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PubMed1999

Deep fungal and higher bacterial skin infections in Thailand: clinical manifestations and treatment regimens.

BACKGROUND: Deep fungal and higher bacterial skin infections occur fairly frequently in Thailand. METHODS: Cases with a provisional diagnosis of deep fungal and higher bacterial infections were prospectively collected from 1994 to 1997 in the Granuloma Clinic, Department of Dermatology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand. Demographic data, clinical manifestations, causative organisms, histologic features, treatment, and outcome were investigated. RESULTS: The total cases in a 4-year period numbered 27. The male to female ratio was approximately 1:1. Mycetoma was most common, followed by chromoblastomycosis. Actinomycetoma was similar in incidence to eumycetoma. The only causative organism that could be identified among the mycetoma cases was Cladosporium carrionii, which caused mycetoma of the buttock of an aplastic anemia patient at the site of bone marrow aspiration. Surgical treatment was recommended for eumycetoma. Chromoblastomycosis was caused by C. carrionii and F. compactum and responded well with itraconazole orally. Mycotic abscesses were found in four cases, basidiobolomycosis in two cases, and cutaneous nocardiosis in one case. Cotrimoxazole was recommended in the treatment of actinomycetoma, cutaneous nocardiosis, and basidiobolomycosis. CONCLUSIONS: Localized, chronic, slow, progressive, and usually asymptomatic were the main cutaneous manifestations of deep fungal and higher bacterial skin infections. A skin biopsy for histologic study and culture identification should be performed in every suspected case. The causative organisms were found in the histologic sections of every case, but only about one-third were found by culture.

Adolescent↗

PubMed2004

Ectophosphatase activity in conidial forms of Fonsecaea pedrosoi is modulated by exogenous phosphate and influences fungal adhesion to mammalian cells.

A cell-wall-associated phosphatase in hyphae of Fonsecaea pedrosoi, a fungal pathogen causing chromoblastomycosis, was previously characterized by the authors. In the present work, the expression of an acidic ectophosphatase activity in F. pedrosoi conidial forms was investigated. The surface phosphatase activity in F. pedrosoi is associated with the cell wall, as demonstrated by transmission electron microscopy. This enzyme activity was strongly inhibited by exogenous inorganic phosphate (P(i)). Accordingly, removal of P(i) from the culture medium of F. pedrosoi resulted in a marked (130-fold) increase of ectophosphatase activity. With the artificial phosphatase substrate p-nitrophenyl phosphate, a Km value of 0.63+/-0.04 mM was estimated for the phosphatase activity of fungal cells strongly expressing the enzyme activity. This enzyme activity was not modulated by cations. Conidia with greater ectophosphatase activity showed greater adherence to mammalian cells than did fungi cultivated in the presence of P(i) (low phosphatase activity). Surface phosphatase activity was apparently involved in the adhesion to host cells, since the enhanced attachment of F. pedrosoi to host cells was reversed by pre-treatment of conidia with phosphatase inhibitor. Since conidial forms are the putative infectious propagules in chromoblastomycosis, the expression and activity of acidic surface phosphatases in these cells may contribute to the early mechanisms required for disease establishment.

Animals↗

PubMed2003

Epidemiology, clinical manifestations, and therapy of infections caused by dematiaceous fungi.

