Abstract
A 7-month-old Central American jaguar (Panthera onca) presented with chronic, profound, and unresponsive inspiratory dyspnea of 1-week duration. Initial bloodwork revealed anemia and severe leukocytosis with a left shift. The animal was treated presumptively with oral antibiotics without amelioration of clinical signs. Radiographs at a second exam revealed atelectasis of the left lung and mediastinal lymphadenopathy. For diagnosis and resolution of disease, an exploratory thoracotomy and total left lung lobectomy were performed. Histopathology of the excised tissue revealed severe disseminated pyogranulomatous pneumonia with intralesional hyphae consistent with Pythium insidiosum, by immunodiagnostics and culture. The animal recovered from the surgery well, but after 2 weeks re-presented with severe inspiratory dyspnea. Despite attempts to nebulize antibiotics and provide oral antifungals to the animal, the cub succumbed 3 weeks after surgery. This is the first report of primary pulmonary pythiosis in any species.
Introduction
Pythiosis, caused by the aquatic oomycete Pythium insidiosum, is a devastating infectious disease of tropical and subtropical climates.1-13 A mammalian pathogen in the class Oomycetes, it was first described by de Cock in 1987 as the causative agent of a chronic granulomatous disease of horses that had been recognized since the mid-19th century. In dogs, it causes either severe transmural gastroenteritis or locally invasive subcutaneous disease, both of which are often fatal. The infective stage of P. insidiosum is believed to be a motile zoospore that is released into stagnant water in warm environments. Infection results from this stage by encysting in the skin or by ingestion.
Case Report
A 7-month-old male Central American jaguar (Panthera onca) presented with chronic inspiratory dyspnea of 1 week duration. The animal was chemically restrained with combined medetomidine and ketamine (Domitor, Pfizer Animal Health, Exton, PA, USA; 0.6 mg IM, and Ketaset, Fort Dodge Animal Health, Fort Dodge, IA, USA; 140 mg IM). Sedation was reversed with atipamezole (Antisedan, Pfizer Animal Health, 7 mg IM). Severely decreased inspiratory sounds were coupled with radiologic images of left lung atelectasis. An initial hemogram revealed a severe leukocytosis with a left shift (WBC 35×103/µl) and a moderate anemia (Hct 20%). Treatment with amoxicillin and clavulanic acid (Clavamox, Pfizer Animal Health, 11 mg/kg BID PO for 3 days), followed by enrofloxacin (Baytril, Bayer Corp., Shawnee Mission, KS, USA, 5 mg/kg BID PO for 4 days) and then clindamycin (Cleocin phosphate, Pharmacia & Upjohn, Kalamazoo, MI, USA, 22 mg/kg TID PO for 10 days) alternated with amoxicillin (Clavamox, Pfizer Animal Health, 20 mg/kg TID PO for 10 days), all failed to resolve the clinically evident dyspnea after 2 weeks.
The animal was sedated for a second exam with the combined medetomidine and ketamine as before. Sedation was reversed with atipamezole (Antisedan, Pfizer Animal Health; 3 mg IM). A second blood sample revealed a decreased leukocytosis (WBC 17×103/µl) without a left shift. Radiography revealed an atelectatic or collapsed lung and a suspected hilar mediastinal mass. Cytology of the mass by fine needle aspirate revealed chronic inflammation with no evident microorganisms. Culture of this aspirate was negative for aerobic and anaerobic bacteria.
Two days later, due to the aggravated dyspnea and respiratory distress, the animal was transported by air to the Louisiana State Veterinary Teaching Hospital. The animal was given midazolam (Versed, Hoffman-La Roche, Nutley, NJ, USA; 10 mg IM) by pole syringe 15 minutes prior to crating for helicopter transport. Transport time was reduced to less than 30 minutes for an 80-mile trip involving two large urban centers. Upon arrival to the hospital, the animal was chemically restrained with ketamine (Ketaset, Fort Dodge Animal Health; 80 mg IM), intubated, and maintained on isoflurane (IsoFlo, Abbott Laboratories, North Chicago, IL, USA). An exploratory thoracotomy was selected as the next course of action based on confirmatory radiographs.
The affected left lung was surgically resected by thoracotomy via removal of the seventh and eight costae. Intraoperative cytology revealed a granulomatous reaction with severe eosinophil infiltration, which was strongly suggestive of a fungal or chronic bacterial pneumonia. Although the dyspnea was partially alleviated by the surgery, the animal still showed signs of labored breathing. Buprenorphine hydrochloride (Buprenex, Reckitt & Colman Pharmaceuticals, Richmond, VA, USA, 0.8 mg IM BID for 2 days) was provided for analgesia and enrofloxacin (5 mg/kg BID PO for 5 days) was given postoperatively. Slowly, the animal’s appetite improved. Eight days after surgery, the animal was unable to vocalize, and was partially anorectic, but was aggressive and active. The animal became dyspneic and moderately anorectic again two days later. Biopsy histopathology revealed severe disseminated pyogranulomatous pneumonia with intralesional hyphae. Immunohistochemistry, immunoblot serology, and culture with molecular as well as morphologic identification of the pathogen indicated that the causative organism was Pythium insidiosum. The possibility of cross-reaction of the animal’s sera to the organism was eliminated by confirmed negative results from banked sera of conspecifics, which were all housed with the affected animal.
Treatment for a deep pulmonary infection was attempted with itraconazole (Itraconazole, Carr Drugs, Gen. DeGaulle Drive, New Orleans, LA, USA, 10 mg/kg SID PO for 10 days) and terbinafine (Lamisil, Novartis Pharmaceuticals Dorval, QC, Canada, 5 mg/kg SID PO for 14 days), but patient compliance was poor. Six days later, the animal received methylprednisolone (Solu-Delta-Cortef, Pharmacia & Upjohn, Kalamazoo, MI, USA, 2.5 mg/kg SID IM for 2 days) which alleviated the dyspnea. Nebulization with 1% clotrimazole (Clotrimazole 1%, Carr Drugs, 40 mg total, nebulized for 1 hour for 10 days) was attempted as a means of intralesional delivery. Appetite and mentation were improved subjectively with this treatment. Twenty-two days after surgery, the animal suffered a severe respiratory crisis during nebulization and expired.
Necropsy revealed a large (7 cm × 10 cm) severely inspissated yellowish granuloma at the carina that completely occluded both bronchi. The remaining lung had severe inspissation, areas of atelectasis, and contained turbid yellowish exudates throughout the bronchial tree. All thoracic lymph nodes were visibly enlarged. Final histopathology revealed multiple coalescing granulomas with hyphal structures in the lung confirmed by immunohistochemistry and culture as P. insidiosum.
Discussion
Pythium insidiosum is an oomycete most frequently associated with water in tropical or subtropical climates. It has never been described as a primary pathogen in a deep pulmonary infection in any species. The exhibit in which this animal and its littermates were housed contained a waterfall and small pond feature, and although Pythium insidiosum was not cultured from the environmental water samples due to interference by severe bacterial overgrowth, they are presumed to have been the source of the organism. It is hypothesized that the organism was nebulized and aspirated by the jaguar, as the original source of infection. Pythiosis has a poor prognosis in most species, even when treated aggressively.
Acknowledgments
The authors are grateful to the Department of Veterinary Clinical Sciences of the School of Veterinary Medicine at the Louisiana State University, and to the staff of the Air Station New Orleans of the National Coastguard Services for their invaluable, generous, and prompt support.
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