29 Pocket Handbook of Nonhuman Primate Clinical Medicine - Courtney

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Edited by

Dr.Angela Courtney

Edited by

Dr.Angela Courtney

Boca Raton London New York

CRC Press is an imprint of the Taylor & Francis Group, an informa business

CRC Press Taylor & Francis Group 6000 Broken Sound Parkway NW, Suite 300 Boca Raton, FL 33487-2742 © 2013 by Taylor & Francis Group, LLC CRC Press is an imprint of Taylor & Francis Group, an Informa business No claim to original U.S. Government works Version Date: 20120530 International Standard Book Number-13: 978-1-4398-6729-7 (eBook - PDF) This book contains information obtained from authentic and highly regarded sources. Reasonable efforts have been made to publish reliable data and information, but the author and publisher cannot assume responsibility for the validity of all materials or the consequences of their use. The authors and publishers have attempted to trace the copyright holders of all material reproduced in this publication and apologize to copyright holders if permission to publish in this form has not been obtained. If any copyright material has not been acknowledged please write and let us know so we may rectify in any future reprint. Except as permitted under U.S. Copyright Law, no part of this book may be reprinted, reproduced, transmitted, or utilized in any form by any electronic, mechanical, or other means, now known or hereafter invented, including photocopying, microfilming, and recording, or in any information storage or retrieval system, without written permission from the publishers. For permission to photocopy or use material electronically from this work, please access www.copyright. com (http://www.copyright.com/) or contact the Copyright Clearance Center, Inc. (CCC), 222 Rosewood Drive, Danvers, MA 01923, 978-750-8400. CCC is a not-for-profit organization that provides licenses and registration for a variety of users. For organizations that have been granted a photocopy license by the CCC, a separate system of payment has been arranged. Trademark Notice: Product or corporate names may be trademarks or registered trademarks, and are used only for identification and explanation without intent to infringe. Visit the Taylor & Francis Web site at http://www.taylorandfrancis.com and the CRC Press Web site at http://www.crcpress.com

Contents introduction ..................................................................................ix acknowledgments ..........................................................................xi about the editor ...........................................................................xiii contributors.................................................................................. xv

1 anesthesia in nonhuman primates .........................................1 Cholawat Pacharinsak and Patrick Sharp introduction ...........................................................................1 record keeping ........................................................................3 definitions ..............................................................................4 premedication/sedation/anesthesia ........................................5 the anesthetic machine ..........................................................5 preoperative management and assessment ...........................13 intraoperative monitoring ..................................................... 14 Intraoperative Procedures Overview ................................ 14 Anesthetic Plane .............................................................15 Cardiovascular System ...................................................15 Respiratory System .........................................................19 Body Temperature ..........................................................23 Gas Analyzers.................................................................24 Fluid Administration ......................................................24 postoperative care and monitoring........................................26 Acute Postoperative Period ..............................................26 Long-Term Postoperative Period ......................................29 acknowledgment ................................................................... 31 references .............................................................................32 bibliography .........................................................................32 v

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2 pain management.................................................................35 Cholawat Pacharinsak and Patrick Sharp pain pathways pathophysiology ............................................35 effects of untreated pain .......................................................39 pain assessment ...................................................................40 effective management of pain ............................................... 41 when to treat pain ................................................................42 analgesic drugs commonly used for acute pain .....................44 neuropathic pain treatment ..................................................50 cancer pain treatment .......................................................... 51 acknowledgment ...................................................................52 bibliography .........................................................................52

3 wounds and wound care .......................................................55 Angela Courtney

4 basic fluid therapy ................................................................59 Angela Courtney fluid therapy .........................................................................59 dehydration and hypovolemic shock ..................................... 61 notes on acid-base disturbance characteristics .....................64 hypoproteinemia...................................................................65 rhabdomyolysis treatment ....................................................66 Treat Aggressively ...........................................................66 Monitor for Other Clinical Complications ........................67

5 management of gastrointestinal/abdominal conditions .........69 Cassondra Bauer and Kari L. Christe oropharyngeal conditions .....................................................69 gastric conditions .................................................................70 intestines ............................................................................. 74 pancreatic diseases ..............................................................78 hepatic conditions ................................................................79 urinary conditions................................................................ 81 organ nonspecific abdominal conditions ...............................84 references .............................................................................87

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6 thorax conditions ............................................................... 103 Melissa A. de la Garza upper airway conditions ..................................................... 103 lower airway conditions ......................................................106 cardiovascular.................................................................... 108 references ........................................................................... 112

7 bacterial, mycotic, viral, and parasitic infections ................ 117 Alfonso S. Gozalo and Karen R. Strait bacterial diseases ............................................................... 117 Bacterial Gastroenteritis (Shigellosis, Salmonellosis, Campylobacteriosis, Colibacilosis, and Yersiniosis)........ 117 Tuberculosis and Mycobacteriosis .................................124 Streptococcal Pneumonia..............................................125 bacterial diseases bibliography ........................................... 127 mycotic diseases ................................................................. 130 Dermatophytosis........................................................... 130 Systemic Mycosis .......................................................... 131 Candidiasis (Moniliasis) ................................................ 133 mycotic diseases bibliography .............................................134 viral diseases .....................................................................134 Alphaherpesviruses ......................................................134 Gammaherpesviruses ................................................... 137 Monkeypox ................................................................... 138 Simian Hemorrhagic Fever Virus .................................. 139 Measles (Rubeola) ......................................................... 140 Retroviruses ................................................................. 141 Rabies........................................................................... 144 Encephalomyocarditis Virus (EMCV) ............................ 145 viral diseases bibliography ................................................. 145 parasitic diseases ............................................................... 148 Protozoa........................................................................ 148 Nematodes .................................................................... 153 Cestodes ....................................................................... 156 Arthropods ................................................................... 157 Other Nonhuman Primate Parasites ............................. 159 parasites references ............................................................ 161 acknowledgments ............................................................... 162

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8 gestational concerns: when to intervene and what to do...... 163 Angela Courtney reference............................................................................. 167

9 dentistry in NHPs ............................................................... 169 Margaret S. McTighe references ........................................................................... 176

10 dermatologic and ophthalmologic conditions....................... 179 Karen Strait dermatologic conditions ...................................................... 179 ophthalmologic conditions .................................................. 193 references ........................................................................... 198

11 strategies for managing behavior problems .........................203 A. J. Warshaw Funk normal behavior .................................................................203 abnormal behavior .............................................................206 self-injurious behavior ........................................................206 environment enrichment ....................................................209 references and suggested reading ....................................... 210

12 formularies: drug dosages .................................................. 213 drug dosages for dental care ............................................... 216 common drug dosages for macaques, squirrel monkeys, and capuchins.................................................................... 217

introduction This book was compiled with the intention of expanding the body of knowledge available to veterinarians working with nonhuman primates in a clinical setting. Nonhuman primate medicine presents a unique set of challenges in the clinical setting; the patient is sedated for examination, and time is a factor in the initial treatment decisionmaking parameters. This book was compiled to give the clinician a quick reference in the clinic to provide guidance and initial direction based on the experiences of the authors. Much of the theory and medical pathophysiology background has been eliminated to keep the book to a portable size with the understanding that the book’s user has this background knowledge obtained as a veterinarian. The exception is the chapter on anesthesiology, which is a very dynamic field, with new knowledge gained daily; the chapter includes an overview of the receptors and notations on background of the recent drugs and medications in use in the field to aid the clinician when determining drug choice and multimodal therapy. It is important to remember that one of the challenges of primate medicine is the variables that can be present in the individual or colony you are caring for. Factors such as housing, diet, genetics, breeding, and environment can cause profound changes in how an individual animal reacts, manifests, and responds to disease and treatments. Clinical pathology values can vary from colony to colony because of these factors. It is important to know your colony. If not already available, a baseline set of normal clinical pathology values should be obtained for your colony by age, species, sex, and breeding season changes. Clinical pathology guidelines given are based on a specific colony’s normal ranges; your colony ranges may differ, so interpret in light of your veterinary clinical judgment and your colony. ix

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The authors were asked not only to give information that is in their direct knowledge base but also to share working dosages and treatment guidance based on past case experience. The authors who collaborated on this work have experience in various species of nonhuman primates. The book was written from the standpoint of treating the rhesus macaque, and the authors denote specific treatments for other species if applicable. Also included in the book are excerpts from a resident’s journal. The first day I became a lab animal resident, I purchased a blank, lined journal that fit in my lab coat. At the end of the day at home, I would record what I had learned, case treatment, and medical data I wanted to keep for quick reference. I carried the journal I created with me daily and found students on rotations would request copies. I have included excerpts as chapters in this book. Every effort was made to have information given as accurately as possible. You may find dosages given may vary from chapter to chapter; this is because of the individual author’s working knowledge of the dosages used successfully in patients in that author’s colony. The reader is to exercise due diligence before using dosages noted to ensure print errors have not occurred unbeknownst to the authors. It is my hope that eventually a dynamic digital version will be available so clinicians can contribute to the body of knowledge in the field for quick, easy digital access to information.

acknowledgments I would like to thank all the contributors for their incredible work and dedication to this project and for sharing their vast knowledge with our readers. This book would not exist without their hard work and effort. I would like to thank the technicians and the support team at the California National Primate Research Center (CNPRC) for their time and patience with all my questions during my time at the center. You are all truly giving of your experiences. I am grateful to Abigail Spinner, the chief of clinical pathology, whose amazing knowledge and ever-present smile kept me going to see the completion of the residency. Thanks also go to my fellow residents; you are all amazing doctors and it has been my pleasure to train with you. Thank you to Dr. Stephen Barthold who, considering his incredible stature in the field, found the time to reach down to show me kindness and support. I thank my children, Summer and Tristan for taking this journey with me without complaint during the study sessions and late nights. Lastly, but not least, thank you to the person who showed me how important it is to contribute to your field and to try to make a difference—my mentor and to whom the book is dedicated, Dr. Nicholas Lerche. Thank you for changing my point of view.

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about the editor Angela Courtney, DVM, MBA, pharmaceutical engineer. Angela Courtney became a licensed animal health technician having earned her associates of science from L.A. Pierce College, Woodland Hills, California. She thereafter joined the United States Army and was stationed at the Presidio in San Francisco, California, during which time she was introduced to biomedical research. Dr. Courtney went on to obtain her doctorate in veterinary medicine from Mississippi State University in 1992. She worked in all aspects of small animal medicine from emergency medicine and general practice to working as a contractor for the California State Veterinary Medical Board. Her fascination with how drugs, medications, and devices entered the commercial pipeline led her to completion of an MBA at University of Phoenix along with obtaining a certification in pharmaceutical engineering from Cal State Fullerton and becoming CEO of a corporation based in Orange County California. Seeking to round out her education in the biomedical research field and return to research, Dr. Courtney completed a residency in laboratory animal medicine at the University of California, Davis in 2011. It was during the residency, while at the California National Primate Research Center, that Dr. Courtney was introduced to the world of nonhuman primate medicine. The uniqueness of nonhuman primates’ medicine coupled with the lack of the same breadth and depth of clinical medical textbooks devoted exclusively to the nonhuman primate that is so obtainable in small animal medicine prompted her to help fill the void with this project. From day one of the residency, Dr. Courtney wrote nightly in a blank journal of each day’s clinical cases and treatments, clinical xiii

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gems from classes, and verbal accounts for her own personal reference in the future. She found rotating students would ask to copy the journal. This became the creative basis for the project. “As a resident,” she says, “I knew I did not possess the breadth of knowledge a book like this would require … so I put out a call to expert clinicians in other primate centers to contribute to the book. … I envisioned the book to be much like my personal clinical journal which I carried with me daily on the clinic floor, portable with a straight to the point of what you need to know approach to treating cases.” The response from clinicians willing to contribute was tremendous and the project came into fruition. At the time of this writing, Dr. Courtney is pursuing a PhD in comparative pathology (integrative pathobiology).

contributors Cassondra Bauer, MS, DVM, attended Michigan State University, where she obtained a BS in zoology, specializing in marine biology. She then completed an MS in biology at Idaho State University. Returning to Michigan State University, she earned her DVM in 2007. Dr. Bauer worked at a contract research organization during summers with nonhuman primates, and that sparked her interest in continuing to work with them. After graduation, she began working at the Southwest National Primate Research Center, San Antonio, TX, where she is currently employed. Kari L. Christe, DVM, Diplomate ACLAM, is an assistant clinical professor in medicine and epidemiology at the University of California Davis School of Veterinary Medicine and chief of primate medicine service, California National Primate Research Center and Veterinary Medical Teaching Hospital in Davis. A. J. Warshaw Funk, BS, DVM, Diplomate ACLAM, is a clinical veterinarian in the Animal Resources Center at St. Jude Children’s Research Hospital (SJCRH) in Memphis, Tennessee. She obtained her undergraduate degree by attending both Florida International University and Colorado State University and received a BS in biology in 1990. While still at Colorado State University, Dr. Funk continued her education and received her DVM in 1996. She spent 7 years in private practice before she found her home in comparative medicine. She first saw nonhuman primates in captivity during a tour at the University of Tennessee Health Science Center (UTHSC) while interviewing for its residency program. Although she did not know it at the time, that it was the beginning of her fascination with monkey xv

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behavior. She completed the lab animal medicine residency program at UTHSC in 2005 and became an ACLAM (American College of Laboratory Animal Medicine) diplomate in 2008. She currently oversees a macaque colony at SJCRH and finds the pursuit of giving them an enriched life enriching to her own life. “There are so many similarities in communication with this species that the more I learn their language, the more I understand my own.” Melissa A. de la Garza, MS, DVM, has an educational background that includes bachelor’s and master’s degrees in biology from the University of Texas at San Antonio and a DVM from Texas A&M University. Her primate experience was gained at Texas Biomedical Research Institute (formerly Southwest Foundation for Biomedical Research), host Institute for the Southwest National Primate Research Center. At TxBiomed, she currently holds the position of associate veterinarian and is the scientific manager for the Animal Biosafety Level (ABSL) 3 facility. Her primary clinical responsibilities include providing care for the chimpanzee colony. Alfonso S. Gozalo, MS, DVM, Diplomate ACLAM, obtained his veterinary medicine degree from Universidad Nacional Mayor de San Marcos, Lima, Peru, in 1985 and a master’s of science degree in animal health from the same university in 2000. In 2004, he completed a 3-year training program in laboratory animal medicine at the Division of Laboratory Animal Medicine, David Geffen School of Medicine, University of California, Los Angeles. In 2006, Dr. Gozalo successfully completed the certifying examination and election to membership in ACLAM and is currently an ACLAM diplomate. After finishing veterinary school, Dr. Gozalo worked for a short time in a small-animal practice and then as a swine veterinarian. In 1987, he joined the Peruvian Primate Center, located in the Amazon rain forest of Peru, where he worked as the laboratory chief and later as the head clinical veterinarian. In 1995, he joined the U.S. Naval Medical Research Center Detachment in Lima, Peru, where he worked as the attending veterinarian. In 2004, on completion of his laboratory animal medicine residency, Dr. Gozalo joined the Comparative Medicine Branch of the National Institute of Allergy and Infectious Diseases, where he works as an attending veterinarian. Dr. Gozalo has been presented a Merit Award and an Exemplary Performance of Duty Award by the National Institute of Allergy and Infectious Diseases and a Meritorious Honor Award presented by the U.S. Department of State for his contributions to science.

