2010 Association of Primate Veterinarians Workshop

Abstracts of Scientific Papers 2010 Association of Primate Veterinarians Workshop

Oral Case Reports Utilization of the Baboon in Biomedical Research

Comparison of Rectal and Tympanic Core Body Temperature GL White*, RF Wolf, JF Papin, R Eberle Measurement University of Oklahoma Health Sciences Center, Oklahoma CT Long*, C Pacharinsak, K Jampachaisri, GP McKeon, AM City, OK Howard, MA Albertelli, SA Felt The baboon is a relative newcomer to the repertoire of non- Research Animal Facility, Stanford University, Stanford, CA human primates used in biomedical research. In less than 50 y baboons have become one of the more popular laboratory primate Obtaining a core body temperature in a manner that is safe species, and its genome is currently being sequenced by the Hu- for veterinary personnel and animals is an important part of a man Genome Sequencing Center. The baboon is larger than the physical examination. For nonhuman primates, this generally most laboratory primates, making it the species of choice in many involves the use of anesthetics and their deleterious effects on biomedical protocols, including experimental surgery, xeno- body temperature measurements. The purpose of this study transplantation, and imaging studies. Baboons closely resemble was to compare 2 noninvasive methods of infrared tympanic humans in many physiologic and disease processes, including thermometers to standard rectal temperatures in adult squir- cholesterol metabolism, development of atherosclerosis, and al- rel monkeys. Tympanic temperatures were collected from 27 cohol liver disease. Baboons also have the same immunoglobulin squirrel monkeys and compared to rectal temperatures us- subclasses as humans, making them ideal for vaccine and other ing a human and veterinary infrared tympanic thermometer. immunotherapy protocols. The worldwide use of baboons as a Compared with rectal temperature measurements, the human model for study of human diseases is underscored by a search tympanic thermometer readings were not significantly differ- of OVID Medline that reveals 1,028 publications over the last 5 ent, while the veterinary tympanic thermometer measurements y with baboons in the running title. The total number of publi- were significantly higher (P < 0.05). There were no differences cations citing the baboon over the last 5 y is 12,360. Our facility between sexes. The tympanic thermometer designed for use in conducts multidisciplinary studies using baboons and serves as humans can be used in adult squirrel monkeys as an alterna- a source of high-quality baboons for NIH-sponsored research tive to rectal thermometry in assessing core body temperature. programs located at institutions across the United States. This resource enables NIH-funded investigators to purchase baboons for Sexual and Reproductive Maturational Definitions for Safety As- their research programs, subcontract with our facility to conduct sessment Studies in Cynomolgus Monkeys (Macaca fascicularis) their study on location, or lease baboons to conduct their studies at their home institution and then return the baboons to our G Fleurie, D Clemons*, L Fernandez, S Rensing, GF Weinbauer breeding colony. During the last 5 y our facility has supplied 31 institutions with over 721 baboons. Our current research activities Covance, Alice, TX involve characterizing endogenous microorganisms of conventional baboons, improving methods for production of baboons The cynomolgus monkey (Macaca fascicularis) is an impor- in a captive environment, developing an SPF colony of baboons, tant model in basic research and safety testing because of the therapy for sickle cell disease and Thalassemia, sepsis studies, comparability of its reproductive process to man, similarity and vaccine development. We are developing a self-sustaining of pharmacologic response to various test substances, and colony of SPF baboons that are free of 6 herpes viruses (analogs of decreased probability of immunogenetic response to biologi- human HSV, VZV, CMV, HHV6, EBV, and HHV8), 4 retroviruses cal therapeutic products. Being able to predict the growth and (simian foamy virus, SRV/D, SIV, and STLV), SV40, measles, sexual development of this animal refines our abilities to assess and poxvirus. Our long range goal is to continue to serve as a drug effect versus normal biologic variability, select a mature major source of high-quality baboons for NIH-funded research animal for reproductive toxicity evaluations, and provide more programs and to further characterize and develop the baboon as comprehensive veterinary care. Recent changes in regulatory an animal model for biomedical research. guidelines have given visibility to the subject of sexual and reproductive maturation in the cynomolgus monkey, and cre- Risk Factors for Dystocia and Other Negative Pregnancy ated significant discussion regarding the specific measures of Outcome in Pigtail Macaques (Macaca nemestrina) maturation and how they should be applied. We identified some parameters to differentiate sexual maturity from reproductive D Stockinger*, AE Torrence, K Vogel, C Hotchkiss, J Ha maturity in both the female and male cynomolgus animals. Our intention is to bring some clarity to the discussion by defining Washington National Primate Research Center, Seattle, WA what parameters apply the best for the purpose of primate toxicology studies. Dystocia is an important component of the management of nonhuman primates and results in fetal and maternal morbidity and increased use of veterinary resources. Dystocias can arise

114 Abstracts of scientific papers

from abnormalities of the pelvis, fetus, or uterine contractions. and protein-losing nephropathy. There have been no reports of Risk factors for dystocias in macaques have not been established. TEG in the laboratory animal medicine literature. We present The objective of this study was to determine maternal and normal reference values (n = 39) from an ongoing study in pigtail fetal risk factors for dystocia in macaques. Retrospective data macaques, which has demonstrated no significant effects of age were collected from 84 pigtail macaques (Macaca nemestrina) and gender on TEG results, contrary to human reports. The lack diagnosed with dystocia. Maternal records of age, reproductive of effects of age and gender on TEG results allows the reduction history, experimental history, clinical records, fetal birth weight, of animal numbers and easier animal selection for future stud- and any applicable fetal necropsy reports were reviewed. The ies. Moreover, we discuss the significant potential applications gestational age of the fetus, the infant’s birth weight, total and the need for further investigation of TEG in research and previous births by the dam, and the proportion of both viable veterinary medicine. For example, we are currently planning birth outcomes and surgical pregnancy interventions in the a study to determine if TEG can detect hypercoagulability in dam’s history provided the best model for predicting dystocia SIV-infected macaques. in the current pregnancy (P < 0.000001, R2 = 0.24, f = 0.32). Of these parameters, the total previous births and the proportion Combination of Systemic and Local Treatment of an Infected of previous surgical births accounted for the majority of the Bite Wound Using an Osmotic Pump in a Gelada (Theropithe- variance. This model can identify breeders that are at risk for cus gelada) dystocias and allow for changes in breeding colony management, more intense monitoring of individuals, or dedication JM Sykes IV*, T Georoff, C Rodriguez of other resources. Global Health Program, Wildlife Conservation Society, New Diagnostic Algorithm for Nonhuman Primate Alopecia York, NY

K Luchins*, M Gilbert, K Baker, R Bohm A 24-y-old male gelada housed in a multimale bachelor group presented for a bite wound (day 0) to the right forelimb Tulane National Primate Research Center, Covington, LA resulting in local infection and carpal dislocation. This species is particularly difficult to medicate orally; treatment with oral Hair is very important as it serves many essential functions. marbofloxacin was successful, but the animal refused other When nonhuman primates are found to have alopecia, it is con- antibiotics. As compliance with marbofloxacin was expected cerning for veterinarians, researchers, the public, and regulatory to wane, local antibiotic treatment was initiated. On day 23, an agencies. The occurrence of alopecia has been linked to psycho- osmotic pump, loaded with amikacin (250 mg/mL), was placed logical wellbeing, and behavioral causes have become the default subcutaneously in the medial antebrachium and connected to diagnosis for captive primates. However, it is important to inves- a polyethelene catheter, which was tunneled subcutaneously tigate the pathogenesis of alopecia to ensure the most accurate to the site of infection. A cast was placed to protect the sutures diagnosis and proper treatment. In this study, we performed a and pump. One week later, the pump was replaced by 2 pumps, medical and behavioral assessment of 39 alopecic and 39 con- the wound and joint flushed, and the cast replaced. The animal trol animals. The medical diagnostics include complete blood was completely noncompliant with marbofloxacin by day 37. count, serum chemistry, endocrine profile for hypothyroidism Pumps were replaced and the area flushed twice more at 14-d and hyperadrenocorticism, surface skin cytology, dermatophyte intervals, after which culture yielded no aerobic bacteria, but culture, skin scrape, aerobic bacterial culture, and skin biopsy for an anaerobe was isolated. On day 73, pumps were removed, histopathology. Animals then underwent a behavioral evalua- the wound left open, and the animal treated with florfenicol tion, which included a total of 6 h of videotaping to look for the (20 mg/kg) via pole syringe or dart every 2 d for 1 mo. Anti- presence or absence of hair plucking. The aim of the study was biotics were discontinued after day 100, and by day 116 there to design a differential diagnosis list and diagnostic algorithm was no further discharge or swelling noted. Six months later for nonhuman primate alopecia, which will serve as a guide for the animal died of cardiac failure and there was no evidence of approaching alopecia in the future. The data is currently being infection at that time. This case demonstrates some challenges analyzed and will be ready for presentation at the Association and solutions to treating animals that may be difficult to treat of Primate Veterinarians workshop. using conventional methods.

An Introduction to Thromboelastography: Applications and Rare Burns Caused by a Closed Conducting Loop Related to Reference Intervals in Pigtail Macaques (Macaca nemestrina) Patient Positioning at Magnetic Resonance Imaging

D Fong*, J Ha, K Vogel, A Torrence, C Hotchkiss J Sohn*

Washington National Primate Research Center, Seattle, WA University of California—Los Angeles, Los Angeles, CA

Thromboelastography (TEG) is a clinical laboratory test uti- A 10-y-old male rhesus macaque (Macaca mulatta) singly- lized to assess global hemostasis. With technological advances housed, with a headcap, cylinder, and bilateral eye coils pre- and increasingly complex surgeries, its utility has reemerged sented 2 d after MRI for burns on his right arm. The animal in human medicine and is beginning to be explored in veteri- was sedated and examined. A 3 cm × 3 cm oval, reddened, nary medicine. Standard coagulation tests (PT, PTT) are only ulcerated lesion was found on the right medial antebrachium performed on platelet-poor plasma, whereas TEG is performed with concomitant cellulitis. The right thumb pad had a ruptured on whole blood. Hence, TEG provides a more accurate, detailed vesicle measuring 2 cm × 1 cm. Bloodwork was collected for representation of coagulation and allows for the identification CBC and chemistry. The area was examined, shaved, cleaned, of hypocoagulable, hypercoagulable, and hyperfibrinolytic and topically treated with silver sulfadiazine. No other wounds states. Reports have utilized TEG to identify hypercoagulable were found. The animal was started on a course of rocephin, states in animals with immune-mediated hemolytic anemia buprenex, and carprofen. Lab results included: ALT = 63 U/L,

