Signalment:  

4-year-old female rhesus macaque, Macaca mulatta, nonhuman primate.A week before necropsy, the animal received intravenous antibiotic therapy (Cefazolin) following surgical placement of hormonal implants as part of a research protocol. A day before necropsy, the animal was lethargic and was reported to be sitting with head tucked under hind limbs and with loss of appetite. On the day of necropsy, abdominal bloating was noted.

The animal was azotemic and hypoglycemic with marked leukopenia and metabolic alkalosis. The animal had not responded to fluid therapy and was euthanized. Candida albicans was isolated from the stomach contents at necropsy.

Gross Description:  

The abdomen was distended and doughy. On opening the abdominal cavity, severe bloating and distension of stomach was noted. The stomach contained about 200 g of partially digested feed material admixed with blood. The mucosa of the esophagus was multifocally ulcerated, thickened with multifocal areas of hemorrhage. The mucosa of the stomach was multifocally ulcerated and hemorrhagic.

Histopathologic Description:

The stratified squamous epithelium of the esophagus is multifocally necrotic and ulcerated. There is a focally extensive suppurative focus characterized by the presence of large numbers of viable and degenerate neutrophils disrupting the mucosa, submucosa and extending into muscular tunics and serosal layer. Overlaying and infiltrating the necrotic mucosa are aggregates of numerous oval to round, 3-6 μm diameter, pale staining, thin-walled yeast; blastoconidia arranged in short chains (pseudohyphae); and slender, 3-4 μm wide, septate, parallel-walled, hyphae that often show acute angle branching. Multifocally, the collagen fibers in the submucosa are disrupted by edema and the walls of medium and small sized blood vessels are necrotic and infiltrated by neutrophils.

Morphologic Diagnosis:  

Esophagus: Esophagitis, necrosuppurative, ulcerative, transmural with vasculitis, intralesional mycelia and yeasts consistent with Candida albicans.

Lab Results:  

Reference Range
RBC	6.37 X106/mm3	5.0 - 6.5 X 106/mm3
WBC	2.8 X103/mm3	6.0 - 15.0 X103/mm3
Lymphocytes	19%	25.0 - 60 %
Monocytes	1%	0 8 %
Eosinophils	0%	0.0 - 5.0 %
pH	7.304	>7.40
Sodium	150 mmol/L	141-153 mmol/L
Potassium	3.0mmol/L	2.9-4.1 mmol/L
Blood Urea Nitrogen	82mg/dl	16-27 mg/dl
Glucose	34 mg/dl	39-82 mg/dl

Condition:  

Candida albicans

Contributor Comment:  

Candida albicans is a normal inhabitant of the nasopharynx, GI tract, and reproductive tract of many species of animals and is opportunistic in causing disease.(2) Predisposing factors include disruption of mucosal integrity, indwelling intravenous or urinary catheters, administration of antibiotics or immunosuppressive drugs and diseases. Activation of virulence factors play a major role in dissemination and colonization in systemic Candida infections.(1)

This animal received multiple intravenous antibiotics following surgical implantation of hormonal depots. The gastritis lesions were chronic and the esophageal lesions are attributed to acid reflux and subsequent colonization by Candida albicans. In rhesus monkeys infected with simian immunodeficiency virus (SIV), candidiasis is a common opportunistic infection; however, this animal has not been infected with SIV. Also, nonhuman primates are an excellent animal model for studying oral candidiasis.(8,9)

Systemic and cutaneous candidiasis has also been described in cattle, calves, sheep, and foals secondary to prolonged antibiotic or corticosteroid therapy.(4) In cats, candidiasis is rare but has been associated with oral and upper respiratory disease, pyothorax, ocular lesions, intestinal disease, and urocystitis. In dogs, C. albicans is reported to cause stomatitis, spondylitis, endophthalmitis and purulent pericarditis.(3,5,6,7)

Candida spp. has been considered a cause of arthritis in horses and mastitis and abortion in cattle. In birds, the infection causes stomatitis, esophagitis and ingluvitis. In piglets, the infection causes stomatitis, esophagitis and gastritis.(1) In horses, C. albicans causes ulcerative gastritis adjacent to margo plicatus.(1)

Candida spp. are pleomorphic, with both yeast and mycelia phases present in tissue. The differential diagnoses include: Aspergillus species., which form septate hyphae with dichotomous branching and bears conidiospores; Zycomycetes species, which form nonseptate, branching hyphae with bulbous enlargement; Histoplasma capsulatum, which are intrahistiocytic yeast; and Blastomyces dermatitidis, which are 7-17 μm large yeast with broad- based budding.

