Abstracts of Scientific Papers

Traumatic Pneumothorax in a Rhesus Macaque (Macaca mulatta)

D Owens, KF Ethun, M Stovall, R Stammen*

Yerkes Regional Primate Research Center, Emory University, Lawrenceville, GA

Following social contact aggression between 2 adult males rhesus macaques, the subordinate male was reported for superficial trauma to the right axillary region, but otherwise appeared to be bright and alert with a normal attitude. The subsequent day, this 7-year-old animal was noted with a quiet attitude, tachypnea, and a moderate amount of dried blood on the thorax and right thigh. Physical examination revealed pale mucous membranes, dyspnea with a labored abdominal component, a 5mm skin puncture to the right axillary region with a palpable muscle defect to the thoracic wall between the sixth and seventh right ribs, marked bruising from the right axillary region to the umbilicus, and multiple other superficial lacerations to the ventral chin, right upper arm, and right inner thigh. Thoracic radiographs revealed marked gas opacity in the subcutaneous tissue of the right axillary region, and a large thoracic wall defect between the sixth and seventh ribs. iSTAT values indicated respiratory alkalosis, mild hypokalemia, hyperglycemia, and mild anemia. Throughout the initial exam, the patient had a progressively increased respiratory effort, progressive change in mucous membranes from light pink to pale, and persistent decline in blood pressure and pulse oximetry values. Because a traumatic pneumothorax injury was highly suspected with hypovolemic shock, the animal was prepped for an emergency surgery and blood transfusion was performed for blood replacement. Surgical incision overlying the palpable thoracic wall depression revealed a large defect in the musculature of the thoracic wall between the sixth and seventh ribs. Surgical closure of the site was performed, and the patient recovered from surgery uneventfully. This case represents an example of delayed clinical presentation of traumatic pneumothorax due to social housing aggression in a rhesus macaque.

Acute Respiratory Disease and Sudden Death in an Agile Gibbon (Hylobates agilis)

J Kylie*, PV Turner

University of Guelph, Guelph, Ontario

A 6-year-old female Agile Gibbon cadaver from a private zoo was presented for postmortem evaluation. The animal had been observed to be weak and died shortly after receiving IV fluid therapy. On submission, the animal was noted to have mildly decreased fat stores and a moderate amount of hemorrhagic nasal discharge. On gross internal examination, moderate amounts of fibrous adhesions were present between the sternum, heart, and lungs. A thick fibrin mat covered the pericardium and epicardium, left lung lobes, and liver capsule. Multiple ulcerations were present in the stomach. The gastrointestinal tract was empty of any feed material, despite a reported history of eating. Microscopically, a moderate to marked fibrinous and pyogranulomatous exudate was present on the pulmonary pleural surface, the pericardium and epicardium, and liver capsule. In addition, there was moderate alveolar hemorrhage in the left lung lobes. A chronic lymphoplasmacytic enteritis was present within the ileum.Culture and sensitivity testing of lung and pericardial tissue demonstrated a significant Pasteurella multocida infection, with resistance to amoxycillin/clavulanic acid and gentamicin, and intermediate resistance to enrofloxacin. A subsequent visit to the private zoo indicated that the site was situated in an area with a high water table. Gibbon pens were poorly drained and were in close proximity to large felid exhibits. Further, animals could be hand fed pellets from a coin-operated food dispenser by visitors. A number of animal management and animal welfare concerns were submitted to the contract veterinarian following the visit. To our knowledge, this is the first reported case of P. multocida in a gibbon, or in any lesser ape, and raises concern regarding possible interspecies and zoonotic spread of antibiotic-resistant strains of P. multocida.

Pyogranulomatous Otitis Due to Staphylococcus spp. in a Rhesus Macaque (Macaca mulatta)

JE Scapa*, MH Gilbert, XD Liu

Tulane National Primate Research Center, New Orleans, LA

In 2013, a 15-year-old female Indian-origin rhesus macaque presented for a left-sided head tilt from the outdoor specific pathogen-free breeding colony. There were no indications of abnormal mentation or ambulation and no nystagmus was observed on cage-side observation. On physical examination (PE), body condition score (BCS) was 5/5 and an incisor fracture with pulp exposure was noted and the tooth extracted. The PE was otherwise within normal limits. Blood work was also within normal limits, and urine collected via cystocentesis was culture negative. Because she was the alpha female within her social group, she was returned to the breeding colony. Sixteen months later, she presented for severe male-pattern trauma, and on recheck examination discharge was noted in the left ear. The aural discharge was malodorous, ceruminous, and hemorrhagic and cultured Corynebacterium sp. She was started on a 14-day course of oral cephalexin (25mg/kg) and an ear-flushing regimen using TrizEDTA aqueous flush and topical antibiotics was implemented a few days later. The otitis responded to treatment initially, but despite several courses of antibiotics and topical application of an antibiotic formulation containing enrofloxacin and clotrimazole, the infection proved refractory. Radiographs taken of the skull showed normal tympanic bullae, and no other significant findings were noted. Due to poor prognosis for resolution of the infection despite repeated attempts, she was euthanized. On necropsy, the left ear canal was abnormally enlarged and filled with a thick, dark brownish-red discharge. There appeared to be a communication through the temporal bone of the skull associated with the external auditory meatus. However, the brain appeared grossly normal. The cerebrospinal fluid (CSF) appeared slightly cloudy but was culture negative. The only other abnormal gross necropsy findings were a slightly thickened, firm, and pale uterine apex and a small amount of purulent exudate within the cervix, that was culture positive for Streptococcus sp., Staphylococcus sp., and Escherichia coli. Histopathologically the left ear had a chronic-active, multifocal, pyogranulomatous otitis media and externa with labyrinthitis, mineralization and perineuritis of the external auditory meatus, tympanic cavity, and the bony and membranous labyrinth of the ear canal. The right ear was grossly and histopathologically normal. There was also a focal area of vacuolization in the white matter of the left occipital lobe of the brain. Our primary data suggest this is a chronic otitis due to an antibiotic resistant Corynebacterium spp infection in this monkey.

A Case of Asthma in an Adult Female Vervet Monkey

L Koster, B Simon, G Rawlins, A Beierschmitt*

Ross University School of Veterinary Medicine, Basseterre, St Kitts, West Indies

A 9-year-old, colony bred female vervet monkey (Chlorocebus atheiops sabaeus) presented with a documented 6-year history of open mouth breathing, tachypnea, and sibilant wheezing. Her respiratory condition did not significantly impact normal activity. Asthma was a suspected diagnosis. Thoracic radiographs and bronchoalveolar lavage supported the diagnosis of asthma. Treatment using intramuscular prednisolone that was tapered from twice daily to every other day dosing over 2 months and twice daily inhaled salmeterol/fluticasone (25/250 µg/actuation) using a mask and metered dose inhaler was successful in restoring normal respiratory pattern. There are various primate models of human asthma but this is, to the authors’ knowledge, the first report of spontaneous asthma in a monkey.

Persistent Thrombocytopenia in a Common Marmoset (Callithrix jacchus)

A Goodroe*, C Moats, J Izzi, S Beck, C Garrett

Johns Hopkins University, Baltimore, MD

An 8-year-old male common marmoset (Callithrix jacchus) with a cranial implant presented for acute lethargy, decreased body condition, and hematochezia. Severe thrombocytopenia (25,000/μL) was the most striking finding noted on hematology. At that time, immune-mediated destruction was suspected and prednisolone therapy resulted in a 2.5-fold increase in platelet count. Despite initial clinical improvement, the animal’s condition declined 3 months later. Marked thrombocytopenia (87,000/μL) was again noted on hematology. Abdominal palpation and ultrasound revealed pronounced splenomegaly. In addition, urinalysis obtained via cystocentesis demonstrated moderate proteinuria and hematuria. Additional differentials for thrombocytopenia considered at that time included splenic sequestration and impaired platelet production. Euthanasia was elected due to poor prognosis. Gross necropsy and histopathological findings included a necrotizing cystitis with hemorrhage, lymphoplasmacytic, and neutrophilic hepatitis with perivascular amyloid, and lymphoplasmacytic inflammation within the kidneys, gastrointestinal tract, and the lungs. Splenomegaly was secondary to extramedullary hematopoiesis. Bone marrow examination showed an adequate and mature megakaryocyte population. Based on the clinical and postmortem findings, immune-mediated destruction of platelets was suspected to be the cause of thrombocytopenia. Chronic infection and inflammation have both been identified as etiologies of immune-mediated thrombocytopenia in humans and companion animals. In the case of this marmoset, there was a history of multiple attempts to treat bacterial and fungal infections associated with the cranial implant margins. This case exemplifies a unique complication that arose secondary to chronic inflammation. Additional common sources of chronic inflammation and infection in marmosets in a research setting include gastrointestinal disease, telemetric and other medical devices, and experimental inoculation with infectious agents.

Clinical Care following Bone Marrow Transplantation Conditioning Regimens

J Coonen*, C Boettcher

Wisconsin National Primate Research Center, Madison, WI

Conditioning regimens for bone marrow transplantation were performed on 3 cynomolgus macaques. Two animals received a nonmyeloablative treatment using fludarabine (50mg/m2 for 3 treatments) followed by total body irradiation (1 treatment of 2 gray). One animal received standard ablative total body irradiation (5 treatments of 1 gray for 2 days). Appetite was transiently reduced following treatments resulting in variable weight loss. Candida albicans was detected and treated for 2 animals that presented with abnormal feces. Moderate to marked pancytopenia was observed in all cases. Treatment with ceftriaxone was initiated for neutropenia (ANC <500 uL) and whole blood transfusions were performed for severe thrombocytopenia (platelets < 9,000 ths/uL with clinical signs of petechiation). Overall, the animals tolerated the conditioning treatments well.