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Margaret S. McTighe, BS, DVM, joined BTG Australasia following 14 years of caring for chimpanzees at the Alamogordo Primate Facility. She has 12 years of laboratory animal experience and has spent the last 8 years primarily caring for nonhuman primates. She became interested in nonhuman primates when a young galago grabbed her lab coat (and ultimately her heart). She volunteered at the Alamogordo Zoo and was a member of the zoo board. Accomplishments include the Meritorious Service Medal and parachutist badge while serving in the U.S. Army Veterinary Corps. Cholawat Pacharinsak, DVM, MS, PhD, Diplomate ACVA, is an assistant professor and director of anesthesia, pain management, and surgery at Stanford University’s Department of Comparative Medicine. He is a diplomate of the American College of Veterinary Anesthesiologists. He received his DVM from Chulalongkorn University, Thailand, and trained in an anesthesiology and pain management residency program and received his master’s degree at Washington State University. He completed his PhD in pain neuroscience from the University of Minnesota. Prior to arriving at Stanford, Dr. Pacharinsak was a faculty member in anesthesiology and pain management at Michigan State University and Purdue University and served as a clinical specialist at the University of California Los Angeles. Patrick Sharp, DVM, MRCVS, Diplomate ACLAM, received his DVM from Purdue University, worked in mixed-animal practice, and completed the comparative medicine training program at the Washington University School of Medicine in St. Louis. Patrick has held academic and industry positions in the United States and overseas at the David Geffen School of Medicine at the University of California Los Angeles, University of Florida, National University of Singapore, and Fundação Champalimaud. He actively supports comparative medicine training, including both ACLAM-approved training programs and international training workshops for laboratory animal graduate veterinarians; he strives to increase the quality of animal care through personnel education at all animal care levels and the design and construction of better vivaria and research support facilities. Karen Strait, DVM, Diplomate ACLAM, obtained her undergraduate degree in biology from Emory University and her DVM from the University of Georgia College of Veterinary Medicine. She later returned to Emory University for her postdoctoral training in laboratory animal medicine. It was during this time that she developed an

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interest in nonhuman primates. On completing her lab animal medicine training, Dr. Strait joined the Yerkes National Primate Research Center as a clinical veterinarian. At Yerkes, she was responsible for clinical and research support with an emphasis on infectious disease studies and surgery. Dr. Strait recently transferred to the Emory University School of Medicine, where she oversees the largeanimal medicine and surgery program, including nonhuman primate studies.

1 anesthesia in nonhuman primates Cholawat Pacharinsak and Patrick Sharp

introduction 1. Primates require anesthesia for a host of nonsurgical and surgical procedures. Employing primate anesthesia carries physical, chemical, and biological hazards. 2. Work closely with knowledgeable occupational health and safety professionals when planning any primate study. a. Personnel conducting anesthesia/surgery are more prone to needle sticks. b. Noninfectious hazards are both physical (e.g., needle stick) and chemical (e.g., volatile anesthetic exposure) in nature. 3. The close phylogenic relationship between primates and human beings permits anthropozoonoses and zoonoses. 4. At a minimum, conduct primate work in an Animal Biosafety Level 2 (ABSL2) environment with proper personal protective equipment (PPE), anesthetic gas scavenging, sharps handling, and other such precautions appropriate for the species and scope of the study.

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pocket handbook of nonhuman primate clinical medicine 5. A thorough, written experimental protocol benefits all involved parties, including occupational health, veterinary staff, Institutional Animal Care and Use Committee (IACUC), and other compliance/accreditation organizations (e.g., USDA [U.S. Department of Agriculture], AAALAC [Association for Assessment and Accreditation of Laboratory Animal Care International]). a. The investigator develops an appropriate protocol for IACUC approval, including a satisfactory preoperative, intraoperative, and (for survival surgery) postoperative procedure description. Investigator and veterinary staff consultation is required during protocol design as an appropriate part of the veterinary oversight process. The investigator ensures all laboratory members conform to the IACUC-approved protocol. b. The IACUC is responsible for evaluating and approving protocols (and protocol amendments) and providing postapproval monitoring. c. Primate survival surgery must be carried out in dedicated surgical facilities; institutions may also require nonsurvival surgery in dedicated surgical facilities. 6. Anesthetic equipment must be in good working order with annual vaporizer certification and other components (e.g., soda lime, tubing integrity) evaluated more frequently. As primate emergencies arise unexpectedly, ready access to a properly maintained, functioning anesthetic machine (or two) is critical in addition to appropriate emergency medicine, drugs, and equipment. 7. Personnel training includes/addresses a. IACUC-related regulatory matters b. Occupational health and environmental health and safety concerns/hazards c. Basic primate husbandry practices and appropriate veterinary care expectations d. Primate restraint and compound administration e. Proper procedure-related training f. Preanesthetic expectations g. Proper anesthetic machine operation h. Expected procedure-related patient monitoring

anesthesia in nonhuman primates i. Record-keeping expectations and medical record overview j. Proper patient recovery k. Pertinent documentation of these items 8. Perform all procedures in compliance with the IACUCapproved protocol, the USDA Animal Welfare Act, Regulations, and Policies1; the Guide for the Care and Use of Laboratory Animals2; and institutional policies, procedures, and guidelines.

record keeping 1. It is important to evaluate an animal’s medical record carefully to determine its suitability for a given anesthetic event. Summarize and investigate previous adverse events. 2. The medical record should be perceived as a legal document with appropriate entries crucial to document the IACUCapproved experimental paradigm. 3. Research staff are to make entries in the animal’s medical record as the primary database; entries into laboratory notebooks are considered secondary. 4. Most research institutions will provide researchers access to the animal’s medical record with sufficient notice and adequate precautions. 5. Anesthetized animals are expected to have an anesthetic record, procedure record, and a postprocedure record, all maintained with the animal’s medical record. 6. The anesthetic record summarizes anesthetic events, permitting detailed physiologic parameter entries, including heart (HR) and respiratory rate (RR), blood pressure (BP), and pulse oximetry values. It is important to record pertinent physiologic parameters and procedure-related events (e.g., initiating surgical procedure, entering body cavities, etc.). This yields robust records and easily permits comparison between multiple related anesthetic events in different animals. Although computerized systems permit automatic anesthetic record entries/ development, one must ensure a human is regularly (e.g., every 15 min) and continuously evaluating the animal and recording the observations to ensure regulatory compliance.

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TABLE 1.1: PATIENT PREEVALUATIONS Cutaneous lesions or infections Assess behavior and attitude Respiratory function • Auscultation • Mucous membrane color • Nasal discharge • Pulse oximetry/capnography? • Blood gas analysis? Gastrointestinal function • Appetite • Nutritional status • Diarrhea/constipation • Hydration status • Normal water intake • Moist mucous membranes • Skin turgor Complete blood count (CBC) • Leukocytosis/left shift • Anemia • Polycythemia (dehydration)

Body temperature Urinalysis? Cardiovascular function • Auscultation • Palpable pulse • Mucous membrane color • ECG? • Indirect blood pressure monitoring Review health history • Chronic diarrhea • Chronic dermatitis • Previous respiratory disease • Previous treatments • Previous surgical procedures • Previous research manipulations Clinical chemistry • Normal electrolyte concentrations • Normal hepatic enzymes • Normal renal function • Previously undiagnosed conditions

7. A procedure record indicates the experimental procedure performed and summarizes investigator contact information, preprocedural findings (e.g., physical exam, complete blood count [CBC], serum chemistry), complications, and postprocedure instructions. 8. Patient preevaluation (Table 1.1). 9. The postprocedure record provides a single, common place for medical entries in the animal’s record. Animals emerging from anesthetic events require continual monitoring with entries about every 15 min; more regular entries may be necessary depending on the animal’s condition.

definitions 1. Anesthesia: Reversible unconsciousness, amnesia, immobilization, and analgesia. 2. Tranquilizers: Anxiety-relieving drugs; an animal is still aware of its surroundings when using these drugs. 3. Sedatives: Drugs causing central depression and drowsiness; an animal is unaware of its surroundings when using these compounds.

anesthesia in nonhuman primates 4. Neuroleptanalgesia: Combination of a tranquilizer or sedative with an opioid (e.g., dexmedetomidine + hydromorphone) providing good sedation and analgesia, but with a reduced dose of each compound, thereby decreasing undesirable side effects. 5. Dissociatives: Dissociative anesthesia induced by a dissociative drug (e.g., ketamine, tiletamine). These drugs also provide mild analgesia. 6. Balanced anesthesia a. A combination of drugs/techniques to provide balanced anesthesia (e.g., sedative + inhalant + opioid + local anesthetic + neuromuscular blocking [NMB] agent). b. Commonly referred to as a cocktail (e.g., ketamine-xylazine).

premedication/sedation/anesthesia 1. Small nonhuman primates (e.g., squirrel monkey) can be physically restrained for intramuscular injection. 2. Large nonhuman primates (e.g., macaque) can be restrained using a squeeze cage or other tools (e.g., dart, pole syringe). 3. Summaries of recommended anesthesia protocols and inhalant anesthesia (isoflurane and sevoflurane parameters) are listed in Tables 1.2 and 1.3, respectively.

the anesthetic machine 1. Anesthetic machine functions: a. Delivers O2 to the patient b. Removes CO2 from the patient c. Supports patient ventilation 2. Cylinder tank a. O2 tank i. Tank color: Green (USA) ii. E tank: 660 L; 1900 psig; empty cylinder weight 14 pounds

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TABLE 1.2: RECOMMENDED A NESTHESIA PROTOCOLS Drugs Ketamine 5–25 mg/kg

Route IM

Notes Surgical anesthesia Somatic analgesia Followed by inhalants Duration 15–30 min

Ketamine 5–10 mg/kg + xylazine 0.5–2 mg/kg

IM

Surgical anesthesia Good analgesia Good muscle relaxation Followed by inhalants Reduce subsequent anesthetics (e.g., inhalants, propofol) May vomit during induction Duration 30–60 min

Ketamine 15 mg/kg + diazepam 0.5–1 mg/kg

IM, IV

Ketamine 15 mg/kg + midazolam 0.05–0.15 mg/kg

IM, IV

Surgical anesthesia Somatic analgesia Muscle relaxation Duration 30–40 min Surgical anesthesia Somatic analgesia Muscle relaxation Duration 30–40 min

Ketamine 2–3 mg/kg + dexmedetomidine 0.02–0.05 mg/kg

IM

Surgical anesthesia Good analgesia Good muscle relaxation Followed by inhalants Reduce subsequent anesthetics (e.g., inhalants, propofol) Duration 40–60 min (Author personal experience)

Ketamine 5 mg/kg + medetomidine 0.1 mg/kg

IM

Surgical anesthesia Good analgesia Good muscle relaxation Followed by inhalants Reduce subsequent anesthetics (e.g., inhalants, propofol) Duration 40–60 min

Propofol 2–10 mg/kg (to effect for tracheal intubation; under ketamine IM) CRI (continuous rate infusion): 0.2–0.6 mg/kg/min

IV

Surgical anesthesia 5–10 min Phenolic agent potentiate GABAA and glycine receptors Short T1/2 and rapid clearance Hypotension, apnea, no analgesia Preoxygenation recommended

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TABLE 1.2 (CONTINUED): RECOMMENDED A NESTHESIA PROTOCOLS Drugs

Route

Thiopental sodium 5–7 mg/kg (to effect for tracheal intubation; under ketamine IM)

IV

Etomidate 0.5–2 mg/kg (to effect for tracheal intubation; under ketamine IM)

IV

TABLE 1.3: ISOFLURANE

AND

Notes Surgical anesthesia 5–15 min Ultrashort-acting barbiturate Activate GABAA receptors causing Cl− influx Myocardial depression, hypotension, sensitize myocardium to cathecholamine, no analgesia Short duration due to muscle redistribution Tissue irritation if perivascular injection Surgical anesthesia 5–20 min Minimal cardiovascular depression

SEVOFLURANE PARAMETERS

Parameter

Isoflurane

Sevoflurane

MAC (%) Blood/gas partition coefficient Vapor pressure (mmHg) Cardiac output

1.28–1.46 1.4 252

~2% 0.69 160

Blood pressure Arrhythmogenicity Respiratory depression Hepatic blood flow Renal blood flow Cerebral blood flow Muscle relaxation Hepatic metabolism Pungency Cost Notes

↓

↓

↓↓↓

↓↓↓

↑

↑

↓↓↓

↓↓

↓↓

↓↓

↓↓↓

↓↓

↑↑

↑↑

↑↑ 0.1% Yes $$ Vasodilation Hypotension

↑↑ 2–3% No $$$$ Can produce compound A (renal toxicity)

↑ = increase; ↓ = decrease

iii. PISS (pin index safety system): 2, 5: Pin-and-receptacle combination on hanger yokes used to prevent inadvertent connection between an inappropriate gas cylinder and a yoke (e.g., cannot connect a N2O tank to an O2 yoke) iv. Stored as a compressed gas: Gas volume remaining in the cylinder is proportional to the cylinder’s pressure

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pocket handbook of nonhuman primate clinical medicine v. Total volume of O2 remaining in the tank may be calculated by __ psig × 0.3 = __ L (e.g., 1000 psig × 0.3 = 300 L left in the tank) vi. Duration: 660 L O2 tank, using 2 L/min → 660/2 = 330 min 3. Pressure regulator a. Maintains constant gas flow b. Pressure-reducing valve reduces the tank pressure to about 45–50 psig. 4. O2 flush valve a. Flushes the O2 into breathing circuit (35–75 L/min; 50 psi) and bypasses the vaporizer b. Safety i. Nonrebreathing circuits (e.g., Bain): Do not flush O2 while connected to the patient as this may cause barotrauma, leading to pneumothorax. To flush O2, first disconnect the breathing circuit from the patient. ii. Flushing O2 to fill the ventilator bellows may cause the animal to develop a lighter anesthetic plane. 5. O2 flowmeter a. Precisely measures and directs O2 from the regulator to the vaporizer b. Comprised of the Thorpe tube or flowmeter, flowmeter knob, and metal ball/rotating float (bobbin) c. Bobbin i. Metal ball: Read at the middle ii. Rotating float: Read at the top d. Safety: Color-coded adjusting knobs i. O2 knob is green (USA) ii. O2 flowmeter is located downstream (closer to the patient) from other flowmeters (N2O, air) 6. Vaporizer a. Stores liquid anesthetics and delivers the desired volume/ percentage of an anesthetic vapor to the fresh gas flow b. Most vaporizers used are precision vaporizers delivering a precise anesthetic concentration to the patient

anesthesia in nonhuman primates 7. Rebreathing bag a. Permits expired and fresh gas accumulation b. Safety device: Prevents rapid pressure increase c. Assists ventilation d. Bag size: A minimum, 5–6× tidal volume (Tidal Volume = 10–20 ml/kg) 8. CO2 absorber a. Removes CO2 from the anesthetic circuit via a chemical reaction resulting in water and heat b. Sodalime (Sodasorb®) or barium hydroxide (Baralyme®) i. 100 g of soda lime absorbs 26 L of CO2 c. Indicators: Ethyl violet i. Color changes from white (fresh absorbent) to purple (exhausted absorbent). When not in use, the exhausted absorbent’s color (purple) will revert to white, giving the false impression that the CO2 absorber is fresh. ii. Estimate a new CO2 canister to last 8–10 hr. iii. Fresh absorbent easily crumbles, while exhausted absorbent is hard. d. Carbon monoxide (CO) accumulates in the canister when unused for 24–48 hr. Flushing the system with 100% O2 before use is recommended. 9. Breathing tube a. Corrugated tubing b. Delivers/removes gasses to and from the patient c. Connects to a Y-piece i. Y-piece has inspiratory, expiratory, and patient ends. ii. Y-piece creates mechanical dead space. 10. Unidirectional valves a. A disk sitting on annular ring within a clear dome i. Inspiratory unidirectional valve ii. Expiratory unidirectional valve b. Directs gas flow in one direction either to or from the patient c. Prevents rebreathing CO2