115 Vol 50, No 1 Journal of the American Association for Laboratory Animal Science January 2011

TP = 5.9 g/DL, HCT = 30, and PLT = 133K/µL. The animal was Biochemical changes included severe hypoproteinemia and a sedated 9 d after MRI to assess healing. Healing was progressing persistent elevation in GGT. Advanced diagnostics, which in- normally and the animal was expected to make a full recovery. cluded vitamin D3, PTH, and ionized calcium levels, in addition Upon questioning, it was found that during the MRI scan the to bone marrow analysis, showed vitamin D3 insufficiencies and animal was positioned on his back with his hands and arms varying degrees of myelofibrosis, myelodysplasia, and other cradled into each other. We hypothesize that a closed conducting bone marrow abnormalities. Animals were provided with sup- loop was inadvertently created by body positioning, leading to portive care and euthanized when they no longer responded to increased local radiofrequency (RF) absorption, resulting in sec- therapy. The most significant lesions found on necropsy were ond degree burns in the contact areas. Burns caused by a closed blunting and fusion of the small intestinal villi. In summary, conducting loop related to body position are very rare and have the clinicopathologic and histologic abnormalities indicates only been reported in a handful of cases in the human literature. a malabsorptive syndrome within the owl monkey breeding In humans, tingling, muscle twitches, or a burning sensation colony. Measures are being taken to characterize the type mal- can indicate loop formation, and often the patient’s discomfort absorption syndrome for the purpose of early intervention, will cause the imager to abort the procedure. However, animals, treatment, and prevention. like children, are usually anesthetized for immobilization, and therefore, unable to exhibit signs of discomfort. Treatment of Self-Biting Behavior in Adult Rhesus Macaques with Oral and Long-Acting Injectable Naltrexone Intracardiac Thrombosis and Aortic Aneurysms in Mous- tached Tamarins (Saguinus mystax) with Cardiomyopathy DJ Kempf*, RP Bohm Jr, KC Baker

A Gozalo*, D Ragland, M St Claire, W Elkins, C Michaud Tulane National Primate Research Center, Covington, LA

Comparative Medicine Branch, National Institute of Allergy Self-injurious behavior (SIB), a multifactorial abnormal behav- and Infectious Diseases, Bethesda, MD ior with a poorly understood etiology, may be defined as any self-directed behavior that results in tissue injury. It is estimated The finding of 2 cases of intracardiac thrombi in Saguinus to spontaneously affect 5% to 13% of the captive rhesus macaque mystax that died as a consequence of cardiac failure, prompted (Macaca mulatta) population, with self-biting being the most us to do a retrospective study to determine the frequency of common expression. Currently, there are no widely accepted this condition. Clinical records, necropsy reports, and tissues treatments for SIB. However, studies with human and nonhuman from 60 S. mystax that died or were euthanized between 1996 primates have shown that therapeutic drugs used to treat alco- and 2009 were reviewed. Ten monkeys (16.6%) had intracardiac holism and drug abuse, such as oral naltrexone hydrochloride, thrombi and 4 (6.6%) had dissecting aortic aneurysms. Three of are effective in reducing the occurrence of SIB. The proposed the 10 animals with intracardiac thrombosis had left ventricular mechanism of action for attenuation of the behavior by these involvement alone. Four monkeys had thrombi only in the right drugs is through competitive inhibition of endogenous opioid ventricle and 3 animals exhibited thrombi in both ventricles. receptors, which limits the resultant euphoria or analgesia that Myocardial fibrosis and chronic renal disease were common is experienced following an SIB episode. The reduction of posi- findings in each affected animal. The cause(s) of intracardiac tive feedback prevents the abnormal behavior from serving as thrombosis and aortic aneurysms in the tamarins in the present motivation for maintenance of the behavior, thereby reducing study is/are not known; however, the clinical signs, as well as incidence. This study examines the value of a long-acting 30-d the gross and microscopic lesions, suggest that hypertension and injectable naltrexone, for the treatment of SIB in 10, otherwise congestive heart failure secondary to cardiomyopathy are major healthy, adult, singly housed, Indian- and Chinese-origin rhesus contributors. Similarities between intracardiac thrombosis and macaques. During the 4-wk before and 4-wk after treatment aortic aneurysms in humans and tamarins suggest the tamarin phases, no therapeutic intervention is administered so that each may be a good model for study of human cardiac disease. This animal may serve as its own control. In the 8-wk treatment phase, is, to our knowledge, the first report of intracardiac thrombosis animals receive 2 consecutive administrations. Data collection for and aortic aneurysms in S. mystax. all phases of the study consists of clinical monitoring and 6 h per phase of videotaped data to evaluate frequencies of self-biting Malabsorption Syndrome and the Secondary Manifestations and other behaviors. Weekly blood samples measuring serum in a Closed Owl Monkey (Aotus nancymaae) Breeding Colony levels of naltrexone and the major metabolite 6-β-naltrexol are obtained and compared to the results of the drug pharmacoki- CS Cooper-Pesco*, A Brady, K Barnhart, C Abee netic study to establish therapeutic range. This study will help establish the efficacy of long-acting injectable naltrexone for University of Texas MD Anderson Cancer Center, Bastrop, TX self-injurious behavior in nonhuman primates.

Chronic wasting syndromes have been described in many Pharmacokinetics and Pharmacodynamics of Oxymorphone nonhuman primate research and breeding colonies. Our facility in Titi Monkeys (Callicebus spp.) as Compared to Rhesus currently maintains the largest breeding colony of owl monkeys Macaques (Macaca mulatta) in the United States. Recently, a modest number of individuals ranging from juveniles to adults presented with a wasting KR Kelly*, BH Pypendop, K Grayson, KL Christe, L Summers, syndrome that presumably developed secondary to intestinal NW Lerche malabsorption. Affected individuals uniformly presented with weight loss without an apparent loss of appetite. Generalized, California National Primate Research Center, Davis, CA nonpruritic alopecia typically accompanied the weight loss. Blood analysis of all affected animals revealed a pancytopenia Oxymorphone is a pure µ-agonist opioid that is commonly that was typically characterized by a severe neutropenia, mild used in nonhuman primate medicine and surgery to minimize to moderate anemia, and moderate to severe thrombocytopenia. moderate to severe pain. We characterized pharmacokinetic

116 Abstracts of scientific papers

profiles and physiologic and behavioral responses to oxymor- Bilateral Hydronephrosis in an Adult Rhesus Macaque (Ma- phone in titi monkeys (Callicebus spp.) compared to rhesus caca mulatta) macaques (Macaca mulatta). Titi monkeys (n = 4) and rhesus macaques (n = 4) were injected intravenously with either a R Baker*, D Schenkman, J Bacon bolus of 0.075 mg/kg oxymorphone or vehicle on multiple occasions, with a minimum 14-d washout period between tri- Wisconsin National Primate Research Center, Madison, WI als. Blood collection was limited to a maximum of 3 samples per trial. Samples were collected at multiple time points up to A 16-y-old female rhesus macaque underwent a routine 10 h. Collection periods, animal order, and testing day were physical examination and blood work to assess her feasibility randomized. Macaques underwent a single serial collection of for assignment to an SIV titration study. The animal seemed all time-points to validate study design. Opiate concentrations fine on physical examination with a body condition score of in serum were quantified using liquid chromatography-mass 3.5, mild tartar and gingivitis, and a grade II/VI holosystolic spectrometry. Pharmacokinetic parameters were estimated murmur. The remainder of the examination was unremarkable. using commercially available computer software. Repeated Serum chemistries, however, revealed severe renal compromise measures analysis of variance was used to evaluate interspe- with a BUN of 83 mg/dL (range 11 to 27), creatinine of 6.35 mg/ cies physiologic and behavioral differences, drug effects, and dL (range 0.7 to 1.2), calcium of 12.7 mg/dL (range 9.1 to 11.0), drug effects over time. A 2-compartment model best described and phosphorus of 1.5 (range 2.1 to 5.9). These results were the disposition of oxymorphone in both species. Clearance was discussed with the PI and it was decided to reject the animal faster in titi monkeys than macaques; however, terminal half-life for this particular study and to try and place her on an acute was longer in titi monkeys. Statistically significant differences nonsurvival project. During this time this animal was bright in heart rate, respiratory rate, and diastolic blood pressure were and alert, continued to eat, and showed no outward signs of found between species. Statistically significant differences in distress. Repeat blood work performed 5 d later revealed that respiratory rate and systolic blood pressure were found between all the values had worsened. BUN = 95 mg/dL, creatinine = 6.1 treatments within species. Oxymorphone did not significantly mg/dL, calcium = 13.1 mg/dL, and phosphorus = 1.0. Ultra- depress physiologic parameters over time. After oxymorphone sonography was performed to assess the kidneys and severe treatment, macaques demonstrated pruritis, while titi monkeys bilateral hydronephrosis was detected. Since there were no acute exhibited sedation. Despite mild side effects, oxymorphone projects that could be performed immediately, euthanasia was should continue to be considered for pain management proto- elected. The necropsy revealed a left kidney that was largely cols in nonhuman primates. hydronephrotic with minimal residual parenchyma. The right kidney was 60% hydronephrotic with collapse of the cortex at Malignant Fibrous Histiocytoma in a St Kitts Vervet the caudal pole. Both ureters were dilated 1.1 cm. Four 3-mm nodules were discovered in the area of the trigone of the bladder, A Beierschmitt*, C Spackman, D Seddon, S Fitzharris, N Keirstead with 2 of them on the mucosal surface resembling large papillae, and the other 2 were found deep in the wall of the trigone. These St Kitts Behavioural Science Foundation, Basseterre, St Kitts masses resulted in an inability to pass a probe from the ureters and Nevis into the bladder. At the time of this abstract, histopathology of the 4 masses is pending. The differential diagnosis includes An 18-y-old St Kitts African green monkey (Chlorocebus aeth- endometriosis with ureteral obstruction and/or neoplasia with iops sabeus) from our facility presented with a rapidly growing ureteral obstruction. This case demonstrates an unusual finding mass on the right antebrachium. Radiographs confirmed an in an animal that appeared clinically normal, despite the severe expansile soft tissue mass with intralesional calcification and terminal pathology that was occurring. adjacent proliferative periosteal reaction of the ulna while fine- needle aspirates suggested that the mass was either a spindle Paraneoplastic Syndrome in a Geriatric Rhesus Macaque cell tumor or granulation tissue. The mass was surgically deb- ulked, including periosteal scraping, as the tumor was firmly C Cruzen adhered to the ulna. Histopathologic evaluation of the resected mass revealed a population of neoplastic spindle cells admixed Wisconsin National Primate Research Center, Madison, WI with abundant, and often aberrant, multinucleated giant cells, most consistent with malignant fibrous histiocytoma. Malignant A 23-y-old female rhesus macaque presented with mild facial fibrous histiocytomas are relatively common in humans, but hyperkeratosis with no other clinical signs. The hyperkeratosis rare in nonhuman primates and other veterinary species. In spread rapidly, affecting most of the body. One week after initial veterinary species, the histogenesis and classification of these presentation, the animal was also noted to have marked throm- tumors are often debated, and they are sometimes instead classi- bocytopenia. Over the next 6 wk, peripheral lymphadenopathy fied as “giant cell tumors of soft parts.” Regardless, it is difficult developed, and the animal began to experience inappetance to predict prognosis from tumor behavior in other species, as and subsequent weight loss. Hyperkeratosis and lichenifica- metastases occurs in some, but rarely in others. Local reoccur- tion of the skin continued to become more severe and affected rence was observed within 8 mo post debulking, and grew to the skin over most of the body. Diagnostics throughout the approximately 3.5 cm × 4.5 cm within the next few months, at course of disease included a complete dermatologic work-up which point amputation was elected. Radiographs at the time (skin scrapings, impression smears, skin biopsies, and bacterial of amputation (1-y post debulking) confirmed deeper growth in and fungal cultures), radiography, ultrasonography, excisional the right antebrachium with significant osteolysis of the radius lymph node biopsies, and a positron emision tomography and ulna, but metastasis to regional lymph nodes or lungs was (PET) scan. The animal underwent antibiotic (cefazolin) and not observed. In this case of malignant fibrous histiocytoma in immunosuppressive (azathioprine and prednisone) therapies. a vervet, the monkey was followed for over 1 y after diagnosis There was no improvement in the skin lesions, but the thrombo- and continues to be monitored to better elucidate the behavior cytopenia did respond to immunosuppressive therapy. Due to of this tumor in African green monkeys. failure to respond to treatment and an equivocal diagnosis, the