The Relationship of Left Ventricular Hypertrophy and Group Housing with Cardiac Biomarkers in Rhesus Macaques (Macaca mulatta)

A Haertel*, K Christe, J Stern

California National Primate Research Center, University of Davis—California, Davis, CA

Left ventricular hypertrophy (LVH) can lead to syncope, congestive heart failure, or sudden death. The disease has only been diagnosed post-mortem in macaques at the California National Primate Research Center (CNPRC), but detailed pedigree analysis of macaques diagnosed with LVH at necropsy allowed us to identify siblings with possibly a familial association of LVH which could be screened with echocardiography. Serum cardiac biomarkers for LVH may also potentially assist in colony-wide surveillance for LVH. Several cardiac biomarkers were tested with macaques including cardiac troponin I (cTnI) and creatinine kinase-MB. cTnI elevations are highly specific and sensitive for myocyte damage; however, moderate exercise can be associated with elevated levels. Macaques housed outdoors in large field pens are herded before serum collection, and the exercise involved with herding may make interpretation of cTnI difficult. We hypothesized cardiac biomarker levels would be higher in animals with LVH than healthy animals, directly related to severity of LVH, and that serum collected from outdoor-housed animals would have higher cTnI levels than indoor-housed animals. Serum analysis with cardiac biomarker assays was conducted in conjunction with animals undergoing echocardiography and animals retrospectively diagnosed with either no LVH, occult LVH, or fatal LVH. In addition, separate groups of healthy macaques housed indoors or outdoors were tested with the cTnI assay. Unfortunately, none of the biomarkers were associated with presence or severity of LVH in retrospectively or prospectively diagnosed macaques. Interestingly, cTnI levels were significantly higher in serum collected from outdoor-housed macaques than indoor-housed macaques (p<0.001). Additionally, echocardiography on siblings with familial associations with LVH lead to the diagnoses of LVH in 5 of 17 (26.3%) living relatives. These findings suggest cTnI may be affected by exercise in rhesus macaques and echocardiography performed on rhesus macaques with a familial association of LVH may be more beneficial for LVH surveillance than serum cardiac biomarkers, further supporting the hypothesis that LVH at the CNPRC may be an inherited hypertrophic cardiomyopathy.

Difficulties Involved in Working up Nonhuman Primate Cases of Alopecia

J Dutton*, L Halliday, J Fortman

University of Illinois at Chicago, Chicago, IL

Determining the etiology of alopecia in nonhuman primates can be problematic. Large surveys and individual case reports have identified various etiologies which differ significantly from those of alopecia in traditional veterinary species. The diagnostic plan in domestic species often relies on a combination of signalment and presentation with initial diagnostic techniques including skin scrape and culture for bacterial, parasitic, and fungal agents. Biopsy and histological examination are only necessary if these initial steps prove unrewarding. However, in nonhuman primates the identified etiologies dictate a different diagnostic paradigm. Etiologies found in the literature for nonhuman primate alopecia include normal hormonal variations, endocrinopathies, and immunologic and inflammatory causes, as well as behavioral causes. These differences in etiology warrant biopsy and endocrine testing earlier in the diagnostic process. Problems with this approach are that few commercial laboratories possess the reagents and expertise to perform endocrine analysis with interpretable results in nonhuman primate species, and veterinary dermatopathologists working with domestic species may not be familiar with the processes involved in nonhuman primate alopecia. Two cases are presented here as examples. The first is that of an 8-year-old female cynomolgus macaque (Macaca fascicularis) received in our colony with a 5-year history of alopecia and dry skin. The second is a 5-year-old female cynomolgus macaque that presented during an annual physical exam with newly acquired generalized alopecia and pruritus, as well as erythema in the axillary, inguinal, and cervical regions. These cases will be used to illustrate the difficulties encountered diagnosing alopecia in nonhuman primates housed in a research setting.

A Plethora of Welfare Assessments: Nearer the Truth or Just More Noise?

P Honess

Bioculture Group, Riviere des Anguilles, Mauritius

Animal welfare science has struggled over recent decades in producing a consensus on the best welfare assessment method. Academic interest in how animals perceive and interpret environmental features and life events has produced increasingly sophisticated tools that aim to probe the animal’s internal, emotional, and hence welfare state. Techniques include the measurement of stress hormones, immune function, growth and development, attentional and cognitive bias, alopecia, social network analyses, and body temperature. Some of these are more complex or more illuminating than others. In many cases these have been promoted as practical tools for routine welfare assessment. While many of these approaches may have high levels of objectivity, they also can require significant experience, expertise, and technical support to conduct at the necessary standard to produce the stated benefits. To the practitioner with large numbers of animals to assess on a routine basis, such a plethora of techniques and reliability claims can be intimidating. The aim is to provide an overview of the major techniques available and their usefulness. The key question of what we are really trying to assess will be addressed and it will examine whether such techniques really tell us anything very different from simple, well-interpreted behavioural observations.

Uterine Leiomyoma in a Common Chimpanzee (Pan troglodytes): A Successful Collaboration in Nonhuman Primate Care

*VA Kirk, MA de la Garza, JM Jones, PB Miller, EJ Dick, M Henderson

Falling Rock Veterinary Clinic, Canyon Lake, TX

Severe menorrhagia in a 27-year old female common chimpanzee, resident of a sanctuary, lead to severe, acute, life-threatening anemia. Following emergency management of the crisis, medroxyprogesterone administration satisfactorily prolonged the first intercycle interval. However, intervals between subsequent cycles were unpredictable and menorrhagia continued to occur. Treatment with medroxyprogesterone eventually became ineffective and an ovariohysterectomy was planned. Preoperative ultrasound evaluation showed very dense nonmineralized uterine leiomyomas, likely ovarian pathology, and bilateral hydronephrosis secondary to ureteral compression from excessive uterine weight. Constructing a qualified surgical team required reaching beyond private veterinary practice due to the patient species. The team was gathered from private gynecology/obstetrical and anesthesiology medical practices as well as biomedical research, leading to a successful outcome in patient care. Collaboration in biomedical research and private practice (veterinary medicine and human medicine), maximizes the quality of health care available to captive nonhuman primates.

An Unusual Presentation of Hemangiosarcoma in a Cynomolgus Macaque (Macaca fascicularis)

K Breyer*, M Simkins, T Boulineau

Novartis Pharmaceuticals, East Hanover, NJ

A 7-year-old male cynomolgus macaque (Macaca fascicularis) was reported for a bleeding wound on the lateral tarsus, suspected to be a result of trauma. On closer inspection, the bleeding area was discovered to be a ruptured skin mass. Additionally, multiple subcutaneous firm nodules were palpated on the foot and lower leg (unilateral). Mild anemia was noted on a complete blood count. The skin mass was removed for histopathology and supportive care was initiated. Histopathology from 2 different diagnostics labs had equivocal results, with main differentials of granulation tissue and fibrous reaction; however, one pathologist mentioned a slight suspicion of hemangiosarcoma due to several atypical cells on the margin. Within several days, the animal was nonweight bearing on the affected leg and the anemia became severe. Thoracic radiographs revealed multiple large nodules within the lungs. The animal was euthanized due to the poor prognosis. On necropsy, there were multifocal coalescing subcutaneous nodules adhered to the muscles of the foot, ankle, and extending up the calf. The spleen, lungs, and pleural cavity contained multifocal nodules. A diagnosis of metastatic hemangiosarcoma was given, though it is unclear if the initial neoplasia started as a dermal or splenic form. This case had a very unusual presentation and neoplasia was not initially considered. A discussion of the clinical signs, diagnostics, and differentials will be presented, along with information about hemangiosarcoma in nonhuman primates.

B Cell Lymphoma in a Chimpanzee

MA de la Garza*, KM Brasky, M Owston

Texas Biomedical Research Institute, San Antonio, TX

A 49-year-old female chimpanzee presented suddenly to her primary caretaker with a decreased activity level that was intermittent and only witnessed by the primary caretaker. On previous evaluations all blood parameters and physical exam findings had been relatively normal. Veterinary staff monitored her cage side and could not discern any deficits or change that would warrant immediate concern. Two days later, her condition worsened and she was scheduled for evaluation. Upon close inspection it was immediately obvious that she had significant disease. All peripheral lymph nodes were grossly enlarged. Peripheral lymph nodes were aspirated and biopsied. Ultrasound exam revealed many lobular cyst-like structures throughout the entire abdomen. She had ascites, pale mucus membranes, elevated HR, and labored breathing. Blood analysis revealed various abnormalities, including anemia, hypoproteinemia, and mildly elevated liver and kidney enzymes. She recovered well from sedation; however, the following day, she was clearly uncomfortable. Based on exam findings and the improbable likelihood of restoring a high quality of life, euthanasia was opted. Gross diagnosis on necropsy was whole body neoplasia. Immunohistochemistry revealed CD20-positive neoplastic cells, indicating B-cell origin. Although neoplasia is not uncommon in chimps, malignancies are rare. A review of the literature failed to identify any previously documented cases of naturally-occurring B cell lymphoma in chimps, making Clyde the first reported case.

Truncal Leiomyosarcoma in a Rhesus Macaque (Macaca mulatta)

C Cullin*, R Zweig, J Stanton, A Lewis

Oregon National Primate Research Center, Beaverton, OR

A 12-year-old, 5kg, female rhesus macaque (Macaca mulatta) presented for loose stool and emesis; the macaque had a prior history of weight management. On exam, a large, cavitated 10 x 15cm mass was identified overlying the animal’s dorsal thorax; two associated cervical masses were present which impinged on normal movement. Radiographic and ultrasound evaluation revealed a close association of the masses with underlying tissues which precluded surgical excision. Due to the macaque’s continued discomfort, euthanasia was elected. Necropsy confirmed the deep invasion of the mass into local tissues, including the cervicothoracic skeletal muscle and fascia, as well as the vertebral spinous processes and left scapula. Histologic evaluation revealed a highly cellular neoplastic mass with interlacing fascicles of pleomorphic mesenchymal cells and low numbers of mitotic figures. The caudal aspect of the mass was characterized by apparent angiogenesis with abnormal vascular structure and central necrosis of the mass. Immunohistologic characterization was performed to identify the cell line of origin. The mass was vimentin and SMA positive, and desmin, CD31, S100, and c-KIT negative, consistent with a poorly differentiated leiomyosarcoma. This neoplasm is rarely reported in nonhuman primates, where it is usually identified in the female reproductive tract.

