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Cerebral Phaeohyphomycosis due to Cladophialophora bantiana in a Huacaya Alpaca (Vicugna pacos)
J. Comp. Path. 2011, Vol. 145, 410e413
Available online at www.sciencedirect.com
www.elsevier.com/locate/jcpa
DISEASE IN WILDLIFE OR EXOTIC SPECIES
Cerebral Phaeohyphomycosis due to Cladophialophora bantiana in a Huacaya Alpaca (Vicugna pacos) C. Frank, R. Vemulapalli and T. Lin Animal Disease Diagnostic Laboratory and Department of Comparative Pathobiology, Purdue University, West Lafayette, IN 47907, USA
Summary Cerebral phaeohyphomycosis, caused by Cladophialophora bantiana, was diagnosed in a Huacaya alpaca (Vicugna pacos). An 8-year-old, intact male Huacaya alpaca from a farm in Indiana was found dead at pasture and submitted to the Animal Disease Diagnostic Laboratory at Purdue University for necropsy examination. Gross lesions were limited to the cerebrum, which had a 2 2.5 5 cm, well-demarcated, firm, mottled, pale grey to brown-red mass with a granular texture, centered on the left and right cingulate gyri. Microscopically, granulomatous and necrotizing meningoencephalitis with intralesional pigmented fungal hyphae effaced the cerebral grey and white matter of the cingulate gyri. The hyphae were 4e6 mm in diameter and septate, with non-parallel walls and occasional branching. Polymerase chain reaction for the internal transcribed spacer1 of the nuclear small-subunit ribosomal RNA genes was performed on extracts from formalin-fixed and paraffin wax-embedded sections of cerebrum. Nucleotide sequence analysis of the amplified fragment identified the fungal agent as C. bantiana. This is the first report of cerebral phaeohyphomycosis attributable to C. bantiana in a camelid. Ó 2011 Elsevier Ltd. All rights reserved. Keywords: alpaca; cerebral phaeohyphomycosis; Cladophialophora bantiana
Phaeohyphomycosis designates uncommon, opportunistic infections caused by dematiaceous fungi that are defined by their melanin-containing cell walls. Infections by dematiaceous fungi occur worldwide and are reported to cause a wide range of clinical conditions, including cutaneous or subcutaneous granulomas, disseminated infections and localized cerebral granulomas or abscesses (Salfelder, 1990; Revankar et al., 2004; Coldrick et al., 2007) in amphibians, reptiles, birds, fish, man and domestic animals. Cladophialophora bantiana is a highly neurotropic, dematiaceous fungus that accounts for most of the reported cases of cerebral phaeohyphomycosis in man, dogs and cats (Revankar et al., 2004; Grooters and Foil, 2006). The present report describes an alpaca with cerebral phaeohyphomycosis caused by infection with C. bantiana. Correspondence to: C. Frank (e-mail: [email protected]). 0021-9975/$ - see front matter doi:10.1016/j.jcpa.2011.02.003
An 8-year-old, intact male Huacaya alpaca (Vicugna pacos) was found dead at pasture and submitted to the Animal Disease Diagnostic Laboratory at Purdue University for necropsy examination. The alpaca was purchased 2 months prior to its death from a breeder in Ohio and had reportedly never travelled outside of Indiana and Ohio. The animal was housed with 40 other alpacas that were clinically normal at the time of submission. On initial examination, the alpaca was in good bodily condition. Gross lesions were limited to the cerebrum, which had a 2 2.5 5 cm, well-demarcated, firm, mottled, pale grey to brown-red mass with a granular texture, dorsal to the corpus callosum and extending from the level of the post-cruciate gyrus caudally to the level of the occipital lobe (Fig. 1A). On cross section taken at the level of the thalamus, the mass effaced the neuroparenchyma of the left and right cingulate gyri and extended Ó 2011 Elsevier Ltd. All rights reserved.
