ABSTRACT Chromoblastomycosis is a chronic subcutaneous mycotic infection caused by pigmented or dematiaceous saprophytic moulds ubiquitous in the environment. The most common etiologic agents are Fonsecaea pedrosoi and Cladophialophora carrionii, both of which can be isolated from plant debris. The infection usually follows traumatic inoculation through penetrating thorn or splinter wounds. The fungal agents develop as small clusters of cells known as muriform bodies. Several months after the injury, painless papules or nodules appear in the affected area progressing to scaly and verrucose plaques. Direct examinations of skin scrapings or histopathologic study demonstrates the typical muriform bodies. Microbiologic culture is necessary for the correct determination of the etiologic agent. Itraconazole is the treatment of choice, often in combination with surgery. Even so, results are often unsatisfactory as patients present late to medical services because of lack of funds and the fact that the disease usually affects the main family earner.
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ABSTRACT: Fonsecaea pedrosoi (F. pedrosoi), a major agent of chromoblastomycosis, has been shown to be recognized primarily by C-type lectin receptors (CLRs) in a murine model of chromoblastomycosis. Specifically, the β-glucan receptor, Dectin-1, mediates Th17 development and consequent recruitment of neutrophils, and is evidenced to have the capacity to bind to saprophytic hyphae of F. pedrosoi in vitro. However, when embedded in tissue, most etiological agents of chromoblastomycosis including F. pedrosoi will transform into the sclerotic cells, which are linked to the greatest survival of melanized fungi in tissue. In this study, using immunocompetent and athymic (nu/nu) murine models infected subcutaneously or intraperitoneally with F. pedrosoi, we demonstrated that T lymphocytes play an active role in the resolution of localized footpad infection, and there existed a significantly decreased expression of Th17-defining transcription factor Rorγt and inefficient recruitment of neutrophils in chronically infected spleen where the inoculated mycelium of F. pedrosoi transformed into the sclerotic cells. We also found that Dectin-1-expressing histocytes and neutrophils participated in the enclosure of transformed sclerotic cells in the infectious foci. Furthermore, we induced the formation of sclerotic cells in vitro, and evidenced a significantly decreased binding capacity of human or murine-derived Dectin-1 to the induced sclerotic cells in comparison with the saprophytic mycelial forms. Our analysis of β-glucans-masking components revealed that it is a chitin-like component, but not the mannose moiety on the sclerotic cells, that interferes with the binding of β-glucans by human or murine Dectin-1. Notably, we demonstrated that although Dectin-1 contributed to the development of IL-17A-producing CD3+CD4+ murine splenocytes upon in vitro-stimulation by saprophytic F. pedrosoi, the masking effect of chitin components partly inhibited Dectin-1-mediated Th17 development upon in vitro-stimulation by induced sclerotic cells. Therefore, these findings extend our understanding of the chronicity of chromoblastomycosis.PLoS ONE 12/2014; 9(12):e114113. DOI:10.1371/journal.pone.0114113 · 3.53 Impact Factor
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ABSTRACT: Knowledge of the currently available antifungal agents, along with clinical, microbiologic and histopathologic methods, can help the medical professional optimally manage skin and nail fungal infections. With regards to treatment of fungal disease of the skin or nail, there are a variety of systemic antifungal agents, including several newer agents that have different formulations, tolerability, adverse effect profiles and spectrum of activity. This review will highlight the clinically important fungal infections of the skin and nail and describe the activity and role of antifungal treatment.Expert Review of Anti-infective Therapy 09/2014; 12(11):1-17. DOI:10.1586/14787210.2014.960849 · 3.06 Impact Factor
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ABSTRACT: Dematiaceous fungi (black fungi) are a heterogeneous group of fungi present in diverse environments worldwide. Many species in this group are known to cause allergic reactions and potentially fatal diseases in humans and animals, especially in tropical and subtropical climates. This study represents the first survey of dematiaceous fungi in Malaysia and provides observations on their diversity as well as in vitro response to antifungal drugs. Seventy-five strains isolated from various clinical specimens were identified by morphology as well as an internal transcribed spacer (ITS)-based phylogenetic analysis. The combined molecular and conventional approach enabled the identification of three classes of the Ascomycota phylum and 16 genera, the most common being Cladosporium, Cochliobolus and Neoscytalidium. Several of the species identified have not been associated before with human infections. Among 8 antifungal agents tested, the azoles posaconazole (96%), voriconazole (90.7%), ketoconazole (86.7%) and itraconazole (85.3%) showed in vitro activity (MIC ≤1 µg/mL) to the largest number of strains, followed by anidulafungin (89.3%), caspofungin (74.7%) and amphotericin B (70.7%). Fluconazole appeared to be the least effective with only 10.7% of isolates showing in vitro susceptibility. Overall, almost half (45.3%) of the isolates showed reduced susceptibility (MIC >1 µg/mL) to at least one antifungal agent, and three strains (one Pyrenochaeta unguis-hominis and two Nigrospora oryzae) showed potential multidrug resistance.PLoS ONE 08/2014; 9(8):e104352. DOI:10.1371/journal.pone.0104352 · 3.53 Impact Factor