Abstract

A 13-month-old, 3.4-kg, juvenile male patas monkey (Erythrocebus patas) presented with acute onset neurologic signs including seizure, periodic paresis, favoring of the left arm, and lethargy. Differential diagnoses for the clinical signs included toxoplasmosis, infection, toxins, parasite migration, and trauma. An examination was performed using ketamine (Keta-Thesia™, Burns Veterinary Supply, Inc., Westbury, NY, USA) induction and isoflurane (IsoFlo®, Abbott Laboratories, North Chicago, IL, USA) maintenance anesthesia. The physical examination and whole-body radiographs were unremarkable. Blood collected for a complete blood count and selected serum chemistries demonstrated hyperglycemia, 175 mg/dl (ISIS⁷ normal 100 mg/dl) and mild hyperproteinemia, 6.9 g/dl (ISIS⁷ normal 6.2 g/dl). A toxoplasma titer, Chlamydophila (direct complement fixation), zinc level, and an Old World monkey viral panel (African monkey herpesvirus antibody, Herpes simplex-1, measles, cytomegalovirus antibody, and simian immunodeficiency virus antibody) were negative or within normal limits. The animal was given doses of dual-pen (Penicillin G benzathine/procaine, GC Hanford Mfg. Co., Syracuse, NY, USA, 20,000 IU/kg SQ), trimethoprim/sulfadiazine (TMP/SDZ, Tribrissen®, Schering-Plough Corp., Kenilworth, NJ, USA, 30 mg/kg SQ), and lactated Ringer’s solution SQ (50 ml/kg BW). Recovery from anesthesia was slightly prolonged but unremarkable and he was returned to the primate night house where he lived with four other conspecifics. The next morning, the keeper reported that he had had two seizures in the early morning but when observed by the veterinarian, he was steady, quiet and alert. Diazepam (Ivax Pharmaceuticals, Inc, Miami, FL, USA, 0.3 mg/kg PO BID) and prednisolone (USP, oral solution, Hi-Tech Pharmacal Co, Inc., Amityville, NY, USA, 0.7 mg/kg PO SID for 2 days) were prescribed for seizures, and sulfamethoxazole/trimethoprim (SMZ/TMP, oral suspension, Hi-Tech Pharmacal Co, Inc., Amityville, NY, USA, 30 mg/kg PO SID) for possible toxoplasmosis or bacterial infection. The animal was reported to be more relaxed and sleeping more than usual later in the day so only a half dose of valium was given that evening.

The third day after presentation, clinical signs had progressed and the animal was becoming more ataxic, paretic, lethargic, sometimes appearing blind. Consultation with a pediatric neurologist at a local hospital, recommended a computed axial tomography (CT) scan. Later that day, he was taken to a local veterinary referral clinic for a CT scan of the brain. The animal was anesthetized by masking under manual restraint, then intubation with isoflurane inhalation. The survey CT scan showed a possibly enlarged right side of the cerebrum (mild deviation to the left from center) with hypodense, irregularly shaped areas. Images taken with intravenous contrast showed multiple large ring enhancing lesions throughout the parietal, temporal, and frontal lobes with the majority of the ring lesions seen in the right frontal lobe. The ring lesions were considered consistent with central nervous system (CNS) toxoplasmosis. Blood collected at the CT scan was still unremarkable (hyperglycemia 240 mg/dl, negative toxoplasma titer). The animal was hospitalized and continued long term on SMZ/TMP and prednisone (tablets, Roxane Laboratories, Inc., Columbus, OH, USA, 1.5 mg/kg PO BID with a tapering dose), pyrimethamine (Daraprim®, DSM Pharmaceuticals, Inc., Greenville, NC, USA, 1 mg/kg PO SID), folic acid (0.12 mg/kg PO SID), and phenobarbital (Qualitest Pharmaceuticals, Inc., Huntsville, AL, USA, 2 mg/kg PO BID). After 5 days of hospitalization, the animal appeared to recover well enough (with very little motor deficits observed), to return to the primate section with continued oral therapy. Two weeks later, the monkey had recovered to almost normal.

Sixteen days after initial presentation, seizure activity was noted again, with pronounced left-sided deficits and states of stupor. Throughout the day he continued to deteriorate and by afternoon the monkey was hard to rouse. Another examination was done under isoflurane anesthesia and blood was collected for repeat testing. The white blood cell count had risen slightly [mild leukocytosis 13.3×10³/µl with neutrophilia (ISIS⁷ normal 7.5×10³/µl)] and the toxoplasma titer was negative. Parenteral dexamethasone, Tribrissen, sodium chloride fluids IV and SQ were administered. The animal recovered well and was again hospitalized for monitoring.

The monkey expired overnight. The primary findings at gross necropsy were slightly reddened lungs, mild splenomegaly, and multiple (5–6) cavitated purulent cysts containing mucoid yellow material in the cerebrum. Histopathology described acute pulmonary edema and congestion, moderate lymphoid hyperplasia in the spleen, and multifocal severe abscessing meningoencephalitis with intralesional gram-negative rods. Aerobic bacterial culture of the abscesses grew moderate Klebsiella pneumoniae with intermediate sensitivity to SMZ/TMP. Anaerobic cultures were not performed. No toxoplasma or amoebic organisms were found.

Klebsiella pneumoniae, from the family Enterobacteriaceae, are ubiquitous, opportunistic, pathogenic, non-motile, gram-negative rod bacteria that have a prominent polysaccharide capsule¹⁴ and variable virulence.¹³ The bacterium can be found as part of normal primate oral and fecal flora, and the mode of infection is thought to be fecal–oral, or possibly by inhalation.⁴ There are thought to be inciting factors that promote development of clinical disease such as stress or immunocompromise.¹³ Klebsiella sp. infections are difficult to treat,⁶ are most sensitive to cephalosporins, gentamicin, and amikacin, and are generally resistant to penicillins.¹³ Primate Klebsiella sp. infections are considered a zoonotic disease.^2,10

Klebsiella infections have been reported in a number of primate colonies.^{3,4,6,8,11,13} Pneumonia was the most common presenting clinical feature of Klebsiella sp. infections but has also caused septicemia, peritonitis, enteritis, and meningitis.^3,4,13 Klebsiella pneumoniae meningitis has been previously reported in primates^3,5,13 although it does not appear to be a major presentation of Klebsiella sp. infections, based on the bulk of the literature. The infections are usually acute, sometime peracute, and often no antemortem diagnosis is available due to the fast course of disease and the high mortality.³ An anti-Klebsiella capsular vaccine was produced by one institution and as found to reduce the incidence of Klebsiella sp. infections without noted side effects.¹²

The juvenile patas monkey of this report succumbed to cerebral abscesses in which Klebsiella pneumoniae was isolated. It was not determined why he was predisposed to this infection, as no evidence of immunocompromise was discovered. It was possible that he had another bacterial infection that was resolving (hence the recovery after initiation of treatment) and the Klebsiella was a secondary opportunistic infection. The primary working antemortem diagnosis was cerebral toxoplasmosis because 7 months prior to his death a dik-dik (Madoqua guentheri smithi) that shared the patas exhibit died of toxoplasmosis¹ and the CT scan highlighted ring lesions, which are often found in imaging cases of toxoplasmosis of the CNS.⁹ Additional diagnostics, such as blood culture and cerebral spinal fluid analysis, may have assisted in diagnosing a bacterial meningoencephalitis or septicemia. With Klebsiella sp. infections, rapid isolation of the offending organism with antibiotic sensitivities is key to appropriate treatment.

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