Metagenomic next-generation sequencing reveals cross-reactivity of lateral flow cryptococcal antigen assay with <i>Trichosporon inkin</i>

Metagenomic next-generation sequencing (mNGS) in plasma, cerebrospinal fluid (CSF), and bronchoalveolar lavage fluid is a relatively new technology that offers a means to potentially provide a diagnosis in cases where infection is suspected, but conventional diagnostic testing has not revealed a pathogen. There have been many publications of individual cases and overall appraisals of its utility in detecting bacteria, fungi, and DNA viruses associated with otherwise undiagnosed systemic infections. A recent article by Phillips et al. published in <i>ASM Case Reports</i> (2:e00053-25, 2025, https://doi.org/10.1128/asmcr.00053-25) presents a case of meningitis in an immunosuppressed child that was ultimately determined to be caused by <i>Trichosporon inkin</i> using mNGS. Elevated ß-1,3-D-glucan (BDG) levels in CSF and serum projected a diagnosis of fungal meningitis. Bacterial, fungal, and mycobacterial cultures were negative. Positive lateral flow cryptococcal antigen titers in serum and CSF complicated the anticipated diagnosis since <i>Cryptococcus</i> spp. are thought to not have sufficient cell wall BDG to produce positive test results. Given the ultimate diagnosis of <i>T. inkin</i> meningitis and the known cross-reactivity with <i>Trichosporon asahii</i> per package insert, the unexpected cryptococcal antigen results raised the possibility of additional cross-reactivity. The authors uncovered this possibility by testing three known clinical isolates of <i>T. inkin</i> which generated positive results. This case adds to the growing literature that highlights the utility of mNGS in providing a diagnosis in otherwise unresolved cases and shows that mNGS can be further instructive in elucidating limitations in commonly used diagnostic tests.