The dematiaceous (brown-pigmented) fungi are a large and heterogenous group of moulds that cause a wide range of diseases including phaeohyphomycosis, chromoblastomycosis, and eumycotic mycetoma. Among the more important human pathogens are Alternaria species, Bipolaris species, Cladophialophora bantiana, Curvularia species, Exophiala species, Fonsecaea pedrosoi, Madurella species, Phialophora species, Scedosporium prolificans, Scytalidium dimidiatum, and Wangiella dermatitidis. These organisms are widespread in the environment, being found in soil, wood, and decomposing plant debris. Cutaneous, subcutaneous, and corneal infections with dematiaceous fungi occur worldwide, but are more common in tropical and subtropical climates. Infection results from traumatic implantation. Most cases occur in immunocompetent individuals. Dematiaceous moulds are also important causes of invasive sinusitis and allergic fungal sinusitis. Infection is thought to follow inhalation. Although cerebral infection is the commonest form of systemic phaeohyphomycosis, other localized deep forms of the disease, such as arthritis, and endocarditis, have been reported. Disseminated infection is uncommon, but its incidence is increasing, particularly among immunocompromised individuals. Scedosporium prolificans is the most frequent cause. A number of dematiaceous fungi are neurotropic, including Cladophialophora bantiana, Ramichloridium mackenziei, and Wangiella dermatitidis. Although cases have occurred in immunocompromised persons, cerebral phaeohyphomycosis is most common in immunocompetent individuals with no obvious risk factors. Most forms of disease caused by dematiaceous fungi require both surgical and medical treatment. Itraconazole is currently the most effective antifungal agent for chromoblastomycosis and subcutaneous phaeohyphomycosis, while ketoconazole remains useful for mycetoma. Extensive surgical debridement combined with amphotericin B treatment is recommended for chronic invasive sinusitis. Long-term treatment with itraconazole has led to improvement or remission in some patients that had failed to respond to amphotericin B. Allergic fungal sinusitis requires surgical removal of impacted mucin combined with postoperative oral corticosteroids. Antifungal treatment is not usually of benefit, but post-operative itraconazole may reduce the need for reoperation. The clinical outcome of cerebral and other deep-seated forms of phaeohyphomycosis is dismal, with long-term survival being reported only when complete surgical resection of discrete lesions is possible. The development of new antifungal agents and combination treatment may help to improve the management of these infections.

Antifungal Agents↗

PubMed1999

[Subcutaneous phaeohyphomycosis of the right thumb].

Black fungi are a group of fungi that are characterized by the development of a pale brown to black color in the cell walls of their vegetative cells, conidia, or both. A mycotic infection caused by a member of black fungi can be subdivided into three clinical entities: phaeohyphomycosis, chromoblastomycosis, and mycetoma. Phaeohyphomycosis is distinguished from mycetoma by the absence of grain (organized, interwoven mycelial aggregates) formation, and from chromoblastomycosis by the absence of sclerotic bodies (thick-walled muriform cells). Phaeohyphomycosis is a rare disease and has been sporadically reported. In the present report, phaeohyphomycosis of the right thumb of a 72-year-old man was presented. A precipitating trauma of two months earlier at the site was recalled. A solitary mass, 10 mm in diameter, was gradually formed in the palm side of the distal right thumb and finally resected. Histological examination disclosed a solitary granulomatous lesion surrounded by an incomplete fibrous capsule. The lesion mainly involved subcutaneous tissue and was composed of multiple pyogranulomas. Pigmented branched septate hyphae and yeast-like cells were sparsely found in the periphery of the abscess and within histiocytic cells of the granulomas. No sclerotic cells were detected. When pigmentation of black fungi in tissue is as faint as in the present case, Fontana-Masson staining is useful to accentuate the presence of melanin-like pigment of fungal cell walls.

Aged↗

PubMed1983

Scanning electron microscopic observation of the parasitic forms of Fonsecaea pedrosoi in a human skin lesion.

The parasitic form of Fonsecaea pedrosoi in the superficial hyperkeratotic layer of the skin, in a patient with chromoblastomycosis, was observed by a scanning electron microscope using some technical improvements. The fungus elements were comprised of branched septate hyphae with spherical cells and sclerotic cells. It was observed that the sclerotic cells, divided into two or three parts, formed a germ tube.

Aged↗

PubMed1991

Treatment of deep mycoses with itraconazole.

Four patients with deep mycoses were treated with itraconazole. Two patients had chromoblastomycosis, one patient each had aspergillosis and Rhinofacial zygomycosis. These patients were either resistant to or showed poor response to Amphotericin B and/or ketoconazole. After the initial clinical and mycological evaluation, itraconazole was given in a daily dose of 200 mg orally. All patients responded to the drug very well. No adverse effects attributable to itraconazole were detected.

Adult↗

PubMed1995

Phialophora verrucosa: a new cause of mycetoma.

A 29-year-old Thai woman had draining sinus tracts, tumefaction, and granules on the plantar aspect of the foot. Phialophora verrucosa was isolated from the lesion. P. verrucosa is a major agent of chromoblastomycosis, which is known to rarely cause subcutaneous phaeohyphomycosis. This dematiaceous fungus has not been previously reported to cause mycetoma. This case illustrates the clinical spectrum of disease of this fungus. The salient features of mycetoma and management options are presented.

Adult↗

PubMed2005

Tropical dermatology: fungal tropical diseases.