Cerebral Phaeohyphomycosis in an Alpaca
411
Fig. 1. Cerebral phaeohyphomycosis in an alpaca. (A) Parasagittal section of the brain demonstrating a 2.5 2 cm, fairly well-demarcated, slightly firm, red to grey mass dorsal to the corpus callosum and extending from the level of the post-cruciate gyrus caudally to the level of the occipital lobe (arrows). Bar, 2 cm. (B) Cross section of the left cerebral hemisphere at the level of the thalamus. The mass effaces the neuroparenchyma of the cingulate gyrus and extends into the corona radiata and adjacent gyri (arrows). Bar, 2 cm.
into the corona radiata and neighbouring gyri (Fig. 1B). Selected samples were fixed in 10% neutral buffered formalin, processed routinely and embedded in paraffin wax. Sections (5 mm) were stained with haematoxylin and eosin (HE). Microscopically, granulomatous inflammation extended from the leptomeningeal surface through the cerebral cortical grey matter to the corona radiata. The granulomatous inflammation consisted of discrete aggregates to sheets of epithelioid macrophages with fewer neutrophils and multinucleated giant cells (Fig. 2A). Most fields contained several brown pigmented fungal hyphae that were either extracellular or within the cytoplasm of macrophages. The hyphae were 4e6 mm in diameter and septate, with non-parallel walls and occasional branching (Fig. 2B). Multifocally, cerebral blood vessels were occluded by fibrin thrombi admixed with fungal hyphae. Vessels were also surrounded and infiltrated by neutrophils and mixed mononuclear inflammatory cells. Several foci of liquefactive necrosis were scattered throughout the mass. The overlying leptomeninges were infiltrated by lymphocytes, plasma cells, macrophages and fewer neutrophils. A diagnosis of necrotizing and granulomatous meningoencephalitis with intralesional pigmented fungal hyphae was made. No significant microscopical lesions were observed in other tissues examined. The fungal agent was identified as C. bantiana by polymerase chain reaction (PCR)-based amplification of the fungal DNA followed by subsequent nucleotide sequence analysis of the amplified products. DNA from five sections (10 mm) of the formalin-fixed and paraffin wax-embedded cerebrum was extracted using
a commercial kit (DNeasy Tissue Kit; Qiagen, Valencia, California, USA) according to the manufacturer’s instructions. A previously described PCR assay (Lau et al., 2007) was performed on the extracted DNA to amplify the internal transcribed spacer-1 (ITS1) region of the ribosomal RNA gene cluster of all fungal agents. The amplified DNA fragment was cloned into pGEM-T vector (Promega, Madison, Wisconsin, USA) and three separate clones were used to determine the nucleotide sequences of the cloned DNA fragments. All of the cloned DNA fragments had an identical size of 278 base pairs (Fig. 3). A BLAST search of all available databases at the National Center for Biotechnology Information (http://www.ncbi.nlm. nih.gov) revealed that the amplified product was 98e100% identical to the corresponding sequences of different strains of C. bantiana (Date not shown; accession numbers GQ258793, AB091211, AF131079, AF397182, EU103989, EU103990, EU103991, AY857513, AY857514, EU103992, EU103993, EU103994, AY857515, AY857516, AY857517). Dematiaceous fungi are ubiquitous, saprophytic organisms, defined by their melanin-containing cell walls. Infections by this group of fungi are uncommon and opportunistic and cause three distinct syndromes: chromoblastomycosis, eumycotic mycetoma and phaeohyphomycosis (Salfelder, 1990; Abramo et al., 2002; Grooters and Foil, 2006). In the host tissue the gross and microscopical characteristics of the pigmented fungi are used to differentiate these syndromes. Typically, chromoblastomycosis is characterized by the formation of spherically shaped, thick, dark-walled yeast-like cells (sclerotic bodies), while eumycotic mycetoma forms macroscopic black ‘grains’ composed of entangled masses of pigmented hyphae and
