Eucoleus aerophilus respiratory infection in a dog with Addison’s disease

Abstract

A 4-year-old, standard poodle was presented to the Ontario Veterinary College for a 3-week history of a moist, productive cough that was first noted while boarding at a kennel. Bronchoalveolar lavage revealed numerous ova identified as Eucoleus aerophilus, previously known as Capillaria aerophila. Clinical signs resolved following treatment with fenbendazole.

A 4-year-old, spayed female, standard poodle was presented to the Ontario Veterinary College, Veterinary Teaching Hospital (OVC-VTH) in October 2006 for evaluation of a moist, productive cough, which was first noted during a 3-week stay at a boarding kennel, 4 to 6 wk prior to presentation. Physical examination by the referring veterinarian revealed pharyngeal inflammation and increased bronchovesicular sounds, bilaterally. Subsequently, there was no response to antibiotic treatment with amoxicillin/clavulanate, 250 mg, PO, q12h for 14 d, and progressive lethargy and inappetance developed prior to referral. Hypoadrenocorticism had been diagnosed 3 y earlier, and had since been managed with prednisone, 7.5 mg, PO, q24h, and fludrocortisone, 0.7 mg, PO, q24h, therapy. The owner reported the dog had free access to 85 acres of rural property and would frequently burrow in the soil. There was no history of travel, routine vaccinations were current, and heartworm prophylaxis had not been administered the previous year.

Case description

On presentation to the OVC-VTH, the patient was lethargic, but responsive. The dog’s heart rate, respiratory rate, and temperature were within reference intervals (114 beats/min, 26 breaths/min, and 38.3°C, respectively). The mucous membranes were tacky and grey-pink. The dog was estimated to be 5% to 7% dehydrated and was in thin body condition (2.5/5) with generalized muscle wasting. Thoracic auscultation revealed increased bronchovesicular sounds, bilaterally, that were most prominent in the cranioventral lung fields, with no evidence of crackles or wheezes. Expiratory effort was increased at rest. The heart sounds were mildly muffled on cardiac auscultation. The haircoat was dull with generalized scaling.

Results from initial blood gas and electrolyte analyses demonstrated mild hyponatremia (sodium 134 mmol/L; reference interval [RI], 140 to 154 mmol/L), hyperkalemia (potassium 6.5 mmol/L; RI, 3.8 to 5.4 mmol/L), and moderate to severe metabolic acidosis (pH 7.27, HCO₃ 13.8 mmol/L, base excess — 11.2). The sodium:potassium (Na:K) ratio was decreased at 21 (RI, 27 to 40). Electrolyte abnormalities were attributed to inadequate control of the previously diagnosed hypoadrenocorticism, most likely secondary to concurrent illness. Results from a complete blood (cell) count (CBC) revealed mild leukocytosis (18 × 10⁹/L; RI, 6.0 to 17 × 10⁹/L) composed of a mature neutrophila (14.6 × 10⁹/L; RI, 3.0 to 11.5 × 10⁹/L) and monocytosis (1.6 × 10⁹/L; RI, 0.2 to 1.4 × 10⁹/L). On serum biochemical profile, mild hyperproteinemia (76 g/L; RI, 54 to 75 g/L), moderately elevated alkaline phosphatase (ALP) activity (511 U/L; RI, 24 to 141 U/L), mildly elevated alanine aminotransferase (ALT) (96 U/L; RI, 5 to 95 U/L), mildly elevated creatinine kinase (CK) enzyme activity (382 U/L; RI, 5 to 235 U/L), and mildly elevated urea (10.2 mmol/L; RI, 3.0 to 10.0 mmol/L) were noted. With the exception of the mildly elevated CK activity, these changes were most consistent with dehydration and previous steroid administration. Thoracic radiographs revealed increased soft tissue opacity in the cranioventral pulmonary fields, which partially to totally silhouetted the pulmonary vessels, creating air bronchograms and lobar signs. Differential diagnoses for the cranioventral alveolar pulmonary pattern included bacterial bronchopneumonia, aspiration pneumonia, parasitic pneumonia, and neoplasia.

