Search

Introduction: The clinical manifestations of cryptococcosis are usually associated with the infecting agents Cryptococcus neoformans (CN) and C. gattii (CG) species complexes and the host. In this study, non-HIV-infected patients, at a university hospital in southeastern Brazil, had epidemiological and clinical data associated with cryptococcal disease and isolated Cryptococcus species: CN - 24 patients and CG - 12 patients., Methods: The comparison was comprised of demographic data, predisposing factors, clinical and laboratory manifestations, and outcomes of cryptococcosis patients treated between 2000 and 2016. Immunocompetent and immunosuppressed patients were also compared, irrespective of the infecting species. Cryptococcus spp. were genotyped by PCR-RFLP analysis of the URA5 gene., Results: Infections by the CN species complex (100% VNI genotype) were associated with drug immunosuppression and fungemia, and patients infected with the CG species complex (83% VG II and 17% VGI genotypes) had more evident environmental exposure and higher humoral response. CN and CG affected patients with or without comorbidities., Conclusions: Diabetes mellitus, other chronic non-infectious diseases, and alcoholism were likely predisposing factors for infection by both CN and CG species. Immunocompetent patients, independent of the infecting Cryptococcus species complexes, showed a higher occurrence of meningitis and a trend toward less fungal dissemination and longer survival than immunosuppressed hosts.

Background: Cryptococcus neoformans/ Cryptococcus gattii species complex is composed of encapsulated yeast species that are causative agents of cryptococcosis. The characterisation of pathogenic Cryptococcus species provides useful data for epidemiological studies as well as the clinical diagnosis and treatment of patients., Objectives: This study aimed to characterise the epidemiology, antifungal susceptibility and virulence of 72 clinical strains isolated from cryptococcosis cases between 2012 and 2017 in a tertiary reference hospital in south-eastern Brazil., Methods: Species and molecular types were molecularly assessed by PCR and PCR-restriction fragment length polymorphism (RFLP) of the URA5 gene. Antifungal susceptibility testing was performed according to the CLSI protocols. The virulence was studied in a Galleria mellonella infection model., Results: The most frequently isolated strain was C. neoformans molecular type VNI (61/72; 84.7%), although C. neoformans molecular type VNII (3/72; 4.2%) was also isolated. Additionally, C. deuterogattii molecular type VGII (8/72; 11.1%) was present, but most frequently from non-HIV-infected patients. Non-wild-type phenotype to the antifungals was observed in 26.4% (19/72) of the C. neoformans and C. deuterogattii clinical isolates, and the latter demonstrated higher MIC to fluconazole and itraconazole than C. neoformans clinical isolates. Finally, the virulence of C. neoformans and C. deuterogattii clinical isolates was diverse in G mellonella larvae and uncorrelated with the virulence factors of melanin and capsule., Conclusions: The assessment of the spread of cryptococcal species and molecular types as well as the pattern of corresponding antifungal susceptibility and virulence aids in surveil the emergence of resistant strains, ensuring more accurate management of the cryptococcal infection., (© 2020 Wiley-VCH GmbH.)

Fluconazole is extensively used for the treatment of candidiasis and cryptococcosis. Among other factors, successful treatment is related to appropriate fluconazole levels in blood and cerebrospinal fluid. In the present study, fluconazole levels were determined in 15 patients, 14 of whom had AIDS and 13 had neurocryptococcosis. The only selection criterion was treatment with fluconazole, which was performed with a generic or similar form of the drug. Fluconazole level was determined by high performance liquid chromatography and the susceptibility profile of Cryptococcus spp. isolated from the patients was assessed by broth microdilution. Blood and cerebrospinal fluid fluconazole levels were found to be related to the fluconazole daily dose, and exceeded the minimum inhibitory concentration of this antifungal for the Cryptococcus spp. isolates. A good correlation was observed between serum and cerebrospinal fluid drug concentration. In conclusion, treatment with non-original fluconazole under usual medical practice conditions results in appropriate blood and cerebrospinal fluid levels of the drug for inhibiting Cryptococcus spp. susceptible to this antifungal drug. The relatively common failures of neurocryptococcosis treatment appear not to be due to insufficient fluconazole levels in the cerebrospinal fluid, especially with the use of daily doses of 400-800mg., (Copyright © 2017 Sociedade Brasileira de Infectologia. Published by Elsevier Editora Ltda. All rights reserved.)