The Case of the Unusual Primate Auscultation

D Collins*, B Dozier, J Stanton, R MacAllister

University of Michigan Unit for Laboratory Animal Medicine, Ann Arbor, MI

A 6-day-old, Indian-origin SPF female rhesus macaque (Macaca mulatta) presented with bradycardia shortly following sedation with ketamine. No other abnormalities were appreciated. On recheck the following day, heart rate was normal and no cardiovascular abnormalities were identified on the physical examination. However, on pre-study examination approximately 2 weeks later, the bradycardia was again present concurrent with a regularly irregular arrhythmia. No signs of cardiovascular insufficiency were appreciated and review of the infant’s medical record indicated normal growth, feed intake, and activity levels. The animal continued to have the arrhythmia present on subsequent physical exams occasionally accompanied by decreased blood pressure. Additional diagnostics were pursued including electrocardiogram, cursory echocardiograph, and bloodwork. Cursory echocardiograph and bloodwork were normal. After consultation with a veterinary cardiologist regarding electrocardiogram results, the infant was diagnosed with intermittent ventricular parasystole. Ventricular parasystole is a separate rhythm caused by an ectopic pacemaker which is insulated from impulses from the sinus node. Ventricular parasystole has been previously described in humans, dogs, cats, and horses with varying clinical relevance and persistence. Ventricular parasystole is generally nonresponsive to medical management. Given this cardiovascular abnormality, the animal was transferred to a short-term study protocol on veterinary recommendation. On final veterinary exam, a mild grade 3/6 systolic murmur and a significant decrease in the frequency of the arrhythmia was appreciated. Gross necropsy the same day revealed mild left ventricular chamber dilation. The case exemplifies the need to appropriately screen juvenile and neonatal animals for cardiac abnormalities which can be occult early in development or intermittent making diagnosis challenging. Additionally, while often considered innocuous, ventricular parasystole was likely a contributing factor to the cardiac dilation observed in this animal at necropsy.

Nonspecific Abdominal Pain in a Rhesus Macaque (Macaca mulatta)

K Jen*, M Nowland

University of Michigan Unit for Laboratory Animal Medicine, Ann Arbor, MI

An 18-year-old intact male macaque presented with a 1-day history of abdominal pain, inappetence, anuria, signs of nausea, and decreased fecal output. On physical exam, a smooth, firm, ovoid mass was palpated in the right cranial abdomen along with scant, hard feces in the intestinal tract. Blood was collected for complete blood count and clinical chemistry and showed no abnormalities. Urinalysis from a cystocentesis showed ketonuria and proteinuria. The animal was provided with supportive care (IV fluids (LRS, 100 mL), famotidine (0.5 mg/kg IV)). Left lateral and VD radiographs were taken. Poor serosal margins and a soft-tissue opacity were evident in the right cranial quadrant of the abdomen. On the day after presentation, the animal showed signs of increased abdominal discomfort and produced only small amounts of firm, dry feces. Pain management was initiated (Carprofen (2 mg/kg) SQ BID, buprenorphine (0.07 mg/kg BID). After discussion with the veterinary staff, laboratory personnel increased dosage of buprenorphine to 0.1 mg/kg IV BID on day 4 and the animal’s mentation began to improve. Supportive care was continued and the animal was eating progressive amounts of food and passing normal stool by day 7. Laboratory personnel then disclosed that the animal had been on a test compound that could have contributed to the nonspecific abdominal pain and inappetence. It was also suspected that because of the history of chronic opioid administration, the animal also experienced withdrawal symptoms to contribute to the clinical picture seen. Nonspecific abdominal discomfort in an older rhesus macaque has many rule outs such as a foreign body, neoplasms, or intussusception; however, it is always pertinent to consider the study in which the animal is enrolled. Specifically, opiate withdrawal symptoms such as grimacing, restlessness, and inappetence which can often be misinterpreted as comorbidities of other systemic illnesses which may mask its interpretation. This case highlights the importance of history taking and considering the effects of study drugs on the clinical picture.

Abdominal Mass in an Indian-Origin Rhesus Macaque (Macaca mulatta)

LE Millen

Covance Research Products, Inc, Alice, TX

A 16-year-old male Indian-origin rhesus macaque (Macaca mulatta) presented for diarrhea, dehydration, and progressive weight loss. A physical examination revealed a large caudal abdominal mass. Due to a poor prognosis for recovery, euthanasia was elected and a complete necropsy was performed. At necropsy, a 20cm x 15cm x 10cm mass was observed in the right caudal abdomen in the region of the seminal vesicles. The vas and ureter on the right side were also enlarged. The reproductive and urinary organs on the left side appeared grossly normal. The caudal abdominal mass was submitted for histopathology. Histopathology of the testicle, epididymis, and seminal vesicle showed impaction with high numbers of viable and degenerating spermatozoa and minimal histiocytic inflammation. A diagnosis of a rare mass was made based on histopathology.

Soft Tissue Mass in the Stifle Joint of a Pigtail Macaque (Macaca nemestrina)

B Skinner*, C Johnson, S Lacy

CDC/NCEZID/DSR/ARB, Atlanta, GA

A 10-year-old pigtail macaque presented with a subcutaneous, soft-tissue mass overlying the right stifle joint. A 9.6 kg, 10-year-old, female pigtail macaque presented with soft-tissue swelling at the craniomedial aspect of the right stifle joint with no visible wounds, bruising, or hair loss present. Examination of the right pelvic limb revealed a full range of motion of the affected and a well-encapsulated, moveable, semi-firm, lobular subcutaneous mass that was approximately 5 cm in diameter. She was observed bearing full weight on the affected limb in her cage. For surgery, the animal was induced with isoflurane gas anesthesia at 5% initially, and then maintained on a 1-3% gas flow rate. A longitudinal incision approximately 1.5 inches (3.81 cm) was made deep to the skin on the craniolateral aspect of the right stifle joint just adjacent to the mass. The mass appeared pale, yellow, and lipomatous grossly. The mass was carefully bluntly dissected away from the surrounding normal tissue using Mayo scissors. The entire mass and some muscular attachments were removed. Due to the proximity of the mass to the patella, verification of the drawer reflex and cruciate ligament integrity were performed. All hemorrhage was controlled with the application of pressure or hemostats and the incision was closed in 3 layers (two simple continuous patterns with 3-0 polyglactin 910 and skin apposition with surgical glue reinforced with simple interrupted sutures of 3-0 nylon, respectively). The excised mass was fixed in 10% neutral buffered formalin and submitted for histopathology. Postsurgical analgesic treatment (0.2mg/kg of sustained release buprenorphine administered intramuscularly, and 0.3mg/kg of meloxicam given peri-operatively by intramuscular administration postoperatively by oral administration for the days after surgery) was administered. No complications occurred during surgery or recovery. The next day, the animal was observed moving around in her cage bearing full weight on the affected limb. There was no drainage observed coming from the incision site and animal did not exhibit any signs of pain. Histology revealed a rare soft tissue neoplasm of fibroblastic origin. To the author’s knowledge, this is the first reported neoplasm of this origin in a pigtail macaque.

Renal Mass in a Rhesus Macaque

J Coonen,* H Simmons

Wisconsin National Primate Research Center, Madison, WI

A 4-year old rhesus macaque presented with acute azotemia on day 199 following renal transplantation. Immunosuppression regimen following transplantation included anti-thymocyte globulin (ATG), total lymphoid irradiation, tacrolimus, and mycophenolate mofetil (MMF). Prior to acute presentation, animal had chronic mild azotemia with moderate hypercalcemia. During routine surgery for a kidney biopsy on day 182, the transplanted kidney was mildly increased in size with a 2cm dark, slightly raised lesion observed under the renal capsule. Following surgery, the mass-like area and kidney increased in size. Azotemia was stable during this time until it acutely increased on day 199. Euthanasia was elected due to poor prognosis.

Severe and Complicated Myopathy in a Common Marmoset (Callithrix jacchus)

A Dodelet-Devillers*, JM Lapointe, JC Gourdon

McGill University, Monteal, Quebec, Canada

We outline an incident of generalized myopathy in a 9-year-old male common marmoset. The animal was paired with a single adult female and presented sudden reluctance to move and dehydration without anorexia. There was no external evidence of trauma, however, the female had aborted 1 day prior to the incident and was reported to be harassing her cagemate. Clinical chemistry showed a marked elevation in serum creatine kinase (CK), aspartate transaminase (AST), sodium, and chloride. At abdominal ultrasonography, the kidneys and liver appeared normal and the colon contained normal, well-formed feces. Despite supportive therapy, the marmoset’s general condition did not improve until an abrupt deterioration and death 7 days after the initial clinical manifestation. At postmortem examination, no marked lesions were observed macroscopically, except for a retained testicle and a focal lung lesion most likely due to aspiration pneumonia. Microscopically, the skeletal muscles showed subacute to acute necrotizing myopathy, most probably of metabolic origin as the lesions were still active at time of death. In addition, there was evidence of chronic renal glomerulopathy, vacuolar hepathopathy, lymphoid depletion, and cerebral edema with indication of metabolic encephalopathy. These changes would indicate a possible metabolic disorder along with chronic systemic stress, rather than caused by a single episode of exertional rhabdomyolysis.

Comparison of 4 Different Anesthetic Protocols in Common Marmosets (Callithrix jacchus)

J Bakker*, S Roubos, S Arndt, P Kronen, J Langermans

Biomedical Primate Research Centre, Rijswijk, Holland

For major invasive procedures in marmosets, such as section cesarean or insertion of telemetric devices into the abdomen, a long-acting, safe and reliable anesthesia is required including sufficient analgesia. Limited data is available on anesthetic protocols in marmosets. Therefore, a crossover study to compare the head-to-head anesthetic effects of four suitable protocols was undertaken. Marmosets (n=10) received each of the 4 anesthetic protocols in random order on 4 occasions (days 28, 56, 84, and 112). The 4 regimens included: (1) 16 mg/kg alfaxalone i.m., (2) 16 mg/kg alfaxalone i.v., (3) 10mg/kg alphaxalone + 0.1 mg/kg medetomidine i.m., and (4) 1.5% isoflurane. To optimize the analgesic level of anesthesia, the protocols were combined with opioids and NSAIDs, i.e. a single dose of each buprenorphine 20ug/kg i.m. and meloxicam 0.40mg/kg s.c. administered one hour prior to anesthetic induction. Induction, immobilization, and recovery times were recorded. During immobilization, cardiopulmonary parameters, muscle relaxation, reflex scores, and rectal temperature were recorded every 5 minutes. Quality of induction and recovery were scored on an ordinal scale. To determine possible local myotoxic effects of the used anesthetics blood samples were collected to determine aspartate aminotransferase, lactate dehydrogenase, and creatinine kinase levels in serum. Data with respect to induction, immobilization and recovery times, cardiopulmonary parameters, rectal temperature, and blood values during the different anesthetic protocols will be discussed.

