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International Journal of Ophthalmology 2022To report 4 cases of () species complex infection with diverse ophthalmic manifestations, and to review the literature to examine pathobiology of disease, classical...
AIM
To report 4 cases of () species complex infection with diverse ophthalmic manifestations, and to review the literature to examine pathobiology of disease, classical ophthalmic presentations and outcomes, and treatment modalities for this emerging pathogen.
METHODS
Cases of meningoencephalitis with ophthalmic manifestations were identified chart review at two institutions in Australia and one institution in the mid-west region of the United States and are reported as a case series. Additionally, a MEDLINE literature review was conducted to identify all reported cases of with ophthalmic manifestations from 1990-2020. Cases were reviewed and tabulated, together with our series of patients, in this report.
RESULTS
Four cases of with ophthalmic manifestations are presented; three from Australia and one from the USA. A literature review identified a total of 331 cases of with visual sequelae. The majority of cases occurred in immunocompetent individuals. Blurred vision and diplopia were the most common presenting symptoms, with papilloedema the most common sign, reported in 10%-50% of cases. Visual loss was reported in 10%-53% of cases, as compared to rates of visual loss of 1%-9% in infection. Elevated intracranial pressure, cerebrospinal fluid (CSF) fungal burden, and abnormal neurological exam at presentation correlated with poor visual outcomes. The mainstays of treatment are anti-fungal agents and aggressive management of intracranial hypertension with serial lumbar punctures. CSF diversion procedures should be considered for refractory cases. Acetazolamide and mannitol are associated with high complication rates, and adjuvant corticosteroids have demonstrated higher mortality rates; these treatments should be avoided.
CONCLUSION
Permanent visual loss represents a devastating yet potentially preventable sequelae of infection. Intracranial hypertension needs to be recognised early and aggressively managed. Referral to an ophthalmologist/neuro-ophthalmologist in all cases of cryptococcal infection independent of visual symptoms at time of diagnosis is recommended.
PubMed: 35047366
DOI: 10.18240/ijo.2022.01.18 -
Virulence Dec 2019Cryptococcus-macrophage interaction is crucial in the development of cryptococcocal diseases. C. neoformans and C. gattii are major pathogenic species that occupy...
Cryptococcus-macrophage interaction is crucial in the development of cryptococcocal diseases. C. neoformans and C. gattii are major pathogenic species that occupy different niches and cause different clinical manifestations. However, the differences of macrophage interaction among these species in affecting different disease outcomes and immune responses have not been clearly addressed. Here, we examined the macrophage uptake rates, intracellular loads and intracellular proliferation rates of C. neoformans and C. gattii clinical isolates from Thailand and analyzed the effect of those interactions on fungal burdens and host immune responses. C. neoformans isolates showed a higher phagocytosis rate but lower intracellular proliferation rate than C. gattii. Indeed, the high intracellular proliferation rate of C. gattii isolates did not influence the fungal burdens in lungs and brains of infected mice, whereas infection with high-uptake C. neoformans isolates resulted in significantly higher brain burdens that associated with reduced survival rate. Interestingly, alveolar macrophages of mice infected with high-uptake C. neoformans isolates showed distinct patterns of alternatively activated macrophage (M2) gene expressions with higher Arg1, Fizz1, Il13 and lower Nos2, Ifng, Il6, Tnfa, Mcp1, csf2 and Ip10 transcripts. Corresponding to this finding, infection with high-uptake C. neoformans resulted in enhanced arginase enzyme activity, elevated IL-4 and IL-13 and lowered IL-17 in the bronchoalveolar lavage. Thus, our data suggest that the macrophage interaction with C. neoformans and C. gattii may affect different disease outcomes and the high phagocytosis rates of C. neoformans influence the induction of type-2 immune responses that support fungal dissemination and disease progression. Abbreviation: Arg1: Arginase 1; BAL: Bronchoalveolar lavage; CCL17: Chemokine (C-C motif) ligand 17; CNS: Central nervous system; CSF: Cerebrospinal fluid; Csf2: Colony-stimulating factor 2; Fizz1: Found in inflammatory zone 1; HIV: Human immunodeficiency virus; ICL: Intracellular cryptococcal load; Ifng: Interferon gamma; Ip10: IFN-g-inducible protein 10; IPR: Intracellular proliferation rate; Mcp1: Monocyte chemoattractant protein 1; Nos2: Nitric oxide synthase 2; PBS: Phosphate-Buffered Saline; Th: T helper cell; Tnfa: Tumor necrosis factor alpha.
