In late January of 2000 a 4-year-old lowland gorilla from the Calgary Zoo’s troop exhibited lethargy, mild fever, one episode of vomiting and mild pain when swallowing. These signs responded well to nonsteroidal anti-inflammatory drugs (NSAIDs) and were consistent with “flu like” signs observed in the rest of the troop intermittently throughout the winter. In early March, the animal was again somewhat lethargic with a decreased appetite and head-holding behavior; as before, the signs were responsive to NSAIDs. On March 9th, the animal was separated from the troop and anesthetized with medetomidine and ketamine; physical exam and radiographs of skull and chest were normal. Blood cultures (aerobic and anaerobic) were negative; rectal culture revealed normal flora, and a palpebral TB test was nonreactive. Results of the CBC and serum chemistries indicated a mild anemia and mildly elevated C-reactive protein (indicator of inflammation). Mild signs persisted for several days, including an occasional hunched posture and stiff neck. Urinalysis and a test for fecal occult blood were carried out. Both were normal. On March 15th, a developing strabismus of the left eye was noted and during a second immobilization a full body computer tomography scan including a contrast study of the CNS, chest radiographs, blood chemistry screen and counts and a repeat blood culture were carried out. C-reactive protein remained mildly elevated, all other results were within normal limits and no changes were seen on the CT scan. A human viral panel for respiratory viruses showed no significant exposure. Tests for rheumatoid factor, antinuclear antibody and evidence of streptococcal disease (ASOT) were negative. The gorilla was placed on azithromycin therapy orally for 2 weeks; while he did seem to improve over the next week, occasional head holding, strabismus and a tendency to hold his neck stiffly continued.
The gorilla’s condition was stable for about 2 weeks following antibiotic therapy; during this time, he was observed to be irritable and somewhat lethargic. On April 16th the animal was markedly depressed, lying in a curled position and wincing his face at regular intervals. At this time, he was anesthetized for chest radiographs, thoracic and abdominal ultrasound examination, blood culture and lumbar CSF collection. The CSF obtained was yellow tinged and very mildly clouded. Protein was elevated, as was the white cell count (60% lymphocytes, 22% neutrophils); glucose was lower than normal. Aerobic and anaerobic bacterial cultures, viral culture, mycobacterial culture, fungal culture and fungal and acid-fast staining of CSF were all negative; volume collected was insufficient for Herpes virus PCR. Serology for Toxoplasma, and several nonrespiratory human viruses was negative for exposure. Viral culture of feces was also negative. Therapy with ceftriaxone, a third-generation cephalosporin was instituted. Clinical improvement was fairly rapid, and injections continued for a 21-day treatment. After 9 days of treatment (on April 25th) a second CT scan revealed no focal lesions in the CNS, although there was slight increases in ventricle size noted by comparison to the March 16th scan. At the end of treatment (on May 8th), a magnetic resonance imaging scan (MRI) was performed of head and spine to rule out focal lesions such as a paraspinal abscess. This procedure revealed an increased signal at the ventral surface of the brainstem, and a mild increase in the size of the ventricles, compatible with a resolving meningitis and an associated mild bout of communicating hydrocephalus. CBC and serum chemistry values, as well as C reactive protein were all within normal limits.
