Institut für Hygiene und Mikrobiologie, Julius-Maximilians-Universität Würzburg, Würzburg, Germany.
Division of Infectious Diseases, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
Mycoses. 2022 Jul;65(7):709-714. doi: 10.1111/myc.13451. Epub 2022 May 31.
The incidence of Aspergillus and Candida CNS infection, which are characterised by high mortality rates, is underestimated. This underdiagnosis presumably results from the limitations of available diagnostic tools and the need for invasive sampling. Little is known about the role of serologic biomarkers in the setting of CNS aspergillosis and candidiasis.
PATIENTS, MATERIALS AND METHODS: Serum and cerebrospinal fluid (CSF; 10) samples of 19 patients, whose CNS specimens yielded growth of Aspergillus or Candida, were analysed for different biomarkers for fungal infection, that is galactomannan (GM), galactomannoprotein (GP), mannan, anti-mannan-antibodies and β-1,3-D-glucan (BDG). Serum and CSF specimens of time-matched patients (two each for every case of fungal CNS infection) were included as controls.
Galactomannan, GP and BDG seropositivity was found in one, two and three of five cases of CNS aspergillosis. BDG and mannan/anti-mannan-antibody sensitivity in proven CNS candidiasis was 40% and 20%, respectively. Applying the serum cut-off, sensitivity in CSF testing was 100% for GM and BDG and 50% for mannans. While serum specificity for all assays ranged from 89 to 97%, specificity for CSF BDG was only 70%. No false-positive GM results from CSF were obtained.
Sensitivity for diagnosing CNS aspergillosis and CNS candidiasis from serum is mediocre for all serological biomarkers. GM testing in CSF proved excellent performance. With a sensitivity of 100% but a specificity of only 70%, CSF BDG might be most useful when used in patients with a high pre-test probability.
曲霉菌和念珠菌中枢神经系统感染的发病率很高，死亡率也很高，但目前这些感染的发病率被低估了。这种漏诊可能是由于现有诊断工具的局限性以及对有创性采样的需求造成的。关于血清学生物标志物在中枢神经系统曲霉病和念珠菌病中的作用，人们知之甚少。
患者、材料和方法：分析了 19 例中枢神经系统标本培养出曲霉菌或念珠菌的患者的血清和脑脊液（CSF；10）样本，以检测不同的真菌感染生物标志物，即半乳甘露聚糖（GM）、半乳甘露糖蛋白（GP）、甘露聚糖、抗甘露聚糖抗体和β-1,3-D-葡聚糖（BDG）。将时间匹配的患者（每种真菌感染的病例各 2 例）的血清和 CSF 标本作为对照纳入研究。
5 例中枢神经系统曲霉病中，有 1 例、2 例和 3 例患者的 GM、GP 和 BDG 血清学呈阳性。确诊的中枢神经系统念珠菌病中 BDG 和甘露聚糖/抗甘露聚糖抗体的敏感性分别为 40%和 20%。采用血清临界值，GM 和 BDG 在 CSF 检测中的敏感性均为 100%，甘露聚糖的敏感性为 50%。虽然所有检测的血清特异性范围为 89%至 97%，但 CSF 中 BDG 的特异性仅为 70%。从 CSF 中获得的 GM 结果均为阴性。
所有血清学标志物诊断中枢神经系统曲霉病和中枢神经系统念珠菌病的敏感性均较差。CSF 中 GM 检测的性能非常出色。CSF BDG 的敏感性为 100%，特异性仅为 70%，因此在具有高预测试概率的患者中可能最有用。