412
C. Frank et al.
Fig. 3. Amplification of fungal DNA by PCR targeting the internal transcribed spacer-1 of nuclear small-subunit ribosomal RNA. The PCR amplicons were separated on a 1% agarose gel. Lane 1, molecular size marker; Lane 2, PCR product from DNA template extracted from brain of another alpaca with no fungal infection; Lane 3, PCR product from DNA template extracted from cerebrum of the affected alpaca; Lane 4, PCR product from no-template control. Numbers at the left indicate the DNA ladder fragment sizes in base pairs (bp). Amplified DNA fragments were 278 bp.
Fig. 2. Photomicrographs of the cerebral granuloma. (A) Sheets of epithelioid macrophages, multinucleated giant cells and rare neutrophils surround intracellular and extracellular pigmented fungal hyphae (arrows). HE. Bar, 25 mm. (B) Brown hyphae, 4e6 mm in diameter and septate with non-parallel walls. HE. Bar, 10 mm.
phaeohyphomycosis produces septate mycelial elements (Salfelder, 1990; Abramo et al., 2002; Grooters and Foil, 2006). Cerebral phaeohyphomycosis has been attributed to 24 fungal organisms (Revankar et al., 2004). Of these fungal species, C. bantiana, Exophiala dermatitidis, Ramichloridium mackenziei and Ochroconis gallopavum are considered to be primarily neurotropic, with C. bantiana accounting for up to 48% of human cases of cerebral phaeohyphomycosis and most cases in dogs and
domestic cats (Revankar et al., 2004; Surash et al., 2005; Grooters and Foil, 2006). C. bantiana is an inhabitant of soil and decomposing plant material, predominately in tropical and subtropical regions of the world (Coldrick et al., 2007). In this case there was no reported history of travel outside of Indiana or Ohio; therefore, the distribution of the fungus is likely more widespread than previously thought. The route of exposure leading to central nervous system infections in most cases is unclear. However, inhalation or contamination of cutaneous wounds followed by haematogenous spread to the brain is the most recognized hypothesis (Elies et al., 2003; Revankar et al., 2004). In this case there was no gross or microscopical evidence of mycotic infection in any non-neural tissues, including cutaneous or pulmonary samples. Therefore, the route of exposure and thus cerebral infection is undetermined. The melanin pigment of this and other dematiaceous fungi is believed to contribute to the organism’s ability to elude host immune responses. This is thought to be achieved through blocking the effects of hydrolytic enzymes on the cell wall and scavenging free radicals released by phagocytic cells during the oxidative burst (Nosanchuk and Casadevall, 2003; Revankar et al., 2004). These immune-modulating functions of melanin may help explain the relatively high proportion of cases of C. bantiana-induced cerebral phaeohyphomycosis in
Cerebral Phaeohyphomycosis in an Alpaca
immunocompetent people and cats (Elies et al., 2003; Revankar et al., 2004). The immune status of the alpaca in this case is uncertain; however, there was no history of previous or concurrent clinical disease or histological evidence of immunosuppression. The diagnosis of phaeohyphomycosis relies on the histological identification of pigmented fungal hyphae within inflamed tissues. However, the microscopical appearance of the different species of dematiaceous fungi that cause phaeohyphomycosis is similar; therefore, culture or molecular diagnostics are required to identify the fungus definitively. In this case the identity of the fungal agent as C. bantiana was confirmed by PCR and sequencing. To the best of our knowledge, the current case is the first report of cerebral phaeohyphomycosis attributable to C. bantiana in an even-toed ungulate. Therefore, C. bantiana should be considered in the differential diagnosis for neurological dysfunction or sudden death in camelids and, potentially, ruminant species outside the typical geographical locations.
Acknowledgments The authors thank Dr. P. Miller, Department of Veterinary Pathobiology, Purdue University, for editing and revisions of the manuscript. The authors would also like to thank the histology laboratory of the Purdue University Animal Disease Diagnostic Laboratory for performing histological procedures.