117 Vol 50, No 1 Journal of the American Association for Laboratory Animal Science January 2011 animal was euthanized. At necropsy, a diagnosis of pancreatic asymptomatic or can have heavy bleeding and menstrual cramps. adenocarcinoma was made. Specific diagnostics to determine Differential diagnoses would include endometriosis, leiomyoma, the cell of origin are pending. fibroids, and neoplasia. There is no treatment for this condition other than hysterectomy but oral contraceptive pills and NSAIDS Diaphragmatic Hernia in a 28-y-old Female Rhesus Macaque can help to decrease blood flow and cramping. Adenomyosis has (Macaca mulatta): Diagnosis, Treatment, and Study of an been reported in primate species, but there is only one case report Inciting Cause of this condition in great apes.

K Flemmen*, SP Larson, C Cruzen Cranial Abdominal Mass in a Rhesus Macaque

Wisconsin National Primate Research Center, Madison, WI D Owens

A 28-y-old female rhesus macaque assigned to a long-term Oregon National Primate Research Center, Beaverton, OR dietary restriction study at our facility presented with mild inappetence progressing to moderate and persistent inappe- A 12-y-old male Indian rhesus macaque housed in an outdoor tence. Clinical history of the animal included diverticulosis, breeding corral was identified with a large, firm abdominal mass endometriosis, and a reducible umbilical hernia. There was in the upper left quadrant during routine processing. The patient also evidence of prediabetes and the animal was currently be- had no previous removals over the past 2 y, but was reported ing treated with pioglitazone. Diagnostics consisted of a physi- for intermittent vomiting while housed indoors at 5-y-old that cal examination, thoracic and abdominal radiographs, and an resolved spontaneously. The patient was transferred to the abdominal ultrasound; the animal was diagnosed with what colony hospital for a diagnostic evaluation of the abdominal appeared to be a peritoneal-pericardial diaphragmatic hernia. mass. Abdominal ultrasound revealed a cavitated mass with Although the animal qualified as a high anesthetic risk, surgery unidentifiable margins in the upper right quadrant. The mass was the only treatment option for this condition and took place appeared to be associated with either the stomach or small intes- 13 d after the animal began demonstrating inappetence. Dur- tine. Differentials included adenocarcinoma, lymphoma, foreign ing surgery, instead of a peritoneal-pericardial diaphragmatic body, fungal, or parasitic mass. The patient was scheduled for a hernia, the animal was discovered to have a 5-cm radial tear fecal occult blood series and a GI barium series. During morning in the ventral/anterior left crus of the diaphragm, through observations 2 d later the animal was noted with a quiet and which the left liver lobe was herniated, as well as a 15-mm depressed demeanor, scant stool production, and poor appetite. radial defect in the right crus of the diaphragm. These defects The patient was subsequently referred for an abdominal explor- were repaired and although anesthetic complications were atory laparotomy for a suspected GI obstruction. The exploratory numerous, the animal recovered from surgery. It is unclear if laparotomy revealed 2 large gastric trichobezoars and one small this hernia was congenital and analogous to diaphragmatic trichobezoar lodged in the small intestine causing a complete hernias discovered in geriatric humans or acquired due to intestinal obstruction. Trichobezoars have been reported in the pathologic collagen degeneration. baboon, rhesus macaque, saddleback tamarin, and a chimpanzee.

Enlarged Uterus in a Chimpanzee Thoracic Schwannoma in a Rhesus Macaque

M Tocidlowski T Alves, CG Benton*, T Bell, E Rushing, R Stevens

Houston Zoo, Houston, TX United States Army Medical Research Institute of Infectious Disease, Fort Detrick, MD In the middle of June 2010, our facility acquired a group of 10 chimpanzees (5 males and 5 females) from a private owner. Annie, A 15-y-old male rhesus macaque was involved in an alterca- a 23-y-old female intact chimpanzee, is the youngest female of the tion with another equally sized male rhesus and suffered severe group. In April 2010, preshipment examinations were performed facial lacerations involving his nose, mouth, and both cheeks. on all animals in the compound (14 total). A firm, slightly move- Twenty-four hours after appropriate care, he developed respira- able mass was palpated in the lower right abdominal quadrant. tory distress. Seventy-two hours later he was still experiencing Blood work, viral testing, and eyelid TB test were unremarkable. labored breathing and had become lethargic and anorexic, at Her history included discomfort during her estrous cycles and which time he was sedated for a complete physical examina- heavy bleeding. She was bred several times over the years but tion and radiographs. Upon examination, auscultation revealed never became pregnant. Diagnoses included an abscess or cystic increased pulmonary sounds bilaterally in the midventral lung ovary, uterine mass, enlarged lymph node, or distended appen- fields. Organomegaly was also appreciated on palpation in the dix. Once relocated, an exam including radiographs, ultrasound, cranial left abdomen. Radiographs revealed a large, round soft- and MRI was conducted. Abdominal palpation revealed a lower, tissue opacity in the caudal thorax and cranial abdomen that mid abdominal mass that could also be seen on radiographs. obliterated the cardiac silhouette on lateral and ventrodorsal Transabdominal ultrasound showed an approximately 14 × 16 cm views. The nonhuman primate was prepped for exploratory uterus of uniform consistency with a thin endometrial stripe in the surgery during which a large intrathoracic mass was removed. center. An MRI confirmed uniform uterine hypertrophy that was The monkey was euthanized on the surgery table. Histology and positive with intravenous gadolinium contrast, consistent with immunohistochemical stains confirmed that the mass was of adenomyosis. Ovaries and cervix were determined to be within peripheral nerve origin and was consistent with a schwannoma. normal limits for this species. A human radiologist and gynecolo- This is the first case of a thoracic schwannoma in a rhesus ma- gist were present at the MRI and ultrasound for guidance and caque, and, to our knowledge, only the second reported case consultation. Both agreed with the diagnosis of adenomyosis. of schwannoma in a nonhuman primate. Adenomyosis is a nonneoplastic condition of the uterus where the endometrial lining grows into the myometrium. Women can be

118 Abstracts of scientific papers

Assessment of the Efficacy of a Canine Distemper Vaccine in Sarcocystis was first reported in 1843 by Miescher in a house Macaques to Protect against Measles Infection mouse, and for years was referred to as Miescher tubules. In 1865 similar structures were found in pig muscle. It was not until 1967, J Larin*, P Morales, K Hopper, S Sowers, W Bellini, J Wagner 124 y later, that the bradyzoites in the sarcocysts were studied by electron microscopy. The life cycle was not discovered until The Mannheimer Foundation, Homestead, FL 1970. Sarcocystosis has been reported in many animal species and humans. We will focus on the disease in macaques. The pres- Measles is a highly infectious, contagious viral disease of ence of sarcocysts in tissues is usually considered an incidental humans and nonhuman primates (NHP). An outbreak in NHP finding or background lesion in macaques; however, there are colonies can cause significant morbidity and mortality. This references describing acute or chronic polymyositis in old world virus, along with the canine distemper virus, belongs to the macaques. The life cycle, incidence, clinical presentation, gross paramyxovirus family and the 2 are closely related. Previously, and microscopic lesions, ultrastructure, clinical pathology find- a canine distemper vaccine that contained a human measles ings, and attempted treatment regimens for sarcocystosis will be component was effective in immunizing monkeys against compared with those cases reported in the literature in humans. measles virus. This combination vaccine is no longer available. It is the opinion of this pathologist that this disease is underdi- Because monovalent human measles vaccine availability is agnosed and could have an adverse effect on research findings. sparse and expensive, canine distemper virus vaccine has been empirically used by some NHP facilities, based on the premise A Respiratory Outbreak among Humans and Nonhuman that it would provide a protective immune response to measles. Primates at a National Primate Research Center Given the presumed cross reactivity between canine antibody and measles virus, a study was initiated to define the efficacy of JK Cohen*, EA Strobert, M Thompson, M Arce, K Arnold, WR canine distemper vaccine in protecting against measles virus in Archer, DM Blau, B Whitaker, T Peret, D Erdman, E Schneider NHP. Sixteen subadult male cynomolgus macaques (Macaca fascicularis) were hypervaccinated with a modified live distemper Yerkes National Primate Research Center, Lawrenceville, GA vaccine. Serum was collected before and after 3 booster injec- tions. Antibody titers were serologically assessed for antibody Human metapneumovirus (hMPV) causes both upper and against measles and canine distemper viruses. Efficacy of canine lower acute respiratory tract infections (ARI) and has been distemper antibody against measles virus was assessed by in documented to cause infections in both humans and nonhuman vitro viral neutralization of live measles virus. Although animals primates. Beginning in May 2009, upper ARI were reported in mounted a robust antibody response against distemper virus, staff and upper and lower ARI in nonhuman primates at one of measles virus antibody levels were infrequent and had poor 2 campuses of a National Primate Research Center. In mid June reactivity. Results indicate that canine distemper vaccine does 2009, the Centers for Disease Control and Prevention and the not provide protection against measles infection in macaques. Georgia Division of Public Health were contacted for laboratory testing. Specimens (respiratory, serum, stool) were collected Maintaining an Outdoor Colony of Macaques in the Presence from a convenience sample of cases during the investigation. of Endemic Tularemia Initially, hMPV was detected in 5 of 10 tracheal aspirates from rhesus monkeys and 6 of 7 naso-oropharyngeal swabs from staff CE Ferrecchia via RT-PCR. hMPV was detected via RT-PCR in an additional 6 of 42 (14%) primate respiratory specimens collected through Oregon National Primate Research Center, Beaverton, OR mid September from both campuses; 3 of which were detected more than 21 d after symptom onset. hMPV was also detected (2 Over the past 2 decades, our facility has faced sporadic surges of 19, 11%) via RT-PCR in nonhuman primate stool specimens. in clinical cases of tularemia (Francisella tularensis), with the most The majority of nonhuman primate serologic samples collected recent of these occurring in the winter of 2010. Tularemia is en- (32 of 45, 71%) showed evidence of hMPV IgG antibodies via demic to many parts of the Northern Hemisphere, and thus to the enzyme immunoassay, indicating recent or past infection. region surrounding us. This facility houses over 4,000 nonhuman Secondary bacterial infections were documented in several primates—the majority of which live outdoors in social groups. animals. Based on symptom onset among groups of nonhuman Exposure to this potentially life-threatening and zoonotic patho- primates, animal-to-animal transmission occurred. hMPV can gen is inevitable, due to its persistence in the environment and cause significant respiratory illness not only in staff, but also in the close proximity of several suitable reservoir species. Recent nonhuman primates. Increasing awareness about this recently colony management efforts have focused mainly on control- identified virus will benefit primate centers. In addition, find- ling the meadow vole population surrounding the corral-style ings from this study can be used to improve our understanding housing. However, strategies continue to evolve with regard of animal models of hMPV disease, replication, immunogenic- to managing a large breeding colony of nonhuman primates in ity, and the affects of disease on animals in a research facility. the presence of this threat. Within a period of 3 mo, 5 cases were confirmed by the Centers for Disease Control and Prevention Detection and Iatrogenic Transmission of Babesia spp. in as being positive for Francisella tularensis. Gross pathologic find- Captive Olive Baboons (Papio cyanocephalus anubis) ings were similar in all cases and highly suggestive of tularemia infection. These findings included, but were not limited to the MV Reichard, KM Gray, JM d’Offay, CM Simecka*, RF Wolf presence of necrotizing splenitis and lymphadenitis. Department of Veterinary Pathobiology, Oklahoma State Uni- Sarcosporidiosis in Macaques: A Review versity, Stillwater, OK

