Entomophthoromycosis, also known as zygomycosis, is caused by the fungus Conidiobolus coronatus (formerly named Entomophthora coronata).6,7,9,10 Although this fungus has a worldwide and ubiquitous distribution, it is much more prevalent in warm, humid subtropical and tropical climates.9,10 Entomophthoromycosis is a rare disease involving facial structures in man9,10 and animals6,13. There are five reports of the disease in nonhuman primates1,8,11,12,15 including a case description in a chimpanzee. The present study reports the clinical aspects, diagnosis and treatment of entomophthoromycosis in an Eastern lowland gorilla.
On 18 August 1994 an orphaned female Eastern lowland gorilla, estimated age 4 years, arrived at the Antwerp Zoo. This wild born animal had been confiscated in Africa, where it was confined to a small cage with a dog. Since arriving at the zoo it was claustrophobic and refused to enter small quarters making veterinary interventions difficult. Apart from occasional protozoal diarrhea and a slight cough, the animal had no major health problems.
In September 2004, an intranasal tumor was noticed on the right side. The animal had no discomfort, and a tentative diagnosis of polyposis was made. Treatment for human nasal polyposis consists of topical corticosteroids.16 Topical application was not possible, so a systemic corticosteroid was chosen based on an approximated body weight of 150 kg. The animal was started on oral methylprednisolone (Medrol-Pfizer, B-1050 Brussels, Belgium) at an anti-inflammatory dosage of approximately 0.21 mg/kg SID.1,2 The intranasal polyp was no longer visible after 7 days of treatment, but within 3–4 days after discontinuing methylprednisolone the swelling reappeared. This regimen was repeated twice over a 1-month interval and each time the swelling reappeared. As a result, the animal was placed on continuous treatment of methylprednisolone at the previously mentioned dosage; however, the swelling reappeared in July 2005. In August 2005 the animal was anesthetized for a polypectomy. Microbiologic cultures were negative, but histopathologic analysis showed a fungal granuloma. In December 2005 the dose of methylprednisolone was gradually reduced. However, within 14 days of reducing the methylprednisolone to 0.05 mg/kg SID, the swelling was noted to again be gradually enlarging. In May 2006, a second surgery was performed, but more diffuse granulomatous tissue was present and could not be removed completely. This time microbiologic cultures grew Conidiobolus coronatus and histopathology of the tissue confirmed that it was a fungal granuloma. One month later the swelling worsened and treatment with methylprednisolone was restarted. Two weeks later the swelling was gone but reappeared in August 2006. This time, the animal was treated with ketoconazole (Nizoral-Janssen-Cilag, B-2600 Berchem, Belgium) at a dosage of 1.33 mg/kg PO BID. The dosage was gradually increased to 4 mg/kg BID. Methylprednisolone treatments were gradually decreased and were ended by mid-March. In February 2007 another swelling was noticed on the nose ridge just ventrally of the medial right eye corner. At the beginning of April 2007 the size of the intranasal swelling was reduced.
Although fungi of the Order Entomophthorales occur worldwide, the preliminary clinical diagnosis of polyposis in this gorilla seemed most probable in our temperate north-western European environment. However, histopathology did not confirm this diagnosis. Much of the swelling consisted of cell-rich mesenchymal tissue which contained numerous young fibroblasts and capillaries along with a mixture of many macrophages and giant cells and many eosinophils. PAS (Periodic acid-Schiff) staining showed hyphae partly contained in the giant cells. Ziehl-Neelsen staining was negative. Immunohistochemistry for cytokeratin was only positive for superficial epithelium and some serous glands. Immunohistochemistry for MAC 387 (a human histiocyte-monocyte marker) was considered negative. Due to negative microbiologic culture results, we concluded that the fungus was not the primary cause of the swelling, but rather secondary contamination.
Tissues obtained from the second surgery provided positive fungal culture results. Glabrous and waxy colonies, which became radially folded grew on Sabouraud’s dextrose agar. The culture contained numerous spherical conidia with prominent papillae. The conidia were forcibly expelled, covering the lid of the petri dish. Histopathologic results were obtained from two independent laboratories. The first laboratory’s diagnosis was granulomatous fungal rhinitis with aggregates of macrophages and giant cells with numerous lymphocytes in between and many neutrophils at the surface in the nasal tissues which was comparable to the previous diagnosis. PAS staining showed many irregularly branched and segmentated fungal hyphae. Again, Ziehl-Neelsen staining was negative. The diagnosis from the second laboratory was rhinoentomophthoromycosis and histopathology was described as diffuse granulomatous inflammation with granulomas consisting of multinuclear giant cells, histiocytes, lymphocytes and neutrophils. Many hyphae were present in the multinuclear giant cells and in the intercellular spaces. Hyphae were irregularly wide, septated and branching in 90° angles. Furthermore, Conidiobolus coronatus was also isolated, as described by Coremans-Pelseneer,3 from wood shavings used as bedding material in the gorilla’s cage.
In human patients, Conidiobolus may cause leukocytosis and eosinophilia.9 This gorilla only showed leukocytosis (17.4 G/l; reference8 values: 4.67–11.8 G/l), and a neutrophilia (13.2 G/l; reference8 values: 2.13–8.49 G/l). All other blood values were within normal limits.8 It has not been determined whether Conidiobolus infections are more prevalent in immunocompetent or -compromised patients;5,9 however, this animal tested negative for HIV1/HIV2 antibodies in an enzyme immunoassay.
Apart from massive doses of iodide, used in 1974 for treating a chimpanzee,11 there has been no treatment regimen for rhinoentomophtoromycosis in nonhuman primates described in recent veterinary literature.1,8 Human medical literature recommends a combination of itraconazole (Sporanox-Janssen-Cilag, B-2600 Berchem, Belgium) and fluconazole (Diflucan-Pfizer, B-1050 Brussels, Belgium) along with continued blood monitoring for hepatotoxicity.14 We decided not to use this combination of drugs because monitoring of blood parameters was not possible in this animal and the long-term use of itraconazole with fluconazole has not been reported in nonhuman primates. We decided to use ketoconazole as there is a report of its successful long-term use in the treatment of entomophtoromycosis in a man.4 We treated this animal with gradually increasing doses of ketoconazole while monitoring for side effects. After 7 months of treatment, the granuloma is reduced. It is possible therapy may need to be changed in the future.
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