White P Lewis, Barnes Rosemary A, Springer Jan, Klingspor Lena, Cuenca-Estrella Manuel, Morton C Oliver, Lagrou Katrien, Bretagne Stéphane, Melchers Willem J G, Mengoli Carlo, Donnelly J Peter, Heinz Werner J, Loeffler Juergen
Public Health Wales Microbiology Cardiff, Cardiff, United Kingdom
Cardiff University, UHW, Cardiff, United Kingdom.
J Clin Microbiol. 2015 Sep;53(9):2832-7. doi: 10.1128/JCM.00905-15. Epub 2015 Jun 17.
Aspergillus PCR testing of serum provides technical simplicity but with potentially reduced sensitivity compared to whole-blood testing. With diseases for which screening to exclude disease represents an optimal strategy, sensitivity is paramount. The associated analytical study confirmed that DNA concentrations were greater in plasma than those in serum. The aim of the current investigation was to confirm analytical findings by comparing the performance of Aspergillus PCR testing of plasma and serum in the clinical setting. Standardized Aspergillus PCR was performed on plasma and serum samples concurrently obtained from hematology patients in a multicenter retrospective anonymous case-control study, with cases diagnosed according to European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) consensus definitions (19 proven/probable cases and 42 controls). Clinical performance and clinical utility (time to positivity) were calculated for both kinds of samples. The sensitivity and specificity for Aspergillus PCR when testing serum were 68.4% and 76.2%, respectively, and for plasma, they were 94.7% and 83.3%, respectively. Eighty-five percent of serum and plasma PCR results were concordant. On average, plasma PCR was positive 16.8 days before diagnosis and was the earliest indicator of infection in 13 cases, combined with other biomarkers in five cases. On average, serum PCR was positive 10.8 days before diagnosis and was the earliest indicator of infection in six cases, combined with other biomarkers in three cases. These results confirm the analytical finding that the sensitivity of Aspergillus PCR using plasma is superior to that using serum. PCR positivity occurs earlier when testing plasma and provides sufficient sensitivity for the screening of invasive aspergillosis while maintaining methodological simplicity.
血清曲霉PCR检测技术操作简单，但与全血检测相比，灵敏度可能降低。对于以筛查排除疾病为最佳策略的疾病，灵敏度至关重要。相关分析研究证实，血浆中的DNA浓度高于血清中的DNA浓度。本研究的目的是通过比较血浆和血清曲霉PCR检测在临床环境中的性能来证实分析结果。在一项多中心回顾性匿名病例对照研究中，对同时从血液学患者中采集的血浆和血清样本进行标准化曲霉PCR检测，病例根据欧洲癌症研究与治疗组织/侵袭性真菌感染合作组和美国国立过敏与传染病研究所真菌病研究组（EORTC/MSG）的共识定义进行诊断（19例确诊/疑似病例和42例对照）。计算了两种样本的临床性能和临床效用（阳性时间）。检测血清时曲霉PCR的灵敏度和特异性分别为68.4%和76.2%，检测血浆时分别为94.7%和83.3%。85%的血清和血浆PCR结果一致。平均而言，血浆PCR在诊断前平均16.8天呈阳性，在13例病例中是感染的最早指标，在5例病例中与其他生物标志物联合使用。平均而言，血清PCR在诊断前平均10.8天呈阳性，在6例病例中是感染的最早指标，在3例病例中与其他生物标志物联合使用。这些结果证实了分析结果，即使用血浆的曲霉PCR灵敏度优于使用血清的灵敏度。检测血浆时PCR阳性出现得更早，为侵袭性曲霉病的筛查提供了足够的灵敏度，同时保持了方法的简单性。
