Lass-Florl Cornelia, Alastruey-Izquierdo Ana, Gupta Renu, Chakroborti Arunloke
Institute of Hygiene, Medical Microbiology and Public Health, Medical University of Innsbruck, Austria.
Mycology Reference Lab, Spain.
Indian J Med Microbiol. 2022 Oct-Dec;40(4):480-484. doi: 10.1016/j.ijmmb.2022.07.013. Epub 2022 Aug 12.
Invasive Fungal Diseases (IFD), account for high morbidity and mortality in immunocompromised and seriously ill patients worldwide. Early, faster and accurate diagnosis with timely and appropriate patient management is critical for improved patient outcome and antifungal stewardship. Clinical/radiological presentations in IFD are non-specific and microscopy/culture based tests have low sensitivity and long turnaround time. Biomarkers have clinical utility for diagnosing IFD but their interpretation is not straight forward.
This review discusses the salient characteristics, clinical usefulness and limitations of common biomarkers such as Galactomannan (GM), 1-3, β D glucan (βDG), mannan, anti-mannan antibody (Mn/antiMn), Cryptococcal antigen test (CrAg), Nucleic Acid Amplification (NAA) tests and next generation sequencing for diagnosing IFD.
Fungal biomarkers are useful adjuncts as screening and diagnostic tools for IFD and are much more suited for 'ruling out' rather than 'ruling in' disease. GM, NAA tests are promising biomarkers for screening of invasive Aspergillosis in high risk asymptomatic patients who are not on antifungal therapy and for diagnosis of breakthrough infections in symptomatic patients. 1-3, β D glucan has limitations both as a 'rule in' and 'rule out' test and is useful in only specific clinical settings. Two consecutive positive 1-3-βDG tests or combined positivity with GM increases its specificity. Mn/antiMn, T2Candida nano diagnostic panel are promising candidates for diagnosing invasive candidiasis. Combining two or more biomarkers improves the sensitivity for prompt initiation of antifungal therapy and the negative predictive value for suspension of empirical treatment. Serum CrAg test is a good 'rule in' rather than a 'rule out' test in immunocompetent patients but has good diagnostic accuracy in immunocompromised patients. Detection of single nucleotide polymorphisms by next generation sequencing is useful for fungal characterization and identification of host determinants responsible for increased susceptibility to fungal infections but is still in experimental stages.
侵袭性真菌病（IFD）在全球免疫功能低下和重症患者中导致高发病率和死亡率。早期、快速且准确的诊断以及及时恰当的患者管理对于改善患者预后和抗真菌药物管理至关重要。IFD的临床/影像学表现不具有特异性，基于显微镜检查/培养的检测方法灵敏度低且周转时间长。生物标志物在诊断IFD方面具有临床实用性，但其解读并不简单直接。
本综述讨论了常见生物标志物如半乳甘露聚糖（GM）、1,3-β-D葡聚糖（βDG）、甘露聚糖、抗甘露聚糖抗体（Mn/抗Mn）、隐球菌抗原检测（CrAg）、核酸扩增（NAA）检测以及用于诊断IFD的下一代测序的显著特征、临床实用性和局限性。
真菌生物标志物作为IFD的筛查和诊断工具是有用的辅助手段，更适合用于“排除”而非“确诊”疾病。GM、NAA检测是有前景的生物标志物，可用于筛查未接受抗真菌治疗的高危无症状患者的侵袭性曲霉病，以及诊断有症状患者的突破性感染。1,3-β-D葡聚糖作为“确诊排除”试验都有局限性，仅在特定临床环境中有用。连续两次1,3-βDG检测呈阳性或与GM联合呈阳性可提高其特异性。Mn/抗Mn、T2念珠菌纳米诊断面板是诊断侵袭性念珠菌病的有前景的候选方法。联合使用两种或更多生物标志物可提高及时启动抗真菌治疗的灵敏度以及暂停经验性治疗的阴性预测值。血清CrAg检测在免疫功能正常的患者中是一种良好的“确诊”而非“排除”试验，但在免疫功能低下的患者中具有良好的诊断准确性。通过下一代测序检测单核苷酸多态性有助于真菌特征分析和确定导致真菌感染易感性增加的宿主决定因素，但仍处于实验阶段。