C Montgomery Babesia spp. are tick-transmitted apicomplexan hemopara- sites that infect mammalian red blood cells. Our purpose was Compath Biomedical, Jay, OK to determine the prevalence of Babesia spp. infection within a

119 Vol 50, No 1 Journal of the American Association for Laboratory Animal Science January 2011 colony of captive baboons and to determine potential iatrogenic SRV4 was first isolated in 1984. In this study, 23 SRV4 positive routes of the transmission of the hemoparasite. DNA was ex- animals were monitored over a 57-wk period. The origin of tracted from the blood of baboons and tested for infection with monkeys, proviral loads, and antibody statuses are reported Babesia by PCR and primers that amplify the 18s rRNA gene of here. Genotyping of SRV4 infected cynomolgus DNA samples the parasite. Overall, the prevalence of infection of Babesia spp. by mitochondria DNA sequencing and microsatellite (STR) within the baboon population was 8.8% (73 of 830). Phylogenetic loci analysis demonstrated an admixture of Indochinese and analysis of the sequenced Babesia spp. DNA from 2 individual Indonesian ancestry. The viral data showed a broad dynamic baboons revealed that Babesia spp. found in captive baboons was range in different infection stages. The fluctuation in viral load a novel species most closely related (97% to 99%) to B. leo. Blood kinetic suggested to be stress-related and was caused by extreme from a Babesia spp.-infected donor baboon was iatrogenically hot/cold weather change and long distance movement from one transmitted via intravenous, intramuscular, and subcutane- colony to another. Antibodies against SRV/D were gradually ous routes to 3 naive principal baboons. The intravenously increased over time, but slightly decreased when viral load was inoculated baboon was PCR positive at 7 d post inoculation elevated at 18 wk (right after the long distance immigration). (dpi). The 2 baboons that were inoculated via intramuscular Because the viral load and antibody status can be triggered by and subcutaneous routes became PCR positive at 10 dpi. All environmental factors, such as temperature and immigration 3 principal baboons remained PCR positive for Babesia spp. from colony to colony, it provides a good model for manipula- through 31 dpi. Baboons infected with Babesia spp. did not have tion and evaluation of viral loads and antibodies in antiviral clinical signs consistent with babesiosis during the experiments. treatment or vaccination studies. We demonstrated that captive baboons are infected with a novel Babesia spp. We also showed that transmission of Babesia spp. Isolation of Stenotrophomonas maltophilia from Several Rhe- can be accomplish without the tick definitive host via transfer sus Macaques (Macaca mulatta) and a Cynomolgus Macaque of infected blood through intravenous, intramuscular, and (Macaca fascicularis) with Conjunctivitis subcutaneous routes to naive baboons. Atypical Mycobacteriosis in a Black Handed Spider Monkey GR Smith*, PR Morales, KJ Hopper, JL Wagner (Ateles goeffroyi) Caused by Mycobacterium szulgai College of Veterinary Medicine, University of Georgia, Athens, GA TP Alvarado*, TN Storms, J Raines, M Garner Stenotrophomonas maltophilia is a gram-negative, nonfermenta- Dallas Zoo, Dallas, TX tive Bacillus that is ubiquitous in the environment. This bacterial species is not normally associated with disease in healthy Mycobacterium szulgai is an uncommon human pathogen and humans or animals, and is considered normal flora. However, a very rare pathogen of animals. Most of the reported cases and in immunocompromised human patients, S. maltophilia infection disease descriptions are from the human literature. This report is associated with morbidity and mortality from bacteremia, describes the first case of clinical disease caused byMycobacterium pneumonia, meningitis, and endocarditis. It can also cause uri- szulgai in a nonhuman primate. A 47-y-old female black handed nary tract infections and conjunctivitis. Because it is resistant to spider monkey (Ateles geoffroyi) was presented for annual physi- multiple antimicrobials, S. maltophilia has been labeled a super- cal exam and a submandibular swelling. Cytology of an aspirate bug and emerging pathogen in the human literature. Reports of the swelling showed a reactive lymph node with moderate of S. maltophilia in nonhuman primates are limited to a study suppurative lymphadenitis. An intrapalpebral tuberculin test of the normal flora found in the oropharynx of captive rhesus with MOT was positive. A rapid lateral-flow TB test was positive. macaques and the oropharynx of wild Central American squirrel An excisional biopsy of the submandibular lymph node cultured monkeys (Saimiri oerstedii). Here, we report conjunctivitis in 3 Mycobacterium szulgai. Results of a MAPIA test showed a pattern rhesus macaques (Macaca mulatta) and one cynomolgus macaque similar to those seen with previous Mycobacterium szulgai isolates. (Macaca fascicularis), from which S. maltophilia was cultured and The monkey was managed symptomatically for 16 mo after the isolated. Two of the 3 cases involving rhesus macaques and the initial diagnosis, when her condition rapidly deteriorated and case involving the cynomolgus macaque were mixed infections she was euthanized. Gross necropsy results included a general- of S. maltophilia in addition to other bacteria. This clinical pre- ized lymphadenopathy, peritoneal effusion, severe abdominal sentation is consistent with human reports where S. maltophilia adhesions, pericardial effusion, and evidence of hepatic and infections occur as part of a mixed population of bacterial spe- renal disease. Histopathology showed a severe granulomatous cies. Treatments given to these animals included triple antibiotic lymphadenitis, peritonitis, and numerous age-related degenera- ophthalmic ointment and systemic treatment with amoxicillin/ tive processes in a variety of tissues. Mycobacterium szulgai was clavulanic acid and/or enrofloxacin. The resolution of clinical cultured from the lymph nodes. signs in all of these cases took several months and was unsatisfac- tory. It was found that S. maltophilia isolates are largely resistant Poster Case Reports to all the treatments used in these cases. It is now suggested that treatment for S. maltophilia infections in nonhuman primates Genetic, Virologic, and Serologic Characterization of SRV4- include triple antibiotic ophthalmic ointment combined with Infected Cynomolgus Macaques (Macaca fascicularis) the systemic trimethoprim-sulfamethoxazole (TMP/SMX) or tigecycline, which are antibiotics to which most S. maltophilia C Zao*, L Tomanek, A Cooke, R Berger, J Satkoski Trask, DG isolates are sensitive. Smith, K Armstrong Acute Dermal Necrosis in Cynomolgus Macaques (Macaca VRL Laboratories, San Antonio, TX fascicularis)

SRV4 is one of the exogenous simian type D retroviruses K Hopper, J Larin, PR Morales*, A Garcia, J Wagner (SRV/D) present in cynomolgus macaques. The nature of SRV4 infection in cynomolgus macaques is still unclear since The Mannheimer Foundation, Homestead, FL

