Emilio Mayayo

MOLECULAR DIAGNOSIS AND EPIDEMIOLOGY OF FUNGAL INFECTIONS

An experimental model of endophthalmitis by Fusarium solani in immunocompetent mice that could be useful for evaluating the efficacy of different treatments and the pathogenicity of the fungus in ocular structures was established. Five clinical isolates of F. solani were injected into the lateral tail vein of groups of 20 mice, in order to produce systemic infection with ocular infection. Inocula of 5 x 10(6) conidia per mouse were used. The eyes of the animals that died were enucleated for histopathological study to determine the degree of ocular infection. We found fungal infections in 34% of the mice studied. Panophthalmitis was detected in 16 animals, four with bilateral infections. Fungal endophthalmitis can become a severe complication of systemic mycoses by F. solani.

Fusarium oxysporum as a multihost model for the genetic dissection of fungal virulence in plants and mammals.

ABSTRACT Fungal pathogens cause disease in plant and animal hosts. The extent to which infection mechanisms are conserved between both classes of hosts is unknown. We present a dual plant-animal infection system based on a single strain of Fusarium oxysporum, the causal agent of vascular wilt disease in plants and an emerging opportunistic human pathogen. Injection of microconidia of a well-characterized tomato pathogenic isolate (isolate 4287) into the lateral tail vein of immunodepressed mice resulted in disseminated infection of multiple organs and death of the animals. Knockout mutants in genes encoding a mitogen-activated protein kinase, a pH response transcription factor, or a class V chitin synthase previously shown to be implicated in virulence on tomato plants were tested in the mouse model. The results indicate that some of these virulence factors play functionally distinct roles during the infection of tomato plants and mice. Thus, a single F. oxysporum strain can be used to study fungal virulence mechanisms in plant and mammalian pathogenesis.

Two Cases of Subcutaneous Infection Due to Phaeoacremonium spp.

ABSTRACT We describe two cases in Brazil of human subcutaneous infections due to Phaeoacremonium spp. The first case was caused by Phaeoacremoniumaleophilum. The patient presented with a unique fistulized nodule on the left ankle. The fungus was detected by direct microscopic examination and was isolated repeatedly from material collected from the lesion. This is the first reported case of human infection caused by this fungus. The second case was caused by Phaeoacremoniumrubrigenum. The patient presented with multiple nodules around the left ankle and foot. The fungus was detected by direct examination of pus and histological sections of the nodules. It was repeatedly isolated from the clinical specimens. This is the second reported case of human infection caused by this species.

Efficacy of micafungin in combination with other drugs in a murine model of disseminated trichosporonosis.

ABSTRACT Using a murine model of disseminated infection caused by Trichosporon asahii, we have evaluated the efficacies of amphotericin B (AMB; 1 mg/kg of body weight/day), fluconazole (FLC; 20 mg/kg/twice a day), and micafungin (MFG; 5 mg/kg/twice a day). We tested these drugs alone and in combination (MFG with AMB and MFG with FLC). MFG with AMB showed a synergistic effect and demonstrated a higher degree of efficacy in prolonging survival and reducing the kidney fungal burden than either agent alone. The combination MFG with FLC was able to reduce significantly the kidney fungal burden in comparison to that achieved with either drug administered alone.

Effect of age on vanadium nephrotoxicity in rats

The present study was designed to assess potential age dependent differences of vanadium nephrotoxicity in the rat following parenteral administration of vanadate. Young (22 days) and adult (62 days) male Sprague-Dawley rats received i.p. injections of sodium orthovanadate at 10 mg/kg/day for 8 consecutive days. Two additional groups of control rats received i.p. injections of 0.9% saline during the same period. Significant age-differences were found in most of the parameters used as indicators of nephrotoxicity in young and adult rats, with adverse renal effects being more severe with age. Vanadium-induced morphologic changes in the kidney were also more pronounced with age. These findings agree with a higher renal concentration of vanadium in the group of adult rats treated with vanadate than in the vanadate-untreated group. The current results can be of concern if in the future, vanadium compounds can be administered in the treatment of diabetic patients.

