OBJECTIVE Determining infection etiology can be difficult because viral and bacterial diseases often manifest similarly. A host protein test that computationally integrates the circulating levels of TNF-related apoptosis-induced ligand, interferon γ-induced protein-10, and C-reactive protein to differentiate between bacterial and viral infection (called MMBV) demonstrated high performance in multiple prospective clinical validation studies. Here, MMBV's diagnostic accuracy is evaluated in febrile children for whom physicians were uncertain about etiology when applied at the physician's discretion. METHODS Patients aged 3 months to 18 years were retrospectively recruited (NCT03075111; SPIRIT study; 2014-2017). Emergency department physician's etiological suspicion and certainty level were recorded in a questionnaire at blood-draw. MMBV results are based on predefined score thresholds: viral/non-bacterial etiology (0 ≤ score <35), equivocal (35 ≤ score ≤65), and bacterial or coinfection (65 < score ≤100). Reference standard etiology (bacterial/viral/indeterminate) was adjudicated by 3 independent experts based on all available patient data. Experts were blinded to MMBV. MMBV and physician's etiological suspicion were assessed against the reference standard. RESULTS Of 3003 potentially eligible patients, the physicians were uncertain about infection etiology for 736 of the cases assigned a reference standard (128 bacterial, 608 viral). MMBV performed with sensitivity 89.7% (96/107; 95% confidence interval 82.4-94.3) and specificity 92.6% (498/538; 95% confidence interval 90.0-94.5), significantly outperforming physician's etiological suspicion (sensitivity 49/74 = 66.2%, specificity 265/368 = 72.0%; P < .0001). MMBV equivocal rate was 12.4% (91/736). CONCLUSIONS MMBV was more accurate in determining etiology compared with physician's suspicion and had high sensitivity and specificity according to the reference standard.

中文翻译：

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实时宿主蛋白感染测试的诊断准确性。

目的 确定感染病因可能很困难，因为病毒性疾病和细菌性疾病通常表现相似。宿主蛋白测试通过计算整合 TNF 相关凋亡诱导配体、干扰素 γ 诱导蛋白 10 和 C 反应蛋白的循环水平来区分细菌和病毒感染（称为 MMBV），在多个前瞻性临床中表现出高性能验证研究。在这里，MMBV 的诊断准确性是在发热儿童中进行评估的，当医生自行决定对发热儿童应用时，医生不确定其病因。方法 回顾性招募 3 个月至 18 岁的患者（NCT03075111；SPIRIT 研究；2014-2017 年）。抽血时将急诊科医生的病因怀疑和确定性水平记录在调查问卷中。MMBV 结果基于预定义的评分阈值：病毒/非细菌病因（0 ≤ 评分 <35）、模棱两可（35 ≤ 评分 ≤65）以及细菌或合并感染（65 < 评分 ≤100）。参考标准病因（细菌/病毒/不确定）由 3 名独立专家根据所有可用的患者数据判定。专家们对 MMBV 视而不见。根据参考标准评估 MMBV 和医生的病因怀疑。结果 在 3003 名可能符合资格的患者中，医生不确定其中 736 例指定参考标准的感染病因（128 例细菌感染，608 例病毒感染）。MMBV 的敏感性为 89.7%（96/107；95% 置信区间 82.4-94.3），特异性为 92.6%（498/538；95% 置信区间 90.0-94.5），明显优于医生的病因怀疑（敏感性 49/74 = 66.2%） ，特异性 265/368 = 72.0%；P < .0001)。MMBV 模棱两可率为 12.4% (91/736)。结论 与医生的怀疑相比，MMBV 在确定病因方面更准确，并且根据参考标准具有较高的敏感性和特异性。