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pocket handbook of nonhuman primate clinical medicine

11. Scavenging system a. To collect waste gasses from anesthetic system b. Two types i. Passive system: Gasses move passively from anesthetic breathing system to disposal system (e.g., activated charcoal canister). ii. Active system: Gasses are moved from anesthetic breathing system by negative pressure (e.g., central vacuum system). 12. Breathing system classifications a. Closed: Circle system in which the O2 flow rate supplied to the patient equals the patient’s metabolic O2 consumption. O2 flow rate is approximately 5–7 ml/kg/min. b. Semiclosed: Circle system in which the O2 flow rate supplied to the patient is greater than the patient’s metabolic O2 consumption. O2 flow rate is about 30 ml/kg/min. c. Semiopen: A nonrebreathing system (e.g., Bain) without valves or CO2 absorber. The high O2 flow flushes expired CO2 from the system. O2 flow rate is about 150–300 ml/kg/ min. d. Open: Chamber induction in which there is no expired gas rebreathing, no reservoir. 13. Breathing circuits a. Nonrebreathing circuit (e.g., Bain; Figure  1.1), modified Mapleson D i. Patient weight < 7–10 kg ii. Absolute minimum flow rate > 500 ml/min regardless of patient’s size to prevent rebreathing iii. Minimum O2 flow rate: 150–300 ml/kg/min iv. Advantages 1. Delivers warmer inspired gas; warmed by the expired gas 2. Delivers an anesthetic concentration close to the vaporizer setting 3. Fewer moving parts 4. Less airflow resistance (i.e., no valves, no CO2 absorber) 5. Less dead space 6. Portable

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Pressure regulator

O2 Flowmeter O2 flush valve

Pop-off valve To scavenger Inspired gas

Patient Expired gas

Vaporizer

O2 tank

Figure 1.1 Nonrebreathing circuit: Bain circuit (modified Mapleson D). The Bain circuit is a simple breathing circuit that includes fresh gas flow, rebreathing bag, corrugated tubing, pop-off valve, and patient end. CO2 rebreathing is prevented by a high fresh gas flow. v. Disadvantages 1. Higher O2 flow rate and anesthetic gas needed 2. Body heat loss from dry O2 flow 3. High O2 flow may interfere with gas analyzers (i.e., capnograph) 4. Cannot be used with malignant hyperthermia 5. Higher anesthetic gas environmental pollution b. Rebreathing circuit (circle circuit, Figure 1.2) i. Patient size > 7–10 kg ii. Minimum O2 flow rate: 30 ml/kg/min iii. Advantages 1. Lower O2 flow rate needed 2. Uses less inhalant anesthetic agent 3. Can be used with malignant hyperthermia iv. Disadvantages 1. Anesthetic machine malfunctions more likely 2. More air circuit breathing resistance (i.e., from absorber canister, unidirectional valves) 14. Laryngoscope (commonly used) a. Miller blade: Straight blade b. Macintosh: Curved blade

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pocket handbook of nonhuman primate clinical medicine

Pop-off valve

Pressure-reducing valve O2 Flowmeter O2 flush valve

CO2 absorber

To scavenger

Unidirectional valve

Rebreathing bag

Patient Y-piece

Vaporizer

O2 tank Unidirectional valve

Figure 1.2 Rebreathing circuit (circle circuit). A more complex breathing circuit that includes fresh gas flow, inspiratory and expiratory unidirectional valves, corrugated tubing, Y-piece, pop-off valve, rebreathing bag, and CO2 absorber. 15. Endotracheal tube (ET tube) a. Three types i. Murphy ET tube: Murphy eye at the patient end provides safety if the main lumen becomes occluded ii. Magill ET tube: No Murphy eye iii. Cole ET tube: Tapered ET with a smaller diameter at the patient end b. ET tube cuff i. Connected to the pilot balloon to provide a better seal ii. Cuff inflation 1. Have assistant squeeze the breathing bag up to 30 cm H2O. 2. Listen for a leak while instilling air into the pilot balloon. 3. Apply sufficient air to stop the leak. 4. Over time, muscle relaxation may cause the leak to reoccur. Repeat from step 1. c. Length: Appropriate ET tube length is measured from the incisors to shoulder level (thoracic inlet). The ET tube length beyond the lips is mechanical dead space and should be minimized.

anesthesia in nonhuman primates 16. Maintenance: inhalants a. MAC: Isoflurane about 1.3%; sevoflurane about 2% (cynomolgus monkeys) b. Maintenance i. With premedication, in general, maintain at 1–1.5 MAC. ii. Isoflurane should be maintained at about 1.3–1.95% (range 0–5%). iii. Maintain sevoflurane should be maintained at about 2–3% (range 0–8%).

preoperative management and assessment 1. Preparatory steps should ensure a. Procedures will be carried out efficiently, professionally, and with adequate record keeping, including records of all drugs administered, noting the dose, time, and route of administration b. The animal’s health is appropriately assessed prior to the anesthetic induction to minimize risk of complications during and after surgery 2. The surgeon is responsible for a. Scheduling operating room time, estimated length of the procedure, necessary instruments and equipment needed, and anesthetic regimen to be used b. Scheduling the procedure with the veterinary staff following institutional policies/guidelines c. Making appropriate logistical arrangements with the designated surgical assistant (within the investigator’s own group) or surgical technician as outlined below d. Ensuring the animal’s food is withheld prior to the procedure, as highlighted in the IACUC-approved protocol and following institutional procedures i. For larger nonhuman primates, food is withheld 8–12 hr; water is withheld 3–6 hr. ii. For smaller species, food and water are withheld for shorter periods.

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pocket handbook of nonhuman primate clinical medicine e. Assessing the animal’s overall status prior to the anesthetic procedure, including visual inspection and assessing the animal’s behavioral status; bringing any previously undetected abnormalities to the veterinary staff’s attention 3. The surgical assistant or technician is responsible for a. Communicating with the surgeon to determine the nature of the procedure, anticipated duration, desired anesthetic technique, necessary monitoring equipment and instruments, and desired operating room configuration b. Preparing all necessary records and record sheets and informing surgeons of any other records that they must complete 4. Give consideration to preoperative hematology and serum chemistry tests prior to major surgical procedures. These tests should be detailed in the IACUC-approved protocol. Recommendations include a. Minor surgical and multiple minor procedures: packed-cell volume (PCV) and total plasma protein (TP) assessment b. Major surgical procedures: CBC plus an assessment of plasma or serum protein and kidney and liver enzymes; need is heightened if there are induced or spontaneous medical or surgical abnormalities

intraoperative monitoring Intraoperative Procedures Overview 1. Acute (terminal) and chronic (recovery) anesthetic procedures result in more than momentary or slight pain that requires appropriate anesthetics, analgesics, and tranquilizers (AATs). 2. Most commonly used AATs can have both short-term and long-term effects on an animal’s ability to maintain homeostasis. Physiologic function monitoring provides important indices of the animal’s homeostatic state. 3. Unconscious or intubated animals must not be left unattended. 4. Monitoring is to be done by trained personnel.

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TABLE 1.4: A NESTHETIC PLANE (MODIFIED) INDICATIONSa Observation

Light

Medium (Surgical)

Deep

Eyeball position Palpebral reflex (stroke along upper/lower eyelids) Nystagmus Cornea Corneal reflex (closure of eyelids; gentle pressure on cornea) Pupil size

Central Yes

Ventromedial No

Central No

Yes (ketamine) Moist Present

No Moist Present

No Dry Absent

Constrict Yes Maybe Yes Yes Present

Constrict No No No No Present

Dilate No No No No Absent

Rapid, deep

Regular, deep

Slow, shallow

Muscle tone Spontaneous movement Response to surgical stimulation Jaw tone Anal tone (used when head access is limited) Breathing pattern a

The table was developed primarily from dogs and cats; however, we feel it accurately reflects the situation in nonhuman primates.

Anesthetic Plane Table 1.4 shows the anesthetic plane. The following are the stages of anesthesia (modified): 1. Light plane 2. Medium plane 3. Deep plane

Cardiovascular System 1. Capillary refill time (CRT): Depends on peripheral perfusion and vascular tone a. The rate of color that returns to the mucous membrane capillary bed after digitally compressing gingival mucous membrane b. Normal mucous membrane: Pink, CRT < 2 sec c. Pale mucous membrane may indicate anemia, blood loss, poor perfusion d. Blue mucous membrane indicates severely low O2 saturation (partial pressure of O2 [PaO2] < 60 mmHg)

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pocket handbook of nonhuman primate clinical medicine e. If CRT > 2 sec, interpreted as i. Excessive anesthetic depth ii. Poor perfusion iii. Hypotension/vasodilation iv. Hypothermia v. Increased vascular resistance from circulatory shock, pain, the use of α2 agonists 2. Heart rate (HR): Heart rate, rhythm, and sounds a. Must be monitored continuously and recorded every 15 min via electrocardiograph (ECG), peripheral pulse palpation, cardiac auscultation, pulse oximetry b. Digital palpation of arterial pulses: Relates to peripheral perfusion, vascular tone, pulse rate/rhythm, cardiac output i. Pulse: Regular, strong, synchronized with auscultation ii. Pulse strength (pulse pressure): Differences between systolic and diastolic blood pressure (BP) iii. Pulse deficits: Pulse fails to correspond with heartbeat iv. Locations: Medial saphenous artery, femoral artery, dorsal pedal artery, digital artery c. Auscultation i. Monitor rate, rhythm, valvular function ii. Stethoscope/esophageal stethoscope d. ECG i. Monitors cardiac electrical function ii. Lead II: Commonly used 3. Arterial blood pressure: Assesses peripheral perfusion a. Cardiac output = HR × SV (stroke volume) b. BP = CO × peripheral vascular resistance (PVR) c. Normal BP i. Mean BP about 70–90 mmHg ii. Systolic BP about 80–120 mmHg iii. Diastolic BP about 60–100 mmHg d. Mean BP during anesthesia should be kept > 70 mmHg. Caveat: ↑BP i. Does not always mean ↑ peripheral perfusion

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ii. Can result from ↑ PVR from α-2 agonists (e.g., dexmedetomidine, xylazine) or α-1 agonists (e.g., phenylephrine) e. Indirect BP measurement i. Digital palpation: Pulse pressure ii. Doppler ultrasound sphygmomanometer

method:

Pressure

cuff

plus

1. Use the “return-to-flow” principle to detect systolic BP. Place a probe (two crystals transmitting and receiving ultrasonic beams from moving red blood cells [RBCs]) over the artery; the signal is converted into an audible signal (“whooshing” sound). Place a pneumatic cuff (cuff width = 40% limb circumference) snugly on the same limb, proximal to the probe. This cuff is connected to sphygmomanometer/aneroid manometer. Inflate the cuff until the whooshing sound ceases (inflate until the cuff pressure is greater than the systolic pressure, therefore stopping arterial flow). Deflate the cuff gradually; the pressure where the first whooshing sound is heard is the systolic BP. 2. Systolic BP should be kept > 80 mmHg. 3. Advantages A. Inexpensive method B. Pulse rate is easily determined 4. Disadvantages A. Only obtains systolic BP B. Time consuming C. Cuff size, placement, movement may affect reading D. Difficult to locate the probe/signal during hypotension iii. Oscillometric method 1. Cuff width 40% limb circumference of the leg/arm/ tail 2. Place the pneumatic cuff snugly on the limb. The cuff is connected to an oscillometric device that automatically inflates/deflates the cuff.

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pocket handbook of nonhuman primate clinical medicine 3. Obtain systolic, diastolic, and mean BP 4. Advantages A. Obtains systolic, diastolic, and mean BP; pulse rate B. Automatic reading 5. Disadvantages A. Cuff placement and size i. Place cuff too tightly → falsely low BP ii. Place cuff too loosely → falsely high BP iii. Cuff too wide → falsely low BP iv. Cuff too narrow → falsely high BP B. Inaccurate during hypotension or in small patients (squirrel monkeys) f. Direct BP measurement i. Place an intravenous catheter into an artery (medial saphenous artery, femoral artery, digital artery) ii. Connect to artery 1. Pressure transducer and amplifier to display waveforms (systolic, diastolic, mean BP, HR); one must zero the air/liquid interface at (right) heart level 2. Aneroid manometer to obtain only mean BP iii. Advantages 1. Accuracy 2. Continuous real-time reading 3. Waveforms are useful for other purposes (e.g., calculating cardiac output using pulse contour method). iv. Disadvantages 1. Need skills 2. Difficult to maintain intravenous catheter patency 3. Tubing can cause erroneous reading (tubing too long, too many stopcocks, rigid tubing, air bubbles). 4. Hematoma formation, infection 5. Expensive equipment

anesthesia in nonhuman primates g. Common causes of hypotension i. Excessive anesthetic depth causing vasodilation, especially with inhalants ii. Hypovolemia/dehydration iii. Blood loss

Respiratory System 1. When intubating animals, confirm endotracheal tube placement by a. Chest auscultation, which will assist in ensuring adequate endotracheal tube placement; airflow, which should be audible in all lung fields b. Using capnogram to see the end tidal CO2 (ETCO2) waveform c. Visualization 2. Monitor gas exchange and ventilation to ensure adequate oxygenation and CO2 removal a. Minute ventilation (MV) = TV (tidal volume) × RR (respiratory rate) b. MV = 200–300 ml/kg/min 3. Mucous membrane: Reflects degree of oxygenation; should be pink and moist 4. Capnography a. Information provided: Ventilation, cardiovascular system, metabolism b. Terms i. Capnometer: Measures CO2 in expired gas; provides only a numerical display ii. Capnogram: Displays a plotted graph of respiratory CO2 iii. Capnograph: Capnometer (numerical data) plus capnogram (graph) iv. ETCO2: Obtained from capnometer; CO2 concentration at the end of expiration v. Partial pressure of arterial CO2 = PaCO2: Requires arterial blood gas analysis

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pocket handbook of nonhuman primate clinical medicine c. Normal values i. PaCO2: 35–45 mmHg ii. ETCO2: Usually 1–10 mmHg < PaCO2 iii. Inspired CO2 = 0 d. Ventilation status i. Normal ventilation: PaCO2 = 40 mmHg ii. Hypoventilation: PaCO2 > 40 mmHg iii. Hyperventilation: PaCO2 < 40 mmHg e. Two types of capnometers i. Mainstream (nondiverting): Gas analysis inline 1. Advantages A. Fast response time B. No expired gas scavenging needed C. Less likely to be contaminated with other gasses D. Easy calibration E. Portable 2. Disadvantages A. Measures only CO2 B. Increases dead space; bulky; located near the patient C. Increases potential for leaks/disconnection D. May cause thermal burns E. Requires manual calibration F. Fragile ii. Sidestream (diverting): Draws gas from a Y-piece port in the breathing system to a sensor located in the monitor 1. Advantages A. Lightweight B. Decreases dead space C. Fast warm-up D. Measures CO2 and other gasses (e.g., inhalant anesthetic agents) E. May be used in a nonintubated patient F. Microstream type is also available

anesthesia in nonhuman primates G. Automatic calibration H. Remote monitoring 2. Disadvantages A. Delayed response time B. Tube obstruction can easily occur C. Gasses must be scavenged D. Removes gas from the circuit E. Calibration of gasses required 5. Pulse oximeter (% SpO2) a. Function i. Indirectly measures hemoglobin (Hb) oxygen saturation of arterial blood ii. Indirectly evaluates PaCO2 depicted by the oxyhemoglobin dissociation curve b. Probe placement: Tongue, nostril, toe, prepuce, vulva, ear, lip c. Advantages i. Noninvasive method ii. Continuous reading iii. Audible sound, alarm iv. Obtains a pulse rate d. Disadvantages i. Expensive ii. Factors affecting instrument reading 1. Movement 2. Ambient light 3. Hair, skin pigmentation, thickness 4. Hypotension 5. Vasoconstriction (e.g., use of α-2 agonists) 6. Poor peripheral perfusion 7. Substantial amount of methemoglobin (metHb), carboxyhemoglobin (carboxyHb) 6. Arterial blood gas analysis a. “Gold standard” method for assessing respiratory and acid-base status

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pocket handbook of nonhuman primate clinical medicine TABLE 1.5: A RTERIAL BLOOD GAS (A NESTHETIZED A NIMALS UNDER 100% O2)a Parameter pH PaCO2 PaO2 HCO3BE TCO2 % O2 saturation a

Value

Units

7.35–7.45 35–45 300–600 18–28 −4 to +4 20–30 95–100

— mmHg mmHg mmol/L mmol/L mmol/L %

The table was developed primarily from dogs and cats; however, we feel it accurately reflects the situation in nonhuman primates.