UNLABELLED: Fungal infections are common in tropical countries and can have an important impact on public health. Lobomycosis is a common fungal infection in the tropical rain forest of South America, and paracoccidioidomycosis (South American blastomycosis) is a widespread and sometimes severe illness. Penicilliosis marneffei is an opportunistic infection of AIDS patients in southeast Asia. Chromoblastomycosis and mycetomas are causes of morbidity around the world. Sporotrichosis is a worldwide subcutaneous mycosis with a high incidence in tropical countries and is an important illness in immunocompromised patients. Rhinosporidiosis was classed as a fungal infection but is now considered a protistan parasite that belongs to the class Mesomycetozoea. It is included in this review because of its historical classification. In the past, most of these mycoses were restricted to specific geographic areas and natural reservoirs. There are, however, situations in which people from other regions come in contact with the pathogen. A common situation involves an accidental contamination of a traveler or worker who has contact with a tropical mycosis. Even minor trauma to the skin surface or inhalation of the fungal conidia can infect the patient. Thus recognition of the clinical symptoms and the dermatologic findings of the diseases, as well as the geographic distribution of the pathogens, can be critical in diagnosis of the tropical mycoses. This review discusses some of the more common tropical subcutaneous and systemic mycoses, as well as their signs, symptoms, methods of diagnosis, and therapies. LEARNING OBJECTIVE: At the completion of this learning activity, participants should be able to recognize the clinical and histologic presentations of tropical fungal diseases with cutaneous manifestations and be familiar with the appropriate therapies.

Animals↗

PubMed2004

A monoclonal antibody to glucosylceramide inhibits the growth of Fonsecaea pedrosoi and enhances the antifungal action of mouse macrophages.

Fungal glucosylceramides (GlcCer) are conserved lipid components in a large variety of pathogenic and non-pathogenic fungal species, but their biological functions are still unclear. Recent studies demonstrate that GlcCer are immunologically active components inducing the production of antifungal antibodies. In this work, a major GlcCer was purified and characterized from mycelial forms of Fonsecaea pedrosoi, the most frequent causative agent of chromoblastomycosis. As determined by fast atom bombardment mass spectrometry (FAB-MS) analysis, the purified molecule was identified as the conserved structure N-2'-hydroxyhexadecanoyl-1-beta-D-glucopyranosyl-9-methyl-4,8-sphingadienine. A monoclonal antibody (Mab) against this structure was used in indirect immunofluorescence with the different morphological stages of F. pedrosoi. Only the surface of young dividing cells was recognized by the antibody. Treatment of F. pedrosoi conidia with the Mab against GlcCer resulted in a clear reduction in fungal growth. In addition, the Mab also enhanced phagocytosis and killing of F. pedrosoi by murine cells. These results suggest that, in F. pedrosoi, GlcCer seem to be cell wall components targeted by antifungal antibodies that directly inhibit fungal development and also enhance macrophage function, supporting the use of monoclonal antibodies to GlcCer as potential tools in antifungal immunotherapy.

Animals↗

PubMed2003

Differentiation of Fonsecaea pedrosoi mycelial forms into sclerotic cells is induced by platelet-activating factor.

Platelet-activating factor (PAF) has been shown to induce the differentiation of several cell types. In this work, we evaluated the effects of PAF on the formation of sclerotic cells of Fonsecaea pedrosoi, the major causative agent of chromoblastomycosis. Cell differentiation was evaluated by light and electron microscopy, which showed that treatment of mycelial forms with PAF results in the generation of sclerotic bodies with typical morphological characteristics. Biochemical features of PAF-induced sclerotic cells were also analyzed and compared with those from sclerotic forms induced by propranolol, a previously described differentiating agent of F. pedrosoi. Chemical analyses of lipid and carbohydrate components from PAF- or propranolol-induced sclerotic bodies revealed that palmitic, stearic, oleic and linoleic acids were the major fatty acid components, while glucose, mannose, galactose and rhamnose were detected as the principal sugar constituents in these cells. Surface carbohydrate components of PAF- and propranolol-induced sclerotic cells were also evaluated, by flow cytometry analysis with twelve different lectins. The profile of reactivity of PAF- or propranolol-induced fungal cells with lectins was also very similar. Hydrolysis of the synthetic substrate p-nitrophenylphosphate by fungal cells demonstrated that the addition of PAF or propranolol to the mycelial cultures similarly promotes a significant increase in ecto-phosphatase activity. These results indicate that the differentiation of F. pedrosoi mycelial cells induced by PAF generates authentic sclerotic forms, as confirmed by the analysis of morphological and biochemical attributes. Since PAF is synthesized in normal conditions by the human host, these observations may have a correlation with the differentiation of F. pedrosoi in vivo.

