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PubMed2006

Evaluation of cryptococcus laurentii meningitis in a patient with HIV infection: a case report and review of the literature.

Cryptococcus neoformans is the most common cryptococci causing infection in humans. Non-neoformans cryptococci have generally been regarded as saprophytes and rarely reported as human pathogens. We report a probable case of Cryptococcus laurentii meningitis in a HIV-infected patient and reviewed the literature on risk factors and treatment of this infection in humans. This patient was successfully treated with amphotericin B followed by fluconazole. Awareness of the emerging antifungal-resistant C. laurentii strains, as reported in the literature, should be emphasized, especially in immunocompromised patients.

AIDS-Related Opportunistic Infections↗

PubMed1988

[The structure of extracellular heteroglycans in various Cryptococcus species].

Extracellular polysaccharides produced by some Cryptococcus species have been structurally investigated. These polymers have identical core structure, which was found to be alpha-1,3-mannan and different degrees of substitution of mannose in the core by xylose and glucuronic acid residues of side chains and different composition of side chains. Heteropolysaccharide from Cr. humicolus, the simplest one, has the same structure as the Cr. neoformans serotype D capsular polysaccharide. The Cr. skinneri polymer proved to be the most branched among Cryptococcus polysaccharides.

Carbohydrate Sequence↗

PubMed1987

[Light and electron microscopic observations of cysts in the brain from an autopsy case of cryptococcus meningitis].

We gave some considerations to the significance of cyst formation in a case of cryptococcus meningitis by examining the cysts themselves and comparing the organisms in the cysts with those disseminated throughout the subarachnoid space by light and electron microscopy. An 18-year-old girl had complained of headache, stiffneck and fever at the onset. These symptoms worsened into confusion without any definite diagnosis, then resulted in an arrest of spontaneous respiration which led to use of respirator for 12 days. The patient died 40 days after the onset. The brain weighed 1440 g and showed moderate swelling with opacity of the leptomeninges, which was very evident over the convexity and around the basal side of the pons. Subarachnoid fresh hemorrhage was also observed around the basal side of the brain stem. Microscopic examination of the subarachnoid space revealed widely disseminated Cryptococcus neoformans varied in size, whose cell wall showed a positive staining reaction to PAS. The organisms had characteristic spicules positively stained with cresyl violet radiating out of the cell body, and were associated with infiltration of lymphocytes, macrophages and polymorphonuclear leukocytes throughout the subarachnoid space. Some portions of arachnoid membrane, dura mater and vessel walls in the subarachnoid space especially the adventitia of the basilar artery were replaced by multiple cysts. The cysts were tightly filled with large numbers of small uniformly sized organisms which often showed budding. These cysts showed no histological evidence for inflammation. Further studies to demonstrate those differences were carried out with electron microscopy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1994

CD4+ T cell-dependent acquired state of immunity that protects the brain against Cryptococcus neoformans.

In immunodeficient hosts, a failure in defense mechanisms allows Cryptococcus neoformans to establish foci of infection in the brain. Immune and nonspecific responses in the primary site of infection in the lung have been described, but those extrapulmonary defense mechanisms that can be mobilized against the yeast have received little attention. This paper describes a response expressed against yeast in the brain of immunocompetent hosts, a response that is weakened in hosts deficient in CD4+ T cells. When a small number of yeast gain access to the vasculature, for example through an i.v. injection, about 0.1% establish themselves in the brain. Normal mice but not SCID mice have the capacity to suppress the multiplication of these yeast cells. The host response is accelerated in mice that are recovering from a primary lung infection, resulting in long term survival without antibiotic chemotherapy. This response is ablated by anti-CD4 mAb treatment and CD4+ cells obtained from infected primed donors are needed to confer immunity on SCID recipients. The critical target for the anti-Cryptococcus immune response are yeast in the brain cortex. However, rather than preventing the colonization of the brain by blood-borne yeast, immunity apparently serves to restrict the growth of yeast in a small number of established foci.