Coldrick O, Brannon CL, Kydd DM, Pierce-Roberts G, Borman AM et al. (2007) Fungal pyelonephritis due to Cladophialophora bantiana in a cat. Veterinary Record, 161, 724e728. Elies L, Balandraud V, Boulouha L, Crespeau F, Guillot J (2003) Fatal systemic phaeohyphomycosis in a cat due to Cladophialophora bantiana. Journal of Veterinary Medicine A, 50, 50e53. Grooters AM, Foil CS (2006) Miscellaneous fungal infections. In: Infectious Diseases of the Dog and Cat, 3rd Edit., CE Greene, Ed., Elsevier, Missouri, pp. 647e650. Lau A, Chen S, Sorrell T, Carter D, Malik R et al. (2007) Development and clinical application of a panfungal PCR assay to detect and identify fungal DNA in tissue specimens. Journal of Clinical Microbiology, 45, 380e385. Nosanchuk JD, Casadevall A (2003) The contribution of melanin to microbial pathogenesis. Cellular Microbiology, 5, 203e223. Revankar SG, Sutton DA, Rinaldi MG (2004) Primary central nervous system phaeohyphomycosis: a review of 101 cases. Clinical Infectious Diseases, 38, 206e216. Salfelder K (1990) Phaeohyphomycosis. In: Atlas of Fungal Pathology, K Salfelder, TR de Liscano, E Sauerteig, Eds., Kluwer Academic Publishers, London, pp. 56e59. Surash S, Tyagi A, De Hoog DE, Zeng JS, Barton RC et al. (2005) Cerebral phaeohyphomycosis caused by Fonsecaea monophora. Medical Mycology, 43, 465e472.
References Abramo F, Bastelli F, Nardoni S, Mancianti F (2002) Feline cutaneous phaeohyphomycosis due to Cladophyalophora bantiana. Journal of Feline Medicine and Surgery, 4, 157e163.
413
January 2nd, 2011 ½ Received, Accepted, February 27th, 2011
Available online at www.sciencedirect.com
www.elsevier.com/locate/jcpa
DISEASE IN WILDLIFE OR EXOTIC SPECIES
Cerebral Phaeohyphomycosis due to Cladophialophora bantiana in a Huacaya Alpaca (Vicugna pacos) C. Frank, R. Vemulapalli and T. Lin Animal Disease Diagnostic Laboratory and Department of Comparative Pathobiology, Purdue University, West Lafayette, IN 47907, USA
Summary Cerebral phaeohyphomycosis, caused by Cladophialophora bantiana, was diagnosed in a Huacaya alpaca (Vicugna pacos). An 8-year-old, intact male Huacaya alpaca from a farm in Indiana was found dead at pasture and submitted to the Animal Disease Diagnostic Laboratory at Purdue University for necropsy examination. Gross lesions were limited to the cerebrum, which had a 2 2.5 5 cm, well-demarcated, firm, mottled, pale grey to brown-red mass with a granular texture, centered on the left and right cingulate gyri. Microscopically, granulomatous and necrotizing meningoencephalitis with intralesional pigmented fungal hyphae effaced the cerebral grey and white matter of the cingulate gyri. The hyphae were 4e6 mm in diameter and septate, with non-parallel walls and occasional branching. Polymerase chain reaction for the internal transcribed spacer1 of the nuclear small-subunit ribosomal RNA genes was performed on extracts from formalin-fixed and paraffin wax-embedded sections of cerebrum. Nucleotide sequence analysis of the amplified fragment identified the fungal agent as C. bantiana. This is the first report of cerebral phaeohyphomycosis attributable to C. bantiana in a camelid. Ó 2011 Elsevier Ltd. All rights reserved. Keywords: alpaca; cerebral phaeohyphomycosis; Cladophialophora bantiana