Ascomycota↗

PubMed2003

Subcutaneous mycoses.

Subcutaneous mycoses include a heterogeneous group of fungal infections that develop at the site of transcutaneous trauma. Infection slowly evolves as the etiologic agent survives and adapts to the adverse host tissue environment. Diagnosis rests on clinical presentation, histopathology, and culture of the etiologic agents. This article considers sporotrichosis, chromoblastomycosis, and mycetoma.

Antifungal Agents↗

PubMed2003

An unusual dematiaceous fungal infection of the skin caused by Fonsecaea pedrosoi: a case report and review of the literature.

BACKGROUND: A case of an unusual dematiaceous fungal infection of the skin in a 43-year-old man with diabetes mellitus treated with steroids for reactive airway disease is presented. He developed chromoblastomycosis in the left wrist and was treated with antifungals and multiple surgical excisions. RESULTS: Histologic examination of the excised tissue revealed widespread suppurative granulomatous inflammation in the dermis and subcutaneous tissue. Thick-walled internally septated brown fungal cells were found both inside multinucleated giant cells and extracellularly. Non-to-lightly pigmented septate hyphal elements, however, were also identified with special stains and, in retrospect, on one of the routinely stained sections. In culture, the organism was reported to initially grow as soft white colonies that soon turned to black and velvety. CONCLUSIONS: The two unusual features of this case include the controversial report of the organism's initial growth in culture as soft white colonies and the presence of hyphal elements in addition to the sclerotic bodies in the dermis and subcutaneous tissue. This has not been reported before in human cases of dermal infection by Fonsecaea pedrosoi.

Adult↗

PubMed1999

Therapeutic potential of terbinafine in subcutaneous and systemic mycoses.

Mycoses vary widely in severity, and may present as superficial, subcutaneous and/or systemic infection. Effective treatments for most superficial mycoses now exist, but new agents with convenient dosing regimens and a low level of adverse events are still needed to reduce morbidity and mortality from serious subcutaneous and systemic fungal infections. In vitro, terbinafine exhibits a broad spectrum of activity against the pathogenic fungi responsible for deep mycoses. Clinical data, while not abundant, suggest that this in vitro activity of terbinafine is reflected in its in vivo efficacy. The limited data show that terbinafine is a useful first-line treatment in chromoblastomycosis patients and has efficacy in pulmonary aspergillosis. There are also data to suggest that terbinafine may be effective in treating histoplasmosis, Pneumocystis carinii infection, fungal mycetoma, and cutaneous leishmaniasis. Moreover, there is some evidence of terbinafine having synergistic activity with amphotericin B, itraconazole, and fluconazole against clinical isolates of Candida species. Thus, the therapeutic potential of terbinafine extends well beyond its current use in acute and chronic dermatophytoses to include a wide range of subcutaneous and systemic mycoses. Studies are needed to determine the optimum dose in each disease, and whether combination therapy would have advantages in certain circumstances.

Antifungal Agents↗

PubMed1986

Identification of sialic acids on the cell surface of hyphae and conidia of the human pathogen Fonsecaea pedrosoi.

Sialic acids were characterized on the cell surface of conidia and hyphae of Fonsecaea pedrosoi, one of the agents of chromoblastomycosis. Neuraminidase-treated conidia had a reduced negative electrophoretic mobility and, in comparison with untreated cells, bound fewer particles of colloidal iron hydroxide and of cationized ferritin. Sialic acid residues in conidia are linked to galactopyranosyl units as indicated by the increased reactivity of neuraminidase-treated cells with peanut agglutinin. N-acetylneuraminic acid was the only derivative found in the mycelium whereas conidia contained both N-glycolyl- and N-acetylneuraminic acids.

Agglutination Tests↗

PubMedDate not supplied

Identification of the conserved coding sequences of three chitin synthase genes in Fonsecaea pedrosoi.

