Wehrle-Wieland Elisabeth, Affolter Kristina, Goldenberger Daniel, Tschudin Sutter Sarah, Halter Joerg, Passweg Jakob, Tamm Michael, Khanna Nina, Stolz Daiana
Division of Infectious Diseases and Hospital Epidemiology, University Hospital of Basel, Basel, Switzerland.
Clinic of Pulmonary Medicine and Respiratory Cell Research, University Hospital Basel, Basel, Switzerland.
Transpl Infect Dis. 2018 Oct;20(5):e12953. doi: 10.1111/tid.12953. Epub 2018 Jun 28.
Accurate diagnosis of invasive mold diseases (IMD) remains challenging. Here, the performance of panfungal PCR, Aspergillus and MucoralesPCR in bronchoalveolar lavage (BAL) was evaluated.
We conducted a single-center study including 167 hematologic patients at risk for IMD with BAL performed 2011-2014. Diagnostic performance of single tests (Aspergillus-, Mucorales-, and panfungal PCR, galactomannan (GM)≥0.5 and ≥1, culture/cytology) or in combination was calculated for predicting IMD comparing proven/probable or proven/probable/possible IMD vs no IMD, respectively.
IMD was classified as proven (n = 6), probable (n = 31), possible (n = 29) and no IMD (n = 101) according to EORTC/MSG criteria. GM ≥ 0.5 in BAL showed the highest sensitivity with 81% for diagnosing IMD whereas the other tests only 5%-35%. By contrast, specificity was highest for panfungal PCR with 99% and GM ≥ 1, Mucorales and AspergillusPCR reached specificity ≥91%. When combining the tests, GM ≥ 0.5 and panfungal PCR show a sensitivity and specificity of 87% and 78% for IMD or with AspergillusPCR a sensitivity and specificity of 88% and 72% for invasive pulmonary aspergillosis, respectively. Including possible IMD patients did not improve the sensitivity of PCRs. In probable/proven IMD patients, the addition of panfungal PCR resulted further in detection of Fusarium species and Alternaria species, and the MucoralesPCR was positive in 2 probable IMD cases.
This study illustrates that the diagnosis of IMD is still very problematic and lacks objectivity. Together with GM in BAL, the PCRs may prove an addition to the current available diagnostic armamentarium in IMD because of their ability to identify molds on a species level.
侵袭性霉菌病（IMD）的准确诊断仍然具有挑战性。在此，我们评估了支气管肺泡灌洗（BAL）中泛真菌PCR、曲霉和毛霉目PCR的性能。
我们进行了一项单中心研究，纳入了2011年至2014年期间接受BAL检查的167例有IMD风险的血液学患者。计算单项检测（曲霉、毛霉目和泛真菌PCR、半乳甘露聚糖（GM）≥0.5和≥1、培养/细胞学检查）或联合检测对IMD的诊断性能，分别比较确诊/拟诊或确诊/拟诊/可能的IMD与无IMD的情况。
根据欧洲癌症研究与治疗组织/美国国立医学图书馆（EORTC/MSG）标准，IMD分为确诊（n = 6）、拟诊（n = 31）、可能（n = 29）和无IMD（n = 101）。BAL中GM≥0.5对诊断IMD的敏感性最高，为81%，而其他检测仅为5%-35%。相比之下，泛真菌PCR的特异性最高，为99%，GM≥1、毛霉目和曲霉PCR的特异性≥91%。联合检测时，GM≥0.5和泛真菌PCR对IMD的敏感性和特异性分别为87%和78%，或与曲霉PCR联合时，对侵袭性肺曲霉病的敏感性和特异性分别为88%和72%。纳入可能的IMD患者并未提高PCR的敏感性。在拟诊/确诊的IMD患者中，添加泛真菌PCR还可进一步检测到镰刀菌属和链格孢属菌种，毛霉目PCR在2例拟诊IMD病例中呈阳性。
本研究表明，IMD的诊断仍然非常困难且缺乏客观性。由于PCR能够在种水平上鉴定霉菌，与BAL中的GM一起，PCR可能成为目前IMD可用诊断方法的补充。
