Abstract
Mucormycosis is an often fatal fungal infection seen mainly in immunocompromised humans, but also encountered in immunocompetent humans incurring black widow spider bites, trauma, or burns.2,5 Historically, treatment of choice has been aggressive surgical debridement (including amputation in some cases) and amphotericin B, which is fungicidal at therapeutic levels but is limited by its nephrotoxicity. By using amphotericin B encapsulated in liposomes, tolerability is significantly improved, allowing larger doses and presumably enhanced effectiveness.1-3 Liposomal amphotericin B (3–5 mg/kg/day) has been used successfully to treat mucormycosis in humans, though there is no consensus on the optimal duration of treatment.2 Mucormycosis can also infect cetaceans, often with rapidly fatal outcomes. In fact, Apophysomyces spp. has been found to cause disease even in immunocompetent cetaceans.6 To date, treatment of infected cetaceans with liposomal amphotericin B has been unsuccessful.4,6
A 17-year-old female bottlenose dolphin (Tursiops truncatus) became acutely anorectic (4/30/96) with a rapidly increasing erythrocyte sedimentation rate (ESR), 26 mm/hr on day 1 and 78 mm/hr on day 3. Zygomycosis was suspected based on these clinical and lab findings, and treatment was initiated immediately (day 3) with intravenous liposomal amphotericin B (AmphocilTM) and Sporonox. On day 8, a small sample was coughed up from the blowhole during a treatment session, and fungal culture confirmed Apophysomyces elegans. Renal function was monitored throughout the course of treatment, and amphotericin B was withheld days 5 through 7 and days 25 and 26 due to worsening renal values. Other adverse side effects noted were anemia, thrombocytopenia, and hepatotoxicity - the latter being attributed to Sporonox. The total cumulative dose of AmphocilTM was 2650 mg. Over the course of treatment, the ESR remained significantly elevated, and the persistent anorexia required nutritional support with gastric tube feedings. The animal ultimately developed respiratory failure and died on day 27. Necropsy revealed lymphadenopathy, splenomegaly, bilateral hemorrhages in cerebral hemispheres, and lesions in the trachea, liver, spleen, and kidneys that were consistent with a multi-organ mucoraceous infection. A. elegans was cultured from the liver, kidneys, and spleen.
This case was retrospectively studied to validate a newly developed diagnostic enzyme-linked immunosorbent assay (ELISA) for Apophysomyces. Serum from the animal had been banked and was submitted to Auburn University College of Veterinary Medicine, Department of Pathobiology diagnostic lab. At the beginning of illness (day 1), there was a negative titer (5% of positive control). Despite the rising ESR (78–122 mm/hr), titers remained negative (< 5%) until day 9 when they were "suspect positive" (28%) and "positive" (77%) on day 11. At this point the titers continued to rise, reaching 130% on day 15 and 169% on day 23, four days before the animal's death. This dolphin's condition did not improve despite treatment with amphotericin B.
This case helps validate the ELISA's ability to diagnose Apophysomyces infection. A possible limitation to this test may be that in this case, a positive titer was not reflected until eleven days from onset of illness and initial clinical suspicion. However, ELISA serum monitoring may prove promising in confirming and following response to therapy of this deadly infection.
Acknowledgements
The authors wish to thank the entire staff of the Florida's Gulfarium, Fort Walton Beach, Florida, for all of their hard work and care of their animals; the staff at the Fungus Testing Laboratory, University of Texas Health and Science Center at San Antonio for their help with this case; and Liposome Tech, Inc., Menlo Park, California, for supplying the AmphocilTM in this case.
References
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