Cryptococcus neoformans is an encapsulated fungal pathogen that causes cryptococcosis, which is a major opportunistic infection in immunosuppressed individuals. Mammalian β-galactoside-binding protein Galectin-3 (Gal-3) modulates the host innate and adaptive immunity, and plays significant roles during microbial infections including some fungal diseases. Here we show that this protein plays a role also in C. neoformans infection. We find augmented Gal-3 serum levels in human and experimental infections, as well as in spleen, lung, and brain tissues of infected mice. Gal-3-deficient mice are more susceptible to cryptococcosis than WT animals, as demonstrated by the higher fungal burden and lower animal survival. In vitro experiments show that Gal-3 inhibits fungal growth and exerts a direct lytic effect on C. neoformans extracellular vesicles (EVs). Our results indicate a direct role for Gal-3 in antifungal immunity whereby this molecule affects the outcome of C. neoformans infection by inhibiting fungal growth and reducing EV stability, which in turn could benefit the host.

Refractory and relapsing crytocococcosis in acquired immune deficiency syndrome (AIDS) patients have a poor prognosis. The risk factors for this complicated infection course were evaluated by comparing refractory and/or relapsing cryptococcosis in human immunodeficiency virus-coinfected patients (cohort 1) with another group of AIDS patients who adequately responded to antifungals (cohort 2). Except for one isolate of Cryptococcus gattii from a cohort 2 case, all other isolates were identified as Cryptococcus neoformans var. grubii, sex type α, genotype VNI, including Cryptococcus reisolated from the relapse or in the refractory state. No differences were observed with respect to Cryptococcus capsule size and in the melanin and phospholipase production. The cohort 1 patients presented higher prevalence of cryptococcemia, cerebral dissemination, chronic liver disease, and leucopenia, and have increased death rate. Apparently, the refractory and/or relapsing cryptococcosis in the AIDS patients were more related to the host and the extent of the infection than to the fungal characteristics., (© The American Society of Tropical Medicine and Hygiene.)

Primary Cutaneous Cryptococcosis is an uncommon infection caused by the yeast Cryptococcus neoformans and C. gattii. Few case reports are available in the literature describing in detail primary cutaneous cryptococcosis due to C. gattii in immunocompetent patients. Herein, we present a case of a 68-year-old immunocompetent male patient with erythematous nodular lesions on the right forearm due to C. gattii mating-type α and molecular type VGI. The virulence factors test was performed for capsule diameter, melanin production and phospholipase activity. In vitro fluconazole testing showed the sensitivity profile of this clinical isolate. In addition, a review of the literature on this subject was carried out and verified that this is the first reported case of VGI in the south-east region of Brazil., (© 2014 Blackwell Verlag GmbH.)

Cryptococcus gattii causes a form of endemic mycosis that most commonly affects the lungs and central nervous system of immunocompetent patients living in tropical and subtropical areas of the world. Case report. A 66-year-old man who had chronic obstructive pulmonary disease without HIV infection and had been on systemic corticotherapy for several years developed extensive ulceration of the left forearm that was associated with ipsilateral supraclavicular adenomegaly, consequent to infection with Cryptococcus gattii. The patient was treated with fluconazole 400mg/day for eight months, which led to complete healing of the lesion. This case emphasizes that, although rare, C. gattii may cause opportunistic cutaneous-lymphatic infection in patients living in the southeastern region of Brazil who are immunocompromised through chronic corticotherapy.

Disseminated infection with Cryptococcus neoformans was observed in a newborn infant who presented fever and respiratory symptoms since the 52 nd day of life. The mother was infected by human immunodeficiency virus and presented pulmonary and meningeal cryptococcal infection. This is a rare case of cryptococcal infection with probable maternal-fetal transmission.