Abstract
Clinical Presentation
A 14-year-old male western lowland gorilla (Gorilla gorilla gorilla) housed at the Milwaukee County Zoo experienced a fatal meningoencephalitis caused by Balamuthia mandrillaris. Initial signs (day 0) were myoclonic jerks of the head, neck, and shoulder muscles, and a subtle ataxia. Nonenhanced magnetic resonance imaging (MRI) of the brain performed on day two was normal. Standard hematologic and serum biochemical tests were unremarkable, and titers against Epstein-Barr and herpes simplex I and II viruses were considered negative. Progression of encephalitic signs was rapid, with development of dysconjugate ocular deviation, progressive lethargy, severe cerebellar ataxia, and generalized weakness by day eight. A second MRI on day nine showed multifocal lesions scattered throughout the cerebrum and diencephalon and extending into the cerebellum. Cerebrospinal fluid was clear, but analysis revealed an elevated protein level of 487 mg/dL (human reference range: 20–45 mg/dL),2 and 45 white blood cells/µl (human reference range: 0–3/µl),2 with 1% neutrophils, 94% lymphocytes, and 5% eosinophils. Fungal and Gram stains were negative for organisms, as were antigen assays for Haemophilus influenza group B, Streptococcus pneumonia, β-hemolytic Streptococcus group B, and Neisseria meningitidis groups A, B, C, Y, and W135. Despite treatment with intravenous metronidazole, broad spectrum antibiotics, and supportive care, the animal became comatose and died on day ten.
Pathology
Necropsy revealed large granulomatous nodules at the base and apex of the heart, as well as smaller nodules within the pancreas and the retropharyngeal lymph nodes. Gross reaction in the cerebral tissue was limited to slight, multifocal, yellowish discoloration and depression. Histopathologic examination revealed multifocal areas of granulomatous cellular proliferation with and without acute necrosis. These foci contained massive neutrophilic and eosinophilic, or mixed eosinophilic and granulomatous infiltrates, accompanying large eosinophilic ovoid to polygonal bodies that resembled amoeba. Lesions often showed a prominent vascular orientation. Cardiac sections contained a similar infiltrate with more fibrosis, and with foreign body giant cells containing amoeba within the mixed inflammatory cell infiltrate. Similar nodules of cellular reaction were seen in the hilar lung, pancreas, and kidney. Tissues were sent to Dr. Visvesvara at the Centers for Disease Control and Prevention, where immunofluorescent studies confirmed the presence of B. mandrillaris.
Discussion
Balamuthia mandrillaris is a free-living amoeba of the Order Leptomyxida and is usually thought of as a soil inhabitant. It has been identified as a cause of both acute and granulomatous amoebic encephalitis in humans and animals,1,3,4,6,8,9 with a number of human cases believed to have been infected via open wounds.5 Serological tests do not exist currently; diagnosis is generally made from biopsies or at necropsy. Pentamidine isethionate has been recommended as treatment for extraneural forms of B. mandrillaris infection; however, treatment of the encephalitic form has not been successful.7
This is the third reported case of fatal amoebic meningoencephalitis in western lowland gorillas caused by B. mandrillaris, and the first to be reported outside the San Diego Zoo.6 Human cases have been reported worldwide, many in acquired immune deficiency syndrome (AIDS) patients, suggesting that immunosuppression and debilitation may be a factor in susceptibility. However, infection has also occurred in immunocompetent persons with severe trauma or extended exposure to soil and water.5 The gorilla in this case was a young vigorous animal with no medical history indicative of immunosuppression or pathology of the lymphoid system. However, underlying immunocompromise secondary to social stress remains possible in this animal. Thirty-one months earlier, an older male silverback gorilla had been added to the collection, and changes in family groups occurred periodically in an attempt to find a compatible breeding group. The extensive granulomatous pericardial lesions suggest that infection was present for some time before the rapidly progressive encephalitic disease occurred. The generalized visceral involvement and vascular orientation of the lesions in this gorilla suggest a hematogenous dissemination of the organism, but the source of infection in this animal is unknown. No amoebae were found in samples of water, sand, or soil collected from the indoor and outdoor exhibit and holding areas.
Amoebic meningoencephalitis and granulomatous peritonitis is an important cause of disease in Old World primates, and a significant cause of death in lowland gorillas. Given the ubiquitous distribution of this soil organism, infection with B. mandrillaris should be considered a possible cause of granulomatous pneumonia, peritonitis, or encephalitis in primates. While the danger of zoonotic transmission from the live animal is unknown, it is presumed to be low. Zoo personnel may be at risk when handling infected tissues during necropsy or biopsy procedures.
Acknowledgments
The authors would like to thank Dr. Visvesvara from the Centers for Disease Control and Prevention, Atlanta, GA, for performing the immunofluorescent antibody tests on the tissues provided, and for attempting to culture amoeba from the soil and water samples supplied.
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