Abstract

Morphological characterization and multi-locus DNA sequence analysis of fungal isolates obtained from 32 clinical cases of equine fungal keratitis (FK) was performed to identify species and determine associations with antifungal susceptibility, response to therapy and clinical outcome. Two species of Aspergillus (A. flavus and A. fumigatus) and three species of Fusarium (F. falciforme, F. keratoplasticum, and F. proliferatum) were the most common fungi isolated and identified from FK horses. Most (91%) equine FK Fusarium nested within the Fusarium solani species complex (FSSC) with nine genetically diverse strains/lineages, while 83% of equine FK Aspergillus nested within the A. flavus clade with three genetically diverse lineages. Fungal species and evolutionary lineage were not associated with clinical outcome. However, species of equine FK Fusarium were more likely (p = 0.045) to be associated with stromal keratitis. Species of Aspergillus were more susceptible to voriconazole and terbinafine than species of Fusarium, while species of Fusarium were more susceptible to thiabendazole than species of Aspergillus. At the species level, A. fumigatus and A. flavus were more susceptible to voriconazole and terbinafine than F. falciforme. Natamycin susceptibility was higher for F. falciforme and A. fumigatus compared to A. flavus. Furthermore, F. falciforme was more susceptible to thiabendazole than A. flavus and A. fumigatus. These observed associations of antifungal sensitivity to natamycin, terbinafine, and thiabendazole demonstrate the importance of fungal identification to the species rather than genus level. The results of this study suggest that treatment of equine FK with antifungal agents requires accurate fungal species identification.

Highlights

  • Fungal keratitis (FK) is a severe, progressive, inflammatory ocular disease resulting from invasive growth of fungi into the cornea

  • Outcome of the 32 eyes included eight (25%) that healed with medical therapy (MT), 12 (37.5%) that healed with surgical therapy (ST), and 12 (37.5%) that were either enucleated or the horse was euthanized because of severe FK (E)

  • 25% of equine FK cases were resolved with medical therapy and over 37% of the patients had loss of the eye due to infection

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Summary

Introduction

Fungal keratitis (FK) is a severe, progressive, inflammatory ocular disease resulting from invasive growth of fungi into the cornea. Fungal keratitis is challenging to manage and can lead to blindness or loss of the affected eye.[1] The incidence of human FK has increased in the past several decades.[2, 3] In subtropical areas, fungal infections are reported to cause up to 35% of all documented keratitis cases in humans, especially in China and India.[1, 3, 4] Fungal keratitis is less common in the US where it is predominantly observed in south Florida and Texas.[2, 5] Nearly half of the causative organisms in FK are filamentous fungi, predominantly species of Aspergillus and Fusarium, of approximately equal frequency, followed in incidence by species of Candida, a dimorphic yeast.[1, 3,4,5] Fusarium spp. and Aspergillus spp. accounted for 31% and 25% of filamentous FK isolates from South India; [4] 28% Fusarium spp. and 22% Aspergillus spp. from East India; [3] and 48% Fusarium spp. and 19% Aspergillus spp. from Northeast China. [1] In these studies, the fungal species associated with FK were not identified The incidence of human FK has increased in the past several decades.[2, 3] In subtropical areas, fungal infections are reported to cause up to 35% of all documented keratitis cases in humans, especially in China and India.[1, 3, 4] Fungal keratitis is less common in the US where it is predominantly observed in south Florida and Texas.[2, 5] Nearly half of the causative organisms in FK are filamentous fungi, predominantly species of Aspergillus and Fusarium, of approximately equal frequency, followed in incidence by species of Candida, a dimorphic yeast.[1, 3,4,5] Fusarium spp. and Aspergillus spp. accounted for 31% and 25% of filamentous FK isolates from South India; [4] 28% Fusarium spp. and 22% Aspergillus spp. from East India; [3] and 48% Fusarium spp. and 19% Aspergillus spp. from Northeast China. [1] In these studies, the fungal species associated with FK were not identified

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