Cryptococcus neoformans: Brain Preference, Gender Bias, and Interactions with Mycobacterium tuberculosis and Toxoplasma gondii in HIV-Positive Patients

Cryptococcus neoformans, a high-priority pathogen (WHO, 2022) and ubiquitous fungus, is responsible for hundreds of thousands of meningoencephalitis cases annually, with a high fatality rate. Its distribution is uneven: it primarily affects immunocompromised individuals (especially HIV-positive patients). Our study aims to explore the Cryptococcus&rsquo: brain tropism in immunosuppressed patients, its gender preference and the possible interactions with other opportunistic neurotropic microorganisms, such as Mycobacterium tuberculosis (MTB) and the brain microbiota, with a particular focus on Toxoplasma gondii (T. gondii). Methods: We conducted a retrospective descriptive analysis of all cases diagnosed with central nervous system cryptococcosis (Crypto-CNS) in HIV-positive patients admitted over 10 years (2010&ndash:2019) in a tertiary Romanian hospital. We examined their demographic, clinical, immunobiological, and imaging data, as well as their medical history, comorbidities, and coinfections. Results: Forty-two cases were admitted, with a male predominance (3.6:1) and a mean age of 33.3 years: 24% were diagnosed concomitantly with HIV infection and Crypto-CNS. All patients were severely immunosuppressed, with CD4 counts &lt:200 cells/mm3 (median = 20.5 [1&ndash:163], mean = 31.6). Recent/concomitant tuberculosis was found in 10 (27.7%). T. gondii-seropositive patients developed Crypto-CNS at a lower immunological state than seronegative ones (27.1 CD4 cells/mm3 vs. 46.7 cells/mm3, means). Of 25 cases with available brain imagery, 28% had high intracranial pressure. Twelve patients (28.5%) died during the hospitalization within 26.3 days (mean, SD = 21.4): 1-year mortality increased to 50%. In-hospital mortality was associated with lower CD4 counts, increased intracranial pressure, and T. gondii-seropositivity. Conclusions: Crypto-CNS in HIV-positive patients mainly affects men and may be promoted by concomitant or recent tuberculosis. T. gondii may confer some protection even at low immune levels but increases mortality when immunity is critically low.