Division of Paediatric Immunology and Infectious Diseases, University Medical Centre Utrecht, Utrecht, Netherlands.
Division Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht, Netherlands.
Lancet Infect Dis. 2017 Apr;17(4):431-440. doi: 10.1016/S1473-3099(16)30519-9. Epub 2016 Dec 22.
A physician is frequently unable to distinguish bacterial from viral infections. ImmunoXpert is a novel assay combining three proteins: tumour necrosis factor-related apoptosis-inducing ligand (TRAIL), interferon gamma induced protein-10 (IP-10), and C-reactive protein (CRP). We aimed to externally validate the diagnostic accuracy of this assay in differentiating between bacterial and viral infections and to compare this test with commonly used biomarkers.
In this prospective, double-blind, international, multicentre study, we recruited children aged 2-60 months with lower respiratory tract infection or clinical presentation of fever without source at four hospitals in the Netherlands and two hospitals in Israel. A panel of three experienced paediatricians adjudicated a reference standard diagnosis for all patients (ie, bacterial or viral infection) using all available clinical and laboratory information, including a 28-day follow-up assessment. The panel was masked to the assay results. We identified majority diagnosis when two of three panel members agreed on a diagnosis and unanimous diagnosis when all three panel members agreed on the diagnosis. We calculated the diagnostic performance (ie, sensitivity, specificity, positive predictive value, and negative predictive value) of the index test in differentiating between bacterial (index test positive) and viral (index test negative) infection by comparing the test classification with the reference standard outcome.
Between Oct 16, 2013 and March 1, 2015, we recruited 777 children, of whom 577 (mean age 21 months, 56% male) were assessed. The majority of the panel diagnosed 71 cases as bacterial infections and 435 as viral infections. In another 71 patients there was an inconclusive panel diagnosis. The assay distinguished bacterial from viral infections with a sensitivity of 86·7% (95% CI 75·8-93·1), a specificity of 91·1% (87·9-93·6), a positive predictive value of 60·5% (49·9-70·1), and a negative predictive value of 97·8% (95·6-98·9). In the more clear cases with unanimous panel diagnosis (n=354), sensitivity was 87·8% (74·5-94·7), specificity 93·0% (89·6-95·3), positive predictive value 62·1% (49·2-73·4), and negative predictive value 98·3% (96·1-99·3).
This external validation study shows the diagnostic value of a three-host protein-based assay to differentiate between bacterial and viral infections in children with lower respiratory tract infection or fever without source. This diagnostic based on CRP, TRAIL, and IP-10 has the potential to reduce antibiotic misuse in young children.
MeMed Diagnostics.
医生经常无法区分细菌感染和病毒感染。ImmunoXpert 是一种新型检测方法，结合了三种蛋白：肿瘤坏死因子相关凋亡诱导配体（TRAIL）、干扰素γ诱导蛋白-10（IP-10）和 C 反应蛋白（CRP）。我们旨在对外验证该检测方法在区分细菌和病毒感染方面的诊断准确性，并将其与常用的生物标志物进行比较。
在这项前瞻性、双盲、国际、多中心研究中，我们在荷兰的四家医院和以色列的两家医院招募了年龄在 2-60 个月的患有下呼吸道感染或发热无明显病因的儿童。一组三位经验丰富的儿科医生根据所有可用的临床和实验室信息（包括 28 天的随访评估）对所有患者的参考标准诊断进行裁决（即细菌或病毒感染）。该小组对检测结果进行了屏蔽。当三位小组成员中的两位同意一种诊断时，我们确定了主要诊断，当三位小组成员都同意一种诊断时，我们确定了一致诊断。我们通过比较检测分类与参考标准结果，计算了该指标检测在区分细菌（检测阳性）和病毒（检测阴性）感染方面的诊断性能（即敏感性、特异性、阳性预测值和阴性预测值）。
在 2013 年 10 月 16 日至 2015 年 3 月 1 日期间，我们招募了 777 名儿童，其中 577 名（平均年龄 21 个月，56%为男性）接受了评估。小组的多数诊断 71 例为细菌感染，435 例为病毒感染。在另外 71 名患者中，小组的诊断存在不确定因素。该检测方法对细菌与病毒感染的区分具有 86.7%的敏感性（95%CI 75.8-93.1）、91.1%的特异性（87.9-93.6）、60.5%的阳性预测值（49.9-70.1）和 97.8%的阴性预测值（95.6-98.9）。在更明确的小组一致诊断病例中（n=354），敏感性为 87.8%（74.5-94.7），特异性为 93.0%（89.6-95.3），阳性预测值为 62.1%（49.2-73.4），阴性预测值为 98.3%（96.1-99.3）。
这项外部验证研究表明，基于 CRP、TRAIL 和 IP-10 的三种宿主蛋白检测方法在区分儿童下呼吸道感染或发热无明显病因的细菌和病毒感染方面具有诊断价值。这种基于 CRP、TRAIL 和 IP-10 的诊断方法有可能减少幼儿抗生素的滥用。
MeMed Diagnostics。
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