A diagnostic blind spot: false-negative IMMY CrAg LFA and CrAg SQ in an immunocompetent patient with Cryptococcus gattii meningitis

Cryptococcal antigen (CrAg) lateral flow assays (LFA) are widely used for the rapid diagnosis of cryptococcal meningitis because of their excellent sensitivity and specificity. We report a rare case of culture- and sequencing-confirmed Cryptococcus gattii VGI meningitis in an immunocompetent 43-year-old man with persistently negative IMMY CrAg LFA and semi-quantitative CrAg SQ results in both cerebrospinal fluid (CSF) and serum. The patient presented with fever, chronic progressive headache, diplopia, and papilledema. CSF analysis demonstrated lymphocytic pleocytosis, hypoglycorrhachia, elevated protein, and budding yeast cells on direct microscopy and India ink preparation. BioFire FilmArray meningitis/encephalitis panel detected C. neoformans/gattii species complex, while fungal culture and sequencing confirmed C. gattii VGI. False-negative CrAg LFA results persisted despite serial sample dilutions up to 1:2560. This case highlights a rare diagnostic pitfall of CrAg testing and underscores the importance of integrating microscopy, culture, and molecular methods when clinical suspicion remains high despite negative antigen assays.