Topics: Animals; Brain; Chemokines; Cryptococcosis; Cryptococcus gattii; Cryptococcus neoformans; Female; Host-Pathogen Interactions; Interferon-gamma; Interleukin-6; Lung; Macrophage Activation; Macrophages, Alveolar; Mice; Mice, Inbred BALB C; Phagocytosis; Phenotype; Th2 Cells; Thailand
PubMed: 30520685
DOI: 10.1080/21505594.2018.1556150 -
Infection and Drug Resistance 2015The incidence of Cryptococcus gattii infections in both Canada and the United States (US) is provided in this literature review beyond the British Columbia (BC) outbreak... (Review)
Review
The incidence of Cryptococcus gattii infections in both Canada and the United States (US) is provided in this literature review beyond the British Columbia (BC) outbreak (1999-2013). Based on a search of the literature, case reports of C. gattii human infections including the prevalent molecular genotypes causing these infections in both Canada and the US have been documented since the C. gattii outbreak in BC. The literature reveals that: i) although C. gattii infections continue to be reported in both countries, the preliminary overall number of confirmed C. gattii infections may be decreasing in both Canada and the US (~23 cases each in 2012 versus ~17 and 20 cases, respectively in 2013); ii) C. gattii genotype distribution is region-dependent; iii) C. gattii is more frequently isolated from infections in the immunocompromised host (including acquired immune deficiency syndrome [AIDS] infection) than previously expected; iv) although pulmonary disease is higher than in C. neoformans infections, central nervous system disease is also reported among patients infected with C. gattii.
PubMed: 25999744
DOI: 10.2147/IDR.S57686 -
BMC Microbiology Mar 2020Infection, even outbreak, caused by Cryptococcus gattii (C. gattii) has been reported in Canada and the United States, but there were sparsely-reported cases of C....
BACKGROUND
Infection, even outbreak, caused by Cryptococcus gattii (C. gattii) has been reported in Canada and the United States, but there were sparsely-reported cases of C. gattii in China. Our interest in occurrence, clinical manifestation, laboratory identification and molecular characterization of Chinese C. gattii strains leads us to this research.
RESULTS
Out of 254 clinical isolates, initially identified as Cryptococcus neoformans (C. neoformans), eight strains were re-identified as C. gattii. Multi-locus sequence typing (MLST) showed genotype VGI accounted for the most (6 / 8), the other two strains were genotype VGII (VGIIa and VGIIb respectively) with 3 specific spectra of molecular weight about 4342, 8686, 9611 Da by MALDI-TOF MS. The minimal inhibitory concentrations (MICs) of Fluconazole with Yeast one was 2~4 times higher than that with ATB fungus 3 and MICs of antifungal agents against VGII strains were higher than against VGI strains. Comparative proteome analysis showed that 329 and 180 proteins were highly expressed by C. gattii VGI and VGII respectively. The enrichment of differentially expressed proteins was directed to Golgi complex.
CONCLUSIONS
Infection by C. gattii in China occurred sparsely. Genotype VGI was predominant but VGII was more resistant to antifungal agents. There was significant difference in protein expression profile between isolates of VGI and VGII C. gattii.
Topics: Adult; Bacterial Proteins; China; Cryptococcosis; Cryptococcus gattii; Fluconazole; Gene Expression Regulation, Bacterial; Genotype; Hospitals; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Multilocus Sequence Typing; Mycological Typing Techniques; Proteomics; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Young Adult
PubMed: 32228457
DOI: 10.1186/s12866-020-01752-4 -
Fungal Genetics and Biology : FG & B May 2015Cryptococcosis is a significant invasive fungal infection with noteworthy morbidity and mortality, primarily caused by Cryptococcus neoformans and Cryptococcus gattii.... (Review)
Review
Cryptococcosis is a significant invasive fungal infection with noteworthy morbidity and mortality, primarily caused by Cryptococcus neoformans and Cryptococcus gattii. In China, C. neoformans var. grubii (especially molecular type VNI) is the most common variety in the environment and responsible for the majority of cryptococcal infections. C. gattii infections are quite rare in China and the primary molecular type is VGI, which is closely related to C. gattii isolates in Australia. Interestingly, the majority of cryptococcosis in China were reported in the HIV-uninfected patients (especially immunocompetent hosts). This unique phenomenon may be attributed to multiple polymorphisms in the genes encoding mannose-binding lectin (MBL) and Fc-gamma receptor 2B (FCGR2B) in the Han population, the major ethnic group in China. Compared to immunocompromised patients, immunocompetent patients with cryptococcal meningitis often presented with more intense inflammatory responses and more severe neurological complications, but less fungal burdens and disseminated infection. The overall prognosis, which is independently associated with amphotericin B-based initial therapy, is similar between immunocompetent and immunocompromised patients. In addition, intrathecal administration of amphotericin B has been proved to be an effective adjunctive treatment for cryptococcosis in China.
