Disease relevance of Cryptococcosis

• Miconazole in cryptococcosis and systemic candidiasis: a word of caution [1].
• Oral fluconazole as suppressive therapy of disseminated cryptococcosis in patients with acquired immunodeficiency syndrome [2].
• CONCLUSIONS: In our experience, primary fluconazole prophylaxis proved safe and effective in the prevention of systemic candidiasis and cryptococcosis in patients with advanced HIV disease but it did not improve overall survival [3].
• Itraconazole therapy for cryptococcal meningitis and cryptococcosis [4].
• Candidiasis, torulopsosis, sporotrichosis, and cryptococcosis were considered in the differential diagnosis, and therapy with amphotericin B was begun [5].

High impact information on Cryptococcosis

• There was no significant difference between the groups in overall mortality due to cryptococcosis (amphotericin vs. fluconazole, 9 of 63 [14 percent] vs. 24 of 131 [18 percent]; P = 0.48); however, mortality during the first two weeks of therapy was higher in the fluconazole group (15 percent vs. 8 percent; P = 0.25) [6].
• Chloroquine might have clinical utility for the prophylaxis and treatment of human cryptococcosis [7].
• The addition of low-dose, intravenous amphotericin B to flucytosine therapy of cryptococcosis has appeared to decrease the frequency of secondary flucytosine resistance [8].
• In addition to cell-mediated immunity, monoclonal antibodies to the major capsular polysaccharide, the glucuronoxylomannan, offer some protection in murine models of cryptococcosis [9].
• The results provide direct in vivo evidence for the importance of quantitative differences in IFN-gamma secretion in human immune control of granulomatous infections, and increase the rationale for adjunctive IFN-gamma in the treatment of refractory HIV-associated cryptococcosis [10].

Chemical compound and disease context of Cryptococcosis

• Rustmicin was efficacious in a mouse model for cryptococcosis, but it was less active than predicted from its in vitro potency against this pathogen [11].
• Three of the four patients who received amphotericin B were cured of their infection; three patients died, including one patient with overwhelming cryptococcosis who had received intensive antifungal therapy and transfer factor [12].
• Twelve patients with primary pulmonary cryptococcosis treated with itraconazole as acute and maintenance therapy were all protected against disseminated cryptococcal disease; seven out of 10 (70%) of those who did not receive a specific anticryptococcal drug developed disseminated cryptococcal disease [13].
• Treatment of cryptococcosis with liposomal amphotericin B (AmBisome) in 23 patients with AIDS [14].
• We studied the efficacy of itraconazole, a new oral triazole, in 33 patients (32 were immunocompromised) with cryptococcosis [4].

Biological context of Cryptococcosis

• C. neoformans mutants lacking Mpk1 are attenuated for virulence in the mouse model of cryptococcosis [15].
• Fluconazole treatment was more effective in preventing esophageal candidiasis than cryptococcosis and was more effective in subjects with a CD4+ cell count less than 0.10 x 10(9)/L [3].
• Overall, IFN-gamma has utility as an adjunctive therapy against systemic cryptococcosis in the severely immunocompromised host [16].
• It is concluded that (i) susceptibility to cryptococcosis is under multigenic control, (ii) the xid locus on the X chromosome influences susceptibility to cryptococcosis, and (iii) xid mice behave differently than CBA/Ca mice in their organ response during the course of the infection [17].
• Heat shock protein 70 (hsp70) as a major target of the antibody response in patients with pulmonary cryptococcosis [18].

Anatomical context of Cryptococcosis

• After administration of amphotericin B for acute disseminated cryptococcosis, and prior to initiation of fluconazole therapy, Cryptococcus neoformans was isolated from the cerebrospinal fluid (CSF) in two patients and from the blood in one patient [2].
• Reduced L-selectin levels on leukocytes in subjects with circulating cryptococcal polysaccharide and increased serum levels of soluble L-selectin indicates that surface L-selectin shedding is a mechanism that likely explains reduced leukocyte extravasation into infected tissues of patients with disseminated cryptococcosis [19].
• These data indicate that purified capsular polysaccharide of C. neoformans could contribute to the in vivo progress of cryptococcosis by suppressing cytokine production of macrophages and suggest that a therapeutic approach to address the suppressive effect of cryptococal polysaccharide could be devised [20].
• Enhanced gamma interferon production through activation of Valpha14(+) natural killer T cells by alpha-galactosylceramide in interleukin-18-deficient mice with systemic cryptococcosis [21].
• Central nervous system cryptococcosis was diagnosed on the basis of growth of Cryptococcus neoformans in fungal culture of CSF, as well as detection of the organism in CSF via microscopy [22].

Gene context of Cryptococcosis

• Immunomodulation with CD40 stimulation and interleukin-2 protects mice from disseminated cryptococcosis [23].
• The cytokine network and infection severity were characterized during disseminated cryptococcosis in tumor necrosis factor (TNF)- and lymphotoxin (Lt)-alpha-deficient mice [24].
• These data demonstrate that IL-2 and GM-CSF are capable of stimulating PBMC-mediated antifungal activity and suggest that these cytokines may play physiological or pharmacological roles in host defenses against cryptococcosis [25].
• Scavengers of GXM and/or IL-10 could be useful in a protective Th1-type response in patients with cryptococcosis [26].
• The course of pulmonary cryptococcosis was studied in more detail in the CD14(-/-), TLR2(-/-), and MyD88(-/-) mice [27].

Analytical, diagnostic and therapeutic context of Cryptococcosis

• Multivariate analysis of the case-control study (158 cases and 423 controls) revealed smoking and outdoor occupations to be significantly associated with an increased risk of cryptococcosis; receiving fluconazole within 3 months before enrollment was associated with a decreased risk for cryptococcosis [28].
• These studies indicate that immunotherapy using anti-CD40 and IL-2 has therapeutic potential in augmenting host resistance to disseminated cryptococcosis and that IFN-gamma is essential for efficacy [23].
• No cryptococcal capsular polysaccharide is detected by the enzyme immunoassay procedure in fluids from subjects not known to have cryptococcosis [29].
• We describe a patient with advanced cutaneous T cell lymphoma who developed pulmonary and cutaneous cryptococcosis after receiving therapy with photopheresis and biweekly methotrexate [30].
• One patient with disseminated cryptococcosis improved after treatment with amphotericin B and 5-fluorocytosine [31].

References