TABLE 1.6: ExPECTED PATIENT BLOOD GAS CHANGES Patient Acid-Base Status

pH

1° Changes

Compensatory Changes

Respiratory acidosis

↓

↑ PCO2

↑ [HCO3−]

Respiratory alkalosis

↑

↓ PCO2

Metabolic acidosis

↓

↓ [HCO3 ]

↓ PCO2

Metabolic alkalosis

↑

↑ [HCO3−]

↑ PCO2

↓ [HCO3−] −

b. Normal values for an anesthetized animal receiving 100% O2 are shown in Table 1.5. c. Acid-base disturbances (expected patient blood gas changes) are shown in Table 1.6. d. Advantages i. Accurate ii. Respiratory and acid-base status can be accessed. iii. With an intravenous catheter, the patient can be monitored periodically. e. Disadvantages i. Invasive method: Either an arterial blood must be drawn as a one-time sample or an arterial catheter must be placed. ii. Need skills for acquiring samples iii. May be difficult to maintain catheter patency iv. Sample handling and equipment (i.e., iStat®) are needed. v. Infection, hematoma

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7. Neuromuscular blocking (NMB) agents/patient monitoring: When neuromuscular blocking agents are used a. The use and need for NMB agents must be determined and clearly incorporated into the IACUC-approved protocol. b. Patient responsiveness and anesthetic depth must be assessed to ensure the patient is adequately anesthetized. c. Proper support and monitoring equipment, including ventilation support and NMB reversal agent, must be available. d. The degree of NMB (i.e., Train-of-Four [TOF]) should be monitored.

Body Temperature Anesthetic agents lower body temperature and inhibit low-temperature coping mechanisms: 1. Hypothermia results in prolonged recovery. a. Other causes of hypothermia include i. Hair removal (large area) ii. Cold alcohol, scrub solution, surgical table, irrigation solution, intravenous fluid b. Prevent heat loss by i. Using warm intravenous fluids, irrigation solutions, water bottles ii. Avoid overshaving iii. Provide external heat sources: Water-Recirculating heating pad, Bair Hugger ® iv. Body/extremity wrap with thermal foil, plastic wrap, bubble wrap v. Recirculating-water heating blankets vi. Heated surgical tables vii. Insulated intravenous fluid jackets viii. Increased room temperature ix. Warm inspired O2 2. Measurement probes a. Rectal temperature thermometer/probes b. Esophageal probes

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pocket handbook of nonhuman primate clinical medicine c. Transcutaneous monitors d. Tympanic membrane thermometer e. Radio-frequency identification (RFID) implantable chips equipped to read patient temperature

Gas Analyzers Gas analyzers monitor the concentration of exhaled/inhaled gasses (e.g., inhalant anesthetic agents, CO2, O2).

Fluid Administration 1. Indication: Replace fluid loss caused by a. Anesthesia (e.g., evaporation, urine, insensible water loss) b. Surgery (e.g., surgical site, hemorrhage, effusion removal [ascites fluid]) c. Disease 2. Anesthetic causes a. Vasodilation causing hypotension; inhalants are potent vasodilators b. Depressed myocardium → ↓ cardiac output → ↓ blood pressure → ↓ O2 delivery to tissues → ↑metabolic acidosis c. Depressed ventilation → respiratory acidosis d. Depressed body coping mechanisms to accommodate hypotension, hypovolemia, hypoxia, and hypothermia 3. Hydration status a. Maintain normal hydration via intravenous, subcutaneous, or intraperitoneal fluid therapy or intraosseous in case of emergency b. Maintenance fluid: 60 ml/kg/24 hr c. Fluid losses during the case (hemorrhage, etc.) 4. Correct dehydration prior to anesthesia a. Previous fluid deficits (dehydration) i. 5% = slight decrease in skin turgor ii. 10% = mild decrease iii. 15% = moderate decrease iv. 20% = severe decrease

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b. __ % Dehydration × __ kg Body weight (BW) = __ ml fluid replacement. Example: If a 10-kg patient is 8% dehydrated, fluid replacement → 0.08 × 10 = 0.8 L fluid replacement needed. c. The patient should receive this fluid volume prior to or when initiating anesthesia. 5. Fluid administration rate during anesthesia: 10–20 ml/kg/hr 6. Fluid types a. Isotonic (balanced electrolyte fluid) solutions include lactated Ringer’s solution, Normosol-R®, Plasma-Lyte®, and others b. Hypotonic solution c. Hypertonic solutions: 7.5% NaCl d. Colloid (5–20 ml/kg): Hetastarch, dextran, oxyglobin e. Blood 7. If potassium (K+) is needed, administer at a rate not greater than 0.5 mEq/kg/hr; note that some solutions contain potassium (e.g., lactated Ringer’s solution). 8. Administer sodium bicarbonate if metabolic acidosis (pH < 7.2) is identified. 0.3 × kg BW × Base excess (BE) = __ mEq NaHCO3 9. Blood administration a. Blood type: A-B-O, M-N, Rh, V-A-B, C-E-F b. Blood volume about 50–75 ml/kg c. Blood transfusion can be initiated when blood loss is greater than 20% of blood volume or if PCV is less than 20%. d. Crossmatching is recommended, with the major crossmatch more crucial than the minor. e. Rate i. Monitor baseline parameter before blood transfusion (e.g., temperature, pulse rate, RR, mucous membrane, PCV, TP) ii. First 15 min: 0.25 ml/kg → then 5–10 ml/kg/hr iii. Do not give more than 22 ml/kg/day. f. Complications i. Consider pretreatment with antihistamines

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pocket handbook of nonhuman primate clinical medicine ii. Hypocalcemic tetany 1. Treat with 10% calcium gluconate 1 ml/kg IV over 30 min 2. If seizure → treat with diazepam 0.25–0.5 mg/kg IV iii. Immune-mediated response 1. Urticaria, tachycardia, tachypnea, fever, edema 2. Acute anaphylactic shock, treat with A. Epinephrine: 0.01 mg/kg B. Fluid administration iv. Vascular overload: Furosemide 1–2 mg/kg IV

postoperative care and monitoring 1. Adequate postoperative care enhances the animal’s recovery, minimizes pain and distress, and is a requirement of both professional and regulatory federal agencies. 2. Adequate postoperative care includes monitoring and documenting the animal’s recovery during the anesthetic recovery period, the acute postoperative period, and the long-term postoperative period. 3. Postoperative care must be arranged by the principal investigator. In some cases, surgical staff may perform part of the postoperative care. 4. The attending veterinarian has appropriate authority to ensure provision of adequate veterinary care during all phases of the postoperative period. Communication between the principal investigator’s staff and the veterinary staff is crucial.

Acute Postoperative Period 1. Goal a. Have a smooth recovery b. Show adequate cardiopulmonary function: HR, % SpO2, direct/indirect BP, capnometer, etc. 2. Recovery area a. Adequate ventilation b. Minimize traffic and noise

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c. Temperature control d. Dedicated staff continuously monitors animals e. Availability of emergency drugs/equipment (e.g., reintubation kits, O2 supply, face masks) f. Sufficient staff personnel to help during emergency situations 3. The acute postoperative period is that period when the animal regains stable physiologic functions, usually over 24–48 hr a. Monitor at least two or three times daily depending on the type of surgical procedure and the animal’s condition. b. The principal investigator’s staff will monitor and record the animal’s postoperative condition at least once daily; the veterinary staff will also evaluate animals at least once daily. 4. Acute postoperative period may require further treatments to stabilize the animal, such as fluid therapy, analgesics, antibiotics, and more intensive monitoring. a. Analgesia is required in all animals, except those on IACUC-approved protocols, as outlined in the IACUCapproved protocol; typically, this includes analgesia, at a minimum, for the first 48 hr. b. It is within the veterinarian’s purview to exercise his or her professional judgment in regard to focusing on the individual animal’s response to the analgesia and other postoperative care. 5. Monitoring parameters during this time include indices of pain or discomfort, RR and character, mucous membrane color, capillary refill time, hydration status, appetite, surgical wound condition, state of arousal (Table 1.7). 6. After discontinuing the inhalant anesthetic, maintain the patient with 100% O2 for 5–10 min, if applicable, to ensure inhalant washout and transition to room air (~20% O2) until the patient shows signs of good ventilation. 7. Once the animal regains a swallowing reflex, deflate the ET tube cuff → ET tube can be removed; continue monitoring until the patient is conscious and in sternal recumbency. a. If vomiting occurs, ET tube cuff can be partially deflated before extubation.

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TABLE 1.7: POSTOPERATIVE MONITORING PARAMETERS Respiratory function • Pneumonia • Pulmonary edema • Thromboemboli • Pneumothorax Temperature regulation • Hypothermia • Hyperthermia Mental status • Depression/lethargy • Incoherence • Seizures • Pain Gastrointestinal function • Diarrhea (infection, irritation) • Constipation (ileus; drug induced, e.g., morphine) • Inappetence • Vomiting

Cardiovascular function • Cardiac arrhythmias • Coronary or peripheral thromboemboli • Shock • Pericardial tamponade Hydration status • Dehydration • Pulmonary edema • Metabolic acidosis • Shock Postoperative infections • Septicemia • Peritonitis/pleuritis • Local infections/abscesses • Incisional infections/dehiscence

b. After extubation, the patient must be monitored closely for at least 15–30 min. c. Delayed extubation can occur in some cases (e.g., prolonged anesthetic procedures, neuroanesthesia, sick animals). 8. If the animal is immobile, HR and core body temperature should be monitored. 9. Administer postoperative treatments (analgesics, antibiotics, fluid therapy, etc.) according to the principal investigator’s research protocol or as determined by the veterinary staff in consultation with the principal investigator. Postoperative treatments may be performed by the veterinary staff or by the principal investigator’s trained staff. All medications, including name, dose, and route of administration, must be recorded in the animal’s postoperative record. 10. Do not give food or water until the patient shows adequate signs of consciousness; premature feeding can cause aspiration pneumonia. 11. Squeeze cages can be used to restrict movement until fully recovered.

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12. Prolonged recovery can be caused by a. Prolonged anesthetic elimination: hepatic/renal disease, ↓ cardiac output, hypotension, hypothermia, lean animals that underwent barbiturate anesthesia b. High anesthetic dosages during pre-, peri-, or postoperative period c. Residual anesthetic adjunct drugs (e.g., NMB drugs) d. Circulatory shock e. Anesthetic complications/troubleshooting and emergency drugs are listed in Tables 1.8 and 1.9, respectively

Long-Term Postoperative Period 1. The long-term postoperative period is from the time of physiologic stabilization to normalization. This usually takes a minimum of 7–10 days for the animal to recover totally from most survival surgical procedures; daily monitoring should continue during this time. 2. Monitoring parameters during this period include indices of pain or discomfort, state of arousal, surgical wound condition, appetite, hydration status, capillary refill time, mucous membrane color, fecal and urine production, and any medication administered. 3. Following the 10-day period, all external or nonabsorbable sutures should be removed, and the animal’s postoperative record should be closed. 4. Some surgical manipulations require extended postoperative monitoring. The appropriate duration and extent of monitoring can be determined by the veterinary staff in consultation with the principal investigator. Situations constituting prolonged monitoring periods include chronic debilitating disease states (e.g., diabetes mellitus), animals undergoing organ transplantation or immunosuppressive therapy, and animals with chronically implanted instruments or catheters. The latter may require regular and chronic anesthetic episodes to clean and maintain the implants appropriately.

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TABLE 1.8: A NESTHETIC COMPLICATIONS Anesthetic Complications Animal wakes up during anesthesia

Slow respiratory rate/apnea

Vomiting/regurgitation

Bradycardia (less than 20–30% of baseline HR)

Tachycardia (more than 20–30% of baseline HR)

Low % SpO2(5 kg start, 50 ml/kg/hr; > 4 kg, start 40 ml/kg/hr for first hour; < 4 kg or after first hour of fluids, 30 ml/kg/hr) • Sodium bicarbonate • 1 mg/kg slow intravenous bolus and place up to 30 mEq/500 ml bag. Can repeat bicarbonate intravenous bolus if required on NOVA recheck. Goal is pH 7.5, HCO30 to obtain a urine pH of 8 and prevent myoglobin from precipitating (into the kidneys). • Acute renal failure (lack of urine production): No diuresis until hydrated • Mannitol 25%: give 500 mg/kg IV over 5 to 10 min (10-kg animal would receive 20 ml)

basic fluid therapy

67

• If no urine production within 20–30 min after mannitol, give 2 mg/kg IV Lasix (furosemide). Repeat if no urine production within 15 min. • If no urine production after second dose Lasix, start dopamine (see low-dose chart) • Hyperkalemia • If not corrected with the bicarbonate administration, give 10% calcium gluconate 100 mg/kg (1.0 ml/kg) slow intravenous bolus over 20 to 30 min. Monitor heart rate; if decreasing rapidly, slow rate or stop. • If potassium values still too high, treat with insulin and dextrose. Administer 2 U insulin (any type) and follow with 2.5–5% dextrose solution (25 ml 50% dextrose in 500-ml bag is 2.5%). • Auscultate lungs for signs of pulmonary edema frequently, particularly when zero urine production or once animal has received 90 ml/kg/day.

Monitor for Other Clinical Complications 1. Compartment syndrome: extreme swelling of tissues; immediate need for fasciotomy (usually not until the second day) 2. Disseminated intravascular coagulation (DIC): heparin, fresh frozen plasma, or platelet transfusion Address severe pain (oxymorphone or buprenorphine). Avoid nonsteroidal anti-inflammatory drugs (NSAIDs) for pain control due to kidney failure. Treat with full-spectrum antibiotics (Gram positive, Gram negative, anaerobes). Repeat NOVA monitor for acid-base disturbances, progressive kidney failure, pulmonary edema, infection, and so on.