JPC Diagnosis:  

Esophagus: Esophagitis, ulcerative and neutrophilic, with moderate numbers of extracellular yeast and pseudohyphae.

Conference Comment:  

Conference participants discussed the distinguishing morphologic features of Candida albicans, a trimorphic fungus that is one of only three species of Candida, along with C. tropicalis and C. dubliniensis, that occur in three vegetative morphologies: yeast, pseudohyphae, and hyphae. The yeast form, also called blastoconidia or blastospores, are oval, single-celled structures; hyphae and pseudohyphae are filamentous multicellular structures in which elongated cells are attached end-to-end. Psuedohyphae can be differentiated from true hyphae by the following characteristics: Pseudohyphal cell walls are not parallel; rather, they are wider at their center and narrower at their ends, with constrictions at cell junctions. Hyphal cells, on the other hand, have parallel walls, and are more uniform in width, with true septa (internal cross walls that divide the cells). Additionally, true hyphal cells have pores in their septa, allowing for cell-to-cell communication. Although pseudohyphae appear more similar to hyphae microscopically, they are actually more closely related to the yeast form, and thus can be thought of as an intermediate between yeast and true hyphae composed of strings of attached, elongated yeast cells.(10)

Pathogenicity of fungal organisms is related to their morphology. In Candida albicans, the single-cell yeast form is thought to be evolutionarily adapted for colonization of mucosal cell surfaces and allows for rapid dissemination via the bloodstream in systemic infections; pseudohyphae are associated with increased virulence properties and enhanced nutrient scavenging; and the formation of hyphae is an important virulence factor which allows the fungus to invade epithelial and endothelial cells and lyse macrophages and neutrophils. The necessity of hyphal formation for pathogenicity is demonstrated by the significant attenuation of virulence in C. albicans cells lacking the filament-induced gene HGC1, which drives hyphal development. In addition, several other hyphalspecific genes are also important for pathogenicity. ALS3 and HWP1 encode adhesins, which allow C. albicans to leave the circulation, colonize tissue, and form a biofilm. Degredative enzymes such as aspartyl proteinase (SAP) contribute to tissue invasion. SOD5, which encodes a superoxide dismutase that protects against oxidative stress, is also induced during hyphal growth. HYR, another hypha-specific gene, plays a role in neutrophil killing. Thus, the ability of C. albicans to form hyphae contributes to their increased virulence compared to other Candida species that only form yeast and pseudohyphae.(10)

References:

1. Brown CC, Baker DC, Barker LK. Alimentary system. In: Jubb KVF, Kennedy PC, Palmer N, eds. Pathology of Domestic Animals, 5th ed. Edinburgh, Scotland: Saunders Elsevier; 2007:1-106.
2. Brown MR, Thompson CA, Mohamed F. Systemic candidiasis in an apparently immunocompetent dog. J. Vet. Invest. 2005;17:272-276.
3. Jadahav VJ, Pal M. Canine mycotic stomatitis due to Candida albicans. Rev Iberoam Micol. 2006;23:233-234.
4. Jones T, Hunt R, King N. Veterinary Pathology. 6th ed. Baltimore, MD: Williams and Wilkins; 1997:528-529.
5. Kuwamura M, Ide M, Yamate J, Shiraishi Y, Kotani T. Systemic candidiasis in a dog, developing spondylitis. J. Vet. Med. Sci. 2006;68(10):1117-1119.
6. Linek J. Mycotic endophthalmitis in a dog caused by Candida albicans. Vet. Ophthal. 2004;7:159-162.
7. Mohri T, Takashima K, Yamane T, Sato H, Yamane Y. Purulent pericarditis in a dog administered immune suppressing drugs. J. Vet. Med. Sci. 2009;71:669-672.
8. Osborn KG, Prahalada S, Lowenstein LJ, Gardner MB, Maul, DH, Henrickson RV. The pathology of an epizootic of acquired immunodeficiency in rhesus macaques. American Journal of Pathology. 1984;114 (1):94-103.
9. Samaranayake Y, Samaranayake LP. Experimental oral candidiasis in animal models. Clini. Microbio. Rev. 2001;14:398-429.
10. Thompson DS, Carlisle PL, Kadosh D. Coevolution of morphology and virulence in Candida species. Eukaryotic Cell. 2011;10(9):1173-1182.

Click the slide to view.

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1-1. Esophagus

1-2. Esophagus

1-3. Esophagus

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