For the next 5 weeks, the gorilla’s behavior and appetite were normal. He gained weight and resumed his position within the troop as the dominant young animal. Some subtle changes in attitude were noted in early June, as well as a stiff neck and mild muscle wasting of the cervical spine. He had a mild facial sweat and slept more often over the next week. On June 13th, the animal was immobilized. Physical exam was normal, CSF collected was clear with a mild elevation in protein and normal cell counts. CBC was normal; however, there was still an elevated C-reactive protein. Bacterial and fungal culture of CSF, as well as acid-fast staining and Herpes virus PCR were all negative. Rectal culture revealed normal flora; a repeat viral culture of stool was also negative. Urinalysis was normal; a second palpebral intradermal tuberculosis test was nonreactive. Ceftriaxone was administered for 4 days until all negative results were obtained. During the following week, the young gorilla exhibited normal behavior some days and was somewhat quiet and sleepy on other days. Decreased hand-eye coordination and a developing weakness in the right arm prompted a second MRI exam on June 29th. This procedure showed the same increased signal in the ventral brainstem, no change in ventricle size, and two new small cystic lesions in the cervical spine. There was little increased signal associated with these signals, and the combined opinions of pediatric neurologists, a pediatric neurosurgeon and radiologists indicated these were most likely syrinxes formed in response to the chronic low-grade communicating hydrocephalus. Other rule-outs included transverse myelopathy, infectious myelitis and spinal abscesses. Serology for Brucella sp., Borrelia sp. and Cryptococcus was negative. CSF had normal color and cell counts. There were no organisms on Gram stain; no fungal elements or yeast were seen; and there was no cryptococcal antigen detected. Stereotactic biopsy of the spinal lesions was considered, but not pursued due to the difficulty in accessing this expertise and in providing post-surgical care. In humans, spinal abscesses are rare, and on this basis conservative medical treatment was chosen: ceftriaxone IM, high-dose dexamethasone PO and ranitidine PO were instituted, with immediate response. All neurologic signs disappeared within 48 hours, and the animal had very good attitude and appetite.
On July 12th, the antibiotic was changed to oral chloramphenicol, and the steroid dose was being tapered. On July 19th, MR imaging indicated shrinkage of the cystic lesions in the spine. Clinically, the animal was doing quite well, though occasional tremors and facial sweats persisted. On August 9th, near the end of planned dexamethasone therapy, he took a turn for the worse with a return of right arm weakness, lethargy and a horizontal nystagmus. He responded positively for several hours after an increased dose of dexamethasone, and an MRI exam was set up for the following day. On August 10th, he was responsive at 7 a.m. but deteriorated to a comatose state by 10 a.m. Dr. Mark Hamilton, a pediatric neurosurgeon, placed an emergency ventriculoperitoneal shunt surgically. CSF seen at surgery was clear and initially at high pressure (though not measured). An MRI that afternoon indicated multiple focal brain lesions. Despite intensive care over the next 36 hours, the gorilla’s condition continued to deteriorate, and when spontaneous breathing began to fail, euthanasia was elected on August 12th, 2000.
Necropsy revealed some chronic pneumonic lesions as well as subacute multifocal pulmonary necrosis caused by Aspergillus sp. The acute multifocal necrotizing meningoencephalitis was also caused by Aspergillus sp. The chronic spinal lesions were abscesses and contained organisms identified tentatively in histologic preparations as Nocardia asteroides. Immunohistochemistry is pending for final identification. Retrospective fungal serology on samples from March, April and May were negative for Aspergillus (several species) and a number of other fungal agents. Nocardia is the assumed pathogen for the protracted illness in this animal.
While there are many cases of Nocardia infection in the human literature, it is considered a rare pathogen, responsible for less than 2% of cerebral abscesses. Nocardial spinal abscesses are considered extremely rare with only four cases reported.2 Early biopsy and aggressive surgical reduction are considered appropriate when neurologic nocardial lesions are identified. Delays in obtaining a biopsy have been related to the accumulation of nonspecific or unhelpful results.1 Mortality in human cases of cerebral nocardiosis can be as high as 80%, often related to difficulties in identifying an organism and associated with late or inappropriate therapy.3 Human cases of nocardiosis are often, though not exclusively associated with immunosuppression or immuno-incompetence. Preliminary investigations reveal no exposure of this animal to HIV or simian foamy virus.
1. Fleetwood, I.G., J.M. Embil and I.B. Ross. 2000. Nocardia asteroides cerebral abscesses in immunocompetent hosts: Report of three cases and review of surgical recommendations. Surg. Neurol. 53(6):605–610.
2. Mukunda, B.N., R. Shekar and S. Bass. 1999. Solitary spinal intramedullary abscess caused by Nocardia asteroides. South Med. J. 92(12):1223–1224.
3. Urbaniak-Kudja, D., S. Cielinski, K. Kapelko-Slowik, G. Mazur and A. Bronowicz. 1999. Disseminated nocardiosis as a complication of Evan’s syndrome. Ann. Hematol. 78(8):385–387.