5 management of gastrointestinal/ abdominal conditions Cassondra Bauer and Kari L. Christe

oropharyngeal conditions 1. Esophageal strictures (Harper et al. 1982, 321–326; Glover et al. 2008, 18–25; White 2011) a. Definition: narrowing of the esophagus that can lead to difficulty swallowing b. Causes/pathophysiology: GERD (gastroesophageal reflux disease), esophagitis, hiatal hernia, healing trauma or postsurgical, foreign bodies, congenital, or parasites c. Clinical signs: anorexia, weight loss, choking, coughing, trouble swallowing, regurgitation, gagging, hematemesis, increased respiratory rate, failure to thrive d. Physical examination/diagnostics: weight loss most common sign, endoscopy, barium swallow radiographs, computed tomography (CT) e. Differential diagnoses: oral trauma, poor dentition, hairball or other stomach malady, intestinal obstruction, megaesophagus, laryngeal paralysis, myasthenia gravis, neoplasia, tuberculosis 69

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pocket handbook of nonhuman primate clinical medicine f. Treatment: treat underlying disease (infection, GERD, etc.), dilate esophagus surgically (may require multiple dilations) g. Prevention: feed solid foods that will stretch the esophagus h. Species differences: baboon, chimpanzee

2. Cleft palate (White 2011; Goldschmidt et al. 2010, 357–360; Siebert et al. 1998, 436–441; Swindler and Merrill 1971, 435–439) a. Definition: a congenital malformation in which the palate does not completely form, leaving a hole in the roof of the mouth that communicates with the nasal passages. Can be seen concurrently with a cleft lip. b. Causes/pathophysiology: congenital malformation (heritable) c. Clinical signs: inability to suckle (cannot form a seal), milk coming from nose when attempting to eat, aspiration pneumonia, abnormal lung sounds, anorexia, dyspnea, regurgitation/emesis, failure to thrive d. Physical examination/diagnostics: may find aspiration pneumonia, hole noted in the roof of the mouth ± lip deformity e. Differential diagnoses: oral trauma f. Treatment: surgical correction (needs to be modified as animal grows and matures), may need to alter feeding regimen to allow for easier swallowing of ingesta g. Prevention: do not breed animals with genetic predisposition for this condition h. Species differences: squirrel monkey, mandrill, macaque, common marmoset, lemur, tamarin, gorilla

gastric conditions 1. Trichobezoars/phytobezoars/hardware disease/rocks (White 2011; Mejido et al. 2009, 302–309; McTighe and Feurtado 2008, 50; Butler and Haines 1987, 232–233; Nolan, Schaffer, and Conti 1988, 63–65; Gillin et al. 1990, 180–182; WalkerRenard 1993, 1663–1666; Mook 2002, 560–562; Sulistiawati 1998, 13–15; Etheridge and O’Malley 1996, 57–59; Reinhardt, Reinhardt, and Houser 1986, 158–164; Brady and Morton 1998, 377–414)

management of gastrointestinal/abdominal conditions a. Definition: a mass of hair, plant material, hardware, or rocks that accumulate in the gastrointestinal (GI) tract. Can cause perforation of digestive tract. Common sites include stomach and cecum. b. Causes/pathophysiology: ingestion of hair, plant materials, metal, or rocks that the body is unable to break down. Often associated with behavioral abnormalities. Can be associated with decreased gastric motility. Objects can cause irritation to the lining of the stomach and, if too large to pass through the intestinal tract, can erode through the mucosa of the stomach. If large enough to pass, may end up lodged in the cecum. c. Clinical signs: weight loss, regurgitation, vomiting, abdominal distention, anorexia, decreased/absent stool output, dehydration, tachypnea, tachycardia, poor hair coat, lethargy. d. Physical examination/diagnostics: may be able to feel a firm mass in the left cranial abdomen (stomach) or right midabdomen (cecum). Often, the mass takes on the shape of the organ (mass is stomach shaped) and cannot be broken up. Hair, plant material, rocks in stool. On radiographs, see swirling hair or plant matter, most often in stomach. Metal can be seen on radiographs. Blood work may show abnormalities. e. Differential diagnoses: neoplasia, high parasite load, diaphragmatic hernia, enteritis, partial obstruction, intussusceptions, volvulus, pancreatitis, peritonitis (many signs are nonspecific). f. Treatment: can attempt to clear with roughage (pineapple). If the hairball is tightly packed, will likely need surgical removal; if less organized, may be able to break down with just pineapple. Additional manipulable enrichment is often provided to help decrease the undesirable behavior (hair or metal eating). For hardware, surgical removal is often required. If small enough, object may be removed endoscopically. Antibiotics and supportive therapy (fluids, pain medication). g. Prevention: in animals noted for hair or metal eating, provide with additional manipulable enrichment to keep occupied. Do not feed plants that are indigestible

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pocket handbook of nonhuman primate clinical medicine to nonhuman primates. Supplement soy lecithin. Ensure caging is in good shape with no pieces that can be removed and ingested. h. Species differences: baboon, macaque, galago, chimpanzee, tamarin, tarsier

2. Ulceration (White 2011; Parker, Gilmore, and Dubois 1981, 445–447; Okui et al. 1998, 26–30; Dubois et al. 1996, 2885–2891) a. Definition: mucosal erosion, either partial or full thickness, in the mucosa of the stomach b. Causes/pathophysiology: Helicobacter pylori infection, chronic nonsteroidal anti-inflammatory drug (NSAID) usage, increased acid production, neoplasia, decreased gastric motility c. Clinical signs: abdominal pain, bloating, vomiting or regurgitation, anorexia, weight loss, melena, hematemesis, ascites, dehydration, tachypnea, pale mucous membranes, tachycardia d. Physical examination/diagnostics: nothing specific seen on physical examination, endoscopic examination, often treated based on signs (melena and hematemesis), fecal occult positive e. Differential diagnoses: gastritis, neoplasia, pancreatitis, cholecystitis, trichobezoar/phytobezoar, inflammatory bowel disease, renal failure f. Treatment: antacid (Tums®, PeptoBismol®), or H2 antagonist (famotidine), omeprazole, COMA (clarithromycin, omeprazole, metronidazole, and amoxicillin), discontinue NSAIDs g. Prevention: couple long-term NSAID with famotidine h. Species differences: macaque, chimpanzee, baboon 3. Emesis/regurgitation (White 2011; Ordy and Brizzee 1980, 215–223; Normile et al. 1992, 524; Costall, Domeney, and Naylor 1986, 375P; Lukas 1999, 237–249; Marsilio, Hill, and Waitt 2010; Marsilio and Waitt 2009, 164–165; Glover, Leland, and Hubbard 2005, 174; Struck et al. 2007, 35–38; Howell et al. 1997, 30–33; Koszdin 2001, 68–69) a. Definition: Emesis is the forceful expulsion of the contents of the stomach through the mouth and/or nose. Regurgitation is the return of food from the stomach up the esophagus to the mouth (not forceful).

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b. Causes/pathophysiology: infection, stress/anxiety, neoplasia, increased intracranial pressure, side effect of some medications, pyloric stenosis, bloat, neurologic disease associated with the brain, electrolyte imbalances c. Clinical signs: dehydration, partially digested or undigested food beneath the cage, salivation d. Physical examination/diagnostics: dehydration, possibly aspiration pneumonia, electrolyte imbalances, partially digested material beneath cage e. Differential diagnoses: dependent on emesis versus regurgitation, bright red blood in contents indicates bleeding in esophagus, dark red blood or clots indicate bleeding in stomach (possible ulcer), coffee ground color/texture indicates severe bleeding in stomach, yellow indicates bile so duodenal contents also being expelled f. Treatment: antiemetics (ondansetron, meclopramide) g. Prevention: dependent on the cause, remove noxious stimuli, treat underlying conditions h. Species differences: baboon, macaque, common marmoset, squirrel monkey, gorilla, chimpanzee, proboscis monkey, spider monkey 4. Bloat/gastric dilatation/volvulus/pneumoabdomen (White 2011; Farah, Chege, and Riday 1993, 278–279; Fanton, Yochmowitz, and Cordts 1987, 524; Stein et al. 1981, 522–523; Boyce and Miller 1980, 130–131; Johnson 1980, 6; Elwell and DePaoli 1978, 1235–1236; Kim, Abee, and Wolf 1978, 1303– 1306; Simmons 1973, 278–279; Couillard et al. 2004, 324– 326; Garcia et al. 2006, 313; Goldston and Few 1974, 116–118) a. Definition: distention of stomach with gas, fluid, or ingesta, termed volvulus if the stomach twists b. Causes/pathophysiology: eating large amount of food rapidly, ileus, obstruction of the GI tract, drinking large volumes of fluids, inappropriate diet, Clostridium perfringens c. Clinical signs: rounded appearance to abdomen, painful posture, reluctance to eat or drink, shock if severe, respiratory distress d. Physical examination/diagnostics: firm abdomen on physical examination, radiographs show distended stomach (gas, fluid, or ingesta filled), complete blood count

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pocket handbook of nonhuman primate clinical medicine (CBC)/chemistries, decreased gut motility sounds on auscultation ± tympanic sounds on percussion e. Differential diagnoses: obstruction, gastritis, irritable bowel disease, constipation f. Treatment: famotidine (Pepcid AC®); simethicone (Gas-X®); passage of stomach tube; if volvulus, emergency surgical correction; correction of electrolyte imbalances; antibiotics; analgesics; fluid therapy g. Prevention: feed small meals; if fasting, restrict water allowance; change of diet h. Species differences: black and white colobus monkey, vervet, macaque, red ruffed lemur, common marmoset, gorilla, squirrel monkey, spider monkey, baboon, chimpanzee

intestines 1. Linear foreign body of the small intestines (Calle et al. 1995, 87–97; Hahn et al. 2000, 556–558; Owens 1982) a. Definition: ingestion of linear foreign object b. Causes/pathophysiology: Linear foreign bodies generally become anchored at the base of the tongue, esophagus, or stomach and can cause a partial or complete intestinal obstruction. c. Clinical signs: abdominal pain, anorexia, enlargement of the abdomen, fever, vomiting, electrolyte disturbances, shock, sepsis d. Physical examination/diagnosis: Based on clinical signs and physical examination, radiographs may show plication or accordion pleating of the small intestines as they become bunched around the linear body. e. Differential enteritis

diagnoses:

intussusception,

obstruction,

f. Treatment: surgical excision and repair, antibiotics, and supportive therapy (fluids, pain medication) g. Prevention: ensure no access to foreign objects h. Species differences: macaque, langur 2. Intussusception (Owens 1982; Fox and Hall 1970, 714–716; Kelts and Bignall 1973, 387–394; Watts 1935, 355–357; Morgan 1992)

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a. Definition: Part of the intestine has invaginated into another section of intestine. b. Causes/pathophysiology: secondary to hypermotility (infection/inflammation) or intestinal stricture c. Clinical signs: abdominal pain, anorexia, vomiting, ileus, electrolyte disturbances, shock, sepsis d. Physical examination/diagnosis: based on clinical signs and physical examination, a “sausage-shaped” mass palpated in the abdomen; also visualize a sausage-shaped mass in the abdomen on radiographs or by ultrasound; using contrast radiographs, the intussusscepted bowel appears as a filling defect e. Differential diagnoses: intestinal obstruction, enteritis f. Treatment: surgical excision, antibiotics, and supportive therapy (fluids, pain medication) g. Prevention: none h. Species differences: macaque, squirrel monkey, baboons 3. Enterocolitis/enteritis/colitis (Adler et al. 1993, 81–87; Fox et al. 2001, 421–429; Chalifoux and Bronson 1981, 942–946; Chalmers, Murgatroyd, and Wadsworth 1983, 270–279; Clapp et al. 1985, 107S–113S; Johnson et al. 1996, 435– 438; Wood et al. 2000, 385–393; Chen, Miller, and Powell 2000, 47–49; Rubio and Hubbard 2001, 109–116; Rubio and Hubbard 2002, 191–195; Line et al. 1992, 240–244; Elmore et al. 1992, 356–359; Hird, Anderson, and Bielitzki 1984, 465– 470; Gozalo and Montoya 1992, 35–38; Bethune et al. 2008, e1614 [online 1–9]; Johnson et al. 2001, 257; Johnson et al. 1996, 102–115) a. Definition: inflammation of the small or large intestines (enteritis of small intestines; colitis of large intestines, especially the colon); most common cause of morbidity and mortality in nonhuman primates, especially juvenile rhesus and callitrichids b. Causes/pathophysiology: local or general infection or inflammatory response to bacterial: Campylobacter sp., Salmonella sp., Shigella sp., Yersinia, enteropathic E. coli, Clostridium, Mycobacterium avian intracellular complex, Helicobacter. Viral: rotaviruses, coronaviruses, paramyxovirus. Parasitic: Giardia, Balatidium coli, Cryptosporidium

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pocket handbook of nonhuman primate clinical medicine sp., Entamoeba histolytica, Trichuris trichura, Strongyloides, strongyles and cestodes. Fungal: Candida albicans; wheatsensitive enteropathy; nonpathogenic (stress, allergy) c. Clinical signs: loose to liquid stool ± blood, mucous, and/ or gas; thickened bowel; abdominal pain; anorexia; weight loss; poor growth/failure to thrive d. Physical examination/diagnosis: based on clinical signs and physical examination e. Differential diagnoses: intestinal obstruction, foreign body f. Treatment: supportive therapy (fluids, pain medication), antibiotics if appropriate, surgical exploration with removal and correction of inciting problem if can be determined g. Prevention: none h. Species differences: macaque, baboon, callitricid 4. Diverticulosis/diverticulitis (Hayama et al. 1988, 423–426; Bunton and Bacmeister 1989, 351–352; Wolfe-Coote 2005, 621; Murray et al. 2000, 452–454; Fraser 1988, 20) a. Definition: out-pocketings of the colonic mucosa and submucosa caused by weaknesses of muscle layers in the colon wall (more common in the sigmoid colon). Infection of diverticulum causes diverticulitis. b. Causes/pathophysiology: etiology unknown, although risk factors are age, constipation, low dietary fiber c. Clinical signs: none unless diverticulitis, then tears in the colon may lead to bleeding or perforations; intestinal obstruction, abscess, peritonitis, abdominal pain, anorexia, enlargement of the abdomen, fever, vomiting, ileus, electrolyte disturbances, shock, sepsis d. Physical examination/diagnosis: Based on clinical signs and physical examination, radiographs may show signs of a thickened wall, ileus, constipation, small bowel obstruction, or free air in the case of perforation. e. Differential diagnoses: obstruction, intussusception f. Treatment: supportive therapy (fluids, pain medication), antibiotics, surgical exploration with removal and correction of inciting problem g. Prevention: adequate dietary fiber to prevent constipation; do not offer nuts or seeds, which can get stuck in diverticuli h. Species differences: macaque, orangutan

