Abstract
Zygomycosis is a fungal infection which has been historically rapid in onset, often resulting in a rapid death after clinical signs appear. Unlike most pathogenic forms of Zygomyces, which infects immunocompromised individuals, Apophysomyces elegans has the ability to infect immunocompetent individuals. Dolphins diagnosed with zygomycosis have not survived this disease even with the treatment of intravenous liposomal Amphotericin B or liposomal Nystatin.
A route of infection in healthy animals in good body condition is believed to be via inhalation of spores from surrounding contaminated soil. This results in colonization of the trachea and a systemic infection with tropism for brain tissue. Fungal invasion into peripheral blood vessels can cause infarction of the dermis supplied by the vessel resulting in an eschar. Zygomycosis can result in brain lesions of meningitis and bleeding into the brain as the fungus grows along and erodes the blood vessels and can cause peracute fatal brain hemorrhage. Diagnosis of A. elegans requires histological studies showing unique features, including: broad, sparsely septate, thin-walled hyphae and angioinvasion with thrombosis. Definitive diagnosis requires fungal culture and species identification. Note that special tissue handling and culture techniques are necessary for successful culture of these fungi.
A new azole, posaconazole, had shown promise in treatment of Zygomycosis in human patients. Formerly known as SCH 56592, posaconazole is a triazole that is structurally related to itraconazole. It has been developed by Schering-Plough Pharmaceuticals, and is currently available in Europe and awaiting approval in the United States. As with all azole antifungal agents, posaconazole works principally by inhibition of cytochrome P450 14a-demethylase (P45014DM). This enzyme is in the sterol biosynthesis pathway that leads from lanosterol to ergosterol.
An adult female bottlenose dolphin, Tursiops truncatus, and her 5-week-old female calf presented in December of 2003 with Zygomycosis. The adult female developed lesions in damaged skin, unresponsive to antibiotics and antifungals. Blood tests showed minimal white cell increase with significant elevated erythrocyte sedimentation rate. The calf developed similar skin lesions prior to the death of her mother. Post mortem findings in the mother included skin/brain lesions showing classical histological Zygomycosis. Subsequent fungal culture and identification revealed A. elegans present in both tissues.
After the post mortem findings of the adult female, the primary skin lesion on the calf was surgically resected. Within 48 hours of surgery, the border of the surgical site had evidence of incomplete removal. The calf underwent another surgical resection with large margins and was placed on 5mg/kg posaconazole PO BID. After the surgery and placement of the calf on posaconazole, the blood work stabilized and no other symptoms related to Zygomycosis were noted. The calf was treated with posaconazol for 17 months. This calf has survived more than 2.5 years after her initial diagnosis with no recurrence of the disease. This is the first cetacean that has been reported to have survived a systemic zygomycosis infection. Prompt diagnosis, aggressive surgical removal of the obvious affected tissue and the new drug posaconazol were instrumental in the successful outcome of this case.
Acknowledgement
The authors wish to thank Schering-Plough for providing this new drug and to FDA for the rapid approval for its use in this case. The Texas Fungal Lab, Annette Fothergill, Diane Sutton and Dr. Rinaldi, for all their help. A special thanks to the staff at Gulf World for their superb care of this dolphin calf during her illness.