Phaeohyphomycosis designates uncommon, opportunistic infections caused by dematiaceous fungi that are defined by their melanin-containing cell walls. Infections by dematiaceous fungi occur worldwide and are reported to cause a wide range of clinical conditions, including cutaneous or subcutaneous granulomas, disseminated infections and localized cerebral granulomas or abscesses (Salfelder, 1990; Revankar et al., 2004; Coldrick et al., 2007) in amphibians, reptiles, birds, fish, man and domestic animals. Cladophialophora bantiana is a highly neurotropic, dematiaceous fungus that accounts for most of the reported cases of cerebral phaeohyphomycosis in man, dogs and cats (Revankar et al., 2004; Grooters and Foil, 2006). The present report describes an alpaca with cerebral phaeohyphomycosis caused by infection with C. bantiana. Correspondence to: C. Frank (e-mail: [email protected]). 0021-9975/$ - see front matter doi:10.1016/j.jcpa.2011.02.003
An 8-year-old, intact male Huacaya alpaca (Vicugna pacos) was found dead at pasture and submitted to the Animal Disease Diagnostic Laboratory at Purdue University for necropsy examination. The alpaca was purchased 2 months prior to its death from a breeder in Ohio and had reportedly never travelled outside of Indiana and Ohio. The animal was housed with 40 other alpacas that were clinically normal at the time of submission. On initial examination, the alpaca was in good bodily condition. Gross lesions were limited to the cerebrum, which had a 2 2.5 5 cm, well-demarcated, firm, mottled, pale grey to brown-red mass with a granular texture, dorsal to the corpus callosum and extending from the level of the post-cruciate gyrus caudally to the level of the occipital lobe (Fig. 1A). On cross section taken at the level of the thalamus, the mass effaced the neuroparenchyma of the left and right cingulate gyri and extended Ó 2011 Elsevier Ltd. All rights reserved.
Cerebral Phaeohyphomycosis in an Alpaca
411
Fig. 1. Cerebral phaeohyphomycosis in an alpaca. (A) Parasagittal section of the brain demonstrating a 2.5 2 cm, fairly well-demarcated, slightly firm, red to grey mass dorsal to the corpus callosum and extending from the level of the post-cruciate gyrus caudally to the level of the occipital lobe (arrows). Bar, 2 cm. (B) Cross section of the left cerebral hemisphere at the level of the thalamus. The mass effaces the neuroparenchyma of the cingulate gyrus and extends into the corona radiata and adjacent gyri (arrows). Bar, 2 cm.
into the corona radiata and neighbouring gyri (Fig. 1B). Selected samples were fixed in 10% neutral buffered formalin, processed routinely and embedded in paraffin wax. Sections (5 mm) were stained with haematoxylin and eosin (HE). Microscopically, granulomatous inflammation extended from the leptomeningeal surface through the cerebral cortical grey matter to the corona radiata. The granulomatous inflammation consisted of discrete aggregates to sheets of epithelioid macrophages with fewer neutrophils and multinucleated giant cells (Fig. 2A). Most fields contained several brown pigmented fungal hyphae that were either extracellular or within the cytoplasm of macrophages. The hyphae were 4e6 mm in diameter and septate, with non-parallel walls and occasional branching (Fig. 2B). Multifocally, cerebral blood vessels were occluded by fibrin thrombi admixed with fungal hyphae. Vessels were also surrounded and infiltrated by neutrophils and mixed mononuclear