120 Abstracts of scientific papers

Here we report a rare complication of gastric catheterization in Partial and full skin thickness eschar formation and slough- macaques. An 8-y-old male rhesus macaque of Indian origin ing of large areas occurred after bleeding or sedation in at least was enrolled in a neuroscience study investigating the role of 53 documented cases in a 7-y period. Most of the cases occurred GABA A receptor subtype and the addictive effects of alcohol. after full volume bleeding, under ketamine sedation, and in the A gastric catheter was surgically implanted by an experienced winter months. Histopathology of recent cases showed acute veterinarian for ethanol administration. The gastric catheter dermal necrosis with minimal inflammation in most biopsies. had been functioning well and routinely evaluated by contrast Cultured bacteria varied and were considered opportunistic. radiography. Fourteen months following placement, the animal The latent time between bleeding and clinical presentation aver- presented with vomiting and abdominal distention. Survey aged 8 d. Animals required hospitalization for an average of 37 radiographs revealed a dilated stomach consistent with gastric d and lost an average of 0.43 kg. Treatment was supportive and bloat. Contrast radiography suggested catheter malposition surgical repair. Indirect blood pressures taken before and after and migration. At exploratory laparotomy, migration of the bleeding of a subset of animals suggest that low mean arterial catheter tip through the pylorus and into the distal jejunum pressure exacerbated by low ambient temperatures leads to with accordioned loops of bowel was observed. An enterotomy low tissue perfusion and precipitates a physiologic cascade of was performed to remove the gastric catheter. No surgical or events consistent with systemic inflammatory response and postoperative complications developed. This case documents ischemia to susceptible areas of skin. Most cases presented a complication of gastric catheter placement presenting as a with lesions on the abdomen, hips, flanks, and thighs. Data classic linear foreign body. suggests that severity of presentation is correlated with low ambient temperature. Clinical Flaviviral Disease in a Rhesus Macaque (Macaca mulatta) Rate of Self-Injurious Behavior in Buspirone-Treated Rhesus Macaques (Macaca mulatta) Across Different Levels of Hu- MH Gilbert*, D Xianhong Liu, RB Tesh man Activity in the Environment Tulane National Primate Research Center, Covington, LA DC Coble*, AL Martin, JE Perlman, KR Strait, ME Wilson, MA Bloomsmith Clinical disease from natural infection of West Nile Virus is exceedingly rare in nonhuman primates. Here we report Department of Animal Resources, Emory University and Yerkes a case in which severe ocular clinical signs in an outdoor- National Primate Research Center, Atlanta, GA reared, 8-mo-old, male Indian-origin rhesus macaque (Ma- caca mulatta) coincided with high antibody titers to at least 2 Self-injurious behavior can severely affect the quality of life of species of Flavivirus. Clinical signs on presentation included rhesus macaques in the research setting. This study examined severe distress, pyrexia, and structural malformation of both the effectiveness of an anxiolytic drug, buspirone, in rhesus eyes. While all other clinical signs resolved over time, ocular macaques with a history of self-injurious behavior. A crossover changes persisted and the animal remained blind. Necropsy 1 experimental design was used in which buspirone (5 mg) or a mo after clinical presentation revealed bilateral retinal detach- control substance was administered orally on a daily basis for ment. Hemagglutination-inhibition (HI) tests of 4 flaviviruses 28 d. Reliable observers who were blinded to the treatments were performed, and a broad anamestic antibody response to collected behavioral data according to an ethogram, which all 4 antigens was observed, indicating infection with at least emphasized self-biting, self-directed, stereotypic, and anxiety- 2 flaviviruses. Based on geography, the 2 most likely species related behaviors. Each of the 6 subjects was observed for 12 to have infected the monkey in this case are West Nile virus h, totaling 72 h of observational data. Behavioral observations (WNV) and St Louis encephalititis virus (SLEV). Both viruses were distributed across the 28-d treatment and divided be- are arboviruses in the family Flaviridae and genus Flavivirus, tween periods of high and low human activity in the animals’ with similar transmission cycles, vectors, and clinical signs surroundings. A multivariate analysis of variance for repeated in human cases. Wild birds are the principal reservoirs and measures indicated that durations of the targeted abnormal amplifying hosts, and mosquitoes, predominantly of the behaviors, including self-biting, did not change with drug genus Culex, serve as vectors. It is estimated that one in 150 administration [F(1,5) = 0.89, P = 0.66], nor was there an inter- people infected with WNV develop neurological complica- action between the drug treatment and the level of activity in tions. Ocular manifestations of WNV in human cases include the environment around the monkeys [F(1,5) = 11.35; P = 0.22]. pain, vitreous inflammation, chorioretinitis, retinal vasculitis, However, self-biting was more prevalent during periods of high chorioretinal scarring, optic neuritis, retinal hemorrhage, and activity [F(1,5) = 12.72; P = 0.02]. Treatment with buspirone was uveitis. SLEV is the third most prevalent arboviral disease in not associated with decreased time in self-biting, stereotypic, the United States (WNV being the first) and is most preva- or anxiety-related behavior, and this finding conflicts with an lent in Louisiana. It has been endemic in the Southern US for earlier published report. decades, and there is no vaccine for the virus. This is the first report of clinical disease associated with either WNV or SLEV Unusual Gastric Catheter Complication Causing a Linear in a rhesus macaque. Foreign Body Gastric Ulceration: A Sequela to Surgery and Ileus in a Macaque K Smith AE Torrence*, D Stockinger, D Fong, C Hotchkiss, K Vogel New England Primate Research Center, Southborough, MA Washington National Primate Research Center, Seattle, WA Reported complications of gastric catheters in macaques include migration, entanglement with ingested string foreign A 5-y-old male pigtail macaque (Macaca nemestrina) presented bodies, and perforation through the proximal duodenal wall. for 8% weight loss and inappetance 8 d after undergoing a surgi-

121 Vol 50, No 1 Journal of the American Association for Laboratory Animal Science January 2011 cal procedure of the cranium involving the masseter muscle. It the first reported spontaneous GBM in an adult female rhesus was surmised that there may be pain during mastication so the macaque. The clinical history of episodic, unilateral wounding animal was placed on a course of nonsteroidal antiinflammatory made diagnosis particularly challenging until signs of hemi- drugs and when fed softened chow, ate readily. Surprisingly, paresis appeared. physical exam, CBC, and chemistry revealed mild abdominal distension, hypoproteinemia, hypoalbuminemia, and anemia Facial Edema, Macular Rash, and Other Skin Lesions in a (HCT = 27%), although no overt hemorrhage was noted during Cohort of Rhesus Macaques (Macaca mulatta) surgery or postoperatively. Episodes of fluid diarrhea, inappetance, and abdominal distention ensued for several months. M St Claire*, D Ragland, R Byrum, R Johnson, P Jahrling No fecal pathogens were identified by multiple cultures or microscopically. Symptomatic therapy did not improve the con- Division of Clinical Research, the Office of the Director of the dition. Plain and barium contrast radiography revealed gastro- National Institute of Allergy and Infectious Diseases, National intestinal ileus and markedly prolonged gastric emptying time. Institutes of Health, Frederick, MD Abdominal ultrasonography was normal. Endoscopy revealed ulceration around the pyloric sphincter. The animal was treated Twelve adult rhesus macaques were assigned to an arterivirus with a histamine H2-receptor antagonist, gastric protectant, and study. All animals had been group-housed in NIH facilities for a combination of antibiotics for 6 wk. The diarrhea and gastric over a year and had been selected for the work based on screening ulcers resolved (confirmed by endoscopy) and the animal is by CBC, serum chemistry analysis, and negative serologic tests clinically stable, although close monitoring continues. This case for SRV, STLV, SIV, and arteriviruses. Animals were moved to the is an example of enteric dysbiosis and gastric ulceration with study facility 2 wk prior to the date of inoculation. One animal, hemorrhage precipitated by an underlying ileus and stressors 03E, had 1- to 2-mm diameter macules on the face and ears noted associated with surgery. as an incidental finding prior to the start of the study. This animal subsequently developed periorbital edema and erythema near the Spontaneous Glioblastoma Multiforme in a Rhesus Macaque lateral canthus of both eyes 6 d after inoculation. Several other (Macaca mulatta) animals in the cohort on study developed facial edema and erythema at approximately the same time point. Two days later, mild M Schutten, A Craig*, M Graham petecchiation was noted on the medial surface of both biceps with similar lesions on the lateral thoracic wall of animal 03E. On day University of Minnesota, St Paul, MN 16, the animal developed diarrhea and had a slightly enlarged left kidney. CBC, serum chemistry analysis, and other diagnostic tests A 6-y-old, captive-bred, pair-housed, female macaque pre- were performed during the study. What other diagnostics should sented in early October 2009 with a hematoma and dermatitis on be done? What differential diagnosis should be considered? her left forearm 2 wk after peripheral catheter use in the cephalic vein for blood collection during semiannual TB testing. The area Multiple Abdominal Masses in a Cynomolgus Macaque healed without treatment. Except for surgery to place a vascular (Macaca fascicularis): What’s Your Diagnosis? access port (VAP) introduced via the saphenous to the inferior vena cava, and training for cooperative handling, she was D Steiner, L Millen* experimentally naïve. Over the next 3 mo, she presented with episodic wounds to her left wrist, forearm, and hand. All were Covance Research Products, Alice, TX treated and healed. Because of the cyclic nature of the wounds, a tentative diagnosis of self-injurious behavior during menses A 4-y-old female cynomolgus macaque was examined as part of was made and medroxyprogesterone administered to prevent a routine preshipment workup. The animal had an unremarkable cycling. In February 2010, she presented with dehydration, clinical history, and had been imported into the US from Asia in weight loss, inappetance, and trembling, and she also favored 2008 and housed in outdoor social housing at our facility in South her left arm. Examination revealed a 6-cm draining tract from a Texas. On physical examination, several abdominal masses were region of cellulitis in her left forearm. She was rehydrated, the palpated. These masses were firm, yielded slightly to pressure, wound flushed, and antibiotics begun in anticipation of wound and were freely movable in the abdomen. Radiographs were exploration surgery the following day. The following morning taken to assess the abdomen, and 2 discrete masses were identi- she presented with left hemiparesis, mydriasis, and abnormal fied. One mass was in the mid-abdominal region, and one smaller mentation. CBC and serum chemistry profile were normal. mass was in the caudal abdomen, near the bladder. Both masses Differential diagnoses included brain emboli from a forearm had radioopaque exteriors with areas of radioopaque material vascular foreign body, or brain neoplasia. She was anesthetized, within the masses as well. Abdominal exploratory surgery was and surgical exploration revealed no foreign material in the ce- performed and 2 masses were removed from the omentum and phalic vessel below the tract. She became hypothermic despite submitted for histopathology. Histopathology revealed cysts rigorous support, and could not be weaned from the ventilator with thick fibrous walls and a multifocal, mild, chronic to granu- after cessation of gas anesthesia. She was euthanized, and a full lomatous inflammatory reaction. The cysts contained a partially necropsy was performed and the major abnormalities were mineralized mixture of amorphous lightly eosinophilic debris. limited to the brain. Microscopic examination of an intraaxial right frontal lobe mass noted at necropsy was consistent with Relationship between Diagnostic PCR and Serological Assays a glioblastoma multiforme (GBM). The neoplasm had classic in the Diagnosis of Simian T-Lymphotropic Virus Infection microscopic features of a GBM including nuclear atypia, cel- in Baboons lular pleomorphism, high mitotic activity, vascular thrombosis, microvascular proliferation, and serpiginous-radiating areas of JM d’Offay*, R Rberle, RF Wolf, GL White necrosis. In humans, GBM is the most common and most malignant brain neoplasm, but in nonhuman primates spontaneous Center for Veterinary Health Sciences, Oklahoma State Univer- brain neoplasms are rare. To our knowledge this case represents sity, Stillwater, OK