Comparison of the Effects of Ketamine and Fentanyl-Midazolam-Medetomidine for Sedation of Rhesus Macaques (Macaca mulatta)

HGMJ Bertrand*, YC Ellen, S O’Keefe, PA Flecknell

Newcastle University, Newcastle Upon Tyne, UK

This study assessed the effects of sedation using a combination of fentanyl, midazolam, and medetomidine in comparison to ketamine. Rhesus macaques (n=16, 5 males and 3 females randomly allocated to each treatment group) received either ketamine (Ket) (10mg/Kg) or fentanyl-midazolam-medetomidine (FMM) (10µg/Kg; 0.5mg/Kg; 20 µg/Kg) both IM. Oxygen (100%) was provided by mask and heart rate, blood pressure, respiratory rate, ET CO2, and depth of sedation were assessed every 5 minutes for 20 minutes. After the last time point, FMM monkeys were reversed with Atipamezole-Naloxone (0.2mg/Kg; 10µg/Kg). Recovery was scored using clinical scoring scheme. Differences in physiological parameters and quality of sedation were compared using Area Under the Curve (AUC) method and a Mann-Witney test, respectively. Heart rate (beats/min) (Ket =119±18; FMM = 89±17; p=0.0066), systolic blood pressure (mmHg) (Ket =109±10; FMM = 97±10; p=0.0313), and respiratory rate (breaths/min) (Ket=39±9; FMM=29±10; p=0.0416) were significantly lower in the FMM group. End-tidal CO2 (%) did not differ between the groups (Ket =4.4±1.1; FMM = 5.7±1.4; p=0.0462). Although some depression of physiological parameters was seen with FMM, the variables all remained within the normal ranges in both groups. Ketamine induction was more rapid (Ket =175±85s; FMM = 477±70s; p=0.0009), but FMM recovery was faster (Ket =1282±804s; FMM = 544±218s; p=0.0379) and of better quality (Ket =1.3±0.9; FMM = 7.4±1.9; p=0.0009). FMM provides an easily reversible immobilization with a rapid and good recovery quality and may prove a useful alternative to ketamine.

Prevalence and Characterization of Methicillin-Resistant Staphylococcus aureus

A Wolf Greenstein*, LC Halliday, CW Maddox, JD Fortman

University of Illinois at Chicago

Methicillin-resistant Staphylococcus aureus (MRSA) was isolated from infected wounds 4 times over a 6-month period. MRSA is known to be carried asymptomatically in human and animal populations, raising suspicions that the bacteria were present in a carrier state within the colony. With the objective of characterizing the prevalence of MRSA carriage in an academic research colony of rhesus and cynomolgus macaques, 300 animals were used in a cross-sectional analysis. Carriers were identified by deep nasal culture with bacterial isolates characterized through selective media, oxacillin sensitivity testing, and PCR amplification of the mecA gene. MRSA isolates underwent antimicrobial sensitivity testing and representative isolates were typed to determine bacterial strain origin. S. aureus was isolated from the deep nasal passages of 59.3% of colony animals with 6.3% carrying MRSA. MRSA isolates were highly resistant to beta-lactam antibiotics, which are not recommended for treatment of methicillin-resistant staphylococcal infections, regardless of sensitivity results. Isolates were also highly resistant to macrolides and lincosamides with 76.1% resistant to erythromycin and 100% resistant to clindamycin. 90.5% of isolates were resistant to chloramphenicol, and 23.8% to tetracycline, which have both been successful at treating MRSA in other species. 95.2% of isolates were resistant to enrofloxacin, which has been linked to the development of methicillin-resistant flora. However, 100% of isolates were susceptible to both rifampin and vancomycin. MRSA infections have the potential to confound research outcomes, particularly in animals that are immunosuppressed or have indwelling devices. Additionally, there is evidence that MRSA can be transmitted between animal and human populations, having both zoonotic and anthropozoonotic potential. This is the first survey of MRSA carriage in laboratory macaques, providing information to guide husbandry and clinical management, and emphasizing the emergence of antimicrobial resistant bacteria in these species.

Genotype and Risk Factors Associated with MRSA Colonization within a Population of Macaques

M Breed*, J Kramer, H Perez, C McCully, K Warren, M Otto, A Villaruz, G Alvord, RF Hoyt, Jr.

Laboratory Animal Sciences Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Bethesda, MD

Methicillin-resistant Staphylococcus aureus (MRSA) remains a significant problem for human and animal health and may significantly affect the health status of nonhuman primate (NHP) colonies and research. However a lack of published research exists on the prevalence, genotype, or risk factors of MRSA in NHPs. Following identification of a clinical MRSA case in a rhesus macaque, we sought to determine the MRSA carrier prevalence, risk factors associated with carrier status, and genotypes of MRSA within a diversely sourced population of research NHPs. Over a 5-week period we collected nasal swabs from all NHPs (n=292) with 28% (n=82) culturing positive for MRSA. We then reviewed each animal’s medical record for a variety of variables including animal housing room, sex, age, number of antibiotic courses, number of surgical interventions, and SIV status. Preliminary statistical analysis suggest that MRSA colonization is strongly associated with the room location, age of the animal, and is mildly associated with sex and the number of antibiotic courses. We used multilocus sequence typing to determine if the MRSA present in NHPs most likely originated from contact with humans. This was performed on a subset of samples (n=30) and indicated there were 2 predominant sequence types of MRSA present in the facility: ST188 and a novel MRSA genotype that most closely resembles ST2817. Neither is a common human isolate in the United States. ST188 is seen sporadically in Asia and Australia but has not previously been reported in NHPs. The second strain appears to identify a novel and previously unreported genotype. To date, no additional clinical cases of MRSA have been recognized, despite the notable prevalence that exists within the colony. This suggests that macaques may be analogous to humans in whom there is a relatively high carrier status of MRSA with low disease prevalence. We are currently investigating whether the origin of MRSA colonization was endogenous to the NHPs or was transmitted from humans. This will raise significant questions regarding how MRSA is transmitted between species and potentially provide avenues to reduce MRSA prevalence in the future if required for clinical or research goals.

Salmonellosis Outbreak in a Captive Marmoset Colony

JM Izzi*, S Smith, C Garrett

Johns Hopkins University, Baltimore, MD

A 5-year-old female common marmoset (Callithrix jacchus) presented for acute onset of lethargy and diarrhea. Rectal culture demonstrated an overgrowth of Salmonella spp. Over the next 2 months, 5 additional cases of Salmonellosis were confirmed within the same colony. Diarrhea was the most consistent presenting sign, although volume and content varied significantly by case. Additional clinical symptoms included weight loss, dehydration, anorexia, hypothermia, and septic shock. As more cases arose, the immediate threat to the health of the colony became apparent. A critical first step was the establishment of an isolation room to prevent further fecal-oral transmission. An epidemiologic investigation revealed that all affected animals either occupied adjacent cages or shared behavioral testing space. In response, strict quarantine practices were implemented, including modified husbandry, lab-wide decontamination, and specialized training of care staff. Environmental testing of laboratory equipment, food, and water sources was performed in an attempt to identify the primary source of infection; however, all results were negative. Once all outbreak control measures were in place, no additional confirmed cases were identified and thus eradication was considered successful. To date, Salmonella spp. has not been reported as a cause of infectious diarrhea in captive marmosets. Of note was the range of different clinical presentations, outcomes, and pathologic lesions observed. At the resolution of this devastating outbreak, only 2 of the 6 animals successfully cleared the infection and survived long-term. While both natural and experimental Salmonella spp. infection has been described in other nonhuman primate species, this case highlights the challenges associated with first-time management and control of this pathogen in a marmoset colony.

Improvement of Food Allergy Induced Dermatitis with Diet Change and Colloidal Oatmeal Oil Application in a Rhesus Macaque

C Sands*, A Trimble, J Goldman

Baylor College of Medicine, Houston, TX

In rhesus macaques food allergies most commonly cause gastrointestinal signs, however in the following 2 cases a different presentation was observed. In the first case a 9-year-old intact male rhesus macaque presented with dry, itchy, erythematous skin of the neck and face and was noticed to be scratching on a regular basis. The second case involved a 5-year-old intact male rhesus macaque with generalized dry, flaking, and cracking skin. This animal also experienced mild to moderate generalized alopecia, which was especially observed in the areas affected by dryness. Both of these monkeys are on neurological study protocols, and therefore wear collars at all times. An allergy to the collar material was eliminated in the first animal and food allergies were thought to be the inciting cause of dermatitis experience by both monkeys. A high-fiber diet from Harlan (the 7195 Teklad diet) was brought in, as it is wheat, gluten, and dairy free. Because food allergies can take weeks to months to improve on a new diet, a colloidal oatmeal bath oil was used directly on the animals skin to help ameliorate the inflammation, itching, and dryness experienced. Within minutes of applying the colloidal oatmeal oil both animals skin decreased significantly in redness and irritation. The oil’s positive result, however, was only short lived and required application on a fairly regular basis. After the animals were on the 7195 Teklad High Fiber diet for over 6 weeks their skin improved dramatically. In these 2 cases, the colloidal oatmeal application and change of the diet to Harlan’s 7195 Teklad diet significantly improved the dermatitis experienced by these animals.

Low-Level Laser Therapy for Chronic Implant Maintenance in Macaques

RS Blackwood

Baylor College of Medicine, Houston, TX

Low-level laser (LLL) therapy is the use of light energy to stimulate tissue repair, control infection, and provide pain management. The laser uses focused red and infrared light of various wavelengths to stimulate tissue at and below the surface of the skin. Laser therapy affects tissues at the cellular level, increasing the production of cellular energy and thus promoting cellular regeneration, production of collagen for tissue repair, and vascular dilation and synthesis for better circulation. LLL therapy decreases inflammation and encourages the release of natural pain relievers. Therapeutic laser can be used to treat a myriad of conditions. Most commonly it is used for postoperative pain management, musculoskeletal injuries, soft tissue injuries, and arthritis. At my institution, we have a small colony of rhesus macaques that are involved in basic neuroscience research. Most of these monkeys are cranially implanted, usually for many years. In some instances, skin margin infections can occur. The use of LLL therapy to treat cranial implant infections in macaques will be discussed, and in addition, the use of laser therapy for other related conditions will be presented.