inflammatory cells. Several foci of liquefactive necrosis were scattered throughout the mass. The overlying leptomeninges were infiltrated by lymphocytes, plasma cells, macrophages and fewer neutrophils. A diagnosis of necrotizing and granulomatous meningoencephalitis with intralesional pigmented fungal hyphae was made. No significant microscopical lesions were observed in other tissues examined. The fungal agent was identified as C. bantiana by polymerase chain reaction (PCR)-based amplification of the fungal DNA followed by subsequent nucleotide sequence analysis of the amplified products. DNA from five sections (10 mm) of the formalin-fixed and paraffin wax-embedded cerebrum was extracted using
a commercial kit (DNeasy Tissue Kit; Qiagen, Valencia, California, USA) according to the manufacturer’s instructions. A previously described PCR assay (Lau et al., 2007) was performed on the extracted DNA to amplify the internal transcribed spacer-1 (ITS1) region of the ribosomal RNA gene cluster of all fungal agents. The amplified DNA fragment was cloned into pGEM-T vector (Promega, Madison, Wisconsin, USA) and three separate clones were used to determine the nucleotide sequences of the cloned DNA fragments. All of the cloned DNA fragments had an identical size of 278 base pairs (Fig. 3). A BLAST search of all available databases at the National Center for Biotechnology Information (http://www.ncbi.nlm. nih.gov) revealed that the amplified product was 98e100% identical to the corresponding sequences of different strains of C. bantiana (Date not shown; accession numbers GQ258793, AB091211, AF131079, AF397182, EU103989, EU103990, EU103991, AY857513, AY857514, EU103992, EU103993, EU103994, AY857515, AY857516, AY857517). Dematiaceous fungi are ubiquitous, saprophytic organisms, defined by their melanin-containing cell walls. Infections by this group of fungi are uncommon and opportunistic and cause three distinct syndromes: chromoblastomycosis, eumycotic mycetoma and phaeohyphomycosis (Salfelder, 1990; Abramo et al., 2002; Grooters and Foil, 2006). In the host tissue the gross and microscopical characteristics of the pigmented fungi are used to differentiate these syndromes. Typically, chromoblastomycosis is characterized by the formation of spherically shaped, thick, dark-walled yeast-like cells (sclerotic bodies), while eumycotic mycetoma forms macroscopic black ‘grains’ composed of entangled masses of pigmented hyphae and
412
C. Frank et al.
Fig. 3. Amplification of fungal DNA by PCR targeting the internal transcribed spacer-1 of nuclear small-subunit ribosomal RNA. The PCR amplicons were separated on a 1% agarose gel. Lane 1, molecular size marker; Lane 2, PCR product from DNA template extracted from brain of another alpaca with no fungal infection; Lane 3, PCR product from DNA template extracted from cerebrum of the affected alpaca; Lane 4, PCR product from no-template control. Numbers at the left indicate the DNA ladder fragment sizes in base pairs (bp). Amplified DNA fragments were 278 bp.
Fig. 2. Photomicrographs of the cerebral granuloma. (A) Sheets of epithelioid macrophages, multinucleated giant cells and rare neutrophils surround intracellular and extracellular pigmented fungal hyphae (arrows). HE. Bar, 25 mm. (B) Brown hyphae, 4e6 mm in diameter and septate with non-parallel walls. HE. Bar, 10 mm.