Animals↗

PubMedDate not supplied

[Cryptococcus neoformans chemotyping. Review of the literature. New epidemiologic data on cryptococcosis. Our experience with the use of C.G.B. media in the study of this yeast].

The purpose of this work was to collect the main information from the literature about the biotyping of Cryptococcus neoformans. The more up-to date research concerning the epidemiology of cryptococcosis comprising quite a few articles, mainly after the advent of AIDS, was also reviewed. The Cryptococcus neoformans varieties neoformans and gattii are well defined biochemically nowadays chiefly through the C.G.B. medium, according to Kwon-Chung et al. (1982). The isolation of C. neoformans var. gattii from flowers and leaves of Eucalyptus camaldulensis and Eucalyptus tereticornis, specially in Australia, through the works of Ellis & Pfeiffer (1990) and Pfeiffer & Ellis (1992) permitted very interesting epidemiological investigations on C. neoformans, a capsulated yeast by which Sanfelice, in Italy (1894; 1895) attracted attention of medical class. Busse, in 1894, described the first human case of cryptococcosis under the presentation of a bone lesion simulating sarcoma. In this paper, the Brazilian researchers focused on this subject were pointed out, followed by the Author's experience with the C.G.B. medium (L-canavanine, glycine and bromothymol blue) proposed by Kwon-Chung et al. (1982) with very good results. It was possible with such medium the study of 50 C.N.S. liquor samples, being 39 from AIDS patients (78%) and 11 from non-AIDS ones (22%). Thirty-seven out of the 39 HIV-positive patients (74%) were identified as C. neoformans var. gattii. From the negative HIV, 8 (16%) were classified as C. neoformans var. neoformans and 3 (6%) as C. neoformans var. gattii. We could not perform the serotyping of the above referred samples. It is evident anyway that in Brazil there exist both varieties gattii and neoformans, agents of neurocryptococcosis, including AIDS patients. The importance of neurocryptococcosis, mainly among AIDS patients, is stressed here, showing once more the value of C.G.B. medium in the typing of C. neoformans in its two varieties. Also, it is of relevant importance the demonstration that some species of eucalyptus may act as "host-trees" of C. neoformans var. gattii.

Animals↗

PubMed1997

Purification and characterization of glutaredoxin from Cryptococcus neoformans.

Glutaredoxin, also known as thioltransferase, was purified from Cryptococcus neoformans by procedures including DEAE-cellulose ion exchange chromatography, Q-Sepharose ion-exchange chromatography, and gel filtration on Sephadex G-50. Its purity was confirmed by SDS-polyacrylamide gel electrophoresis and its molecular weight was estimated to be 12,000 Da. The purified enzyme has a K(m) value of 1.03 mM with 2-hydroxyethyl disulfide as a substrate. The enzyme also utilizes L-sulfocysteine, L-cystine, and bovine serum albumin as substrates in the presence of reduced glutathione. The enzyme has K(m) values of 0.34-2.50 mM for these substrates. It was greatly activated by thiol compounds such as reduced glutathione, dithiothreitol, L-cysteine and beta-mercaptoethanol. It is partially inactivated at 60 degrees C or higher temperatures. It plays an important role in thiol-disulfide exchange in Cryptococcus neoformans.

Cryptococcus neoformans↗

PubMed1992

[Detection of anti-Cryptococcus neoformans antibodies in 3 groups of human sera].

The tube agglutination (TA) technique was normalized in order to determine anti-Cryptococcus neoformans antibodies, according to Palmer et al., by employing positive and negative control sera and an antigenic suspension prepared from an autochtonous strain of Cryptococcus neoformans varneofornnans. Three groups of human sera were studied and the role of TA in detecting antibodies in the group of sera from patients with active cryptococcosis (100%) was shown. In sera from banks positiveness was only 6%, while in the group of fowl breeders, considered to be "exposed", positiveness was found to be 16%, although with low titres. A discussion is carried out about the value of this technique as a complement in the diagnosis and prognosis of cryptococcosis.