122 Abstracts of scientific papers

To determine the simian T-lymphotropic virus (STLV) infec- completely and the ventral area of the distal ventral aspect of tion status of baboons in a large breeding facility, 178 baboons the forearm was also covered but showed a concave aspect due were screened for infection by 1) nested PCR to detect STLV to loss of muscles and partial destruction of tendons. One year provirus in peripheral blood cells, 2) a commercially available after surgery, the monkey was doing well and transferred to HTLV1-based ELISA/WB serological assay, and 3) 4 ELISA us- another facility. In this case, lateral abdominal skin provided ing recombinant STLV1 proteins (gag p19 and p24, glycoprotein a suitable donor site. gp46, and the tax protein). Using PCR as the gold standard, the specificity and sensitivity of the serological assays were com- Optimizing Nasal Delivery in Cynomolgus Macaques (Ma- pared. Of the 178 baboons screened, 57 (32%) tested positive caca fascicularis) for STLV1 by PCR. When sera from all baboons were analyzed by the HTLV1-based ELISA/WB assay, 41 of 57 PCR-positive DMB Sergio*, V Liang, S Somanasen, SN Abraham, HF Staatsc baboons also tested positive; the sensitivity and specificity of this serological assay were 72% and 98%, respectively. When Singapore Health Services Pte, Singapore, Singapore the same sera were screened by ELISA using the combined 4 recombinant STLV proteins, 55 of 57 (96%) PCR-positive baboons Recent studies in rodents and rabbits showed that activators tested positive. Although the sensitivity of the recombinant of mast cells could serve as potent adjuvant for nasally admin- protein-based ELISA was higher than that of the HTLV1-based istered vaccines. However, when testing the efficacy and safety ELISA/WB assay (96% versus 72%), the specificity was lower of the mast cell activator peptide in cynomolgus macaques (92% versus 98%) due to a higher number of false positives. The using a protein subunit antigen, we were only able to evoke a p24-based assay had a low sensitivity (42%) and had the lowest very low immune response after nasal immunization. Gamma specificity (94%) of all the recombinant protein based assays. scintigraphy revealed that the nasal inocula was not retained Although IgG to the STLV1 tax protein was detected in only in the nasal cavities and was swallowed within minutes and 7 baboons (sensitivity = 12%), the specificity of this tax-based presumably degraded in the stomach. Our objectives were to assay was 100%. Of all the recombinant protein-based ELISA, employ gamma scintigraphy to determine if the state of seda- the p19-based assay was the most sensitive and specific (88% tion influences the delivery and nasal clearance in cynomolgus and 97%, respectively) followed by the gp46-based assay with a macaques and to maximize the delivery and retention of liquid 60% sensitivity and 97% specificity. In this study, it appears that formulations in the nasal regions of cynomolgus macaques. Six the p19-based ELISA assay was as sensitive but more specific animals from the vaccination groups were chosen for the study. than the commercially available HTLV-1 based ELISA/WB for Animals were placed either in supine position or supine with serological screening of baboons for STLV-1 infection. head slightly tilted forward. Animals were sedated with either ketamine or ketamine/xylazine combination, and 150 μL of Autologous Mesh Skin Grafting in a Rhesus Macaque (Ma- 99Tcm-sulfur colloid were administered to the left nostrils of the caca mulatta) with Electrical Burns macaques and the amount of radiotracer in the nasal cavity was measured noninvasively using gamma camera. 99Tcm-sulfur HR Perez colloid was given either as a bolus or at 5 doses of 30 μL each at 30-s interval. Radioactive counts at different time points were Caribbean Primate Research Center, Sabana Seca, Puerto Rico taken at different anatomic location from the time of the last delivery and at various time intervals up to 75 min. Animals A young adult, feral, 5-kg, male rhesus macaque in good were euthanized with an overdose of pentobarbitone at the body condition was presented to our facility by officers of the end of the procedure. The conducted study provided valuable State Natural Resources Department with third degree skin information in optimizing nasal delivery in sedated macaques. burns on the dorsal part of the metacarpal region and distal Scintigraphy revealed that nasal retention of liquid inoculate ventral portion of the radioulnar region. The skin burns had could be greatly enhanced by the positioning of a well-sedated occurred because the monkey came in contact with power animal at supine position with head slightly tilted forward and cables in a nearby town. The wound on the distal ventral aspect by delivering the inocula incrementally in small volumes and of left forearm was approximately 7 cm × 4.5 cm with an oval not in a single bolus. Thus, before nasal immunization is under- shape. The wound on the dorsal area of the left metacarpal taken in macaques, a concerted effort to optimize the delivery bones showed exposition of the metacarpal bones 2, 3, and 4, of the nasal formulation is required. and was approximately 4 cm × 3 cm in size also with an oval shape. These injuries correspond to fourth and fifth degree The Effect of Environmental Enrichment on Time Budgets burns according to Dupuytren classification. After the period and Behavior of Socially Housed Long-Tailed Macaques given to promote the formation of a granulation bed (prepa- (Macaca fascicularis) ration of the recipient site), the monkey was prepared for the skin graft procedure. Harvested skin was obtained from both L Levallois, SL Desvaux * lateral lumbar regions. Graft tissue was placed on the wounds by suturing them to the viable skin borders. Nonadherent Noveprim, Vieux Grant Port, Mauritius absorbent dressing with a thin coat of silver sulfadiazine was placed and a secondary absorbent layer of bandage was placed International biomedical research practices, ethical guide- with a plastic splint covered with cohesive bandage material lines, policies, and regulations have constantly evolved in the to protect the graft and prevent joint motion. This bandage direction of improving animal welfare. Concepts like the 3Rs was replaced every 2 to 3 d, depending on the amount of are now recognized worldwide as a valuable working stan- discharge seen during each bandage change. The animal was dard. Refinement of practices through the enrichment of the treated postoperatively with antibiotics and pain medications. environment is more than ever at the center of all efforts, and By approximately 2 mo the meshed areas were covered by even more so when dealing with NHP. We have developed a epithelium. Retention of graft tissue was approximately 75% to plan that aims at promoting species-specific behaviors through 80%. The dorsal area of the left metacarpal bone was covered environmental management and enrichment. It is based on

123 Vol 50, No 1 Journal of the American Association for Laboratory Animal Science January 2011 practical scientific validation of newly proposed devices and ulcerative, and exudative dermatitis with pruritus on the pal- practices, in order to evaluate and measure their impact on mar surfaces of both hands. The axillary lymph nodes were behavior and ensure safety for staff and primates. The success also moderately enlarged. This individual had been housed in of the enrichment program depends directly on the practical a corncrib enclosure made of galvanized-coated steel for most integration of the plan into the daily husbandry routine, the of her life. The lesions were not observed on any other area of choice of targeted behaviors, and the quantity, type, and timing the body or on any other animals in the enclosure. Complete of enrichment used. In this protocol, we evaluated the impact blood count, serum chemistry, skin biopsy, axillary lymph node of the set of enrichments on the daily time budget of juvenile biopsy, skin scrape, cultures, and sensitivities were submit- monkeys. We used 2 groups of 25 female cynomolgus of 26 ted for analysis. Skin biopsy results showed eosinophilic and mo of age that were followed over 3 mo. The control group suppurative dermatitis, mast cell hyperplasia, and acanthosis. was housed in an outdoor pen containing only structural The axillary lymph node biopsy indicated multifocal moder- elements, while the other group was housed in a similar pen, ate eosinophilic lymphadenitis with hemorrhage. The CBC but the latter was environmentally enriched according to our demonstrated marked eosinophilia and neutrophilia without enrichment plan. The experimental pen is equipped with a an elevated total white blood cell count. Skin cultures showed variety of devices including structural perches, platforms, and secondary growth of opportunistic normal flora. Results from ladders to promote locomotion as well as space occupation and other tests were unremarkable. For the next 3 y this animal was positive social behaviors. Puzzle feeders filled with a mix of recurrently presented to the hospital with the same lesions. grains are used in the morning, while fruit puzzle feeders are Various topical, systemic, and oral treatments were prescribed supplied in the afternoon to increase foraging time. Free toys with partial or no resolution of clinical signs. Treatments pro- and ropes are available throughout the day for the macaques ducing the best results included systemic corticosteroids, and to play with, encouraging object manipulation and provid- immunosuppressive/immunomodulating drugs. An etiology of ing sensitive stimulation. Each group was observed using contact allergy from galvanized metal enclosure was suspected. 30-s interval scan samplings. The behaviors detected were The animal was released from the hospital to a different type of categorized into subsets according to a previously defined enclosure with a sand floor and minimal metal contact. After 6 ethogram. This allowed us to establish for both groups a time mo in a new environment, the lesions spontaneously resolved. budget representative of the day. Here we describe the enrich- This report suggests a change of environmental condition was ment program implemented at our facility, its impact on the successful in eliminating the cause of an idiopathic palmar daily time budget of socially housed cynomolgus, and how it dermatitis. compares to the Mauritian macaque time budget in the wild. Cervical Intraepithelial Neoplasia in a Rhesus Macaque Pathology of Recurrent Idiopathic Gingival Hyperplasia in (Macaca mulatta) a Male Olive Baboon J Mitchell K Kolappaswamy*, S Shipley, MA Reynolds, C McLeod, L DeTolla Armed Forces Radiobiology Research Institute, Bethesda, MD

University of Maryland School of Medicine, Baltimore, MD A 13-y-old female rhesus macaque presented with an acute onset of anorexia and pallor of the oral mucous membranes and A 14-y-old male baboon was reported to the clinical veteri- facial skin. This primate was assigned to a study examining the narian for difficulty in labial closure. The nonhuman primate (a role of Helicobacter pylori in gastric oncogenesis. Physical exami- breeding male not subjected to any experimental procedures) nation revealed a tense, distended abdomen. Ultrasonography had a history of moderate gingival hyperplasia surgically showed a significant amount of free fluid in the abdomen with resected 2 y prior to development of the recurrent gingival cranial displacement of the gastrointestinal tract and ill-defined hyperplasia described in this report. Oral examination revealed urogenital organs. An exploratory laparotomy was immedi- moderate plaque with mild calculus accumulation, most severe ately performed. After incision of a thickened peritoneum, an over the upper and lower incisors and canines. Generalized dif- extensive amount of brown, serous fluid was aspirated from the fuse gingival enlargement with a smooth surface was noticed on peritoneal cavity. All abdominal organs were covered in fibrous both the maxilla and mandible involving all canine and incisor mat and there was extensive adhesion of the organs to each other teeth. There was no gingival enlargement in the premolar or or the visceral peritoneum. Given the severity of the lesions, molar areas. The overgrowth was partially extended over the euthanasia was elected. Histopathology revealed the invasion labial surface of the upper incisors and canines. The results of of endometrial stoma and glands into the serosal surface of the the biochemical profile and complete blood count were within spleen, gastrointestinal tract, liver, urinary bladder, and the peri- normal limits. A diagnosis of idiopathic generalized gingival toneal aspect of the diaphragm. The endometriosis replaced the hyperplasia was made based on gross and microscopic histo- omental adipose, but only extended superficially into the serosa patholgical evidence. and muscularis of the intestinal tract and to a lesser extent into parenchymal organs of the abdomen. Examination of the cervi- Idiopathic Palmar Dermatitis in a Rhesus Macaque (Macaca cal tissue revealed distinctive regions of epithelial hyperplasia mulatta) and dysplasia with multiple proliferative islands of basiloid cells, all of which displayed marked anaplasia, a high mitotic K Rivas, K Hopper, PR Morales*, A Garcia, D Frankenfield, J rate and loss of normal architectural polarity. In no instance did Wagner the dysplastic cells break through the basement membrane. A diagnosis of cervical intraepithelial neoplasia (CIN) was made. The Mannheimer Foundation, Homestead, FL This disease has been previously reported in cynomolgus and rhesus macaques. Associations have been made between this An adult female rhesus macaque was admitted to the hospital lesion and a papillomavirus (PV) similar to the association of with a clinical presentation of extensive multifocal, inflamed, human papillomavirus (HPV) and the development of cervical