phaeohyphomycosis produces septate mycelial elements (Salfelder, 1990; Abramo et al., 2002; Grooters and Foil, 2006). Cerebral phaeohyphomycosis has been attributed to 24 fungal organisms (Revankar et al., 2004). Of these fungal species, C. bantiana, Exophiala dermatitidis, Ramichloridium mackenziei and Ochroconis gallopavum are considered to be primarily neurotropic, with C. bantiana accounting for up to 48% of human cases of cerebral phaeohyphomycosis and most cases in dogs and
domestic cats (Revankar et al., 2004; Surash et al., 2005; Grooters and Foil, 2006). C. bantiana is an inhabitant of soil and decomposing plant material, predominately in tropical and subtropical regions of the world (Coldrick et al., 2007). In this case there was no reported history of travel outside of Indiana or Ohio; therefore, the distribution of the fungus is likely more widespread than previously thought. The route of exposure leading to central nervous system infections in most cases is unclear. However, inhalation or contamination of cutaneous wounds followed by haematogenous spread to the brain is the most recognized hypothesis (Elies et al., 2003; Revankar et al., 2004). In this case there was no gross or microscopical evidence of mycotic infection in any non-neural tissues, including cutaneous or pulmonary samples. Therefore, the route of exposure and thus cerebral infection is undetermined. The melanin pigment of this and other dematiaceous fungi is believed to contribute to the organism’s ability to elude host immune responses. This is thought to be achieved through blocking the effects of hydrolytic enzymes on the cell wall and scavenging free radicals released by phagocytic cells during the oxidative burst (Nosanchuk and Casadevall, 2003; Revankar et al., 2004). These immune-modulating functions of melanin may help explain the relatively high proportion of cases of C. bantiana-induced cerebral phaeohyphomycosis in
Cerebral Phaeohyphomycosis in an Alpaca
immunocompetent people and cats (Elies et al., 2003; Revankar et al., 2004). The immune status of the alpaca in this case is uncertain; however, there was no history of previous or concurrent clinical disease or histological evidence of immunosuppression. The diagnosis of phaeohyphomycosis relies on the histological identification of pigmented fungal hyphae within inflamed tissues. However, the microscopical appearance of the different species of dematiaceous fungi that cause phaeohyphomycosis is similar; therefore, culture or molecular diagnostics are required to identify the fungus definitively. In this case the identity of the fungal agent as C. bantiana was confirmed by PCR and sequencing. To the best of our knowledge, the current case is the first report of cerebral phaeohyphomycosis attributable to C. bantiana in an even-toed ungulate. Therefore, C. bantiana should be considered in the differential diagnosis for neurological dysfunction or sudden death in camelids and, potentially, ruminant species outside the typical geographical locations.
Acknowledgments The authors thank Dr. P. Miller, Department of Veterinary Pathobiology, Purdue University, for editing and revisions of the manuscript. The authors would also like to thank the histology laboratory of the Purdue University Animal Disease Diagnostic Laboratory for performing histological procedures.
Coldrick O, Brannon CL, Kydd DM, Pierce-Roberts G, Borman AM et al. (2007) Fungal pyelonephritis due to Cladophialophora bantiana in a cat. Veterinary Record, 161, 724e728. Elies L, Balandraud V, Boulouha L, Crespeau F, Guillot J (2003) Fatal systemic phaeohyphomycosis in a cat due to Cladophialophora bantiana. Journal of Veterinary Medicine A, 50, 50e53. Grooters AM, Foil CS (2006) Miscellaneous fungal infections. In: Infectious Diseases of the Dog and Cat, 3rd Edit., CE Greene, Ed., Elsevier, Missouri, pp. 647e650. Lau A, Chen S, Sorrell T, Carter D, Malik R et al. (2007) Development and clinical application of a panfungal PCR assay to detect and identify fungal DNA in tissue specimens. Journal of Clinical Microbiology, 45, 380e385. Nosanchuk JD, Casadevall A (2003) The contribution of melanin to microbial pathogenesis. Cellular Microbiology, 5, 203e223. Revankar SG, Sutton DA, Rinaldi MG (2004) Primary central nervous system phaeohyphomycosis: a review of 101 cases. Clinical Infectious Diseases, 38, 206e216. Salfelder K (1990) Phaeohyphomycosis. In: Atlas of Fungal Pathology, K Salfelder, TR de Liscano, E Sauerteig, Eds., Kluwer Academic Publishers, London, pp. 56e59. Surash S, Tyagi A, De Hoog DE, Zeng JS, Barton RC et al. (2005) Cerebral phaeohyphomycosis caused by Fonsecaea monophora. Medical Mycology, 43, 465e472.
References Abramo F, Bastelli F, Nardoni S, Mancianti F (2002) Feline cutaneous phaeohyphomycosis due to Cladophyalophora bantiana. Journal of Feline Medicine and Surgery, 4, 157e163.
413
January 2nd, 2011 ½ Received, Accepted, February 27th, 2011