Agglutination↗

PubMed1995

Laryngeal cryptococcus. Treatment with oral fluconazole.

We treated a case of laryngeal Cryptococcus neoformans infection in a glucocorticosteroid-dependent patient with chronic obstructive pulmonary disease. To our knowledge, this is the first report of successful treatment of laryngeal cryptococcus using oral fluconazole as a single agent.

Administration, Oral↗

PubMed1999

Cryptococcus meningoencephalitis in AIDS: parenchymal and meningeal forms.

CT and MRI in one case of Cryptococcus neoformans infection showed contrast-enhancing parenchymal lesions resembling granulomata or abscesses. After an initial phase without contrast enhancement, the full extent of the lesions was visible within 2 weeks of presentation. The enhancing masses were assumed to represent intracerebral cryptococcomas. Despite evidence of massive meningeal infection on cerebrospinal fluid (CSF) examination, no radiological signs of meningitis, invasion of the Virchow-Robin spaces or ventriculitis could be demonstrated. With antimycotic treatment the contrast enhancement disappeared and cystic, partly calcified lesions remained. Recurrence of meningeal infection without radiological correlates was apparent in this stage. In a second case of proven cryptococcus meningitis, dilation of Virchow-Robin spaces or cysts in the adjacent parenchyma were the main abnormalities on MRI. Enhancing masses were not detected. These cases may represent two different reactions of the immunocompromised hosts to infection with C. neoformans: widening of the perivascular spaces as a correlate of the more typical meningeal infection and enhancing parenchymal lesions as a sign of further invasion from the CSF spaces. Enhancement of cryptococcomas, indicating an inflammatory response in the surrounding brain, is not typical in patients with impairment of immune function.

AIDS-Related Opportunistic Infections↗

PubMed1993

Ophthalmic manifestations of infections with Cryptococcus neoformans in patients with the acquired immunodeficiency syndrome.

The present study was undertaken to determine the nature and the prevalence of ophthalmic manifestations of infections with Cryptococcus neoformans in human immunodeficiency virus seropositive patients and to analyze whether the presence or absence of ocular signs is associated with improved survival. Eighty human immunodeficiency virus seropositive patients with cryptococcal infection were enrolled. We observed papilledema in 26 of the 80 patients (32.5%). Visual loss and abducens nerve palsy occurred in seven patients (9%). Only two patients (2.5%) had optic atrophy. Visual loss caused by optic nerve involvement was less frequent among the 62 patients treated with oral conazoles exclusively than among the 18 patients who had received amphotericin B or a combination of amphotericin B and conazoles. Actual invasion of the intraocular structures with Cryptococcus neoformans was an uncommon complication in our series. In addition to the ocular manifestations attributable to cryptococcal disease, human immunodeficiency virus-related retinopathy was present in nearly half of the patients. Cytomegalovirus retinitis was diagnosed in four patients (5%). The 26 patients (32.5%) with papilledema had a median survival of 182 days vs 160 days for the patients without papilledema. The median survival for 18 patients (22.5%) with cotton-wool spots was 102 days vs 186 days for those without cotton-wool spots. The differences between these subgroups were not statistically significant.

AIDS-Related Opportunistic Infections↗

PubMed2002

[Susceptibility to antifungal agents of Cryptococcus species of clinical interest].

BACKGROUND: Studies on the susceptability of Cryptococcus species to antifungal agents are scarce. METHOD: We investigate the susceptibility of 54 clinical and environmental strains from six different species using the Sensititre and the NCCLS methods. RESULTS: Environmental strains were less susceptible than clinical strains. We found MICs >= 64 mg/l for fluconazole, MICs >= 1 mg/l for itraconazole and MICs >= 32 mg/l for 5-fluorocytosine in C. albidus, C. neoformans and C. uniguttulatus. CONCLUSIONS: These findings point at the importance of determining the antifungal susceptibility of Cryptococcus species.

Antifungal Agents↗

PubMed1999

Drug resistance in Cryptococcus neoformans.