Spontaneous Diverticulosis in a Female Rhesus Macaque

NR Compo*, C Crandall, J Handforth, PV Turner, AN Winterborn

University of Guelph, Guelph, Ontario

In August 2011, a 15-year-old female, ovariectomized rhesus macaque exhibited signs of colic, decreased appetite, weight loss, and scant, firm feces following sedation with ketamine for a routine, biannual health check. Minor bloodwork abnormalities were attributed to stress and dehydration. She was treated with Cerenia, meloxicam, meotclopramide, and IV fluids, after which her demeanor improved and normal feces passed. For subsequent health checks, she was treated with IV fluids and metoclopramide and she continued to gain weight, with no return of clinical signs over the next 3 years. At the July 2014 health check, an approximately 4 mm umbilical hernia was noted on physical exam. Due to previous anesthetic complications, it was decided to implement weight loss tactics and to monitor the hernia. At her next health check in January 2015, the hernia was approximately 13 mm; hernia repair was performed in February. Recovery was unremarkable, with complete healing of the hernia site. On March 2, she was observed in lateral recumbency for prolonged periods and frequently rolling, with a poor appetite. She was treated with meloxicam and tramadol with minimal improvement. On March 9, physical exam was normal other than dehydration of ∼10% and weight loss of 12.5% from her surgery date; bloodwork abnormalities were attributed to stress and dehydration. She was treated with subcutaneous fluids, metoclopramide, and meloxicam. She had continued decreased appetite and had irregular, small, firm bowel movements. On March 16, abdominal radiographs showed moderate gas distention of the large intestines, but were otherwise within normal limits. SC fluids and metoclopramide were continued daily, and ceftiofur and tramadol were initiated. Over the following month, her appetite did not improve and she frequently spit treats out. Efforts were taken to stimulate her appetite to no avail. Due to her continued decline, she was euthanized on April 27. On postmortem exam, she was diagnosed with severe diverticulitis and an acute intussusception, with ∼500 ml of greenish fluid in her stomach, despite overnight fasting. On histology, findings of the colon included mixed inflammation and edema of the lamina propria, food material surrounded by smooth muscle and inflammatory cells, and profiles of mucosa within the submucosa (diverticulosis). To our knowledge, this is the only documented case of spontaneous, clinically significant, diverticulitis in a female rhesus macaque.

Palpebral Edema in Juvenile Marmosets (Callithrix jacchus)

KA Grove*, C Zeiss, S Compton, L Conour

Princeton Neuroscience Institute, Princeton, NJ

In February 2014, a female juvenile marmoset presented with bilateral palpebral edema. Closer examination revealed corneal abrasions. Initial presumptive diagnosis following consultation with an ophthalmologist was a herpesviral infection primarily affecting the eyes. The marmoset continued to decline over the next month, and was ultimately euthanized. Over the next year, a total of 14 marmosets, newborns to ∼2years of age, demonstrated similar clinical signs and pathology findings. All cases were fatal despite multiple treatment modalities. Clinical chemistry and hematology consistently revealed severe hypoproteinemia and severe lymphocytosis. Tissue histology was consistent with a herpesviral infection. Subsequent PCR of affected tissues demonstrated the presence of lymphocryptovirus in all affected tissues. This report will review the various clinical cases that presented, the subsequent diagnostics performed, and the ongoing investigations to determine the exact role of lymphocryptovirus in these cases.

Update on Owl Monkey Wasting Disease

AG Brady*, CR Abee

University of Texas MD Anderson Cancer Center, Bastrop, TX

At the 2011 APV Workshop, we described a clinical syndrome in owl monkeys that we called owl monkey wasting disease (OMWD). The syndrome was characterized by gradual weight loss, poor hair coat, leukopenia or pancytopenia, hypoproteinemia, altered GI tract transit time, and brain lesions. Animals continue to have normal or even ravenous appetite, and OMWD has similarities to malabsorption syndromes. Except as noted below, weight loss in OMWD animals progresses until euthanasia is required (25-40% loss of body weight). A variety of metabolic, infectious, nutritional, toxic, and other etiologies have been investigated, but to date the etiology of OMWD has not been identified. Over 30 animals have been identified with clinical signs and clinical pathology results consistent with OMWD. We have developed a treatment regimen for OMWD using a combination of vitamin B12 and acupuncture that shows promise for reversing the syndrome. Ten animals have been treated with this regimen during the last 12 months, with reversal of clinical signs in a majority of animals. In some cases, treated animals matched or exceeded their maximum previous weight. Treatment generally continued for 60-90 days. Animals removed from treatment have shown no return of clinical signs after as much as 6 months.

Neurologic Disease in a Rhesus Macaque

DJ Schwahn*, JA Smith, MB Fontenot

DJSchwahn Pathology, Madison, WI

A 1.55kg 10-month-old female rhesus macaque, body condition score 3/5, was found obtunded during afternoon rounds in June 2012. The animal had 1 previous clinical presentation of an eye irritation at 2 weeks of age that resolved within 3 days. At the time of presentation she demonstrated altered mentation, ataxia, and proprioceptive deficits, but there were no obvious signs of trauma. She was nonresponsive to noise stimuli and sluggishly responsive to tactile stimuli. She was treated with dexamethasone, ampicillin, and LRS, and was tube-fed. The next morning she was laterally recumbent and nonresponsive with intermittent paddling of the limbs. She was euthanized due to lack of response to treatment. There are numerous differential diagnoses for neurological presentations in nonhuman primates; many are infectious. The only gross necropsy finding was overly engorged subdural vessels. Cerebrospinal fluid testing failed to identify evidence of cytomegalovirus. Bloodwork identified a moderate leukocytosis with neutrophilia and lymphocytosis; a few Dohle bodies were noted. A mild thrombocytopenia was also present. Histological lesions included necrosuppurative encephalitis of both gray and white matter (worst in the cerebrum), neuronolysis, a marked suppurative response, mild satellitosis, and minimal perivascular cuffing. No demyelination, inclusion bodies, bacteria, protozoa, or cytomegaly were identified. The histologic lesions in conjunction with the rapid clinical course are suggestive of Eastern Equine Encephalitis, and this alphavirus was identified by the CDC. The animal was housed outdoors as part of a breeding colony at the University of Louisiana at Lafayette New Iberia Research Center and was thereby exposed to many mosquitoes. A human case of Eastern Equine Encephalitis was reported in this area earlier in 2012. Differential diagnoses for neurologic disease in macaques include Listeria monocytogenes, West Nile Virus, St. Louis Encephalitis Virus, and Simian virus 40. Eastern Equine Encephalitis Virus is a select agent and a reportable disease with important consequences for the colony and its employees.

Reported Post-Operative Analgesic Administration to Nonhuman Primates: 2010-2015

HGMJ Bertrand*, PA Flecknell

Newcastle University, Newcastle Upon Tyne, UK

It is widely accepted that animal undergoing invasive experimental procedure should receive an appropriate analgesic regimen consistent with the nature of the procedure and the aims of the research protocol. We reviewed the reported use of analgesics in nonhuman primates used in research procedures. The Pubmed online database was searched using the key words “macaca” and “surgery” and the results were sorted using the option “most recent.” A first pool of 620 scientific publications covering the period from 2015 to end of 2010 was extracted. From this first pool, 257 papers were selected based on the following inclusion criteria: the use of a nonhuman primate in a research protocol involving invasive surgery. Each paper was reviewed to extract information concerning the use of postoperative analgesia. In papers where only a general reference to national and international guidelines about the use and the care of laboratory animals was made, these guidelines were consulted to determine their recommendations on analgesic use. Clear statement about the use of postoperative analgesia was made in only 73 publications (28%) but 21 (29%) of these did not specify the analgesic agent. When used as a sole analgesic agent, 16 (22%) these papers reported the use of NSAIDs and 18 (25%) an opioid. Carprofen and buprenorphine were the most frequently used agents. Multimodal analgesia, combining opioids and NSAIDs, was also noted and represented 22% of the totality of analgesia regimen reported. Overall of the 184 publications (72%) that did not report any use of analgesia, 117(64%) made a reference to relevant guidelines such as the National Institute of Health Guide for the Use and the Care of Laboratory Animals or the European Directive, both of which require use of analgesics unless they are specifically contraindicated. The remaining 67 papers (26%) gave no indication as to whether analgesics had been administered. This review highlighted the lack of reporting of analgesics regimens in the peer-reviewed literature. It may represent either under-reporting, or under-use. A similar lack of reporting has previously been noted in in laboratory rabbits, rodents, and ruminants. The use of all animals, but particularly nonhuman primates, in scientific research is of considerable public concern. A particular concern is that pain is prevented whenever possible. It is therefore important that measures taken to improve animal welfare, such as analgesic administration, are reported. It is also important to report the agents used, dose, and frequency and duration of administration, since this will enable more effective sharing of experience amongst those responsible for the post-surgical management of these animals. We hope that the results of this review will promote better reporting of analgesic use. This can be encouraged by appropriate feedback from those undertaking peer-review of articles, and by journals adopting reporting practices such as those outlined in the ARRIVE guidelines.

An Unusual Presentation of Hemangiosarcoma in a Cynomolgus Macaque (Macaca fascicularis)

KE Breyer*, M Simkins, T Boulineau

Novartis Pharmaceuticals, East Hanover, NJ

A 7-year-old male cynomolgus macaque (Macaca fascicularis) was reported for a bleeding wound on the lateral tarsus, suspected to be a result of trauma. On closer inspection, the bleeding area was discovered to be a ruptured skin mass. Additionally, multiple subcutaneous firm nodules were palpated on the foot and lower leg (unilateral). Mild anemia was noted on a complete blood count. The skin mass was removed for histopathology and supportive care was initiated. Histopathology from 2 different diagnostics labs had equivocal results, with main differentials of granulation tissue and fibrous reaction; however, one pathologist mentioned a slight suspicion of hemangiosarcoma due to several atypical cells on the margin. Within several days, the animal was nonweight bearing on the affected leg and the anemia became severe. Thoracic radiographs revealed multiple large nodules within the lungs. The animal was euthanized due to the poor prognosis. On necropsy, there were multifocal coalescing subcutaneous nodules adhered to the muscles of the foot, ankle, and extending up the calf. The spleen, lungs, and pleural cavity contained multifocal nodules. A diagnosis of metastatic hemangiosarcoma was given, though it is unclear if the initial neoplasia started as a dermal or splenic form. This case had a very unusual presentation and neoplasia was not initially considered. A discussion of the clinical signs, diagnostics, and differentials will be presented, along with information about hemangiosarcoma in nonhuman primates.

