Primary cutaneous cryptococcosis (PCC) has been confirmed as a distinct clinical entity with secondary cutaneous cryptococcosis from systematic infection since 2003. Although it has been confirmed as a distinct clinical entity, little has progressed on PCC in immunocompetent hosts compared to their immunocompromised counterpart. We reviewed the literature on cases of PCC in immunocompetent patients from 2004 to 2014, and 21 cases from 16 reports were identified. Males are more likely to develop PCC infections, with a ratio of 17:4 male to female. These patients were found to be almost all senior population except for patients from Asia. Asymptomatic or moderate itching manifesting in a painful nodule is the most common presentation, although there is no typical clinical manifestation recorded. Upper limbs are the most common site of infection, accounting for 71.4 % of all patients. Of the 12 identified isolates, 6 strains are identified as C. neoformans, 5 as C. gattii, and 1 as C.laurentii. Fluconazole was used in 10 cases; however, only 80 % of the 10 cases could confirm that fluconazole was effective in clearing the infections. Interestingly although not approved as a treatment option, Itraconazole was effective in the seven cases it was used to treat cryptococcosis, with a dosage range of 100-400 mg/d and duration from 3 to 6 months. Even though the prognosis of these patients was generally good, more data are need to determine which antifungal azole is the better treatment option and whether primary skin infections could disseminate to systematic infection.

To describe clinical characteristics, treatment and outcome of cryptococcal meningitis in immunocompetent children. Immunocompetent children with cryptococcal meningitis who attended Changzheng Hospital between 1998 and 2007 were retrospectively reviewed. During the 10 years reviewed, 11 children with cryptococcal meningitis were admitted to Changzheng hospital and identified as immunocompetent. The 11 children had a median age of 7.25 years. Headache (100%), fever (81.8%), nausea or vomiting (63.6%) and visual or hearing damage or loss (36.4%) were the most common symptoms before treatment. There is no evidence for other site infection of cryptococcus although all the cryptococcal antigen titre is high in blood. All the patients received amphotericin B or AmB liposome with 5-flucytosine for at least 6 weeks followed by fluconazole or itraconazole as consolidation treatment for at least 12 weeks. Nine patients were cured mycologically; however, sequela of visual damage was showed in one patient. Cryptococcal meningitis seems to be uncharacteristic of symptoms, and central nervous system may be the only common site for infection. Amphotericin B with 5-flucytosine should be the choice of induction treatment in this group of patients.

Amphotericin B deoxycholate (AmB), a classic antifungal drug, remains the initial treatment of choice for deep fungal infections, but it is not appropriate for treatment of cryptococcal meningitis due to its inability to pass through the blood–brain barrier (BBB). We examined the efficacy of amphotericin B-polybutylcyanoacrylate nanoparticles (AmB-PBCA-NPs) modified with polysorbate 80 that had a mean particle diameter less than 100 nanometers (69.0 ± 28.6 nm). AmB-PBCA-NPs were detected in the brain 30 minutes after systemic administration into BALB/c mice and had a higher concentration than systemically administered AmB liposome (AmB-L, P < 0.05); AmB was not detected in the brain. Following infection for 24 hours and then 7 days of treatment, the survival rate of mice in the AmB-PBCA-NP group (80%) was significantly higher than that of the AmB (0%) or AmB-L (60%) treatment groups. Fungal load was also lower when assessed by colony-forming unit counts obtained after plating infected brain tissue ( P < 0.05). Our study indicates that AmB-PBCA-NPs with polysorbate 80 coating have the capacity to transport AmB across the BBB and is an efficient treatment against cryptococcal meningitis in a mouse model.

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Cryptococcus neoformans is a medically important fungus and can infect all the organs of the body. As vascular endothelial cell is an important target for C. neoformans to penetrate any organs, the differential protein expression of human umbilical vascular endothelial cell (HUVEC) after incubating with C. neoformans may be the key to penetration. The proteins of HUVECs incubated with C. neoformans and normal HUVECs were collected and purified. After two-dimensional electrophoresis, the differential protein expression was identified by matrix-assisted laser desorption ⁄ ionisation mass spectrometry. The mRNA levels of some proteins were measured by real-time PCR. Three proteins were found significantly overexpressed in HUVECs incubated with C. neoformans, and nine other proteins were downregulated. The mRNA levels of S100A10 and peroxiredoxin I fluctuated with the protein levels. These results suggested that the expressions of peroxiredoxin I and S100A10 were regulated during the process of invasion of HUVECs by C. neoformans. We hypothesise that these proteins take part in the modifications of HUVEC cytoskeleton and the tolerance to oxidative stress, which may affect the process of invasion by C. neoformans.