In Vitro and In Vivo Activities of Posaconazole and Amphotericin B in a Murine Invasive Infection by Mucor circinelloides: Poor Efficacy of Posaconazole

ABSTRACT The in vitro susceptibility of 17 strains of Mucor circinelloides to amphotericin B and posaconazole was ascertained by using broth microdilution and disk diffusion methods and by determining the minimal fungicidal concentration (MFC). We evaluated the efficacy of posaconazole at 40 mg/kg of body weight/day and amphotericin B at 0.8 mg/kg/day in a neutropenic murine model of disseminated infection by M. circinelloides by using 6 different strains tested previously in vitro. In general, most of the posaconazole MICs were within the range of susceptibility or intermediate susceptibility, while the small inhibition zone diameters (IZDs) were indicative of nonsusceptibility for all isolates tested. The MFCs were ≥3 dilutions higher than the corresponding MICs. In contrast, amphotericin B showed good activity against all of the strains tested regardless of the method used. The in vivo studies demonstrated that amphotericin B was effective in prolonging survival and reducing the fungal load. Posaconazole showed poor in vivo efficacy with no correlation with the MIC values. The results suggested that posaconazole should be used with caution in the treatment of infections caused by Mucor circinelloides or by strains of Mucor not identified to the species level.

Comparative effects of the chelators sodium 4,5-dihydroxybenzene-1,3-disulfonate (Tiron) and diethylenetriaminepentaacetic acid (DTPA) on acute uranium nephrotoxicity in rats.

Sodium 4,5-dihydroxybenzene-1,3-disulfonate (Tiron) and diethylenetriaminepentaacetic acid (DTPA) are two chelating agents that have been demonstrated to be effective in the treatment of experimental poisoning by a number of heavy metals. In this study, the effects of Tiron and DTPA on uranium-induced nephrotoxicity were evaluated in a rat model. A series of four Tiron or DTPA injections was administered intraperitoneally to adult male Sprague-Dawley rats immediately after a single subcutaneous injection of uranyl acetate dihydrate (5 mg/kg) and at 24, 48 and 72 h thereafter. Positive and negative control groups received 0.9% saline with or without uranyl acetate, respectively. Tiron effectiveness was assessed at 400, 800 and 1600 mg/kg, whereas DTPA was administered at 250, 500 and 1000 mg/kg. Although the urinary excretion of uranium was significantly enhanced by Tiron administration, significant amounts of uranium still remained in the kidney at the end of the treatment. However, the partial reduction of the renal uranium concentrations was in accordance with the amelioration noted in some urinary and serum indicators of uranium nephrotoxicity. Moreover, Tiron administration also reduced the severity of the uranium-induced histological alterations in the kidney. According to these results, Tiron offers only a modest encouragement with regard to its possible therapeutic potential to treat acute uranium-induced nephrotoxic effects. In turn, DTPA was less effective than Tiron in protecting against the nephrotoxicity of uranium in rats.

Subcutaneous Phaeohyphomycosis Caused by Wallemia sebi in an Immunocompetent Host

ABSTRACT We report a case of subcutaneous phaeohyphomycosis due to Wallemia sebi in a 43-year-old-female, the first case reported since 1950. The lesion presented as a nonhealing ulcer on the dorsum of the left foot. Diagnosis was based on histological demonstration of the fungus and its recovery in culture.

Efficacy of Posaconazole in Murine Experimental Sporotrichosis

ABSTRACT We developed a murine model of systemic sporotrichosis by using three strains of each of the two commonest species causing sporotrichosis, i.e., Sporothrix schenckii sensu stricto and Sporothrix brasiliensis, in order to evaluate the efficacy of posaconazole (PSC). The drug was administered at a dose of 2.5 or 5 mg/kg of body weight twice a day by gavage, and one group was treated with amphotericin B (AMB) as a control treatment. Posaconazole, especially at 5 mg/kg, showed good efficacy against all the strains tested, regardless of their MICs, as measured by prolonged survival, tissue burden reduction, and histopathology.

Unusual morphologies of Cryptococcus spp. in tissue specimens: report of 10 cases

Ten cases of cryptococcosis due to unusual microscopic forms of Cryptococcus sp. observed over a twenty-eight year period (1981-2009) are presented. The most important clinicopathological and laboratory data are tabulated. The uncommon forms of cryptococcal cells given are: structures resembling germ tube (one case), chains of budding yeasts (one case), pseudohyphae (two cases) and nonencapsulated yeast-like organisms (eight cases). The diagnosis was based on the histopathological findings. The causative organism was isolated and identified in seven cases; five were due to C. neoformans, and two to C. gattii. In addition, the importance of using staining histochemical techniques - Grocotts silver stain (GMS), Mayers mucicarmine stain (MM) and Fontana-Masson stain (FM) - in the diagnosis of cryptococcosis is argued.