Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
SAR Laboratories, Sandra Rotman Centre for Global Health, University Health Network-Toronto General Hospital, Toronto, Ontario, Canada.
Clin Infect Dis. 2023 Feb 8;76(3):e1079-e1086. doi: 10.1093/cid/ciac457.
Current malaria diagnostic tests do not reliably identify children at risk of severe and fatal infection. Host immune and endothelial activation contribute to malaria pathogenesis. Soluble urokinase-type plasminogen activator receptor (suPAR) is a marker of these pathways. We hypothesized that measuring suPAR at presentation could risk-stratify children with malaria.
Plasma suPAR levels were determined in consecutive febrile children with malaria at presentation to hospital in Jinja, Uganda. We evaluated the accuracy of suPAR in predicting in-hospital mortality, and whether suPAR could improve a validated clinical scoring system (Lambaréné Organ Dysfunction Score [LODS]).
Of the 1226 children with malaria, 39 (3.2%) died. suPAR concentrations at presentation were significantly higher in children who went on to die than in those who survived (P < .0001). suPAR levels were associated with disease severity (LODS: 0 vs 1, P = .001; 1 vs 2, P < .001; 2 vs 3, 0 vs 2, 1 vs 3, and 0 vs 3, P < .0001). suPAR concentrations were excellent predictors of in-hospital mortality (area under the receiver operating characteristic curve [AUROC], 0.92 [95% confidence interval {CI}, .91-.94]). The prognostic accuracy of LODS (AUROC, 0.93 [95% CI, .91-.94]) was improved when suPAR was added (AUROC, 0.97 [95% CI, .96-.98]; P < .0001).
Measuring suPAR at presentation can identify children at risk of severe and fatal malaria. Adding suPAR to clinical scores could improve the recognition and triage of children at risk of death. suPAR can be detected with a point-of-care test and can now be evaluated in prospective trials.
目前的疟疾诊断检测无法可靠地识别出有严重和致命感染风险的儿童。宿主免疫和内皮细胞激活有助于疟疾发病机制。可溶性尿激酶型纤溶酶原激活物受体（suPAR）是这些途径的标志物。我们假设在就诊时测量 suPAR 可以对患有疟疾的儿童进行风险分层。
在乌干达金贾的医院就诊的连续发热性疟疾儿童中测定血浆 suPAR 水平。我们评估了 suPAR 在预测住院死亡率中的准确性，以及 suPAR 是否可以改善经过验证的临床评分系统（Lambaréné 器官功能障碍评分[LODS]）。
在 1226 例疟疾患儿中，有 39 例（3.2%）死亡。与存活的患儿相比，死亡患儿就诊时的 suPAR 浓度明显更高（P<0.0001）。suPAR 水平与疾病严重程度相关（LODS：0 与 1 相比，P=0.001；1 与 2 相比，P<0.001；2 与 3 相比，0 与 2 相比，1 与 3 相比，0 与 3 相比，P<0.0001）。suPAR 浓度是住院死亡率的极好预测指标（受试者工作特征曲线下面积[AUROC]，0.92[95%置信区间{CI}，0.91-0.94]）。当添加 suPAR 时，LODS 的预后准确性（AUROC，0.93[95%CI，0.91-0.94]）得到改善（AUROC，0.97[95%CI，0.96-0.98]；P<0.0001）。
在就诊时测量 suPAR 可以识别出有严重和致命疟疾风险的儿童。将 suPAR 添加到临床评分中可以提高对死亡风险儿童的识别和分诊。suPAR 可以通过即时检测进行检测，现在可以在前瞻性试验中进行评估。
