When the test lies: Fatal cryptococcosis and the prozone effect in advanced HIV infection

Cryptococcal meningitis is a life-threatening opportunistic infection in advanced HIV disease. Cryptococcal antigen (CrAg) detection by lateral flow assay (LFA) is the diagnostic cornerstone, offering high sensitivity and specificity. However, false-negative results may arise from the prozone effect - antigen excess disrupting antibody-antigen lattice formation. We report a 37-year-old man with newly diagnosed advanced HIV infection (CD4+ count 26 cells/µL) presenting with altered mental status. Initial CrAg LFA on serum and cerebrospinal fluid (CSF) was negative. India ink staining revealed encapsulated yeasts, prompting serial dilution retesting, which yielded positive CrAg at 1:10 and 1:20 (serum) and 1:40 (CSF). Cultures confirmed Cryptococcus neoformans in CSF and skin biopsy of violaceous papular lesions, establishing disseminated cryptococcosis. Despite induction therapy with liposomal amphotericin B and flucytosine, the patient died from progressive neurological deterioration. This case underscores the prozone effect as a critical diagnostic pitfall and the indispensable role of complementary methods and clinical-laboratory integration.