BACKGROUND Considerable progress has been made in dengue management, however the lack of appropriate predictors of severity has led to huge number of unwanted admissions mostly decided on the grounds of warning signs. Apoptosis related mediators, among others, are known to correlate with severe dengue (SD) although no predictive validity is established. The objective of this study was to investigate the association of plasma cell-free DNA (cfDNA) with SD, and evaluate its prognostic value in SD prediction at acute phase. METHODS This was a hospital-based prospective cohort study conducted in Vietnam. All the recruited patients were required to be admitted to the hospital and were strictly monitored for various laboratory and clinical parameters (including progression to SD) until discharged. Plasma samples collected during acute phase (6-48 h before defervescence) were used to estimate the level of cfDNA. RESULTS Of the 61 dengue patients, SD patients (n = 8) developed shock syndrome in 4.8 days (95% CI 3.7-5.4) after the fever onset. Plasma cfDNA levels before the defervescence of SD patients were significantly higher than the non-SD group (p = 0.0493). From the receiver operating characteristic (ROC) curve analysis, a cut-off of > 36.9 ng/mL was able to predict SD with a good sensitivity (87.5%), specificity (54.7%), and area under the curve (AUC) (0.72, 95% CI 0.55-0.88; p = 0.0493). CONCLUSIONS Taken together, these findings suggest that cfDNA could serve as a potential prognostic biomarker of SD. Studies with cfDNA kinetics and its combination with other biomarkers and clinical parameters would further improve the diagnostic ability for SD.

中文翻译：

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血浆无细胞DNA：早期预测严重登革热的潜在生物标志物。

背景技术在登革热管理方面已经取得了相当大的进步，但是，缺乏适当的严重程度预测因素已经导致大量不受欢迎的入院，这些入院大多是基于警告标志来决定的。尽管尚无预测的有效性，但已知与凋亡相关的介质与严重登革热（SD）相关。这项研究的目的是调查血浆无细胞DNA（cfDNA）与SD的关联，并评估其在急性期SD预测中的预后价值。方法这是在越南进行的一项基于医院的前瞻性队列研究。所有入选患者均需入院，并严格监测各种实验室和临床参数（包括进展为SD）直至出院。在急性期（去热前6-48小时）收集的血浆样本用于估算cfDNA的水平。结果61例登革热患者中，SD患者（n = 8）在发烧后4.8天内出现休克综合征（95％CI 3.7-5.4）。SD患者退热前的血浆cfDNA水平显着高于非SD组（p = 0.0493）。根据接受者工作特征（ROC）曲线分析，截止值> 36.9 ng / mL能够以良好的灵敏度（87.5％），特异性（54.7％）和曲线下面积（AUC）预测SD（ 0.72，95％CI 0.55-0.88； p = 0.0493）。结论综上所述，这些发现表明cfDNA可以作为SD的潜在预后生物标志物。