Topics: Amphotericin B; Antifungal Agents; China; Cryptococcosis; Cryptococcus neoformans; Genotype; HIV Infections; Humans; Injections, Spinal; Molecular Epidemiology; Mycological Typing Techniques; Survival Analysis; Treatment Outcome
PubMed: 25445309
DOI: 10.1016/j.fgb.2014.10.017 -
Scientific Reports Apr 2019In this study, we characterized Cryptococcus gattii biofilm formation in vitro. There was an increase in the density of metabolically active sessile cells up to 72 h...
In this study, we characterized Cryptococcus gattii biofilm formation in vitro. There was an increase in the density of metabolically active sessile cells up to 72 h of biofilm formation on polystyrene and glass surfaces. Scanning electron microscopy and confocal laser scanning microscopy analysis revealed that in the early stage of biofilm formation, yeast cells adhered to the abiotic surface as a monolayer. After 12 h, extracellular fibrils were observed projecting from C. gattii cells, connecting the yeast cells to each other and to the abiotic surface; mature biofilm consisted of a dense network of cells deeply encased in an extracellular polymeric matrix. These features were also observed in biofilms formed on polyvinyl chloride and silicone catheter surfaces. We used RNA-Seq-based transcriptome analysis to identify changes in gene expression associated with C. gattii biofilm at 48 h compared to the free-floating planktonic cells. Differential expression analysis showed that 97 and 224 transcripts were up-regulated and down-regulated in biofilm, respectively. Among the biological processes, the highest enriched term showed that the transcripts were associated with cellular metabolic processes, macromolecule biosynthetic processes and translation.
Topics: Biofilms; Cryptococcus gattii; RNA-Seq; Transcriptome
PubMed: 31015652
DOI: 10.1038/s41598-019-42896-2 -
Frontiers in Microbiology 2019This study investigated the presence of and species complex isolates on olive trees growing in the Eastern part of Sicily (Italy) characterized by the presence of the...
This study investigated the presence of and species complex isolates on olive trees growing in the Eastern part of Sicily (Italy) characterized by the presence of the volcano Etna and the ability of these fungal pathogens to sexually reproduce on medium containing volcanic soil. Samples from 124 olive trees were collected from 14 different sites around Mount Etna. Eighteen trees (14.5%) resulted colonized by VNI-αA isolates, one (0.8%) by VNIV-αD isolates, and two (1.6%) by VGI-αB isolates. The ability of environmental and reference strains belonging to VNI, VNIV, and VGI molecular types to sexually reproduce on a medium containing volcanic soil was also tested. VNI and VNIV strains were able to produce filaments and basiodiospores more vigorously than on the control medium, whereas VGI strains were not fertile. In conclusion, the present study identified which and species complex genotypes are circulating in Eastern Sicily and confirmed the ecological role of olive trees as environmental reservoir of these pathogens. It also showed that is able to colonize and sexually reproduce in inhospitable environments such as the slopes of a volcano.
PubMed: 31681242
DOI: 10.3389/fmicb.2019.02390 -
Microorganisms Sep 2021Cryptococcosis, a systemic mycosis that affects both the immunocompromised and immunocompetent, is caused by the inhalation of dehydrated yeasts or fungal spores of or...
Cryptococcosis, a systemic mycosis that affects both the immunocompromised and immunocompetent, is caused by the inhalation of dehydrated yeasts or fungal spores of or . The spp. polysaccharide capsule is composed mainly of glucuronoxylomannan-GXM, its major virulence factor. The capsule thickness increases to more than 15 μm during titanization, favoring the pathogenesis of cryptococcosis. Previous studies demonstrated that cytotoxic T cells that had been bioengineered with GXM-targeting chimeric antigen receptor (GXMR-CAR) were able to recognize by promoting the control of titanization. GXMR-CAR, a second-generation CAR, contains a single-chain variable fragment that originates from a 18B7 clone: a human IgG4 hinge, followed by a human CD28 (transmembrane/cytoplasmic domains) and a CD3ς chain. In the current study, we redirected T cells to target distinct and cell types by GXMR-CAR. Lentiviral particles carrying the GXMR-CAR sequence were used to transduce Jurkat cells, and these modified cells interacted with the GXM of the R265 strain. Moreover, GXMR-CAR mediated the recognition of and yeasts with both thin and thick polysaccharide capsules, and GXMR-CAR Jurkat cells interacted with titan cells sourced from both spp. Thus, bioengineered cells using CAR can improve the treatment of cryptococcosis.