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5. Megacolon (Wolfe-Coote 2005, 621; O’Farrell et al. 1996, 96–97; Krasnow and Courtney 1992, 616–619; Eisele, Markovits, and Paul-Murphy 1991, 436–441; Cantrell and Padovan 1986, 1223–1224; Bolomo et al. 1980, 667–672) a. Definition: an abnormal dilation of the colon. The dilation is often accompanied by a paralysis of the peristaltic movements of the bowel b. Causes/pathophysiology: disorder of motility, primary or secondary to disease that obstructs the normal passage of feces, causing chronic constipation c. Clinical signs: abdominal distension with or without pain, depression, weakness, anorexia, dehydration, unthrifty appearance, recurrent episodes of constipation with increasing severity d. Physical examination/diagnosis: based on clinical signs, possible intraabdominal adhesions or a prior history of abdominal surgery; survey radiographs should confirm dilation with or without impaction; a barium enema or colonoscopy should be considered to identify any possible strictures, tumors, or inflammatory bowel disease e. Differential diagnoses: bloat, hardware disease, pancreatitis f. Treatment: if mild/moderate dilation without impaction, try dietary management, stool softeners or laxatives, enemas, increased exercise, or weight reduction if needed; otherwise, surgical resection of nonfunctional colon and possible strictures g. Prevention: adequate dietary fiber to prevent constipation h. Species differences: macaque, cebus 6. GI adenocarcinoma (Clapp et al. 1985, 107S–113S; Johnson et al. 1996, 435–438; Wolfe-Coote 2005, 621; Simmons and Mattison 2010; O’Sullivan and Carlson 2001, 212–215; Valverde et al. 2000, 540–544; Kerrick and Brownstein 2000, 40–42; Uno et al. 1998, 19–27; Brack 1998, 319–324; Lembo et al. 1997, 229–232; DePaoli and McClure 1982, 104–125; Lowenstine 2003, 92–102; Rodriguez et al. 2002, 74–83) a. Definition: epithelial neoplasia originating in glandular tissue of the GI b. Causes/pathophysiology: risk factors include age, low dietary fiber, history of enterocolitis

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pocket handbook of nonhuman primate clinical medicine c. Clinical signs: weight loss, microcytic anemia, and fecal occult positive; anorexia, constipation, and obstruction generally occur quite late in the disease course d. Physical examination/diagnosis: based on clinical signs and physical examination, ultrasonography, contrast radiography, or exploratory laparotomy e. Differential diagnoses: partial obstruction, enteritis, other tumors (leiomyoma, leiomyosarcoma, lymphoma, etc.) f. Treatment: Surgical excision is generally curative provided there are no metastases to the liver and mesenteric lymph nodes. g. Prevention: none h. Species differences: macaque, cotton-top tamarin, baboon, African green monkey

pancreatic diseases 1. Pancreatitis (White 2011; Baskerville et al. 1991, 415–421; Tsuchitani and Narama 1988, 439–444; Chandler and McClure 1982, 171–180; Doepel, Anver, and Hofing 1980, 505– 508; Rosenberg, Anderson, and Henrickson 1979, 988–989) a. Definition: the inflammation of the pancreas (acute or chronic) b. Causes/pathophysiology: idiopathic, gallstones, ethanol, trauma, steroids, autoimmune, scorpion sting, hypercalcemia, hypertriglyceridemia, hypothermia, drugs (diuretics, azothioprine), pregnancy, irritation during surgery c. Clinical signs: none, severe upper abdominal pain, nausea and vomiting, ± elevated blood pressure, elevated respiratory rate, elevated heart rate, ileus, subclinical d. Physical examination/diagnostics: abdominal pain, serum lipase ± amylase more than three times the upper limit of normal e. Differential diagnoses: liver abnormalities/failure, intussusceptions, strangulated loops of intestines f. Treatment: supportive care (pain relief; fluid replacement with appropriate electrolyte supplementation; limit oral intake, especially that containing fat)

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g. Prevention: none h. Species differences: macaque, squirrel monkey, baboon

hepatic conditions 1. Hepatitis (Wolfe-Coote 2005, 621; Sa-nguanmoo et al. 2010, 167–170; Sa-Nguanmoo et al. 2009, 73–82; Arankalle and Ramakrishnan 2009, 214–218; Arankalle, Goverdhan, and Banerjee 1994, 125–129; Lanford, Chavez, Barrera, et al. 2003, 7814–7819; Lanford, Chavez, Notvall, et al. 2003, 72–80; Robertson 2001, 233–242; Slighter et al. 1988, 73–81; Montali et al. 1989, 759–765; Lemon et al. 1982, 25–36; Shevtsova et al. 1988, 177–194; Williams-Blangero et al. 1996, 26–30; Burke and Heisey 1984, 940–944; Lankas and Jensen 1987, 340–344; Brown, Jansen, and Lemon 1989, 4932–4937; Eichburg 1980, 541–543) a. Definition: inflammation of the liver (acute or chronic) b. Causes/pathophysiology: bacterial, viral (hepatitis A, B, C, D, E, G, TT; callitrichid hepatitis due to lymphocytic choriomeningitis virus in callitrichids and owl monkeys; GBA-A-like flavivirus of tamarins), parasitic (schistosomiasis, trematodiasis, toxoplasma, leptospira), or fungal c. Clinical signs: none, anorexia, depression, lethargy, fever, vomiting, diarrhea, jaundice d. Physical examination/diagnosis: based on clinical signs, physical examination, increased liver enzymes e. Differential diagnoses: hepatic lipidosis, hepatic amyloidosis f. Treatment: supportive therapy (fluids, pain medication), antibiotics or antiinflammatories if appropriate g. Prevention: none h. Species differences: chimpanzee, orangutan, gorilla, gibbon, baboon, macaque, African green monkey, langur, woolly monkey, tamarin, marmoset, owl monkey 2. Hepatic lipidosis (Wolfe-Coote 2005, 621; Christe and Valverde 1999, 12–15; Gliatto and Bronson 1993, 198–202; LaberLaird, Jokinen, and Lehner 1987, 205–209; Bronson et al. 1982, 187–192) a. Definition: accumulation of lipid within the cytoplasm of the hepatocytes

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pocket handbook of nonhuman primate clinical medicine b. Causes/pathophysiology: rapid weight loss causing a negative energy balance c. Clinical signs: anorexia, lethargy, weight loss, depression, sudden death d. Physical examination/diagnosis: clinical signs, physical examination, history (rapid weight loss in an obese animal), laboratory results; ultrasonography reveals a diffuse increased echogenicity, but definitive diagnosis is only made by histopathologic examination of a liver biopsy e. Differential diagnoses: hepatitis, hepatic amyloidosis f. Treatment: early diagnosis and aggressive nutritional support to reverse the negative energy balance; if persistent anorexia, force-feed to meet daily caloric requirements; otherwise, consider a PEG (percutaneous endoscopic gastrostomy) tube for long-term nutritional support g. Prevention: ensure animals do not go 3 days without nutritional intake to prevent negative energy balance h. Species differences: macaque, African green monkey

3. Hepatic amyloidosis (MacGuire et al. 2009, 168–173; Hukkanen et al. 2006, 119–127; Naumenko and Krylova 2003, 92–95; Hubbard et al. 2001, 260–267; Hubbard et al. 2002, 84–90; Arslan, Nisbet, and Guvenc 2007, 655–659) a. Definition: tissue deposition of insoluble protein fibrils in a beta sheet configuration; amyloid is most frequently found in the GI tract, liver, spleen, and occasionally kidney b. Causes/pathophysiology: usually secondary to chronic inflammation (seen with enterocolitis, osteoarthritis, chronic valvular catheterization, and type D retrovirus) c. Clinical signs: related to the organs involved and extent of the deposition; include weight loss, diarrhea, thickened bowel, hepatomegaly, splenomegaly, enlarged kidneys, poor body condition, sparse hair coat d. Physical examination/diagnosis: based on clinical signs, physical examination, lab results; ultrasonography reveals a diffuse generalized decreased echogenicity, but definitive diagnosis is only made by histopathologic examination of a biopsy e. Differential diagnoses: hepatitis, hepatic lipidosis

management of gastrointestinal/abdominal conditions f. Treatment: none; amyloidosis is slowly progressive, and animals can maintain remarkably long after diagnosis depending on the organ involved and the extent of deposition g. Prevention: none h. Species differences: chimpanzee, orangutan, baboon, macaque, squirrel monkey, Diana monkey, tree shrew

urinary conditions 1. Glomerulonephritis/nephrotic syndrome (White 2011; Adachi et al. 2005, 669–674; Clarke et al. 2008, 42–48) a. Definition: inflammation of the glomeruli, or small blood vessels in the kidneys b. Causes/pathophysiology: may occur in conjunction with acute or chronic renal failure, viral or bacterial infection, secondary to liver or intestinal disease c. Clinical signs: abnormal quantities of urine, discolored urine ± odor, edema, dyspnea d. Physical examination/diagnostics: hematuria, proteinuria, hypoalbuminemia, hyperlipidemia, generalized edema, hypertension, anemia, dyspnea e. Differential diagnoses: cardiovascular abnormalities, liver abnormalities, UTI, neoplasia f. Treatment: supportive care, treat underlying cause (i.e., antibiotics if infection) g. Prevention: none h. Species differences: macaque 2. Hydronephrosis/renal cysts (White 2011; Roberts and Wolf 1971, 143–147; Roberts 1976, 1–4; Kessler, Roberts, and London 1984, 147–152; Ooms et al. 2005, 73) a. Definition: distention and dilation of the renal pelvis calyces, leading to renal atrophy b. Causes/pathophysiology: usually caused by obstruction of free flow of urine (i.e., kidney stones, neoplastic obstruction, etc.)

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pocket handbook of nonhuman primate clinical medicine c. Clinical signs: depends on chronicity: intense pain (acute) to no pain (chronic), nausea, vomiting, bladder distention, urinary tract infection (UTI) with blood or pus in the urine, kidney failure d. Physical examination/diagnostics: elevated creatinine, urea, and electrolyte imbalances on blood work, elevated urine pH, enlarged kidneys, may see calculi or mass on ultrasound e. Differential diagnoses: renal failure, amyloidosis, bacterial/viral infection f. Treatment: removal of obstruction, treat any concurrent conditions (UTIs) g. Prevention: feed a well-balanced diet to prevent stone formation h. Species differences: macaque

3. Urolithiasis and urinary obstruction (White 2011; Burdick et al. 2010, 90; Faltas 2000, 18–19; Ramachandra, Ramesh, and Rao 1995, 778–780; Pryor, Chang, and Raulston 1969, 862– 865; Matsell, Mok, and Tarantal 2002, 1263–1269; Gaertner, Lytton, and Morgenstern 1991, 1772–1774; Bahnson et al. 1988, 731–733; Caligiuri et al. 1990, 206–214; Cheever and Duvall 1981, 604–608) a. Definition: urinary calculi formed in the urinary tract, usually in the bladder or urethra b. Causes/pathophysiology: inflammation of the urinary tract, frequent urinary catheterization, kidney stones migrating through urinary tract, enlargement of prostate in males, nerve dysfunction, side effects of some medications (anticholinergics, antidepressants, cyclooxygenase 2 [COX-2] inhibitors, opiates), schistosoma c. Clinical signs: frequent, painful, or difficult urination; may observe hematuria d. Physical examination/diagnostics: pain in the pelvic region, distended bladder, usually occurs when the urine is very concentrated or the patient is dehydrated, ultrasound, radiographs (many calculi are calcium and will be visible), urinalysis, elevated BUN (blood urea nitrogen) and creatinine on blood work e. Differential diagnoses: UTI, prostate enlargement/obstruction of urethra, urinary tract neoplasia

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f. Treatment: fluid load/diurese the patient to flush the stones from the bladder; if calculi do not pass, may need to remove with cystoscope or cystotomy; if urethra is obstructed, pass a urinary catheter g. Prevention: offer plenty of fluids at all times to prevent formation, change of diet h. Species differences: males are more susceptible when the prostate is enlarged; macaque, chimpanzee, gibbon 4. Renal failure (White 2011; Barnhart and Bernacky 2008, 52–53; Kalk et al. 1984, 299–306; Steinhausen et al. 1981, 151–156; Clayton, Mylniczenko, and Greenwell 2003, 67–71; Baitchman et al. 2006, 182–185; Garner et al. 2003, 149–152) a. Definition: Kidneys fail to filter toxins and waste products from the blood adequately (acute or chronic). b. Causes/pathophysiology: Acute: crush syndrome, reperfusion injury, leptospirosis, ureteral occlusion. Chronic: diabetes mellitus, long-standing hypertension, polycystic kidneys, overuse of NSAIDs, aging, ischemia, renal dysplasia c. Clinical signs: Acute: oliguria, azotemia, fluid retention. Chronic: can develop slowly and few signs are seen. Acute and chronic: vomiting; nausea; weight loss; change in urination quality, quantity, and frequency; blood in urine; edema; arrhythmias; anemia; anorexia d. Physical examination/diagnostics: Kidney size may be reduced if chronic, normal or large if acute; elevated BUN and creatinine; elevated potassium, calcium, and phosphate. If chronic, may develop anemia. May note hematuria, proteinuria, or glucosuria. Possible fluid retention and edema. e. Differential diagnoses: amyloidosis of the kidneys f. Treatment: Acute: Kidneys can often recover following supportive care (fluids, antibiotics if bacteria involved, etc.). Chronic: Kidneys are permanently damaged and may require supportive care to maintain life (e.g., dialysis). g. Prevention: monitor kidney values if long-standing NSAID usage, give adequate fluid therapy during treatment, correct diets based on species needs h. Species differences: chimpanzee, baboon, macaque, lemur, marmoset, howler monkey

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organ nonspecific abdominal conditions 1. Diaphragmatic hernia (White 2011; Boyce and Miller 1980, 130–131; Morgan, Watcyn-Jones, and Garner 2010, 139– 144; Randolph et al. 1981, 396–401; Dalgard, Adamson, and Vermess 1975, 753–756; Swenson and Keeling 1974, 194; Hendrickx and Gasser 1967, 66–74; Bush et al. 1996, 346–357) a. Definition: a defect or hole in the diaphragm that allows abdominal contents to move into the thoracic cavity b. Causes/pathophysiology: congenital or traumatic c. Clinical signs: may be found incidentally; signs may be associated with the dysfunction of the entrapped organ d. Physical examination/diagnostics: radiographs ± contrast; hear GI sounds when auscultating chest e. Differential diagnoses: none f. Treatment: may require no treatment; often requires surgical intervention g. Prevention: none h. Species differences: macaque, gold lion tamarin, chimpanzee, baboon 2. Inguinal/peritoneal/umbilical hernia (White 2011; Dabic et al. 2010, 49–54; Strait and Orkin 2007, 107; Krugner-Higby et al. 2003, 561–570; Vielgrader et al. 2002, online(1–2); Johnson-Delaney 1999, 7–10; Taylor, Smith, and Eichberg 1989, 415–417; Jaax et al. 1982, 10; Carpenter and Riddle 1980, 194–199; Warren and Piccolie 1979, 400–401; Chaffee and Shehan 1973, 638; Rawlings et al. 1971, 621–622) a. Definition: protrusion of the abdominal contents through the inguinal canal (common) or a rent in the abdominal wall (most often at the umbilicus) b. Causes/pathophysiology: Inguinal: indirect—failure of the embryonic closure of the internal inguinal ring after the testicle passes through (congenital); direct—breakthrough of abdominal contents through a weakened point in the fascia of the abdominal wall (acquired most often as an adult). Peritoneal: umbilical—most often congenital. Other sites: Increased abdominal pressure (due to obesity,

