR1升高可预测登革病毒感染门诊患者随后是否需要住院治疗。它有望作为一种标志物，在资源有限的环境中指导分流，以减轻登革热带来的巨大医疗负担。
