Journal of medical and veterinary mycology : bi-monthly publication of the International Society for Human and Animal Mycology最新文献

L-733,560 and L-743,872 are water-soluble pneumocandins with potent antifungal activity. By beginning with the NCCLS M27-T method and varying test format (microdilution vs macrodilution), time of reading (24 h vs 48 h), and test medium (RPMI 1640 vs Antibiotic Medium 3), we have demonstrated that the MICs for these compounds can be altered significantly: the microdilution format, reading after 24 h and use of Antibiotic Medium 3 all reduced the measured MIC. No cross-resistance was demonstrated with either fluconazole or amphotericin B.

Paranasal sinus mycoses are endemic in rural populations of northern India. To study host-parasite interactions, we developed an animal model of paranasal sinus mycoses. After failure in small animals such as mice and rats, we used New Zealand white rabbits weighing 2.5-3 kg. Inoculum sizes consisted of 0.75-1.0 x 10(8), 0.75-1.0 x 10(7), 0.75-1.0 x 10(6) conidia of a clinical isolate of Aspergillus flavus. The inoculum was injected at a spot 0.5 cm in front of the alveolar process of the maxilla and 0.5 cm below the maxillary process of frontal bone and vertically to a depth of 0.5 cm across the bone directly into the nasal sinus. Paranasal sinus mycoses proven by culture and histopathology developed in 67% of animals injected with 0.75-1.0 x 10(8) conidia and 17% of animals with 0.75 x 10(7) conidia. No lesions were found in the group injected with 0.75-1.0 x 10(6) conidia. Precipitating antibody against culture filtrate antigen was found in rabbits with paranasal sinus mycoses. Therefore, rabbits can be used as an animal model to study paranasal sinus mycoses.

Clinical and environmental isolates of Cryptococcus neoformans exhibit a high degree of karyotypic variability. Analysis of the molecular basis of karyotypic differences requires a large set of chromosome-specific probes. We have determined the chromosomal distribution of a set of randomly selected C. neoformans cDNA clones and have explored the feasibility of identifying these clones through partial DNA sequencing. Forty-four randomly selected cDNA clones were labelled and hybridized to PFGE blots of C. neoformans. Expressed sequence tags were generated by sequencing the 5'-end of each clone. Thirty-five clones hybridized to single bands on PFGE blots. At least seven chromosomes were recognized by these probes. Homology searches identified potential homologs of several groups of proteins not previously studied in C. neoformans. PFGE hybridization and sequencing of random cDNA clones is an efficient method for identifying chromosomal-specific probes in fungi that lack extensive sets of genetic markers.

Cryptococcus neoformans is an opportunistic pathogen infecting AIDS patients. However, infection caused by C. neoformans var. gattii in AIDS patients is reportedly rare. We report herein the first culture proven C. neoformans var. gattii serotype B infection in an AIDS patient in India.

Cell-mediated immunity is critical to host defenses against the fungal infection cryptococcosis. Here, two functions critical to effective cell-mediated immunity (CMI), lymphoproliferation and cytokine release, were studied in Cryptococcus neoformans-stimulated peripheral blood mononuclear cells (PBMC) from seven healthy donors (controls) and two patients with cryptococcosis. PBMC responses to C. neoformans were compared with responses to Candida albicans. Control and patient PBMC had significant lymphoproliferation in response to whole C. neoformans, with peak proliferation seen following 8 days of culture, but only patient PBMC proliferated when stimulated with C. neoformans mannoprotein. C. neoformans-stimulated control PBMC released IL-2, IFN-gamma, and IL-10 into the supernatant with peak or near peak concentrations of these three cytokines generally seen by day 1. Release of IL-4 was low or undetectable. In contrast, C. neoformans-stimulated patient PBMC released IFN-gamma, which peaked on day 7, as well as IL-4, IL-10, and in one of two patients, IL-2. Cytokine release occurred later in patient (compared with control) PBMC. Lymphoproliferation and cytokine release were similar comparing control PBMC stimulated with C. neoformans versus Candida albicans. Thus, the magnitude and kinetics of the lymphoproliferative response to whole C. neoformans is similar comparing PBMC from controls and patients, but the cytokine profiles differ. Moreover, the capacity of patient PBMC to respond to soluble mannoprotein lends support to studies of mannoprotein components as vaccine candidates.

Phagocytosis, oxidative metabolism and phagolysosomal pH of rat alveolar macrophages (AM) were studied at different points of time after challenge with Cryptococcus neoformans. Phagocytosis was evaluated using a fluorescent quenching technique which distinguishes between attached and ingested organisms. The nitroblue tetrazolium (NBT) test was used as an indirect measurement of the oxidative metabolism of the phagocytes. The pH of the phagolysosomes was measured using a cytofluorometric technique. Both the attachment and ingestion of serum opsonized C. neoformans by AM were slow during the first hours of incubation, but were considerable after 24 h. The oxidative metabolism of Am challenged with the yeast was insignificant during the first hour, but reached high levels after 24 h. Most phagolysosomes in AM with ingested cryptococci had a pH < 5.5. Our results indicate that these AM defence mechanisms, although poor during the first hours after exposure to the yeast, are of significance after 24 h. Thus, in the immunocompetent host the AM should prevent the dissemination of C. neoformans from the lungs.

We report an intracranial epidural abscess caused by Aspergillus fumigatus in an immunocompetent patient. Infection occurred in a 20-year-old man 2 months after a frontal craniotomy following trauma. The abscess was encapsulated by a thickened dura and although the fungus did not invade the brain, frontal bone was infected and the patient presented with a subcutaneous frontal cellulitis. Initial management combined surgical drainage, resection of necrotic bone and liposomal amphotericin B (1 mg kg-1 per day). After 3 weeks of antifungal treatment a second evaluation surgery was performed. A clinically and radiologically unsuspected new abscess was found and evacuated. Treatment was completed with instillation into the cavity of amphotericin B at a concentration of 5 mg ml-1 and prolonged oral itraconazole (400-600 mg day-1). Treatment was successful and the patient is free of infection after 3 years.