124 Abstracts of scientific papers

carcinomas in human females. Postmortem findings such as Acute Staphylococcal Sepsis Secondary to a Bite Wound these suggest that routine examinations of the cervices of older female macaques may be warranted. However, the morbidity M Chavez-Suarez*, GL White, SD Kosanke, RF Wolf and mortality of cervical neoplasia in macaques has not been widely studied. University of Oklahoma Health Sciences Center, Oklahoma City, OK Megaesophagus in a Male Cynomolgus Macaque (Macaca fascicularis) An 11.8-y-old female baboon (Papio spp.) delivered a still- born infant at 166 d gestation. A day later, she was found T Lass*, I Bolton, J Simmons recumbent and nonresponsive. An external physical examination revealed a purulent exudate coming from the left ear. Charles River Laboratories, Houston, TX The initial working diagnosis was systemic shock secondary to a bacterial infection due to penetrating wound. Laboratory We will present a clinical case of megaesophagus in a Mauri- evaluations (CBC, clinical chemistry, and urinalysis) were tian origin male cynomolgus macaque with gross and histologi- consistent with bacterial sepsis. Treatment involved shock- cal photos. Additional discussions of treatment and causes of dose intravenous fluids, broad spectrum antibiotics (initially this condition will be addressed. intravenous then intramuscular), shock dose steroids, and nutritional support. In spite of all actions, the animal failed to The Effect of Season on Inflammatory Response in Captive respond and died within 3 d. At necropsy, the lungs revealed Baboons multiple, variable-sized abscesses which were cultured for bacteria. The left ear canal contained a purulent exudate and D McFarlane*, RF Wolf, KA McDaniel, GL White the subcutaneous tissues above and behind the left ear were severely hemorrhagic and acutely inflamed. This appeared to Oklahoma State University, Stillwater, OK be associated with a penetrating bite wound. The meninges, involving an area of the left dorsal cerebral hemisphere and The intensity of immune response has been shown to vary the left portion of the cerebellum, were markedly discolored with season in humans, rodents, birds, amphibians, and fish. with what appeared to be abscess formation. A penetrating Little is known about the effect of season on immune reactiv- wound was observed within the left cerebral hemisphere. The ity in nonhuman primates. Seasonal variation in immune left adrenal was dark in color and enlarged. Histologic exami- response could have profound implications in experimental nation of the lung abscesses revealed them to be comprised design and data interpretation, as well as general herd health. mostly of an acute purulent exudate. Some of these contained We hypothesized that baboons housed in outdoor corrals aggregates of bacteria. A culture of the lesions mostly revealed would experience seasonal fluctuations in inflammatory re- Staphylococcus aureus. The left external ear canal contained a sponse, whereas animals maintained indoors under a constant moderate amount of an acute purulent exudate along with schedule of 12-h artificial light:dark cycle would not. To test evidence of hemorrhage. One of the adjacent salivary glands this hypothesis, 24 healthy, 2- to 4-y-old male baboons were and soft tissues also contained areas of an acute purulent, divided into 2 groups; half were housed in outdoor corrals, necrotizing inflammation. The left cerebral hemisphere re- the other half indoors under 12 h/d of artificial lighting. vealed a penetrating wound 8 to 10 mm in depth. The wound After 3 mo of acclimation, blood samples were collected in area was acutely inflamed, necrotic, and hemorrhagic. The March, June, September, and December. Serum C-reactive overlying cerebral and cerebellar leptomeninges were acutely protein and IL6 concentration were measured by ELISA; inflamed with numerous gram-positive cocci being present. serum cortisol, DHEA-S, IGF1, ACTH, insulin, and α-MSH There was marked adrenal cortical hemorrhage and necrosis by radioimmunoassay. Peripheral blood mononuclear cells consistent with the Waterhouse–Friderichsen syndrome. The (PBMC) were stimulated with lipopolysaccharide (LPS) for 4 cause of death appears to be related to the sepsis secondary h; TNFα and IL6 release were measured by ELISA. The effect to the penetrating bite wound that significantly affected the of season on inflammatory mediators was assessed by repeated brain and meninges. measures one-way ANOVA (IL6, sCRP, cortisol) or Friedman test (sIL6,TNFα) with Bonferroni or Dunn post hoc correction The Baboon: A Model for Translational Vaccine Research for multiple comparisons. The correlation between hormone concentration and immune response was calculated using a JF Papin*, RF Wolf, R Eberle, GL White Pearson coefficient of correlation. Baboons housed outdoors had a greater sCRP concentration (P < 0.01) and increased University of Oklahoma Health Sciences Center, Oklahoma PBMC cytokine release (TNFα, P < 0.001; IL6, P < 0.01) follow- City, OK ing immune stimulation in June and September compared to March and December. Serum hormones and IL6 concentration Baboons are among the very few primates species for which did not show a seasonal pattern. Indoor baboons had a similar there are large and sustainable colonies available for biomedical cytokine response to LPS (TNFα and IL6, P < 0.0001); however, research. The advantages of using captive baboons for non- CRP did not differ by season. A greater release of TNFα was human primate model development are numerous. Baboons found in animals associated with a decrease in serum DHEA-S are readily available for experimental intervention, as well as concentration. Captive baboons have an increased inflamma- extensive observational studies on a long-term basis, and have tory response in June and September; therefore, season must been used since the 1950s for the purpose of transplantation be considered when designing immune studies in baboons. research due to their physiological and genetic similarities to Further work is needed to determine the specific environmen- humans. Baboons express 4 subtypes of IgG like humans and tal factors responsible for this seasonal effect. have a similar blood composition. In addition, their MHC-I expression has been characterized. As such, the baboon, Papio cynocephalus anubis, is rapidly becoming the foremost nonhu-

125 Vol 50, No 1 Journal of the American Association for Laboratory Animal Science January 2011 man primate model for translational vaccine research. In 2002, ates disease progression, and a cDNA sequence of Mamu-B*03 NIH announced the strategic plan to increase the diversity of that reduces viremia. Recently, the same cDNA sequence in nonhuman primate models in the US namely due to the lack the binding domain of Mafa-B*7601 has been identified with of availability of rhesus monkeys and the need for a more di- Indonesian cynomolgus macaques, offering a second primate verse research resource. Since this time our group has focused model. Matching genetic and biomarkers between humans and on the development of vaccine models using the Papio species, macaques provides their improved selection as animal models. including collaborative efforts with external organizations and Within the macaque populations of countries of origin, inter- researchers. Here we report a summary of these efforts, includ- grade zones exist that mix subspecies of macaques. In central ing efficacious vaccines for bacterial (Streptococcus pyogens, Southeast Asia, intergrade zones of rhesus and cynomolgus Borrelia burgdorferi) parasitic (Entamoeba histolytica, Schistosoma macaques are found that have moved northward and southward mansoni), and viral diseases (West Nile virus, dengue virus, with varying Pleistocene glacial conditions leading to extensive influenza, human immunodeficiency virus). Our research and gene flow between the 2 species. Cynomolgus macaques phe- collaborative studies highlight the importance of the baboon as notypically resemble rhesus monkeys within known intergrade a nonhuman primate model for translational vaccine research. zones. Macaques originating from various source populations have already been mixed in captive breeding colonies. To bet- HVP2 as a Model for Testing Drug Efficacy against Monkey ter define these macaques, we are developing a DNA database B Virus to compare genes and genome regions of interest among regional populations of cynomolgus macaques. Macaques R Eberle, D Black, L Maxwell, RF Wolf, J Ritchey, K McCormack* with optimized genetic definitions are critical for the rigors of genomic-based research. Genomics advance the disciplines of Oklahoma State University, Stillwater, OK predictive diagnosis, molecular-based therapeutics, and genetic basis of diseases. Currently, human B virus (BV) cases are treated with ACV or, if neurological signs are evident, GCV. Both ACV and GCV Nine Clinical Cases of Zygomycosis in Colony-Born Sooty are effective against herpes simplex virus (HSV) infections, but Mangabeys (Cercocebus atys atys) BV is known to be less sensitive to these drugs than is HSV. Furthermore, ACV- and GCV-resistant HSV mutants occur M Arce*, JK Cohen, P Sharma, A Patricia Garcia, D Anderson with a significant frequency, suggesting that it is only a mat- ter of time until drug resistant mutants of BV appear. Current Yerkes National Primate Research Center, Emory University, drug regimens for treatment of human BV infection thus lack Atlanta, GA optimal efficacy and will be completely ineffective for treatment of infections due to drug resistant mutants. Research on BV is Zygomycosis is a disseminated fungal infection that has been not only dangerous and expensive due to the biocontainment reported in multiple nonhuman primate species. Nine clinical facilities necessary for such work, but is also limited to very few cases of zygomycosis have been identified over the last 10 y in laboratories since BV is listed as a select agent. HVP2 is a BSL2 sooty mangabeys born at our institution. Immunosuppression herpesvirus of baboons that is genetically very closely related caused by preexisting conditions such as diabetes, malnutrition, to BV, and so HVP2 might serve as a model system for screen- viral infection, and iatrogenic immunosupression have been ing new antiviral therapies for BV. This study was undertaken suggested as predisposing factors in humans. Zygomycosis is to determine if HVP2 has a similar drug sensitivity profile to caused by opportunistic fungi in the class Zygomycetes, which BV in vitro and in vivo. Results to date from plaque reduction includes 2 orders: Mucorales and Entomophthorales. The order assays and testing of ACV, PCV, and GCV in a mouse model Mucorales has been implicated in cases of nonhuman primates suggest that HVP2 parallels BV in its drug sensitivity profile, and includes multiple organisms such as Absidia and Mucor. with ACV being least and GCV being most effective. While Organisms in the order Entomophthorales are less commonly comparative testing of additional drugs is necessary to confirm observed, but in humans it causes cutaneous infections. Infec- this, it appears that HVP2 can serve as a safe and accurate sur- tion is usually acquired through trauma or inhalation with rogate for testing of new and combined drug therapy regimens several clinical forms of zygomycosis described in humans. for improved treatment of BV infections. Presenting clinical signs in these 9 sooty mangabeys included lethargy, anemia, weight loss, diarrhea, exophthalmos, and Primate Genomics: Advances in Biomedical Research anorexia. Gross lesions observed at necropsy included gastric ulcers, peritonitis, periorbital granulomas, orchitis, hepatitis, DK Johnson*, DG Smith, P Houghton pneumonia, nephritis, and lymphadenopathy. Histological evaluation revealed granulomatous inflammation with nonsep- Harlan Laboratories, Sisters, OR tate branching hyphae consistent with zygomycete. Although fungal cultures were not often done, 2 were positive for Muco- The completion of the human genome and rhesus macaque rales (Absidia and Mucor). Five of the animals in this report were (Macaca mulatta) genome along with rapid completion of the naturally infected with simian immunodeficiency virus (SIV) and cynomolgus macaque (Macaca fascicularis) genome emphasize 4 were seronegative for SIV. Although diabetes is commonly seen the value of primate models in biomedical research and trans- in older sooty mangabeys, in our colony it was not a cofactor in lational medicine. These commonly used species cover broad any of the animals with fungal infection (age range of 4 to 24 y geographic ranges. Advances in genomic methodologies allow of age; median age of 10 y). The treatment for human zygomy- comparative genetics between humans and primates. Currently cosis usually consists of surgical resection and administration of rhesus macaques from India rather that China are preferred antifungal drugs. Antemortem diagnosis was made in only one models of AIDS research because they exhibit several genes animal with bilateral orchitis; 3 of the animals were found dead shown to influence disease progression; these include a high and the other 5 animals had clinical presentations of a nonspecific frequency of the Mamu-A*01 class I mhc allele that restricts the nature that would not have suggested fungal infection. To the SIV gag protein, a lower copy number of CCL3L that acceler- authors’ knowledge, this is the first report of zygomycosis in the