Introduction to the Benefits of Acupuncture in Laboratory Animal Medicine

SJ Buchl*, ER Magden

MD Anderson Cancer Center, Bastrop, TX

Acupuncture is an integrative therapy that can enhance clinical outcomes for a variety of health conditions. In the laboratory animal field, acupuncture has recently been used to treat pain associated with arthritis in nonhuman primates, with a demonstrable benefit. These observed benefits can extend to numerous other laboratory animal species. Here we present an introduction to a few acupuncture points that have significant benefits when used in emergency situations or to stimulate healing in the course of clinical treatments. This introduction focuses on 6 acupuncture points that may help you in a critical or clinical situation. The introductory acupuncture points that will be covered include GV26, ST4, Wei Jian (tip of the tail), CV1, GV1, and PC6. For formal training on veterinary acupuncture, there are several courses offered that provide a comprehensive overview of the benefits of acupuncture.

Accuracy of Human and Veterinary Point-of-Care Glucometers in Nonhuman Primate Species

EA Clemmons*, MM Crane, DJ Kempf, D Owens, M Stovall, KF Ethun

Yerkes National Primate Research Center, Emory University, Atlanta, GA

Data from animal studies indicate that point-of-care glucometers should be species-specific due to differences in red blood cell glucose concentrations. Hematocrit levels also influence glucometer readings. Given that these parameters vary across NHP species, it is currently unknown whether human or veterinary glucometers are more appropriate for use in particular NHP species. Therefore, the first aim of this study was to compare the accuracy of 2 human and 2 veterinary glucometers in 3 NHP species with different hematocrit ranges. Subsequent aims assessed the impact of hypoglycemia, hyperglycemia, and sampling site on glucometer accuracy. Subjects were 80 rhesus macaques (Macaca mulatta), 50 sooty mangabeys (Cercocebus atys), and 12 chimpanzees (Pan troglodytes). Human glucometers, ACCU-CHEK® and FreeStyle®, and companion animal glucometers, AlphaTRAK2® and GlucoPet®, were evaluated. Accuracy was defined as the mean difference in blood glucose (BG) between each glucometer and a laboratory glucose analyzer. In all NHP species, mean differences in BG between the veterinary glucometers and analyzer were significantly different from the human glucometers. Specifically, the veterinary glucometers overestimated the true BG value by 26-75 mg/dl in all species, whereas both human glucometers were within 7 mg/dl. The 2 human glucometers performed similarly in all 3 NHP species in a euglycemic state. When assessing each human glucometer in hypoglycemic and hyperglycemic mangabeys and macaques, only the FreeStyle glucometer significantly underestimated the true BG value in hyperglycemic (diabetic) mangabeys compared to euglycemic mangabeys. This finding was not shared by ACCU-CHEK, suggesting that ACCU-CHEK maybe more accurate than FreeStyle glucometers in diabetic mangabeys. Venous-derived BG values were significantly lower than those derived from capillary samples, emphasizing the importance of sampling site during glucometer interpretation. Overall, findings from this study show that glucometers intended for companion animals are inappropriate for use in these NHP species, whereas the human glucometers showed clinically acceptable accuracy.

Optimization of Leukapheresis in Rhesus Macaques

J Coonen*, K Brunner, J Post

Wisconsin National Primate Research Center, Madison, WI

Leukapheresis is an alternative to bone marrow harvest to collect hematopoietic stem cells (HSC) for transplantation. The small size of rhesus macaques poses a challenge for this procedure due to the large extracorporeal blood volume needed to prime the apheresis machine. The Spectra Optia apheresis system has begun to be used in macaques as a replacement for an older apheresis system. The lower extracorporeal volume of the Spectra Optia apheresis system makes it more ideal for use for rhesus macaques weighing at least 5kgs. Mobilization regimens, anesthesia, catheter placement, apheresis machine set-up, fluid support, and clinical monitoring for leukapheresis procedures in rhesus macaques will be discussed.

Validation of a Multiplex Antibody Diagnostic Test for Tuberculosis in Nonhuman

RK Dhawan*, ME Dodge, R Ravindran, IH Khan

Charles River Laboratories, Wilmington, MA

Tuberculosis (TB) in nonhuman primates is highly contagious and often produces rapid disease. Identification of animals infected with Mycobacterium tuberculosis (M. tb.) in a timely manner is therefore critical. Animals in breeding colonies are periodically tested using the tuberculin skin test (TST) and/or a commercially available in vitro blood-based assay of cell-mediated immunity. However, these tests lack desirable sensitivity, specificity, efficiency, and/or throughput. We have developed a blood-based multiplex immunoassay based on antibody profiling in M. tb.-infected animals that can be used potentially for routine colony surveillance. In continuation of our previously published proof-of-concept studies we have used a Luminex bead-based multiplex panel with 28 M. tb antigens/assays in the current validation study. Antibody levels were examined in plasma samples from several cohorts of well characterized specific pathogen-free (SPF) colonies at several. A total of 684 healthy macaques were used in the validation study to determine specificity of the test. Sera from two different rhesus macaque (Macaca mulatta) colonies (n=460) and 2 cynomolgus macaque (Macacca fasicularis) colonies (n=224) were used in the study. The cut-offs were calculated and overall specificity of the test was found to be 90%. The panel was screened for sensitivity using experimentally infected rhesus (M. tb. strains: Erdman, n=6 and H37RV, n=4) and cynomolgus macaques (Erdman, n=9). The panel sensitivity was between 80-100% at various time points (8, 12, 16, and 24 weeks) during seroconversion. In conclusion, we have validated a blood-based test which is highly sensitive and specific for screening of M. tb. in nonhuman primates and can be performed in a user friendly and high-throughput format.

Use of Automated Feeding Stations to Enhance the Veterinary Care and Management of Socially Housed Rhesus Macaques (Macaca mulatta)

KF Ethun*, S Dicker, B Hughes, ZP Johnson, ME Wilson

Yerkes National Primate Research Center, Emory University, Lawrenceville, GA

As part of a research program to understand how social factors affect food preference and calorie intake, automated feeding stations were developed in collaboration with Research Diets, Inc. to quantify individual calorie consumption in free-feeding, socially housed rhesus macaques. As animals obtain food pellets, the computer-controlled system reliably records grams obtained in real-time by detecting unique RFID microchips implanted in each hand of individual animals. The Yerkes NPRC Field Station currently has 8 runs and 4 compounds with automated feeding stations, consisting of approximately 575 animals of various ages and genders. Validation studies reveal that animals readily learn to obtain food with no training, animals eat what they obtain, and, because food is continuously available, dominant animals do not restrict access of more subordinate animals to feeders, thus maintaining ad libitum access. In addition to novel scientific value for assessing appetite, these feeding stations offer several veterinary care and management advantages over standard bin feeding practices. First, use of automated feeders in large breeding groups provide valuable insight into how age, gender, social rank, and reproductive status influence feeding behavior. This information can then be used to enhance the clinical monitoring of group-housed animals. Animals with reduced appetite, based on age, gender, and reproductive status, can be identified from daily feeding reports, alerting veterinarians to possible impending clinical problems. The daily feeding reports also provide a continual census of group-housed animals. Furthermore, software has the capability to limit individual food availability and thus consumptio, thereby identifying a method to treat obesity in socially housed monkeys. Additionally, animals fed from automated feeders discard significantly less food compared to bin-fed animals, which may result in cost-savings through food waste reduction. Information gained from this report will be beneficial to others interested in alternative feeding strategies for captive macaque colonies.

Antibodies against Zoonotic Arboviruses in Wild-Caught Neotropical Nonhuman Primates

*AS Gozalo, EJ Montoya, WR Elkins

Comparative Medicine Branch, National Institute of Allergy and Infectious Diseases, National Institutes, Bethesda, MD

Serum samples from 102 recently wild-caught nonhuman primates (40 Saimiri spp. monkeys, 25 Aotus vociferans, and 37 A. nancymae) were tested for IgM and IgG antibodies by enzyme-linked immunosorbent assay (ELISA) against Mayaro, Venezuelan equine encephalitis, Yellow Fever, Oropouche, and Dengue 1-4 viruses. These viruses were chosen because they are recognized causes of human disease in the region. All antibody positive sera were diluted and tested to determine the titers. Sixteen out of 102 monkeys (15.7%) were found to have antibodies to at least 1 of 3 viruses in the arbovirus panel tested. Ten monkeys (9.8%) showed antibodies to Mayaro virus (9 IgG and 1 IgM), 5 monkeys (4.9%) showed IgG antibodies to Venezuelan equine encephalitis, and 3 monkeys (2.9%) were positive to antibodies against Yellow Fever virus (2 IgM and 1 IgG). Out of 40 Saimiri spp. tested, 6 (15%) had IgG antibodies against different arboviruses. These were distributed into 5 (12.5%) against Mayaro virus and 1 (2.5%) against Yellow Fever virus. Out of 25 Aotus vociferans tested, 1 (4%) had IgM antibodies against Mayaro virus suggesting a recent infection. And out of 37 Aotus nancymae tested, 9 (24.3%) were found to be antibody positive for at least 1 arbovirus, distributed as follows: 5 (13.5%) had IgG antibodies to Venezuelan equine encephalitis virus, 4 (10.8%) had IgG antibodies to Mayaro virus and 2 (5.4%) were positive to Yellow Fever virus IgM antibodies suggesting also a recent infection. One adult female A. nancymae had IgG antibodies to Mayaro and Venezuelan equine encephalitis viruses, and IgM antibodies against Yellow Fever virus. No antibodies were detected against Oropouche or Dengue viruses. The potential presence of antibodies against arboviruses in wild-caught monkeys must be weighed when using these animals as experimental models. Routine screening may be recommended.

Unilateral Hydronephrosis Secondary to Endometriosis in a Rhesus Macaque (Macaca mulatta)

AJ Haertel*, R Sammak

California National Primate Research Center, Davis, CA

A 12-year-old, female, rhesus macaque (Macaca mulatta) presented with poor appetite and 11% weight loss over 2 months. Attempts to breed this animal were unsuccessful in the 2 years prior to presentation. A physical exam and results of routine hematologic and serum biochemical analyses revealed a body condition score of 2.5 and a mild azotemia with creatinine 1.6 mg/dL (range: 0.8-1.2 mg/dL). Abdominal ultrasound revealed a severely dilated left renal pelvis and severe dilation of the left ureter until the insertion on the bladder. Additionally, 3 round hypoechoic structures were identified on the serosal surface of the uterus near the trigone and the cervix. A presumptive diagnosis of ureteral obstruction secondary to endometriosis was made. Due to the poor long-term prognosis, the animal was euthanized. Necropsy revealed entrapment of the left ureter by endometrial cysts and unilateral hydroureter and hydronephrosis. The residual left kidney parenchyma was pale. Two 3 mm pale tan masses were clustered in the bladder epithelium at the trigone in possible obstruction of the left ureter. The right kidney was unremarkable on gross examination. A left ureter urine biochemistry analysis showed a mildly elevated protein/creatinine (UPC) ratio of 0.6. Representing right kidney function, urine from the bladder had a moderately elevated UPC of 1.9. The combination of mild azotemia and protein loss confirmed renal disease in the right kidney. Ureteral obstruction by endometriosis has been reported in a Guinea baboon (Papio papio) and humans, but this is the first report of such a case in a rhesus macaque.

