CHAPTER 67 Respiratory Fungal Infections
Fungi are eukaryotic organisms with a cell wall made up of chitins, glucans, and mannans. The plasma membrane contains ergosterol, a sterol that is targeted by several antifungal drugs. Fungal infections in horses are relatively uncommon, although geographic prevalence is highly variable. Mycotic granulomas have been found in nasal passages, nasopharynx, paranasal sinuses, guttural pouches, the trachea, bronchioles, lungs, and mediastinum of infected horses. Upper respiratory tract disease caused by fungi is frequently acquired via the inhalation route. Systemic fungal infections and some cases of fungal pneumonia are of hematogenous origin, arising through a compromised gastrointestinal tract or via open wounds.
In most instances of mycosis involving the upper respiratory tract in horses, there are no obvious predisposing causes. Conidiobolus coronatus, Cryptococcus neoformans, Blastomyces dermatitidis, Histoplasma capsulatum, and Coccidioides immitis are considered primary pathogenic fungi and usually infect immunologically normal horses. Opportunistic fungi, including Pneumocystis carinii, Aspergillus spp., Candida spp., Fusarium spp., and Emmonsia crescens, have caused fungal disease in horses that are immunocompromised or have severe concurrent disease.
Horses with discrete or diffuse pulmonary fungal granulomas or fungal pleuropneumonia can have clinical signs similar to those of bacterial pneumonia. Coughing, nasal discharge, tachypnea, respiratory distress, and hemoptysis may be observed, along with weight loss if the condition is chronic. The radiographic appearance of fungal pneumonia can be variable, with patchy bronchopneumonia or miliary patterns being most common. Differential diagnoses include bacterial pneumonia, recurrent airway obstructive disease, silicosis, granulomatous disease complex, or neoplasia. Fungal infections can affect multiple organ systems and body cavities. Weight loss, colic, or diarrhea can often develop when there is a fungal infection within the abdominal cavity.
Fungal organisms such as C. coronatus, C. neoformans, and C. immitis form granulomatous masslike lesions in the upper respiratory tract, whereas Aspergillus organisms tend to form mycotic plaques. The most common clinical signs of fungal infection in the upper respiratory tract include unilateral or bilateral serosanguinous or mucopurulent nasal discharge and inspiratory or expiratory noise. Other clinical signs include facial deformation, coughing, and respiratory distress caused by partial blockage of nasal passages by granulomatous masses. Differential diagnoses for mycotic granulomas of the respiratory tract include squamous cell carcinoma, ethmoidal hematoma, amyloidosis, and exuberant granulation tissue.
Horses with guttural pouch mycosis usually have episodic serosanguinous nasal discharge that may progress to potentially fatal epistaxis because the fungal plaques are frequently located over an artery (see Chapter 53, Disorders of the Guttural Pouch). Horses may also have cranial nerve abnormalities. The duration of clinical signs can range from days to many months.
Fungal pneumonia can be diagnosed on the basis of samples obtained by tracheal wash, bronchoalveolar lavage, or lung biopsy. Lung biopsy is associated with significant risk if a pulmonary vessel is accidentally cut. Ideally biopsy should be performed after radiographic evaluation or with concurrent ultrasound guidance, and the specimen should be obtained from the periphery of the lung; however, fatal hemorrhage has resulted from inadvertent biopsy of a vessel only 2 cm from the periphery. The lung is rich in plasminogen, so bleeding complications can be severe. Spring-loaded biopsy needles are safer for lung biopsy than Tru-Cut biopsy instruments. Ultrasound evaluation can be used to monitor the site for bleeding after the procedure.
Endoscopic examination can be used to observe directly lesions in the nasal passages, nasopharynx, guttural pouches, trachea, and bronchioles, whereas masses in para-nasal sinuses and lungs can be observed radiographically. Computed tomography or magnetic resonance imaging can be used to determine the extent of lesions and bony invasion in the skull. A sterile rigid arthroscope or flexible endoscope can be passed into the conchal or maxillary sinus via a hole drilled with an 8- to 20-mm trephine for direct viewing of lesions and to obtain biopsy specimens.
Large biopsy specimens for cytologic analysis, histologic analysis, and microbial culture can be obtained from the nasal passages or nasopharynx by use of a uterine biopsy instrument passed nasally with visual guidance from a flexible endoscope. Excisional biopsy or surgical debulking may be performed through a sinus flap or via laryngotomy.
Fungal hyphae can be identified in airway fluid or in impression smears obtained from a biopsy sample of the suspected fungal mass. Fungal hyphae, such as the nonpathogenic barn fungus Alternaria, are often found either free or inside large mononuclear cells in tracheal aspirates from healthy horses. Clinicians must be careful in attributing significance to the presence of fungal elements in tracheal aspirates, especially when cellular cytology is normal. In horses with fungal pneumonia, aspirates may contain predominantly neutrophils that often are degenerate and may contain fungal hyphae. Some fungi have characteristic morphologic features that can yield an early presumptive identification.
For identification of fungal hyphae on histologic sections, slides are best stained with periodic acid Schiff stain, Gridley fungus stain, and Grocott-Gomori methenamine-silver nitrate. Immunohistochemistry, fluorescent in situ hybridization, and DNA probes can be used to detect fungal organisms in histologic sections.
Some fungi have fastidious growth requirements in culture. They may be outcompeted by contaminant bacteria and may take up to several weeks to grow on culture media. For transport of tissue for microbiologic culture, the sample should be placed in a prepared culture medium and transported at room temperature. Specific culture media such as Sabouraud’s dextrose agar, inhibitory mold agar containing cycloheximide, and chloramphenicol are useful. A pan-fungal real-time polymerase chain reaction (PCR) assay can be used to detect a variety of fungal organisms in body fluids and fungal isolates and can be followed by species-specific real-time PCR to identify the organism.