PubMed: 34576780
DOI: 10.3390/microorganisms9091886 -
MSphere Oct 2019R265 is a hypervirulent fungal strain responsible for the recent outbreak of cryptococcosis in Vancouver Island of British Columbia in Canada. It differs significantly...
R265 is a hypervirulent fungal strain responsible for the recent outbreak of cryptococcosis in Vancouver Island of British Columbia in Canada. It differs significantly from in its natural environment, its preferred site in the mammalian host, and its pathogenesis. Our previous studies of have shown that the presence of chitosan, the deacetylated form of chitin, in the cell wall attenuates inflammatory responses in the host, while its absence induces robust immune responses, which in turn facilitate clearance of the fungus and induces a protective response. The results of the present investigation reveal that the cell wall of R265 contains a two- to threefold larger amount of chitosan than that of The genes responsible for the biosynthesis of chitosan are highly conserved in the R265 genome; the roles of the three chitin deacetylases (CDAs) have, however, been modified. To deduce their roles, single and double deletion strains and a triple deletion strain were constructed in a R265 background and were subjected to mammalian infection studies. Unlike where Cda1 has a discernible role in fungal pathogenesis, in strain R265, Cda3 is critical for virulence. Deletion of either alone or in combination with another CDA (Δ or ) or both () rendered the fungus avirulent and cleared from the infected host. Moreover, the ΔΔΔ strain of R265 induced a protective response to a subsequent infection with R265. These studies begin to illuminate the regulation of chitosan biosynthesis of and its subsequent effect on fungal virulence. The fungal cell wall is an essential organelle whose components provide the first line of defense against host-induced antifungal activity. Chitosan is one of the carbohydrate polymers in the cell wall that significantly affects the outcome of host-pathogen interaction. Chitosan-deficient strains are avirulent, implicating chitosan as a critical virulence factor. R265 is an important fungal pathogen of concern due to its ability to cause infections in individuals with no apparent immune dysfunction and an increasing geographical distribution. Characterization of the fungal cell wall and understanding the contribution of individual molecules of the cell wall matrix to fungal pathogenesis offer new therapeutic avenues for intervention. In this report, we show that the R265 strain has evolved alternate regulation of chitosan biosynthesis under both laboratory growth conditions and during mammalian infection compared to that of .
Topics: Amidohydrolases; Animals; Cell Wall; Chitosan; Cryptococcosis; Cryptococcus gattii; Female; Fungal Proteins; Gene Deletion; Gene Expression Regulation, Fungal; Humans; Mice; Mice, Inbred C57BL; Mice, Inbred CBA; Virulence; Virulence Factors
PubMed: 31597720
DOI: 10.1128/mSphere.00644-19 -
Journal of Fungi (Basel, Switzerland) Apr 2021Cryptococcosis, a potentially fatal mycosis, is caused by members of the and species complexes. In Latin America, cryptococcal meningitis is still an important health... (Review)
Review
and Species Complexes in Latin America: A Map of Molecular Types, Genotypic Diversity, and Antifungal Susceptibility as Reported by the Latin American Cryptococcal Study Group.
Cryptococcosis, a potentially fatal mycosis, is caused by members of the and species complexes. In Latin America, cryptococcal meningitis is still an important health threat with a significant clinical burden. Analysis of publicly available molecular data from 5686 clinical, environmental, and veterinary cryptococcal isolates from member countries of the Latin American Cryptococcal Study Group showed that, as worldwide, molecular type VNI is the most common cause of cryptococcosis (76.01%) in HIV-infected people, followed by molecular type VGII (12.37%), affecting mostly otherwise healthy hosts. These two molecular types also predominate in the environment (68.60% for VNI and 20.70% for VGII). Among the scarce number of veterinary cases, VGII is the predominant molecular type (73.68%). Multilocus sequence typing analysis showed that, in Latin America, the population is less diverse than the population ( of 0.7104 vs. 0.9755). Analysis of antifungal susceptibility data showed the presence of non-wild-type VNI, VGI, VGII, and VGIII isolates in the region. Overall, the data presented herein summarize the progress that has been made towards the molecular epidemiology of cryptococcal isolates in Latin America, contributing to the characterization of the genetic diversity and antifungal susceptibility of these globally spreading pathogenic yeasts.
PubMed: 33918572
DOI: 10.3390/jof7040282