Retrospective Analysis of Trichobezoar and Phytobezoar Cases in Rhesus Macaques (Macaca mulatta)

AJ Haertel*, L Garzel

California National Primate Research Center, University of California—Davis, Davis, CA

Trichobezoars and phytobezoars are stomach masses composed of compact hair or plant material, respectively, and mucus. Both can present asymptomatically in rhesus macaques (Macaca mulatta); however they may be associated with vomiting, anorexia, and weight loss. The incidences of these gastric masses are unknown in rhesus macaques, and contributing factors are not yet completely understood. Retrospective analysis of surgery and necropsy records from 2001 to 2014 revealed 33 phytobezoars and 106 trichobezoars. Trichobezoar incidence (1.48 cases per 1000 animals per year) was significantly higher than phytobezoar incidence (0.43 cases per 1000 animals per year; p<0.01). Females were 1.8 times more likely to develop trichobezoars and 3.0 times more likely to develop phytobezoars than males (p<0.01). The mean age of animals with trichobezoars and phytobezoars was not statistically different. Recurrences were not significantly different between trichobezoars (10% of animals) and phytobezoars (11.4% of animals). The mean time of bezoar recurrences were not significantly different. Fifteen trichobezoar cases were from females in a single outdoor field pen that houses multiple families of macaques. Overall, with up to 19 cases a year, gastric trichobezoars and phytobezoars are relatively common at the CNPRC. These masses are more often seen in females than males and appear to be uncommon in animals less than 2.5 years old. Bezoar recurrences accounted for a minority of cases, but related animals from a single field pen accounted for a large proportion of trichobezoar cases. Further investigations of field pen risk factors may be needed to clarify risk factors related to this cluster.

Arteriovenous Fistulas in Rhesus Macaques as a Consequence of Phlebotomy

AL Hoggatt*

Harvard Medical School, Boston, MA

Arteriovenous fistulas (AVFs) are abnormal communications between tangential arteries and veins. The cause of AVFs can be congenital, secondary to penetrating trauma or iatrogenically induced after catheterization or phlebotomy. Significant clinical consequences can result from the hemodynamic left-to-right shunt induced by AVFs and thus their prevention is important in the research setting to minimize confounding factors caused by AVFs in experimental studies. This report describes the signalment and circumstances that surround 6 cases of AVFs in research rhesus macaques at the New England Primate Research Center over a period of 3 years. Summarized in the report are simple methods of characterization of AVFs including basic ultrasound localization and measurement and assessment of hemodynamic impact. Risk factors associated with AVF formation are hypothesized related to location of femoral phlebotomy technique. Finally, treatment options are presented including one method of surgical correction and the related outcomes.

What’s Your Diagnosis: Unexplained Neurologic Disease in a Black-and-white Ruffed Lemur (Varecia variegata)

J Kylie*, PV Turner

University of Guelph, Guelph, Ontario

In November 2014, a 12 year-old male, black-and-white ruffed lemur from a private zoo suffered a cardiac arrest during routine examination and vaccination. The animal was revived with epinephrine and oxygen, but developed severe neurological signs 3 days later. The lemur was ataxic with poor mentation for an additional 6 days while being treated orally with glucocorticoids. Because of the poor prognosis, the animal was euthanaized and a postmortem evaluation was conducted. On external examination, the animal was in good physical condition and gross lesions included mild, chronic, multifocal renal infarction, mild pulmonary congestion and edema, mild cardiac ventricular hypertrophy, and hemorrhagic pancreatitis. No neurologic abnormalities were identified. Microscopically, there was a focal area of neuropil effacement with replacement by moderate numbers of macrophages containing foamy eosinophilic cytoplasm (gitter cells), occasional neutrophils, and necrotic neurons within the cerebral white matter. A smaller focus composed of similar cells was present adjacent to this, giving a tract-like appearance to the lesion. There was also occasional lymphoplasmacytic cuffing of vessels and focal gliosis within the mid-to-outer lamina of the section. Additional microscopic changes identified included moderate renal tubular degeneration and regeneration with glomerulosclerosis and a focal chronic infarct, chronic hepatic hemochromatosis with moderate single cell hepatic necrosis, fibrosis and bile ductule hyperplasia, intestinal hemochromatosis, and acute pancreatitis. While the histologic changes observed in the brain could account for the neurologic signs observed clinically, the underlying pathogenesis was not identified. Brain lesions were most consistent with infectious disease, such as Toxoplasma gondii or Baylisascaris procyonis; however, no bradyzoites or parasite sections were identified and immunohistochemistry for toxoplasmosis was negative. Additional diagnostics were limited due to the premortem administration of steroids and the CITES 1 status of this animal, leaving the cause of this chronic, focal, granulomatous encephalomalacia and mild gliosis still unknown.

Nonhuman Primate Body Temperature Comparison Method

MM Laffins, C Almlie, A Regalia, D Reims*

Charles River, Reno, NV

We compared NHP temperature data to evaluate the differences between rectal, infrared (inguinal and chest), and telemetry temperature readings in sedated NHPs. Our focus was to show that we could replace the standard rectal temperature with the infrared device and not compromise our evaluation of body temperature for diagnostic or clinical examination purposes. The rectal thermometer, which requires physical restraint or sedation, has a slight risk of rectal trauma and it takes 30 seconds to 1 minute to record the temperature. The infrared thermometer readings are instantaneous and require no contact with the animal. We collected body temperature data on 206 (138 male and 68 female) cynomolgus macaques under ketamine (10mg/kg) IM sedation over a 3-month period of time as part of scheduled physical examinations. All animals were evaluated with our digital rectal and TempIR infrared devices. The infrared device measurements were taken 5cm from the chest and inguinal areas (least hair interference). We then used 10 ketamine (10mg/kg) IM sedated cynomolgus macaques (5 male and 5 female) instrumented with a commercially available telemetry signal simulator in a muscular pouch between the internal and external abdominal oblique muscles on the flank to compare the telemetry temperature to rectal and infrared inguinal and chest measurements. We determined the body temperature mean, median, and standard deviation for the telemeterized and non-telemeterized animals. Results of the non-telemeterized animals showed a mean value of 102.30 F for inguinal, 101.41 F, for chest and 101.33 F for rectal. The data set for these animals showed a slight but statistically significant difference between inguinal and rectal measurements and no significant difference between chest and rectal measurements. The telemeterized group showed a mean of 100.6 F for rectal, 99.5 F for telemeterized animals, 99.5 F for inguinal, and 99.6 F for chest measurements. The trend for this group was excellent consistency between infrared methods and telemetry (core body temp) readings and a consistent deviation of approximately 1 degree F between rectal and telemetry readings.The results confirmed our hypothesis that the infrared thermometer could be used to replace our standard rectal thermometer due to all readings being within the macaques normal temperature range of 99.5-102.5 F.

Viral Serological Surveillance of a SPF Cyno Colony in Mauritius

S Lefin D de Marigny*, L Levallois

Noveprim Ltd, Vieux Grand Port, Mauritius

The Cynomolgus macaque (Macaca fascicularis) is the most widely used nonhuman primate (NHP) in biomedical research. Cynos are mainly used in safety toxicology and pharmacokinetics, but depending on their genetic and health backgrounds they can also be of strong interest in other fields of research like immunology, immunotherapy, gene therapy, and fundamental research in infectious diseases and neuroscience. NHPs can harbor a variety of pathogenic and opportunistic organisms, which can compromise animal health and welfare as well as studies outcomes. In addition, background infections may also present a zoonotic risk to animal care staff. The Mauritius cynomolgus is renowned for its natural SPF status which makes it the model of choice for many researchers. Noveprim has been breeding cynos on Mauritius for 25 years and currently houses 15,000 NHPs. We run a viral screening program in order to prove the maintenance of the SPF status as well as to develop new models for better refined research. Screening panels include common simian retroviruses but also other viruses, such as hepatitis viruses, measles, or adenovirus that can impact study designs. We disclose serology results collected on Noveprim’s colony and highlight their interest in specific research fields.

Blood Parameters in Sexually Mature Female and Male Long-Tailed Macaques (Macaca fascicularis) from Mauritius

S Naiken, M Griffiths, J Hurdial, S Narainapoulle, P Honess*`

Bioculture Group, Riviere des Anguilles, Mauritius

The long-tailed macaque (Macaca fascicularis) is the most commonly used nonhuman primate model in biomedical research and those of Mauritian origin are particularly important in many areas of research. Despite this, few data are available on blood parameters of this species. Determining reference intervals for blood measures provides important tools for clinical diagnosis and preclinical research. To determine some of these measures, blood samples from sexually mature female (n=90; body weight range; 3.05 to 6.96 kg; age range: 2.7 to 12.5 years) and male (n=110; body weight range: 6.18 to 9.58 kg; age range: 4.9 to 7.3 years) long-tailed macaques of Mauritian origin were analysed. Samples from the females were analysed for biochemistry only, whereas those from the males were analysed for both biochemical and haematological parameters. We presemt blood reference interval data (females: 9 biochemical parameters; males: 13 biochemical and 13 haematological parameters) as well as results of analyses of the effects of age, weight, body mass index, crown-rump length and breeding origin (captive-bred or wild-caught) on blood parameters. It is expected that these data will provide important background information on long-tailed macaques of Mauritian origin both for those who use them in their research and for primate veterinarians in their diagnosis and treatment of similar animals.

Use of the Baboon as a Model for Biomedical Research

AN Preno*, RF Wolf, JF Papin, MD Chavez, GL White

University of Oklahoma Health Science Center, Oklahoma City, OK

Over the last half century the baboon has become one of the most common nonhuman primates used in biomedical research. A recent Medline search revealed over 1,000 scientific publications over the last 5 years that used the baboon as the animal model. Baboons are ideal for vaccine and immunological studies because they possess all four IgG subclasses similar to man. Recent infectious disease and vaccine studies by our resource group include: Respiratory Syncial Virus, Bordetella pertussis, Ebola, Schistosoma mansoni, West Nile Virus, and Entamoeba histolytica. Our baboon resource supports baboons as the recipient in xenotransplantation studies for several outside institutions. Currently we conduct collaborative studies using the baboon as a model for therapeutic studies for sickle cell disease and thalassemia. Baboons have long been the model of choice for septic shock studies conducted at the University of Oklahoma Health Science Center. The baboon ranks third as the most commonly used nonhuman primate in biomedical research due to its similar characteristics and phylogenetic makeup of man.