Primers having designs based on highly conserved stretches in the deduced amino acid sequences of chitin synthase (CHS) genes were used in PCR reactions to amplify 600 bp and 366 bp products from the genomic DNA of three major causal agents of chromoblastomycosis. Cloning and sequencing of the PCR products of one of these fungi, Fonsecaea pedrosoi, identified three CHS sequences designated as FpCHS1, FpCHS2 and FpCHS3. FpCHS1 and FpCHS2 were homologous to regions of CHS1 and CHS2 of Saccharomyces cerevisiae, and their derived amino acid sequences fell into chitin synthase classes I and II, respectively. FpCHS3 was homologous to a region of the CAL1/CSD2 gene of S. cerevisiae, which codes for the chitin synthase three (Chs3) enzyme in that fungus. Phylogenetic trees constructed using the deduced amino acid sequences of PCR-amplified CHS products from many fungi clustered F. pedrosoi with other dematiaceous fungi, providing new molecular evidence for the genetic relatedness of these organisms. The identification of these CHS genes in F. pedrosoi will facilitate future studies of the functional roles of chitin synthases in the unique in vivo dimorphism exhibited by chromoblastomycotic fungi.

Amino Acid Sequence↗

PubMed2004

Highly specific and sensitive, immunoblot-detected 54 kDa antigen from Fonsecaea pedrosoi.

Chromoblastomycosis (CBM) is a chronic subcutaneous mycosis caused by a group of different dematiaceous fungi, first described by Rudolph in 1914. In Brazil there is a clear predominance of Fonsecaea pedrosoi. Sixty sera samples obtained from patients with F. pedrosoi-caused CBM were analysed. Sera obtained from 36 sporothricosis (SPT) patients, 34 cutaneous leishmaniasis (CL) patients and from 48 blood donors (HBD) were used as control. F. pedrosoi metabolic antigen was obtained from F. pedrosoi sample no. 884 (Instituto de Medicina Tropical de São Paulo Collection). IE reaction disclosed an anodic migrating arch, which was eluted and used as antigen. Both metabolic and eluate F. pedrosoi antigens were submitted to SDS-PAGE and two fractions, weighing approximately 54 and 66 kDa were identified. The 66-kDa fraction reacted against 43 of 60 CBM (71.7%) sera samples and was recognized by 10 SPT and eight CL sera (15.3%). No reactivity was observed against HBD sera. The 54-kDa fraction reacted against 58 of 60 CBM sera (96.7% sensitivity) and was not recognized by HBD, SPT nor CL sera (100% specificity). Such high sensitivity and specificity levels suggest this antigenic fraction is immunodominant and might prove a useful tool for further studies on F. pedrosoi-caused CBM.

Antibodies, Fungal↗

PubMed2004

Molecular ecology and pathogenic potential of Fonsecaea species.

The genus Fonsecaea is revised on the basis of ribosomal DNA internal transcribed spacer (ITS) sequence data. Two species are recognized, F. pedrosoi and the new defined F. monophora. The distinction between these species does not correspond with the classical distinction of F. pedrosoi and F. compacta. The latter appears to be no more than a morphological variant. Both species recognized in this study are agents of human chromoblastomycosis; however, in F. pedrosoi a strict association with this disease is noted, while F. monophora is a more general opportunist. Subspecific randomly amplified polymorphic DNA (RAPD) typing revealed a high degree of strain diversity, although clonal reproduction is also likely to occur. Most strains with Fonsecaea-like morphology isolated from environments to which symptomatic human patients were exposed were found to be more closely related to species of Cladophialophora than to Fonsecaea.

Ascomycota↗

PubMed2005

Cerebral phaeohyphomycosis caused by Fonsecaea monophora.

We report a case of cerebral phaeohyphomycosis in a 53-year-old immunocompetent diabetic male, caused by Fonsecaea monophora. Computerized tomography of the brain revealed an abscess, which yielded F. monophora in pure culture. The patient's condition deteriorated on treatment with voriconazole and 5-fluorocytosine, and improved subsequently with high-dose itraconazole. The genus Fonsecaea has recently been revised and the new species F. monophora generated from molecular analysis of isolates, most of which were originally identified as Fonsecaea pedrosoi. This is the fourth case of cerebral infection known to have been caused by F. monophora, although only the first reported as such. These cases suggest that the clinical potential of F. monophora differs from that of F. pedrosoi, one of the main agents of chromoblastomycosis, with F. monophora being predominantly neurotropic in the human host.

Ascomycota↗