126 Abstracts of scientific papers

sooty mangabey (Cercocebus atys atys). Nonhuman Primate Research Center Consortium Activities and Information Resources: An Update A Technique for Endoscopic Placement of a Capsule Endo- scope in Rhesus Macaques (Macaca mulatta) C J Doane*, J Nylander, GD Lawrence, LM Watchman, AD Lewis, JG Else, KC Baker, B Ferguson, J Rogers, R Bohm K Strait*, J Orkin, F Villinger, EE Peters Oregon National Primate Research Center, Beaverton, OR Yerkes National Primate Research Center, Emory University, Atlanta, GA The goal of the Nonhuman Primate Research Center (NHPRC) Consortium is to strengthen communications, lever- Capsule endoscopy is a method used in human medicine to age system-wide resources, and facilitate sharing of information noninvasively visualize the small intestinal lumen. The device, and best practices across institutions. Established in partnership which is swallowed, consists of a miniature video camera inside with the National Center for Research Resources (NCRR), the of a smooth capsule that transmits images to a remote record- Consortium consists of working groups in the areas of genetics, ing device. As part of a study of SIV-induced gastrointestinal training, colony management, DNA banking, pathology, and pathology, we developed a technique for endoscopic placement behavioral management. The Consortium has existed since of a capsule endoscope in rhesus macaques. The ability of the 2007. Our purpose is to provide an overview of each working capsule to safely pass through the monkey gastrointestinal group and to summarize how the Consortium has adopted the tract was first tested by administering a radiopaque dissolvable Biomedical Informatics Research Network (BIRN) to facilitate capsule of the same size and shape as the capsule endoscope interaction and information sharing between the centers. The into the esophagus of 2 animals. Although safe passage through ultimate goal of the Consortium is to leverage the synergy of the gastrointestinal tract was confirmed, it was determined collaboration to provide a comprehensive national resource that that the capsule must be delivered directly into the duodenum serves the biomedical research community. to ensure entry into the small bowel before expiration of the capsule battery life. Five rhesus macaques underwent cap- Suspected Brown Recluse Envenomation in Chimpanzees: sule placement in the duodenum. A reinforced net standard Case Reports and Review of Treatment Modalities retriever was placed through the channel of a 5.9-mm flexible gastroscope. A capsule endoscope was secured in the net and K Brasky*, M del Garza, D Pineda, N Martin, D Alonzo, J Vallejo the gastroscope was inserted into the esophagus and advanced into the stomach. After insufflating the lumen, a J-maneuver Southwest National Primate Research Center, San Antonio, TX was performed to advance the scope to the pyloric sphincter. The retriever was advanced through the sphincter and the net A small percentage of spider species in the world are medi- was opened to free the capsule within the duodenum. Images cally important, with the majority causing systemic injury. were recorded by a remote recording device attached to the Spiders of the genus Loxosceles, such as the brown recluse spi- outside of the cage. Capsule endoscopy was well tolerated in der, can cause necrotic dermatologic injury through a unique all animals and suggests that this method may be an attractive toxin containing sphingomyelinase D. There are 13 species of option for noninvasive visualization of the small intestine in Loxosceles spiders in the US. These spiders inhabit south and rhesus macaques. south central states from Texas through Georgia and north to Herpetic Vesicular Dermatitis in an Adult Cynomolgus Mon- southern Wisconsin. These spiders are nocturnal and live in key (Macaca fascicularis) dark, warm areas around human habitation. Loxosceles spider bites have been shown to cause dermatonecrosis in humans, GA Ignacio*, S Mohanan, SB Gray, ND Kock guinea pigs, and rabbits, but not mice or rats. A classic “bulls eye” lesion develops at the site of the bite and a dark necrotic Wake Forest University, Winston-Salem, NC center develops as the lesion matures. Healing is slow and these ulcers can persist for months leaving a deep scar. Systemic signs An adult male cynomolgus macaque (Macaca fascicularis) such as fever, malaise, nausea, and vomiting may also be seen. presented with a generalized, nonpruritic, mildly erythematous Diagnosis is made clinically based on a long list of ruleouts as vesicular dermatitis over the entire body, without other apparent there are no commercially available tests for envenomation. clinical abnormalities. The monkey was treated with diphen- Treatment is symptomatic with many controversial therapies hydramine over the next several days, and observed closely, present in the human literature. Three suspected cases of brown with the dermatitis diminishing rapidly and resolving by the recluse envenomation are presented in chimpanzees to make third day. On the day of presentation, a 3-mm punch biopsy veterinary clinicians aware of this condition and the subsequent was collected, which revealed intraepidermal vesicles contain- care involved in these cases. ing brightly eosinophilic keratinocytes, which had 4- to 8-μm diameter eosinophilic intranuclear inclusions and marginated Morphometric Variables Related to Metabolic Profile in Cap- chromatin. Several syncytial cells that had similar inclusions tive Chimpanzees (Pan troglodytes) were also noted. Immunohistochemical staining for herpes simplex was negative. Swabs of mucous membranes from the MCR Andrade*, PB Higgins, VL Mattern, M de la Garza, KM monkey were negative for active cercopithecine herpesvirus Brasky, AG Comuzzie 1 (B virus) infection, although the serum ELISA for antibody was equivocal. A definitive diagnosis of simian varicella virus Southwest Foundation for Biomedical Research, San Antonio, TX (SVV) infection was confirmed by serology testing and poly- merase chain reaction analysis on preserved biopsy tissue. The Obesity is a risk factor for several diseases including type 2 presentation of the case is consistent with previous reports of diabetes and cardiovascular disease. We undertook this study to SVV reactivation in cynomolgus macaques. investigate the relationships between waist circumference (WC) and body weight (BW) and circulating markers of metabolic,

127 Vol 50, No 1 Journal of the American Association for Laboratory Animal Science January 2011 cardiovascular, hepatic, and renal function in chimpanzees (Pan What’s Your Diagnosis: A Case of Oral Squamous Cell Carci- troglodytes). Twenty-four female (22.3 ± 11.5 y of age) and 18 male noma in a Pigtail Macaque (Macaca nemestrina) (20.9 ± 7.9 y of age) captive chimpanzees were studied. During each animal’s physical exam BW and WC were measured and D Stockinger*, D Fong, A Torrence, K Vogel, C Hotchkiss a fasted blood sample was obtained from which serum glucose, BUN, creatinine, albumin, cholesterol, ALT, AST, ALP, total and Washington National Primate Research Center, Seattle, WA direct bilirubin, and triglyceride were measured. WC was posi- tively correlated with systolic (r = 0.32, P = 0.048) and diastolic A 9-y-old, gravid (124 GD fetus) Macaca nemestrina presented blood pressure (r = 0.55, P < 0.001), and triglyceride (r = 0.41, for facial swelling. On physical exam she had a spherical left P = 0.01). BW was significantly correlated with albumin (r = mandibular mass that extended from the ramus across the 0.35, P = 0.01) and triglyceride (r = 0.44, P = 0.005). Males were symphysis rostrally and extended to the right I2. The jaw re- heavier (64.8 ± 12.2 versus 55.7 ± 12.2 kg), had lower diastolic mained 0.8 cm ajar and opened 1.5 cm. CBC was normal and blood pressure (56.6 ± 13.7 versus 66.2 ± 13.2 mm Hg), greater chemistry revealed hypoalbuminemia, low A:G ratio, elevated creatinine (1.14 ± 0.20 versus 0.95 ± 0.25 mg/dL), albumin (3.57 BUN, elevated ALP, and elevated GGT. Radiographs revealed ± 0.19 versus 3.33 ± 0.34 g/dL), ALT (37.4 ± 18.5 versus 28.1 ± 6.2 an expansile osteolytic mass. Differentials included neoplastic U/L), and AST (33.8 ± 11.8 versus 21.4 ± 7.0 U/L) than females. (osteosarcoma, chondrosarcoma, fibrosarcoma, and squamous The relations between WC and blood pressure and triglyceride cell carcinoma) inflammatory or infectious (osteomyelitis) are consistent with those reported in humans and other primate etiologies. Supportive therapy of NSAIDS, antibiotics, calcium species. Sex differences in diastolic blood pressure, creatinine, supplementation, prenatal vitamins, and soft chow was ad- and hepatic function markers should be taken into account when ministered until the fetus could be delivered. Two weeks after undertaking metabolic studies in this species. presentation her appetite decreased, the jaw could completely close and open 2.4 cm. Both the dam and the fetus were eutha- Persistent Eosinophilia and Ischial Callosity Eosiniphilic nized. The final diagnosis determined by histopathology; gross Spongiotic Dermatitis in an Adult Rhesus Macaque (Macaca necropsy revealed a locally invasive expansile tumor of the left mulatta) mandible that replaced portions of the soft/hard palate, sinuses, ear canal, and calvarium. Histology demonstrated poorly cir- L Román*, S Duarte, K Lencioni, G Lawson, J Baer cumscribed and unecapsulated neoplastic tissue with polygonal cells that breached the epithelial basement membrane forming David Geffen School of Medicine at University of California— nests, cords, and trabeculae. Most nests contained keratin pearls. Los Angeles, Los Angeles, CA These findings were consistent with an aggressive squamous cell carcinoma. Eosinophilia (1,183 cells/μL) was discovered during routine bloodwork on an adult male rhesus macaque (Macaca A Technique for Intraosseous Access in the Owl Monkey mulatta). Two weeks later, follow up bloodwork confirmed the (Aotus Nancymaae) eosinophilia with no additional abnormalities. A presumptive diagnosis of a parasitic infection was made and a course of fen- CS Cooper-Pesco*, P Hanley, K Barnhart bendazole was started. Three weeks later the monkey presented with viscous, straw-colored exudative fissures of the ischial University of Texas MD Anderson Cancer Center, Bastrop, TX callosity and several soft, shrunken nails on all 4 limbs. Nail lesions were noted on previous exams, but concluded to be a Intraosseous access is a practical substitute to intravenous ac- sequela to recent trauma, although other differentials included cess in patients with a collapsed peripheral circulatory system. bacterial or fungal paronychia. Based on previous history of This alternate route allows for the administration of intravenous MRSA infection, empirical treatment with trimethoprim sulfa drugs or the performance of fluid therapy. An ultimate benefit and ibuprofen was provided, pending further diagnostic results of intraosseous access is the ability to aspirate bone marrow in (histopathology of the ischial callosities). Diagnostics revealed a an effort to diagnose hematopoetic disorders. Recently at our persistent, progressive eosinophilia and eosinophilic spongiotic facility’s owl monkey breeding colony, it became necessary to dermatitis of the ischial callosity tissue. Topical Clobetasol gel perform bone marrow aspirates on a number of individuals. We was initiated. Follow up examination revealed a significant outline the method used to gain intraosseous access in an owl decrease in eosinophil levels (272 cells/μL) and moderate im- monkey and showcases the diagnostic quality of the samples provement of the ischial callosity lesions. After 2 wk without obtained. We also discuss the potential for application of this further significant improvement, treatment was discontinued. technique in other neotropical and neonatal old world nonhu- One week following cessation of treatment, a recurrence of man primate species. Intraosseous access is straightforward the eosinophilia (2,128 cells/μL) and ischial callosity lesions and practical and learning this technique broadens the arsenal was observed. The etiologic diagnosis on this case is currently of therapeutic options available to clinician and researchers. unknown. Further histopathologic evaluations are pending.

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