Cryptococcus neoformans has become a major opportunistic fungal pathogen worldwide. Successful treatment of invasive disease with this fungus has used amphotericin B, flucytosine and various azoles. However, treatment failures continue to occur for a variety of reasons including direct antifungal drug resistance. Issues and mechanisms for antifungal drug resistance in Cryptococcus neoformans are reviewed. Furthermore, approaches and strategies for prevention and treatment of antifungal drug resistance are identified and these include host immune modulation, dose optimization, prophylaxis/empirical regimens, improved drug delivery systems such as lipid preparations of amphotericin B, surgery, combination antifungal treatments and development of new antifungal agents. Copyright 1999 Harcourt Publishers Ltd.

Journal Article↗

PubMed2004

Scleral ulceration caused by Cryptococcus albidus in a patient with acquired immune deficiency syndrome.

PURPOSE: To describe a case of a scleral ulceration caused by Cryptococcus albidus in a patient with acquired immune deficiency syndrome (AIDS). DESIGN: Interventional case report. A 16-year-old girl with AIDS was admitted to the hospital with a 1-week history of cough, fever, and sudden onset of a painless scleral lesion on her left eye. Culture of the lesion revealed the fungus Crypotococcus albidus. RESULTS: The patient was treated with topical amphotericin B and systemic itraconazole, and she recovered fully over 4 weeks without sequelae. CONCLUSION: Cryptococcus albidus rarely causes disease in humans. It should be considered as a potential cause of ocular and systemic disease in patients with AIDS.

AIDS-Related Opportunistic Infections↗

PubMed2005

Cryptococcus albidus keratitis after corneal transplantation.

PURPOSE: To report suspected donor-to-host transmission of Cryptococcus albidus after penetrating keratoplasty. METHODS: Review of the literature and a case report of a 69-year-old woman who underwent penetrating keratoplasty for Fuchs corneal dystrophy and developed persistent corneal infiltrates 7 months postoperatively are presented. RESULTS: Cryptococcus albidus was cultured from the original donor tissue at the time of the repeat keratoplasty. CONCLUSION: This case demonstrates an unusual case of cryptococcal keratitis after keratoplasty suspected to be a donor-to-host transmission.

Aged↗

PubMed2025

Tracing the evolution and genomic dynamics of mating-type loci in Cryptococcus pathogens and closely related species.

Sexual reproduction in basidiomycete fungi is governed by MAT loci (P/R and HD), which exhibit remarkable evolutionary plasticity, characterized by expansions, rearrangements, and gene losses often associated with mating system transitions. The sister genera Cryptococcus and Kwoniella provide a powerful framework for studying MAT loci evolution owing to their diverse reproductive strategies and distinct architectures, spanning bipolar and tetrapolar systems with either linked or unlinked MAT loci. Building on recent comparative genomic analyses, we generated additional chromosome-level assemblies, uncovering distinct trajectories shaping MAT loci organization. Contrasting with the small-scale expansions and gene acquisitions observed in Kwoniella, our analyses revealed independent expansions of the P/R locus in tetrapolar Cryptococcus, possibly driven by pheromone gene duplications. Notably, these expansions coincided with a pronounced GC-content reduction best explained by reduced GC-biased gene conversion following recombination suppression, rather than relaxed codon usage selection. Diverse modes of MAT locus linkage were also identified, including three previously unrecognized transitions: one resulting in a pseudobipolar arrangement and two leading to bipolarity. All three transitions involved translocations. In the pseudobipolar configuration, the P/R and HD loci remained on the same chromosome but genetically unlinked, whereas the bipolar transitions additionally featured rearrangements that fused the two loci into a nonrecombining region. Mating assays confirmed a sexual cycle in C. decagattii, demonstrating its ability to undergo mating and sporulation. Progeny analysis in K. mangrovensis revealed substantial ploidy variation and aneuploidy, likely stemming from haploid-diploid mating, yet evidence of recombination and loss of heterozygosity indicates that meiotic exchange occurs despite irregular chromosome segregation. Our findings underscore the importance of continued diversity sampling and provide further evidence for convergent evolution of fused MAT loci in basidiomycetes, offering new insights into the genetic and chromosomal changes driving reproductive transitions.