The dog was placed under general anesthesia for bronchoscopy and bronchoalveolar lavage (BAL). On bronchoscopy, the trachea and bronchi were diffusely erythemic, and moderate amounts of thick, mucoid material were visualized within the bronchial airways. Mucoid material was collected by BAL and submitted for cytologic examination and aerobic bacterial culture. The nucleated cell count of the fluid was moderately increased at 4.2 × 10⁹/L. Cytological examination of concentrated slide preparations (modified Wright’s stain) revealed copious amounts of mucus in which large numbers of non-lytic neutrophils were entrapped. Eosinophils were also found in low numbers along with occasional macrophages. Numerous extracellular, barrel shaped ova containing bipolar opercula were noted (Figure 1). These ova were identified as Eucoleus aerophilus (formerly known as Capillaria aerophila), based on their size and morphology. Culture of the BAL fluid revealed no bacterial growth.

Figure 1.

Bronchoalveolar lavage. Modified Wright’s stain. Extracellular Eucoleus aerophilus ovum with moderate, predominantly suppurative, inflammation on a mucoid background. Bar = 10 μm.

Recovery from anesthesia was uneventful and the patient was monitored postoperatively for 4 d in the intensive care unit. During this time, IV fluids; prednisone (Novo-prednisone; Novopharm, Toronto, Ontario), 0.3 mg/kg BW, PO, q12h; fludrocortisone (Florinef; Shire Biochem, Saint Laurent, Quebec), 0.017 mg/kg BW, PO, q12h; sodium chloride, 1/4 tsp mixed with food q24h; and fenbendazole (Panacur; Intervet Canada, Whitby, Ontario), 50 mg/kg BW, PO, q24h, were administered, in addition to nebulized sterile saline and coupage. Over the first 24 h, the cough worsened in intensity with frequent episodes of expectoration. Over the next 48 h, a dramatic improvement in respiratory effort, severity of coughing, patient mentation, energy level, and appetite was noted. Electrolyte evaluation was repeated daily, and normalization of the sodium and potassium levels was demonstrated within 48 h. The patient was discharged after 4 d of hospitalization with prednisone, 0.3 mg/kg BW, PO, q12h; fludrocortisone, 0.017 mg/kg BW, PO, q12h; and sodium chloride supplementation (1/4 tsp table salt mixed with food) q24h, for long-term therapy of hypoadrenocorticism. Fenbendazole powder (Panacur), 50 mg/kg BW, PO, q24h for a further 10 d, was prescribed for treatment of the parasitic pneumonia. At the 3-month follow-up, the patient continued to do well clinically with no recurrence of coughing. Fecal analysis to confirm resolution of the parasitic infection was declined at this time.

Discussion

Although uncommon, respiratory parasites are one of the many potential etiologies that should be considered in the investigation of respiratory disease in dogs. Clinical signs of respiratory parasitic infections are variable; they result not only from the presence of the parasite, but also the inflammatory response they induce. Although eosinophilic inflammation is typical of parasitic infections, mixed inflammation can predominate, and a definitive diagnosis requires identification of the organism (1). In addition to Eucoleus aerophilus, Paragonimus kellicotti, Oslerus (Filaroides) osleri, Filaroides spp., Crenosoma vulpis, Angiostrongylus vasorum, and Dirofilaria immitis should be considered differential diagnoses in suspected parasitic respiratory disease in dogs.

Paragonimus kellicotti, lung flukes, reside in cysts within the pulmonary parenchyma causing chronic lung infection (1). Dogs, cats, humans, and other mammals may be infected through ingestion of crayfish, intermediate hosts containing metacercariae, with subsequent fluke migration from the intestinal tract into the pleural cavity and lungs (2,3). Infection in dogs may be subclinical, or dogs may be presented for chronic cough; exercise intolerance; dyspnea; gagging; hemoptysis; fever; weight loss; anorexia; or pneumothorax, secondary to cyst rupture. The observation of air-filled cysts or tissue densities, generally in the caudal lobes of the lung and averaging 1 cm in diameter, is a unique radiographic feature of P. kellicotti in dogs. Definitive diagnosis, however, requires the identification of unioperculate eggs, 75 to 118 by 42 to 67 μm in size, in tracheal wash fluid or feces (1,4).