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pregnancy, etc.) causes strain on the abdominal wall, which weakens and tears. c. Clinical signs: present as a bulge in the inguinal region; may or may not be reduced; if bowel strangulated, may see abdominal discomfort d. Physical examination/diagnostics: bulging in the inguinal, umbilical, or other region; determine whether reducible or nonreducible e. Differential diagnoses: lipoma, testicular torsion, lymphadenopathy, abscessation f. Treatment: If reducible, monitor for strangulation of tissue or enlargement of hernia (may require surgical correction). If nonreducible, may not require intervention, just monitoring to ensure not enlarging or causing a problem. g. Prevention: none h. Species differences: squirrel monkey, macaque, mandrill, chimpanzee, baboon 3. Peritonitis/ascites/hemoabdomen (White 2011; Etheridge and O’Malley 1996, 57–59; Gozalo and Montoya 1992, 35–38; Murray et al. 2000, 452–454; Pollock et al. 2008, 476–479; Pisharath et al. 2005, 35–37; Kinasewitz et al. 2000, 100– 109; Kaufmann and Quist 1969, 1158–1162; Whitney and Kruckenberg 1967, 907–908; Rife 1951, 10) a. Definition: Peritonitis is inflammation of the peritoneum; ascites is accumulation of free fluid in the abdomen; hemoabdomen is blood accumulation free in abdomen. b. Causes/pathophysiology: local or general infection or inflammatory response to an insult such as perforation of GI tract; disruption of the peritoneum; bacterial infection; systemic infections; leakage of body fluids into the abdomen (blood, gastric secretions, urine, pancreatic secretions, bile); foreign body left in the abdomen following surgery; endometriosis c. Clinical signs: abdominal pain, abdominal distention, fever, vomiting, ileus, electrolyte imbalances, shock, sepsis, anorexia, dehydration, diarrhea, lymphadenopathy, prolonged capillary refill time (CRT), poor body condition, weight loss

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d. Physical examination/diagnosis: based on clinical signs and physical examination; radiographs may show free fluid or gas; may need to do paracentesis if ascites or hemoabdomen present e. Differential diagnoses: bloat, hardware disease, pancreatitis, gastric obstruction f. Treatment: supportive therapy (fluids, pain medication); antibiotics if appropriate; surgical exploration with removal and correction of inciting problem if can be determined g. Prevention: removal of foreign bodies (i.e., sponges) during surgery h. Species differences: orangutan, common marmoset, baboon, macaque, tamarin, mangabey, chimpanzee, squirrel monkey 4. Rectal prolapse (White 2011; Johnson-Delaney 1999, 7–10; Kalema-Zikusoka and Lowenstine 2001, 509–513; Kalema 1999, 251; Chi and Ju 1997, 132–136; Tribe 1965, 551) a. Definition: protrusion of distal colon from the rectum b. Causes/pathophysiology: commonly seen in animals that are stressed, have recurrent gastroenteritis, or high parasitic loads; seen in animals with chronic diarrhea or constipation. Often seen in conditions that cause tenesmus c. Clinical signs: visible tissue protruding from rectum, blood in stool and beneath cage d. Physical examination/diagnosis: tissue protruding from rectum; collect feces for ova and parasite tests/fecal flotation to determine parasite load e. Differential diagnoses: tissue sloughing of the digestive tract due to infection (i.e., Shigella, Yersinia) f. Treatment: can self-reduce or be manually reduced (facilitate with cool fluids or lubricant). May need to place pursestring suture to ensure tissue stays in (stay suture later removed when underlying condition resolved or after 7 days). Nonreducible or severely traumatized rectal prolapses require surgical resection. May require pain management, treatment of bacterial or parasitic infection, supportive therapy. If caused by constipation, may need to supplement diet with fiber or fruit (prunes, raisins, etc.). In marmosets, constipation can lead to fatal obstruction of intestines.

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g. Prevention: regular deworming of individuals, reduce stress h. Species differences: gorilla, orangutan, macaque, baboon, marmoset

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Bethune, M. T., J. T. Borda, E. Ribka, M. X. Liu, K. PhillippiFalkenstein, R. J. Jandacek, G. G. M. Doxiadis, G. M. Gray, C. Khosla, and K. Sestak. 2008. A non-human primate model for gluten sensitivity. Plos One 3, (2): e1614. Bolomo, N., J. Milei, P. M. Cossio, E. Segura, R. P. Laguens, L. M. Fernandez, and R. M. Arana. 1980. Experimental Chagas disease in a South American primate (Cebus sp.). Medicina 40: 667–72. Boyce, L., and C. Miller. 1980. Acute gastric dilatation with herniation in a rhesus monkey. Veterinary Medicine/Small Animal Clinician 75: 130–1. Brack, M. 1998. Gastrointestinal tumors observed in nonhuman primates at the German Primate Center. Journal of Medical Primatology 27 (6): 319–24. Brady, A. G., and D. G. Morton, eds. 1998. Digestive system. In Nonhuman primates in biomedical research: diseases, eds. B. T. Bennett, C. R. Abee, and R. Henrickson. San Diego, CA: Academic Press, pp. 377–414. Bronson, R. T., M. O’Connell, N. Klepper-Kilgore, L. V. Chalifoux, and P. Sehgal. 1982. Fatal fasting syndrome of obese macaques. Laboratory Animal Science 32: 187–92. Brown, E. A., R. W. Jansen, and S. M. Lemon. 1989. Characterization of a simian hepatitis A virus (HAV): antigenic and genetic comparison with human HAV. Journal of Virology 63 (11): 4932–7. Bunton, T. E., and C. X. Bacmeister. 1989. Diverticulosis and colonic leiomyosarcoma in an aged rhesus macaque. Veterinary Pathology 26 (4): 351–2. Burdick, J., R. Cianciolo, L. Meunier, and R. Coatney. 2010. Obstructive urolithiasis in a cynomolgus macaque (Macaca fascicularis). Journal of the American Association for Laboratory Animal Science 49 (1): 90. Burke, D. S., and G. B. Heisey. 1984. Wild Malaysian cynomolgus monkeys are exposed to hepatitis A virus. American Journal of Tropical Medicine and Hygiene 33 (5): 940–4. Bush, M., B. B. Beck, J. Dietz, A. Baker, A. E. James Jr., A. Pissinatti, L. G. Phillips Jr., and R. J. Montali. 1996. Radiographic evaluation of diaphragmatic defects in golden lion tamarins (Leontopithecus rosalia rosalia): implications for reintroduction. Journal of Zoo and Wildlife Medicine 27 (3): 346–57. Butler, T. M., and R. J. Haines Jr. 1987. Gastric trichobezoar in a baboon. Laboratory Animal Science 37 (2): 232–3.

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Clapp, N. K., C. C. Lushbaugh, G. L. Humason, B. L. Gangaware, and M. A. Henke. 1985. Natural history and pathology of colon cancer in Saguinus oedipus oedipus. Digestive Diseases and Sciences 30 (12, Suppl.): 107S–13S. Clarke, C. L., M. A. Eckhaus, P. M. Zerfas, and W. R. Elkins. 2008. Peripheral edema with hypoalbuminemia in a nonhuman primate infected with simian-human immunodeficiency virus: a case report. Journal of the American Association for Laboratory Animal Science 47 (1): 42–8. Clayton, L., N. Mylniczenko, and M. Greenwell. 2003. Ante-mortem diagnosis and management options for renal disease in a pygmy marmoset (Callithrix pygmaea). Paper presented at AAZV Annual Conference Proceedings, Minneapolis, MN, October. Costall, B., A. M. Domeney, and R. J. Naylor. 1986. A model of nausea and emesis in the common marmoset. British Journal of Pharmacology 88 (Suppl.): 375P. Couillard, N., J. Wallace, R. Young, and N. Kock. 2004. Cecal volvulus in two African green monkeys (Cercopithecus aethiops sabeus). Comparative Medicine 54 (3): 324–6. Dabic, D., S. Cerovic, B. Azanjac, B. Maric, and I. Kostic. 2010. Prolene Hernia System, Ultrapro Hernia System and 3D patch devices in the treatment of inguinal, femoral, umbilical and small incisional hernias in outpatient surgery. Acta Chirurgica Iugoslavica 57 (2): 49–54. Dalgard, D. W., R. H. Adamson, and M. Vermess. 1975. Diaphragmatic herniation of the liver in macaques demonstrated by intravenous hepatography. Laboratory Animal Science 25: 753–6. DePaoli, A., and H. M. McClure. 1982. Gastrointestinal neoplasms in nonhuman primates: a review and report of eleven new cases. Veterinary Pathology 19 (Suppl. 7): 104–25. Doepel, F. M., M. R. Anver, and G. L. Hofing. 1980. Pancreatitis in two New World monkeys. Veterinary Pathology 17: 505–8. Dubois, A., D. E. Berg, E. T. Incecik, N. Fiala, L. M. Heman-Ackah, G. I. Perez-Perez, and M. J. Blaser. 1996. Transient and persistent experimental infection of nonhuman primates with Helicobacter pylori: implications for human disease. Infection and Immunity 64 (8): 2885–91. Eichburg. 1980. Hepatitis A and B: serologic survey of human and nonhuman primate sera. Laboratory Animal Science 30 (3): 541–3.

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Eisele, P. H., J. E. Markovits, and J. R. Paul-Murphy. 1991. Partial colectomy for treating acquired megacolon in long-tailed macaques. Laboratory Animal Science 41 (5): 436–41. Elmore, D. B., J. H. Anderson, D. W. Hird, K. D. Sanders, and N. W. Lerche. 1992. Diarrhea rates and risk factors for developing chronic diarrhea in infant and juvenile rhesus monkeys. Laboratory Animal Science 42 (4): 356–9. Elwell, M. R., and A. DePaoli. 1978. Gastric dilatation and volvulus in a squirrel monkey. Journal of the American Veterinary Medical Association 173: 1235–6. Etheridge, M. E., and J. O’Malley. 1996. Diarrhea and peritonitis due to traumatic perforation of the stomach in a rhesus macaque (hardware disease). Contemporary Topics in Laboratory Animal Science 35 (5): 57–9. Faltas, N. H. 2000. Urolithiasis in cynomolgus monkey (Macaca fascicularis): a case report. Contemporary Topics in Laboratory Animal Science 39(5): 18–9. Fanton, J. W., M. G. Yochmowitz, and R. E. Cordts. 1987. Acute gastric dilatation in rhesus monkeys: evaluation of abnormal gastric motility as an etiologic factor. Laboratory Animal Science 37 (4): 524. Farah, I. O., G. K. Chege, and A. M. Riday. 1993. Acute gastric dilation in two black and white colobus monkeys. Journal of Medical Primatology 22 (4): 278–9. Fox, J. G., and W. C. Hall. 1970. Fluke (Gastrodiscoides hominis) infection in a rhesus monkey with related intussusception of the colon. Journal of the American Veterinary Medical Association 157: 714–6. Fox, J. G., L. Handt, S. L. Xu, Z. L. Shen, F. E. Dewhirst, B. J. Paster, C. Dangler, K. Lodge, S. Motzel, and H. Klein. 2001. Novel Helicobacter species isolated from rhesus monkeys with chronic idiopathic colitis. Journal of Medical Microbiology 50 (5): 421–9. Fraser. 1988. Case report: diverticulosis of the colon in a cynomolgus monkey. TPC NEWS 7 (1): 20. Gaertner, D. J., B. Lytton, and S. Morgenstern. 1991. Perineal urinary bladder diverticulum resulting in partial urinary obstruction in a rhesus monkey. Journal of the American Veterinary Medical Association 199 (12): 1772–4. Garcia, N., A. Sanchez, L. Martinez, J. Martinez, A. Munoz, and P. Ramirez. 2006. Clinicopathological studies of acute gastric dilatation in captive baboons. Folia Primatologica 77 (4): 313.

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Garner, M. M., J. E. Wynne, R. F. Aguilar, J. T. Raymond, L. J. Lowenstine, and R. W. Nordhausen. 2003. Glomerular atherosclerosis and nephrosclerosis in howler monkeys. Paper presented at AAZV Annual Conference Proceedings, Minneapolis, MN, October. Gillin, A. G., A. F. Phippard, J. F. Thompson, W. J. Harewood, R. C. Waugh, and J. S. Horvath. 1990. Gastric haemorrhage and perforation caused by a trichobezoar in a baboon (Papio hamadryas). Laboratory Animals 24 (2): 180–2. Gliatto, J. M., and R. T. Bronson. 1993. Fatal fasting syndrome of obese macaques. In Nonhuman primates I, ed. R. D. Hunt. Berlin: Springer-Verlag, 198–202. Glover, E. J., M. M. Leland, E. J. Dick Jr., and G. B. Hubbard. 2008. Gastroesophageal reflux disease in baboons (Papio sp.): a new animal model. Journal of Medical Primatology 37 (1): 18–25. Glover, E. J., M. M. Leland, and G. B. Hubbard. 2005. An association between gastric regurgitation and disease in nonhuman primates (Papio spp., Macaca nemestrina, Cercopithecus aethiops). American Journal of Primatology 66 (Suppl. 1): 174. Goldschmidt, B., C. A. Lopes, M. Moura, D. M. Nogueira, M. A. Goncalves, D. M. Fasano, M. C. Andrade, L. W. Nascimento, and A. M. Marinho. 2010. Cleft lip and palate associated with other malformations in a neotropical primate (Saimiri ustus). Journal of the American Association for Laboratory Animal Science 49 (3): 357–60. Goldston, R. T., and A. B. Few. 1974. Acute gastric dilatation in subhuman primates. Paper presented at AAZV Annual Proceedings, Atlanta, GA, November. Gozalo, A., and E. Montoya. 1992. Mortality causes of the moustached tamarin (Saguinus mystax) in captivity. Journal of Medical Primatology 21 (1): 35–8. Hahn, N. E., D. Lau, K. Eckert, and H. Markowitz. 2000. Environmental enrichment-related injury in a macaque (Macaca fascicularis): intestinal linear foreign body. Comparative Medicine 50 (5): 556–8. Harper, J. S. III, M. R. Johnston, D. L. Sly, and W. T. London. 1982. Successful treatment of an esophageal stricture in a chimpanzee. American Journal of Primatology 3 (1–4): 321–6. Hayama, S., R. Akamatsu, M. Kishimoto, M. Suzuki, and H. Nigi. 1988. A case of diverticular disease of the colon in a Japanese monkey (Macaca fuscata). Primates 29 (3): 423–6.

