Diagnostic challenges of cryptococcal infection in patients with HIV: disseminated cryptococcosis with discordant blood and cerebrospinal fluid microbiology

Abstract

Background: Cryptococcal infection remains a major cause of morbidity and mortality in people with advanced HIV disease, particularly in settings with delayed diagnosis and limited access to specialized diagnostics. Diagnostic uncertainty may arise when systemic microbiological evidence is present despite non-confirmatory cerebrospinal fluid findings. Case presentation: We report the case of a 54-year-old man with recently diagnosed advanced HIV infection who presented with persistent headache, fever, and later dyspnea. Immunological evaluation showed severe immunosuppression, with an HIV viral load of 84,481 copies/mL and a CD4+ T-cell count of 32 cells/µL. Blood cultures grew Cryptococcus neoformans, confirming disseminated cryptococcal infection. However, repeated cerebrospinal fluid studies showed low glucose and markedly low cellularity but remained negative by Gram stain, potassium hydroxide preparation, Ziehl–Neelsen stain, and culture. The patient received amphotericin B followed by fluconazole consolidation, together with prophylaxis for opportunistic infections. Antiretroviral therapy was initiated after antifungal stabilization. The patient subsequently improved clinically, and no immune reconstitution inflammatory syndrome was reported during follow-up. Conclusions: This case highlights the diagnostic discordance that may occur in advanced HIV-associated cryptococcal infection and underscores that negative cerebrospinal fluid microbiology does not exclude clinically significant disease in profoundly immunocompromised patients. In low-resource settings, blood-based microbiology and integrated clinical reasoning may be decisive for diagnosis and treatment.