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. 2011 Jul;55(7):3150-5.
doi: 10.1128/AAC.00399-11. Epub 2011 May 9.

Establishment of a novel model of onychomycosis in rabbits for evaluation of antifungal agents

Tsuyoshi Shimamura  1 , Nobuo Kubota, Saori Nagasaka, Taku Suzuki, Hideki Mukai, Kazutoshi Shibuya
Affiliations

Establishment of a novel model of onychomycosis in rabbits for evaluation of antifungal agents

Tsuyoshi Shimamura et al. Antimicrob Agents Chemother. 2011 Jul.

Abstract

We developed a novel model of onychomycosis in which we observed fungi in the deep layer of the nail, and we used the model to evaluate the efficacy of two topical antifungal drugs. To establish an experimental, in vivo model of onychomycosis, we applied Trichophyton mentagrophytes TIMM2789 to the nails of the hind limbs of rabbits that underwent steroid treatment. The nails were taken from the rabbits' feet at 0, 2, and 6 weeks after a 2-week infection. The localization of the fungi was evaluated histopathologically. Some fungi were seen to penetrate to the nail bed, and the infection rate in the sample at 0, 2, and 6 weeks after infection was 57, 87, and 93%, respectively. In addition, fungi proliferated and moved proximally into the nail plate in a manner that depended on the duration of infection. Second, using this model we evaluated antifungal efficacy both by the culture recovery method and histopathological examination. Two topical antifungal drugs, 8% ciclopirox nail lacquer and 5% amorolfine nail lacquer, were applied to the nail for 4 weeks in each group. On histopathological examination, two antifungal treatment groups showed no significant difference against the nontreated control group. However, there were a significantly low fungus-positive rate and intensity of the recovery of fungi on culture between antifungal treatment and nontreated control groups. We therefore suggest that we have established an in vivo model of onychomycosis that is useful for the evaluation of the efficacy of antifungal agents.

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Figures

Fig. 1.
Fig. 1.
Diagram of histopathology of rabbit nail. The histological examination was carried out according to the six regions separated: a, dorsal and distal; b, dorsal and medium; c, dorsal and proximal; d, ventral and distal; e, ventral and medium; and f, ventral and proximal side of nail plate.
Fig. 2.
Fig. 2.
Gross appearance of infected nails at 6 weeks postinfection in an experiment to establish a model of onychomycosis. A cloudy appearance like that of human onychomycosis was observed in some infected nails.
Fig. 3.
Fig. 3.
Histological findings in infected nails at 6 weeks postinfection (A) and 2 weeks postinfection (B). Many fungi and a cluster of necrotic tissue in the nail deep layers were observed (A), and some of the infected nails showed chains of spores near the surface of the nail (B). Bar = 100 μm.
See this image and copyright information in PMC

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