Canine Tooth Pathology following Canine Crown Reduction and Canine Blunting in Rhesus Macaques

RL Sammak*, C Meier, R Keesler

California National Primate Research, Davis, CA

Rhesus macaques are a social species, but group housing puts them at risk for deep muscle lacerations due to conspecific trauma. Preliminary research evaluating canine tooth modification has shown decreased rates of injury involving muscles and tendons when either canine crown reduction or canine blunting has been performed. Canine crown reduction is currently considered an unacceptable practice according to Animal Care Policy 3 due to the potential for dental complications. To evaluate the effects on group trauma, 38 adult male macaques were enrolled in the study to evaluate potential group welfare benefits of each canine tooth modification procedure. Concurrently, these animals were monitored for any signs of tooth compromise. Animals in 9 large outdoor enclosures were involved in this study. Twelve male macaques had canine crown reduction performed, 12 male macaques had canine blunting performed every 6 months, and 14 male macaques had no manipulation of their teeth. All animals received an oral exam and dental radiographs prior to any manipulation, and follow-up oral examinations and radiographic monitoring were performed after 3, 6, 12, 18, and 24 months in addition to routine physical exams twice per year. Animals with evidence of pulp exposure or radiographic evidence of tooth root abscess development received veterinary care as indicated. At the 18-month time point, 6 animals (50%) in the canine crown reduction group, 6 animals (50%) in the canine blunting group, and 1 animal (7%) in the unmanipulated group required at least one canine tooth extraction. Histopathology was performed on 11 of the extracted teeth. Animals in the canine blunting group were most likely to present with pulp exposure evident on oral examination. Animals with canine crown reduction sometimes had gross evidence of pulp exposure, but 3/6 animals (50%) had only radiographic evidence of pathology at a routine screening timepoint. The 1 animal from the unmanipulated group presented with pulp exposure on oral examination due to a tooth fracture. Histopathology of extracted teeth from the blunting group showed dentin remodeling in 2/3 (67%) of animals evaluated. In this study, both canine crown reduction and canine blunting with a nonirrigated tool have the potential to result in tooth compromise. Canine tooth pulp exposure following blunting may be secondary to behavioral changes with an increase in honing and excessive wear versus a direct effect of the blunting procedure. Further studies are required to optimize the blunting technique and evaluate for a behavioral component.

Ampullary Carcinoma in a Geriatric Rhesus Macaque (Macaca mulatta)

C Sands*, JL Goldman, RE Price

Baylor College of Medicine, Houston, TX

The ampulla of Vater, also known as the hepatopancreatic ampulla, is a small structure that projects into the lumen of the duodenum in humans and rhesus macaques. In humans, a carcinoma of the ampulla carries a better prognosis when compared to peri-ampullar carcinomas, so it is important to be able to distinguish between these. The most common clinical signs are weight loss, anorexia, nausea, vomiting, jaundice, and diarrhea. In this case a 28-year-old intact male rhesus macaque presented with increased liver enzymes, jaundice, and lethargy on biannual physical exam. One week later, repeat blood work revealed further elevation in liver enzymes, increased cholesterol and bilirubin, and a decreased total protein. Due to the animal’s poor prognosis, euthanasia was elected. On necropsy, a severely distended and tortuous bile duct was seen. Other significant findings included an enlarged and firm liver and a 3.75cm mass incorporating the duodenum, pancreas, and biliary tract. Histological examination of the tissues revealed an ampullary carcinoma, which led to occlusion of the pancreatic and common bile duct. This partial to complete occlusion of the bile duct was the basis of the clinical signs exhibited in this patient.

Prevention of Sciatic Nerve Injuries from Injectable Anesthetics in Cynomolgus Macaques

JL Seeman*, W Dochterman, S Van Adestine, N Kaplewski

Covance Laboratories, Inc, Madison, WI

Cynomolgus macaques are used for various ocular studies in our facility. These animals undergo a test article dosing phase followed by a monitoring phase with several ophthalmic exams performed by board-certified veterinary ophthalmologists and technical staff. They also undergo specialized imaging techniques to assess the impact of the drug on the eye. The animals are generally sedated for these procedures, primarily with ketamine alone or with combinations such as ketamine/dexmedetomidine. We have recently seen cases where an animal presents with lameness of the injected hind limb. The clinical presentation typically involves an animal not using a hind limb normally while moving about the cage. Examination reveals a limb with atrophied hamstring musculature as compared to the other leg. The grip of the foot is weak and withdrawal from a toe pinch is often not elicited. As time passes, there may be a contracture of the limb at the stifle from the disuse. In long-term injury, the limb cannot be fully extended and technical staff will report the knee is swollen due to atrophy of the surrounding musculature. This typical presentation is often observed several weeks after the injury occurred. In an effort to prevent these types of injuries, management mandated that primates be hand caught by one technician so that another can restrain the limb and administer the injectable anesthetic agents directly into the quadriceps musculature, avoiding the lateral limb entirely. In addition, training of the ocular group has been performed. It’s difficult to find an accurate picture of the sciatic nerve route that can be readily pictured and understood by the technicians. A better means to address these issues was to obtain the carcass of a recently euthanized macaque and perform a dissection of 1 hind limb to expose the sciatic nerve pathway from the spine. Reflecting the musculature reveals the pathway. Technicians were presented this model with the opposite limb left intact to allow comparisons and palpation of the intact musculature once the nerve had been viewed. The most predominant comment was that they couldn’t believe the large size of the nerve. Feedback revealed this was a more understandable training method as opposed to previous lectures. The training group also viewed this model to assist their training of new technical staff on administration of IM injections. A PowerPoint presentation was developed using photographs taken of the exposed sciatic nerve to use as a teaching tool.

Preoperative Antiemetic Use in Macaques

JR Steinbach*, G Roble

New York University, New York, NY

Postoperative complications are a major concern after prolonged inhalation anesthetic time in NHPs. Vomiting during recovery from anesthesia can lead to asphyxiation and aspiration pneumonia. Macaques are recognized to frequently vomit during recovery, necessitating immediate prone positioning and oral cleansing. Beyond the risk of aspiration, this also poses a risk to personnel handling the animal as this requires close manipulation of the mouth, increasing the risk of a bite wound. Postoperative nausea and vomiting (PONV) is a recognized complication in upwards of 30% of human anesthesia cases. We estimate that we see postoperative vomiting in approximately the same percentage of our macaque anesthetic cases. We aim to eliminate or decrease vomiting postoperatively by adding an antiemetic, maropitant, to the pr-medication protocol. Maropitant citrate is a veterinary-use labeled neurokinin (NK1) receptor antagonist antiemetic that is used very commonly in clinical practice to prevent and treat vomiting. NK1 receptor antagonists are also frequently used in human medicine to reduce PONV. We believe the standard use of antiemetic drugs prior to Macaque inhalation anesthesia will improve postoperative recovery.

Epidemiological Study of Yersinia pseudotuberculosis Infection in Macaques

C Zao*, L Tomanek, A Krueger, L Garcia, A Cooke, R Berger, B Bernacky, E Mendoza, P Hidalgo, MH Cottingham

VRL, San Antonio, TX

Yersinia pseudotuberculosis infected primates can be asymptomatic or become chronic carriers. Acute infection without proper treatments could lead to death. A survey of Yersinia infection in cynomolgus, pigtailed, and rhesus monkeys demonstrated that 99 Yersinia isolates collected during 2014-2015 June were all identified as Y. pseudotuberculosis and none was Y. enterocolitica. Genotyping PCR performed for 16 isolates sampled from colonies located in different states showed that only wbyK+ O:3 genotype was detected among 21 known O-genotypes. This atypical O:3 Y. pseudotuberculosis was also found to cause fatal yersiniosis in cynomolgus monkeys. To evaluate whether stool or rectal swab was the more suitable specimen type for Yersinia isolation and PCR, both stool and rectal swab samples were collected from 32 animals. A higher positive rate was obtained if stool was used for isolation (46.9% vs. 34.3%) and for PCR (87.5% vs. 84.4%). Antimicrobial susceptibility patterns of 9 isolates showed a few differences, but overall they were sensitive to amoxicillin/clavulanic acid, ampicillin, azithromycin, cefazolin, cefoxitin, ceftazidime, gentamicin, piperacillin/tazobactam, and tetracycline. Since atypical O:3 was the only genotype detected in all infected macaques selected to be tested so far, vaccine development for preventative treatment will aim to elicit protective immunity against wbyK+ O:3 genotype Y. pseudotuberculosis in our future study.

Detection of a Novel Simian Retrovirus Type from Cynomolgus Monkeys in the U.S.

C Zao*, L Tomanek, A Cooke, R Berger

VRL, San Antonio, TX

Exogenous simian retroviruses (SRV) found in nonhuman primates have been named as SRV-1 to SRV-7 based on the neutralization or molecular genetic analysis. A new SRV type, which was discovered in China from Cambodian-origin cynomolgus monkeys in 2013 expands SRV types to be eight total. The similar new SRV type had not been seen in the U.S. until recently 15 positive cynomolgus monkeys were diagnosed to be SRV positive in our routine screening tests. Three typical SRV serological and PCR patterns were observed within these positive animals: (1) 4 animals were SRV serology and PCR positive; (2) 6 animals were SRV serology positive, but PCR negative (implying in late infection stage); (3) 5 animals were SRV serology negative, but PCR positive (implying in newly infection stage, all were seroconverted to positive in the follow-up samples). SRV was successfully isolated from 8 infected animals. Histopathology examination from two of necropsied animals showed multifocal lymphoplasmacystic and histocytic inflammation. The whole genome sequences demonstrated to have a 1.03% (84/8138 b.p.) difference compared to the new SRV type isolated in China, but they were grouped together in the phylogenetic analysis. While our new SRV type is only 67.5-73.6% identical to SRV-1, 2, 3 & 4, the current serologic and PCR diagnostic methods utilized to detect SRV-1, 2, 3, 4, 5 cross react with each other and would not cause false negative to diagnose this new SRV type.