MAT genes↗

PubMed1998

Decreased resistance to primary intravenous Cryptococcus neoformans infection in aged mice despite adequate resistance to intravenous rechallenge.

It is often stated that impaired immune functions in the aged underlie their greater susceptibility to infections. Indeed, in many experimental settings, T-cell responses in aged mice have been shown to be deficient compared with those from young adults. Nonetheless, there are very few examples where a greater susceptibility to infection in aged mice has been demonstrated to result from impaired T-cell function. The clinical importance of understanding the basis for increased susceptibility to infection that accompanies advanced age dictates a need for experimental models with which to study the effect that aging has on immunological resistance to infection. This study was undertaken to investigate whether aged mice were less resistant than young adult control mice to infection with the fungus Cryptococcus neoformans. After a primary intravenous challenge with yeast, aged mice died sooner and developed higher organ burdens of yeast than did young adults. Deficient in vitro responses were observed in T cells from aged mice; however, greater susceptibility to intravenous infection appeared not to result from less effective T-cell-dependent resistance in vivo. In fact, T-cell-replete aged mice were more susceptible to intravenous cryptococcal infection than were T-cell-depleted young adults. Furthermore, aged mice were as resistant to primary pulmonary challenge with Cryptococcus as were young adults. Similarly, vaccinated aged mice were as resistant to rechallenge as were young adult counterparts. Therefore, despite demonstrably deficient in vitro responses of T cells from aged mice, their T-cell-dependent resistance to C. neoformans is as effective as that of young adults.

Aging↗

PubMed2003

Prior exposure to live Mycobacterium bovis BCG decreases Cryptococcus neoformans-induced lung eosinophilia in a gamma interferon-dependent manner.

Some common childhood infections appear to prevent the development of atopy and asthma. In some Mycobacterium bovis BCG-vaccinated populations, strong delayed-type hypersensitivity responses to mycobacterial antigens are associated with a reduced risk of atopy. Although BCG exposure decreases allergen-induced lung eosinophilia in animal models, little attention has been given to the effect of immunity to BCG on responses against live pathogens. We used the murine Cryptococcus neoformans infection model to investigate whether prior BCG infection can alter such responses. The present study shows that persistent pulmonary BCG infection of C57BL/6 mice induced an increase in gamma interferon, a reduction in interleukin-5, and a decrease in lung eosinophilia during subsequent Cryptococcus infection. This effect was long lasting, depended on the presence of live bacteria, and required persistence of mycobacterial infection in the lung. Reduction of eosinophilia was less prominent after infection with a mutant BCG strain (DeltahspR), which was rapidly cleared from the lungs. These observations have important implications for the development of vaccines designed to prevent Th2-mediated disease and indicate that prior lung BCG vaccination can alter the pattern of subsequent host inflammation.

Adoptive Transfer↗

PubMed2002

Cryptococcus infection in a patient with nasopharyngeal carcinoma: imaging findings mimicking pulmonary metastases.

An asymptomatic pulmonary mass was found in a 42-year-old unmarried male with controlled nasopharyngeal carcinoma (NPC) during routine follow-up chest radiography 8 months following completion of radiotherapy. Chest CT demonstrated a 3x2 cm(2) left lower lobe (LLL) mass, with further small nodules in the same lobe. A presumptive diagnosis of lung metastases was made, and the patient underwent surgical resection with left lower lobectomy and mediastinal lymph node dissection. Pathologic examination of the masses in the LLL revealed granulomatous inflammation with cryptococcus infection. The dissected lymph nodes revealed anthracosis. The patient received 6 months of antifungal treatment with fluconazole. His NPC showed no evidence of local recurrence or distant metastases. Recognition that pulmonary cryptococcus infection can mimic metastases is important in reaching the correct diagnosis and therefore determining the correct treatment.

Adult↗