Chapter 36 Antifungal Drugs
Introduction
Indigenous Fungal Organisms
The gastrointestinal (GI) tract is readily colonized by small numbers of fungal organisms that become part of the indigenous microflora, maintain stable populations, and may even contribute to the nutrient economy of the host. Many of these organisms are undetectable by routine microbiology standards. With the advent of molecular fingerprinting techniques, the role of these organisms in the health of the mammalian host is becoming more readily apparent (see Chapter 2).
Opportunists
Most fungal species, whether transitory or part of the permanent habitat of the gut, appear to be of low pathogenicity. Given appropriate circumstances, however, commensal organisms may become pathogenic to the host. Inflammatory bowel disease, for example, is accompanied by an increase in the number and type of fungal organisms found in the GI tract, although it is still unknown whether this is cause or effect. Candida spp. are dimorphic fungi that are normal inhabitants of the GI tract, but they too can become opportunistic infections in some patients.1 Other opportunistic organisms are sometimes isolated from immunosuppressed patients. Reported opportunists are typically from the Zygomycetes class (zygomycosis), and include members of the Entomophthoraceae (e.g., Basidiobolus spp., Conidiobolus spp.) and Mucoraceae (e.g., Absidia spp., Rhizopus spp., Mucor spp., and Mortierella spp.).1
Pathogenic Fungal Infection of the Gastrointestinal Tract
Histoplasma capsulatum
Etiology
Histoplasmosis is a systemic fungal disease of dogs and cats caused by H. capsulatum. In the environment, H. capsulatum organisms are mycelial, saprophytic soil fungi. In infected tissue or when cultured at 30°C to 37°C (86°F to 98.6°F), the organism is a yeast. The fungus is endemic throughout most of the temperate and subtropical regions of the world. Most cases of histoplasmosis in the United States occur in the central states, with the geographic distribution following the Mississippi, Ohio, and Missouri Rivers.2,3
Pathophysiology
Infection is probably via inhalation or ingestion of infective conidia from the environment. The respiratory system is thought to be the primary route of infection in cats and dogs, although the GI tract may also be an important route in the dog. After inhalation or ingestion, conidia transform from the mycelial phase and are phagocytized by macrophages, where they grow as facultative intracellular organisms. Hematogenous and lymphatic dissemination results in multisystemic disease. Organisms can be disseminated to any organ system, but the lungs, gastrointestinal tract, lymph nodes, liver, spleen, bone marrow, eyes, and adrenal glands are the most common organs of dissemination in the dogs; lungs, liver, lymph nodes, eyes, and bone marrow are most commonly affected in cats. Cell-mediated immunity induces a granulomatous inflammatory response in most infections.4
Diagnosis
Organism identification is required for definitive diagnosis. The most common means of organism identification is cytology. Cytology from affected tissue reveals pyogranulomatous inflammation, often with numerous small, round to oval intracellular yeast cells (2 to 4 µm in diameter) characterized by a basophilic center and a light halo. Exfoliative cytology during colonoscopy (or upper GI endoscopy) is considered useful in diagnosing the disease.5 Histopathology is helpful if cytology is nondiagnostic or inconclusive. Multiple endoscopic colonic biopsies are usually sufficient to diagnose the disease. The yeast form does not stain well with routine hematoxylin and eosin stains, periodic acid-Schiff and Gomori methenamine silver stain are often used. Fungal culture from affected tissue can be used for diagnosis, but is rarely needed in clinical cases. Currently available serologic tests have poor specificity and sensitivity.4
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