RESUMEN
Onychomycosis is estimated at a prevalence of 10% worldwide with the infecting organism most commonly Trichophyton rubrum (T. rubrum). Traditional culture identification of causative organisms has inherent risks of overestimating dermatophytes, like T. rubrum, by inhibiting the growth of possible nondermatophyte mould (NDM) environmental contaminants which could be causative agents. Recently, molecular methods have revealed that a proportion of onychomycosis cases in North America may be caused by mixed infections of T. rubrum as an agent co-infecting with one or more NDM. Determining the global burden of mixed infections is a necessary step to evaluating the best therapies for this difficult-to-treat disease. To determine the prevalence of mixed infections in a global population, nail samples from onychomycosis patients in Brazil, Canada, and Israel (n = 216) were analyzed by molecular methods for the presence of dermatophytes and five NDMs. If an NDM was detected, repeat sampling was performed to confirm the NDM. T. rubrum was detected in 98% (211/216) of infections with 39% mixed (84/216). The infection type was more likely to be mixed in samples from Brazil, but more likely to be a dermatophyte in samples from Canada and Israel (Χ2 = 16.92, df = 2, P<0.001). The most common cause of onychomycosis was T. rubrum. In all countries (Brazil, Canada and Israel combined) the prevalence of dermatophyte (Χ2 = 211.15, df = 3, P<0.001) and mixed (dermatophyte and NDM; Χ2 = 166.38, df = 3, P<0.001) infection increased with patient age. Our data suggest that mixed infection onychomycosis is more prevalent than previously reported with the aging population being at increased risk for mixed infections.
Asunto(s)
Coinfección/diagnóstico , Onicomicosis/diagnóstico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Arthrodermataceae/genética , Arthrodermataceae/aislamiento & purificación , Brasil/epidemiología , Canadá/epidemiología , Niño , Coinfección/epidemiología , Coinfección/microbiología , ADN de Hongos/aislamiento & purificación , ADN de Hongos/metabolismo , Femenino , Dermatosis del Pie/diagnóstico , Dermatosis del Pie/epidemiología , Dermatosis del Pie/microbiología , Carga Global de Enfermedades , Humanos , Israel/epidemiología , Masculino , Persona de Mediana Edad , Onicomicosis/epidemiología , Onicomicosis/microbiología , Prevalencia , Adulto JovenRESUMEN
Bioassay-guided fractionation of Chimaphila umbellata (L.) W. Bart (Pyrolaceae) ethanol extracts led to the identification of 2,7-dimethyl-1,4-naphthoquinone (chimaphilin) as the principal antifungal component. The structure of chimaphilin was confirmed by 1H and 13C NMR spectroscopy. The antifungal activity of chimaphilin was evaluated using the microdilution method with Saccharomyces cerevisiae (0.05mg/mL) and the dandruff-associated fungi Malassezia globosa (0.39mg/mL) and Malassezia restricta (0.55mg/mL). Pronounced antioxidant activity of C. umbellata crude extract was also identified using the DPPH (2,2-diphenyl-1-picrylhydrazyl) assay, suggesting this phytomedicine has an antioxidant function in wound healing. A chemical-genetic profile was completed with chimaphilin using approximately 4700 S. cerevisiae gene deletion mutants. Cellular roles of deleted genes in the most susceptible mutants and secondary assays indicate that the targets for chimaphilin include pathways involved in cell wall biogenesis and transcription.
Asunto(s)
Antifúngicos/farmacología , Antioxidantes/farmacología , Malassezia/efectos de los fármacos , Naftoquinonas/farmacología , Pyrolaceae/química , Saccharomyces cerevisiae/efectos de los fármacos , Antifúngicos/química , Antifúngicos/aislamiento & purificación , Antioxidantes/química , Antioxidantes/aislamiento & purificación , Compuestos de Bifenilo/química , Relación Dosis-Respuesta a Droga , Hidrazinas/química , Espectroscopía de Resonancia Magnética/métodos , Malassezia/clasificación , Malassezia/crecimiento & desarrollo , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Naftoquinonas/química , Naftoquinonas/aislamiento & purificación , Picratos , Saccharomyces cerevisiae/crecimiento & desarrollo , Relación Estructura-ActividadRESUMEN
While visiting Jamaica, a 50-year-old woman stumbled on an outdoor wooden staircase and sustained an injury to the right leg. The wound was cleaned topically and the patient was given antibacterial therapy. Five weeks later, in Canada, she presented with an ulcer at the injury site. An excisional biopsy showed copious broad, septate, melanized fungal filaments penetrating into tissue. Culture yielded a nonsporulating melanized mycelium. The isolate was strongly inhibited by cycloheximide and benomyl but grew at 37 degrees C. After 16 weeks cultivation on modified Leonian's agar at 25 degrees C, it developed pycnidia characteristic of Lasiodiplodia theobromae, a common tropical phytopathogen mainly known previously as a rare agent of keratitis and onychomycosis in humans. The patient was not given antifungal chemotherapy, and the ulcer, which had been broadly excised in the biopsy procedure, ultimately resolved after treatment with saline compresses. The six-month follow-up showed no sign of infection. This case, interpreted in light of previously reported cases, shows that on rare occasions L. theobromae is able to act as an agent of subcutaneous phaeohyphomycosis and that, when this occurs, debridement alone may be sufficient to eradicate it.