Serology anno 2021-fungal infections: from invasive to chronic

Background: Diagnosing invasive or chronic fungal infections is a challenge, particularly in the immunocompromised host. Microscopy and culture remain the reference standard, but are insensitive. The use of non-culture-based techniques is recommended in conjunction with conventional methods to improve the diagnostic yield.

Objectives: The aim was to provide an updated 2021 inventory of fungal antigen and serology tests for diagnosing invasive and chronic fungal infections, the key focus was set on Aspergillus, Candida and Cryptococcus species.

Sources: Pubmed search for publications with the key words fungal antigen tests, laboratory-based diagnosis of invasive pulmonary aspergillosis, chronic pulmonary aspergillosis, invasive candidiasis, invasive fungal infections and cryptococcal infections published from 2017 to 2020.

Content: Antigen assays such as the galactomannan (GM) and β-d-glucan detection systems are frequently used, but these tests vary in sensitivity and specificity, depending on the patient population involved, specimens inspected, cut-offs defined, test strategy applied and inclusion or exclusion of possible fungal case definitions. Multiple different detection systems are available, with recently introduced new point-of-care tests such as the lateral flow device and the lateral flow assay. Despite a wide heterogeneity in populations evaluated, studies indicate a better diagnostic performance of bronchoalveolar lavage GM in comparison with serum GM, and a suboptimal specificity of GM bronchoalveolar lavages (cut-off ≥1) and serum β-d-glucan in non-neutropenic individuals. Point-of-care cryptococcal antigen tests show excellent performance.

Implications: There are fungal antigen detection tests available with excellent to reasonable clinical performance to diagnose invasive fungal infections. Only a few assays are useful to monitor therapeutic response. There are multiple marketed IgG antibody tests to detect Aspergillus fumigatus antibodies, the titres vary widely and the performance differs significantly. In general, diagnostic tests are vulnerable to being affected by the host, the microbe and laboratory setting.