Oslerus osleri is typically the most common respiratory nematode in dogs and has been associated with kennel environments (1,5). As a result, it was a consideration in the case described here. This parasite typically resides in the tracheobronchial tissue at the carina, but it is occasionally found in larger bronchi (1). Bitches with subclinical infections are considered the primary source of infection for puppies, through direct contact with the bitch’s saliva and subsequent ingestion of larvae (6). Patients are most commonly presented for a chronic, mild to severe, nonproductive cough, and inspiratory wheezing that worsens with exercise (1,6). Radiographic visualization of large parasitic nodules at the tracheal bifurcation may be possible in cases with extensive disease. Infective first-stage larvae, and occasionally eggs, can be identified in sputum, tracheal mucus, or feces after a prepatent period of 10 to 18 wk (1,6). The eggs are 50 × 80 μm in size, thin-shelled, colorless, and larvated. The larvae are 325 to 378 μm and 232 to 266 μm long when recovered from the trachea and feces, respectively, with a distinctive kinked tail (1,4). Although historically the Baermann technique has been the preferred diagnostic method for detection of O. osleri, it has been suggested that due to the lethargic migration of these larvae from fecal samples, the zinc sulphate concentration technique may be more sensitive (7). It is extremely important that the feces used in either technique is fresh, as delayed processing can allow Ancylostoma and Uncinaria (hookworm) eggs to hatch, confusing the diagnosis (4).

Respiratory infection with F. hirthi or F. milksi in dogs is relatively uncommon. Organisms reside in the lung parenchyma, alveoli, and, occasionally, the terminal bronchioles (1,8). The majority of infections are subclinical; however, clinical disease may occur in immunocompromised adults, young toy-breed dogs with a history of stress, or adult dogs after boarding at a kennel (8). The Baermann technique was historically recommended for the diagnosis of Filaroides spp., similar to O. osleri; however, the zinc sulphate concentration technique is now suggested to be more sensitive (7). The first stage larvae of Filaroides spp. are indistinguishable from those of O. osleri (4,7). Larvae may also be obtained in airway washings (8).

Despite the relatively uncommon occurrence of lungworms in North America, a recent survey of chronically coughing, afebrile dogs in Atlantic Canada revealed a 20.8% prevalence of C. vulpis infection (9). In Ontario, this is a relatively uncommon diagnosis. The Baermann technique is the preferred diagnostic approach for C. vulpis, and the larvae can be distinguished from those of other parasites by a characteristic straight tail (4). In contrast to O. osleri and Filaroides spp., C. vulpis larvae are not immediately infective and require a mollusk intermediate host, with the red fox (Vulpes vulpes) being the natural definitive host (1). Mature parasites reside in the distal aspect of the bronchial tree, bronchi, and trachea, with signs of tracheobronchitis being the most common presenting complaint (9).

As with C. vulpis, A. vasorum infection is generally uncommon in North America. Historically, angiostrongylosis had been reported in Europe, Africa, and South America (10). However, since 1996, autochthonous canine angiostrongylosis has been described in Newfoundland, specifically on the eastern part of the Avalon peninsula, with larvae identified in 23.9% of chronically coughing afebrile dogs (9,11). Gastropods appear to be the primary intermediate host. However, the specific gastropod species, their distribution, and the seasonal variation in total numbers of infected intermediate hosts remain poorly characterized (10,12). The adult metastrongylid nematode infects the pulmonary arteries and right ventricle (10). Eggs are produced and lodge in pulmonary capillaries, where they develop into larvae and can result in a multifocal-to-coalescing granulomatous interstitial pneumonia (10,11). Diagnosis is made using the Baermann technique. Larvae are 322 to 368 μm in length and can be distinguished from other larvae by the severe kink and dorsal spine of the tail (11).

Treatment protocols for the above mentioned parasites have been reviewed elsewhere, and include the use of fenbendazole, albendazole, milbemycin oxime, and ivermectin (1,5,6,8,9,11).

Dirofilaria immitis, despite a generally low prevalence in Canada, is the most well known of the parasites that can result in clinical signs of pulmonary disease (13). Therefore, the reader is referred to current textbooks for further information on clinical signs, pathogenesis, diagnosis, and therapy (1).

The subfamily Capillariinae is large, including 300 described species, and is challenging to classify (14). Numerous attempts have been made to define genera. Currently, the species found in dogs and cats have been placed into 3 genera: (i) Eucoleus for those found in the airways, (ii) Aonchotheca for the worms found in the intestinal tract, and (iii) Pearsonema for those that occur in the bladder (15). Eucoleus aerophilus, previously known as Capillaria aerophila, parasitizes both dogs and cats and can be found embedded in the superficial epithelium of the trachea, bronchi, and bronchioles (1,16). The life cycle of E. aerophilus has not been well described, but it appears to involve direct transmission, as well as indirect transmission through an earthworm intermediate host (15). Ingested ova hatch in the intestine of the canine host and larvae migrate hematogenously to the lungs within 1 wk (17). The prepatent period is 3 to 5 wk, at which time the female nematode lays her eggs, which are subsequently coughed up, swallowed, and passed in the feces (16). Once the eggs are deposited in the soil, approximately 40 d are required for the ova to become infective; infective ova are hardy and can survive in harsh environments up to 1 y (16,17). The red fox is considered the most important reservoir host in the wild (18,19).

The majority of dogs parasitized with E. aerophilus are subclinically infected (1). Comparable with the presented case, the most common clinical sign is a chronic cough (1). Eucoleus aerophilus infection in a cat has been attributed to immunosuppression due to concurrent Feline immunodeficiency virus (FIV) infection (17). Immunosuppression from glucocorticoid administration and inadequately controlled hypoadrenocorticism may have predisposed the dog described here to clinical infection. It is also possible that polyphagia, secondary to glucocorticoid therapy, caused this dog to have increased environmental exposure to E. aerophilus eggs through frequent burrowing in the soil.

Radiographic abnormalities are generally nonspecific, as in this case, with patchy interstitial to alveolar infiltrates (1).

Diagnosis is based on identification of the 59- to 83-μm long by 26- to 40-μm wide, often asymmetrical, bipolar eggs in feces or tracheal mucus (15,16). A network of branching and anastomosing ridges cover the surface of the egg, as shown in Figure 2 (15). This feature can be used to distinguish E. aerophilus eggs from E. böhmi, a close relative and the etiologic agent of nasal capillariasis, which, in contrast, has tiny pits covering the surface of its egg (15). Finally, E. aerophilus ova can be confused with Trichuris vulpis eggs in fecal samples. Trichuris vulpis eggs are large (70- to 80-μm long by 30- to 40-μm wide), barrel shaped, and in contrast to E. aerophilus eggs, are usually not asymmetrical, have ring-like thickenings at the base of the bipolar plugs, and a smooth shell surface (20).

Figure 2.

Bronchoalveolar lavage. Modified Wright’s stain. Eucoleus aerophilus ovum exhibiting the network of branching and anastomosing ridges covering the surface of the egg (a distinguishing feature from ova of E. böhmi). Bar = 5 μm.

Although there has been little investigation into specific treatment protocols for E. aerophilus, the use of fenbendazole, levamisole, and ivermectin has been described (1). Fenbendazole administration appeared efficacious in the case described here, based on the dramatic clinical response with decreased respiratory effort, decreased coughing intensity and frequency, improved mentation, increased appetite, and absence of clinical signs at the 3-month recheck appointment. Because the life cycle of this parasite can be direct, sanitation is imperative for disease control and for outbreak prevention in group housing situations (16). The owner of the dog was advised to limit access to the surrounding property and to remove feces from the area on a daily basis. In order to promptly detect reinfection, routine fecal examinations are generally required for 6 mo to 1 y after successful therapy (20).

Although an uncommon etiology of respiratory disease, respiratory parasites should be considered in its investigation, particularly in cases where immunosuppression could be a predisposing factor, or where antibiotic therapy has proven ineffective. There are unique radiographic features associated with P. kellicotti; however, nonspecific radiographic signs are common in the remaining respiratory parasites. Definitive diagnosis for each of these parasites depends on identification of ova or larvae in airway washings or fecal matter.