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Hendrickx, A. G., and R. F. Gasser. 1967. A description of a diaphragmatic hernia in a sixteen week baboon fetus (Papio sp.). Folia Primatologica 7: 66–74. Hird, D. W., J. H. Anderson, and J. T. Bielitzki. 1984. Diarrhea in nonhuman primates: a survey of primate colonies for incidence rates and clinical opinion. Laboratory Animal Science 34 (5): 465–70. Howell, S. M., J. Fritz, S. Downing, and M. Bunuel. 1997. Treating chronic regurgitation behavior: a case study. Lab Animal 26 (2): 30–3. Hubbard, G. B., D. R. Lee, K. E. Steele, S. Lee, A. A. Binhazim, and K. M. Brasky. 2001. Spontaneous amyloidosis in twelve chimpanzees, Pan troglodytes. Journal of Medical Primatology 30(5): 260–7. Hubbard, G. B., K. E. Steele, Davis, K. J. III, and M. M. Leland. 2002. Spontaneous pancreatic islet amyloidosis in 40 baboons. Journal of Medical Primatology 31 (2): 84–90. Hukkanen, R. R., H. D. Liggitt, D. M. Anderson, and S. T. Kelley. 2006. Detection of systemic amyloidosis in the pig-tailed macaque (Macaca nemestrina). Comparative Medicine 56(2): 119–27. Jaax, G. P., G. A. McNamee Jr., J. C. Donovan, W. S. Stokes, R. D. Montrey, and H. Rozmiarek. 1982. An incarcerated inguinal hernia involving the urinary bladder in a cynomolgus monkey (Macaca fascicularis). Fort Detrick, MD: Defense Technical Information Center. Johnson, L. D., L. M. Ausma, R. M. Rolland, L. V. Chalifoux, and R. G. Russell. 2001. Campylobacter-induced enteritis and diarrhea in captive cotton-top tamarins. During the first year of life. Comparative Medicine 51 (3): 257. Johnson, L. D., L. M. Ausman, P. K. Sehgal, and N. W. King. 1996. A perspective of the epidemiology of colitis and colon cancer in the cotton-top tamarin. Gastroenterology 110 (1): 102–15. Johnson, E. H., S. E. Morgenstern, J. M. Perham, and S. W. Barthold. 1996. Colonic adenocarcinoma in a rhesus macaque (Macaca mulatta). Journal of Medical Primatology 25 (6): 435–8. Johnson, P. T. 1980. Acute gastric dilatation in a squirrel monkey. Laboratory Primate Newsletter 19 (1): 6. Johnson-Delaney, C. 1999. Surgical procedures in nonhuman primates: [rectal prolapse reduction; scrotal hernia repair]. Exotic DVM 1 (4): 7–10.

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Marsilio, D. L., and C. D. Waitt. 2009. The impact of browse and fruit consumption on regurgitation and reingestion in captive western lowland gorillas (Gorilla gorilla gorilla). Folia Primatologica 80 (2): 164–5. Matsell, D. G., A. Mok, and A. F. Tarantal. 2002. Altered primate glomerular development due to in utero urinary tract obstruction. Kidney International 61 (4): 1263–9. McTighe, M. S., and M. Feurtado. 2008. Trichobezoar prevention using soy lecithin supplementation in galagos (Otolemur garnetti). Journal of the American Association for Laboratory Animal Science 47 (1): 50. Mejido, D. C., E. J. Dick Jr., P. C. Williams, R. M. Sharp, M. C. Andrade, C. D. DiCarlo, and G. B. Hubbard. 2009. Trichobezoars in baboons. Journal of Medical Primatology 38 (5): 302–9. Montali, R. J., E. C. Ramsay, C. B. Stephensen, M. Worley, J. A. Davis, and K. V. Holmes. 1989. A new transmissible viral hepatitis of marmosets and tamarins. Journal of Infectious Diseases 160 (5): 759–65. Mook, D. M. 2002. Gastric trichobezoars in a rhesus macaque (Macaca mulatta). Comparative Medicine 52 (6): 560–2. Morgan, R., ed. 1992. The handbook of small animal practice. 2nd ed. New York: Churchill Livingston. Morgan, B. S., T. Watcyn-Jones, and J. P. Garner. 2010. Traumatic diaphragmatic injury. Journal of the Royal Army Medical Corps 156 (3): 139–44. Murray, S., J. M. Zdziarski, M. Bush, S. B. Citino, F. Y. Schulman, and R. Montali. 2000. Diverticulitis with rupture and fatal peritonitis in a Sumatran orangutan (Pongo pygmaeus). Comparative Medicine 50 (4): 452–4. Naumenko, E. S., and R. I. Krylova. 2003. [Amyloidosis in macaques in adler primatological center.]. Byulleten’ Eksperimental’Noi Biologii I Meditsiny 136 (7): 92–5. Nolan, T. E., L. Schaffer, and P. A. Conti. 1988. A gastric trichobezoar in a chimpanzee. Journal of Medical Primatology 17 (1): 63–5. Normile, H. J., H. J. Altman, M. J. Callahan, and R. E. Davis. 1992. Ondansetron improves short-term memory and blocks cholinomimetic-induced emesis in rhesus monkeys. Society for Neuroscience Abstracts 18 (Pt. 1): 524.

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O’Farrell, L., J. W. Griffith, M. Hargaden, J. U. Dennis, A. U. Hoglund, C. A. Johnson, S. W. Tobias, and C. M. Lang. 1996. Diagnostic exercise: megacolon in a cynomolgus monkey. Laboratory Animal Science 46 (1): 96–7. Okui, A., Y. Fukuda, I. Yamamoto, S. Shintani, and T. Shimoyama. 1998. Helicobacter pylori infection affects gastric ulcer healing in Japanese monkeys. Journal of Gastroenterology 33 (Suppl. X): 26–30. Ooms, T. G., L. C. Halliday, T. Hewett, V. E. Valli, and J. D. Fortman. 2005. Polycystic kidney disease and chronic progressive nephropathy in a stump-tailed macaque (Macaca arctoides) colony: clinical and pathological findings. Contemporary Topics in Laboratory Animal Science 44 (4): 73. Ordy, J. M., and K. R. Brizzee. 1980. Motion sickness in the squirrel monkey. Aviation, Space, and Environmental Medicine 51 (3): 215–23. O’Sullivan, M. G., and C. S. Carlson. 2001. Colonic adenocarcinoma in rhesus macaques. Journal of Comparative Pathology 124 (2–3): 212–5. Owens, J. M. 1982. Radiographic interpretation for the small animal clinician. St. Louis, MO: Ralston Purina. Parker, G. A., C. J. Gilmore, and A. Dubois. 1981. Spontaneous gastric ulcers in a rhesus monkey. Brain Research Bulletin 6 (5): 445–7. Pisharath, H. R., T. K. Cooper, A. K. Brice, R. E. Cianciolo, A. L. Pistorio, L. M. Wachtman, J. L. Mankowski, and C. E. Newcomer. 2005. Septicemia and peritonitis in a colony of common marmosets (Callithrix jacchus) secondary to Klebsiella pneumoniae infection. Contemporary Topics in Laboratory Animal Science 44 (1): 35–7. Pollock, P. J., R. Doyle, E. Tobin, K. Davison, and J. Bainbridge. 2008. Repeat laparotomy for the treatment of septic peritonitis in a Bornean orangutan (Pongo pygmaeus pygmaeus). Journal of Zoo and Wildlife Medicine 39 (3): 476–9. Pryor, W. H. J., C. P. Chang, and G. L. Raulston. 1969. Urolithiasis in a Taiwan monkey (Macaca cyclopis). A literature review and case report. Laboratory Animal Care 19: 862–5. Ramachandra, S. G., V. Ramesh, and A. J. Rao. 1995. Urolithiasis in a bonnet monkey: a case report. Indian Veterinary Journal 72 (7): 778–80.

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Randolph, J., M. Bush, M. Abramowitz, D. Kleiman, and R. J. Montali. 1981. Surgical correction of familial diaphragmatic hernia of morgagni in the golden lion tamarin. Journal of Pediatric Surgery 16: 396–401. Rawlings, C. A., J. H. Kirk, J. F. Harwell Jr., and W. F. Capps Jr. 1971. Indirect inguinal hernia in two rhesus monkeys. Journal of the American Veterinary Medical Association 159: 621–2. Reinhardt, V., A. Reinhardt, and D. Houser. 1986. Hair pulling and eating in captive rhesus monkey troops. Folia Primatologica 47 (2–3): 158–64. Rife, C. C. 1951. Tubercular peritonitis in a chimpanzee. Georgia Veterinarian 3 (4): 10. Roberts, J. A. 1976. Hydronephrosis of pregnancy. Urology 8: 1–4. Roberts, J. A., and R. H. Wolf. 1971. Hydronephrosis of pregnancy: a naturally occurring disorder in non-human primates closely resembling that in man. Folia Primatologica 15: 143–7. Robertson, B. H. 2001. Viral hepatitis and primates: historical and molecular analysis of human and nonhuman primate hepatitis A, B, and the GB-related viruses. Journal of Viral Hepatitis 8 (4): 233–42. Rodriguez, N. A., K. D. Garcia, J. D. Fortman, T. A. Hewett, R. M. Bunte, and B. T. Bennett. 2002. Clinical and histopathological evaluation of 13 cases of adenocarcinoma in aged rhesus macaques (Macaca mulatta). Journal of Medical Primatology 31 (2): 74–83. Rosenberg, D. P., J. H. Anderson, and R. V. Henrickson. 1979. Acute pancreatitis in a baboon. Journal of the American Veterinary Medical Association 175: 988–9. Rubio, C. A., and G. B. Hubbard. 2001. Chronic colitis in baboons: similarities with chronic colitis in humans. In Vivo 15 (1): 109–16. Rubio, C. A., and G. B. Hubbard. 2002. Chronic colitis in Macaca fascicularis: similarities with chronic colitis in humans. In Vivo 16 (3): 191–5. Sa-nguanmoo, P., P. Rianthavorn, S. Amornsawadwattana, and Y. Poovorawan. 2009. Hepatitis B virus infection in non-human primates. Acta Virologica 53 (2): 73–82. Sa-nguanmoo, P., N. Thawornsuk, P. Rianthavorn, A. Sommanustweechai, P. Ratanakorn, and Y. Poovorawan. 2010. High prevalence of antibodies against hepatitis A virus among captive nonhuman primates. Primates 51 (2): 167–70.

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Shevtsova, Z. V., B. A. Lapin, N. V. Doroshenko, R. I. Krilova, L. I. Korzaja, I. B. Lomovskaya, Z. N. Dzhelieva, et al. 1988. Spontaneous and experimental hepatitis A in old world monkeys. Journal of Medical Primatology 17 (4): 177–94. Siebert, J. R., B. Williams, D. Collins, L. A. Winkler, and D. R. Swindler. 1998. Spontaneous cleft palate in a newborn gorilla (Gorilla gorilla gorilla). The Cleft Palate-Craniofacial Journal: Official Publication of the American Cleft Palate-Craniofacial Association 35 (5): 436–41. Simmons, H. A., and J. A. Mattison. 2010. The incidence of spontaneous neoplasia in two populations of captive rhesus macaques (Macaca mulatta). Antioxidants & Redox Signaling (Advance online publication): online. Simmons, L. G. 1973. Fatality in an infant gorilla due to acute gastric dilitation. Paper presented at AAZV Annual Proceedings, Columbus, OH, October. Slighter, R. G., J. P. Kimball, T. A. Barbolt, A. D. Sherer, and H. P. Drobeck. 1988. Enzootic hepatitis A infection in cynomolgus monkeys (Macaca fascicularis). American Journal of Primatology 14 (1): 73–81. Stein, F. J., D. H. Lewis, G. G. Stott, and R. F. Sis. 1981. Acute gastric dilatation in common marmosets (Callithrix jacchus). Laboratory Animal Science 31: 522–3. Steinhausen, M., F. D. Dallenbach, R. Dussel, and D. Nelinski. 1981. Pathophysiological mechanisms of acute renal failure. Contributions to Nephrology 25: 151–6. Strait, K. R., and J. L. Orkin. 2007. Scrotal herniation of the bladder in a squirrel monkey (Saimiri scieueus). Journal of the American Association for Laboratory Animal Science 46 (4): 107. Struck, K., E. N. Videan, J. Fritz, and J. Murphy. 2007. Attempting to reduce regurgitation and reingestion in a captive chimpanzee through increased feeding opportunities: a case study. Lab Animal 36 (1): 35–8. Sulistiawati, E. 1998. [Case report: Trichobezoar in Tarsius sp.]. Jurnal Primatologi Indonesia 2 (1): 13–5. Swenson, R. B., and M. E. Keeling. 1974. Hiatal hernia in a chimpanzee. Paper presented at AAZV Annual Proceedings, Atlanta, GA, November.

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Swindler, D. R., and O. M. Merrill. 1971. Spontaneous cleft lip and palate in a living nonhuman primate, Macaca mulatta. American Journal of Physical Anthropology 34 (3): 435–9. Taylor, A. F., M. Smith, and J. W. Eichberg. 1989. Inguinal hernial surgery in an infant chimpanzee. Journal of Medical Primatology 18 (5): 415–7. Tribe, G. W. 1965. Rectal prolapse in a Macaca mulatta monkey. Veterinary Record 77: 551. Tsuchitani, M., and I. Narama. 1988. Chronic pancreatitis in macaca monkeys. Japanese Journal of Veterinary Science 50 (2): 439–44. Uno, H., P. Alsum, M. L. Zimbric, W. D. Houser, J. A. Thomson, and J. W. Kemnitz. 1998. Colon cancer in aged captive rhesus monkeys (Macaca mulatta). American Journal of Primatology 44(1): 19–27. Valverde, C. R., R. P. Tarara, S. M. Griffey, and J. A. Roberts. 2000. Spontaneous intestinal adenocarcinoma in geriatric macaques (Macaca sp.). Comparative Medicine 50 (5): 540–4. Vielgrader, H., U. Denison, T. Voracek, and W. Zenker. 2002. Case report of a hernia inguinalis and a hernia scrotalis of a Mandrillus sphinx. Paper presented at European Association of Zoo and Wildlife Veterinarians (EAZWV) 4th Scientific Meeting, Heidelberg, Germany, May. Walker-Renard, P. 1993. Update on the medicinal management of phytobezoars. The American Journal of Gastroenterology 88 (10): 1663–6. Warren, R. G., and A. Piccolie. 1979. Bilateral inguinal hernia in a pigtailed monkey (Macaca nemestrina). Laboratory Animal Science 29: 400–1. Watts, J. W. 1935. Influence of the cerebral cortex on GI movement. Journal of the American Medical Association 104 (5): 355–7. White, M. E. Consultant: a diagnostic support system for veterinary medicine. 2011. Available from http://www.vet.cornell.edu/consultant/Consult.asp (accessed January 3, 2011). Whitney, R. A. Jr., and S. M. Kruckenberg. 1967. Pentastomid infection associated with peritonitis in mangabey monkeys. Journal of the American Veterinary Medical Association 151: 907–8.

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Williams-Blangero, S., J. Blangero, K. K. Murthy, and R. E. Lanford. 1996. Genetic analysis of serum alanine transaminase activity in normal and hepatitis C virus-infected chimpanzees: an application of research-oriented genetic management. Laboratory Animal Science 46 (1): 26–30. Wolfe-Coote, S., ed. 2005. The laboratory primate. San Diego, CA: Elsevier Academic Press. Wood, J. D., O. C. Peck, K. S. Tefend, M. J. Stonerook, D. A. Caniano, K. H. Mutabagani, S. Lhotak, and H. M. Sharma. 2000. Evidence that colitis is initiated by environmental stress and sustained by fecal factors in the cotton-top tamarin (Saguinus oedipus). Digestive Diseases and Sciences 45 (2): 385–93.

6 thorax conditions Melissa A. de la Garza

upper airway conditions 1. Polyps (nasal pharyngeal, sinusoidal) (White 2011; Van Zele et al. 2010, 1069–1076; Rastogi, Murthy, and Vinudha 2009, 380–382; Wilczynski et al. 2005, 430–431; Dumonceaux et al. 1997, 215–219; Dumonceaux et al. 1995, 269–270; Bennett et al. 1998, 512; Anonymous 2011b) a. Definition: growths originating from the mucous membrane in the nasal cavity, pharyngeal sinusoidal tissue b. Causes/pathophysiology: infectious, environmental irritant, allergic, parasites c. Clinical signs: labored breathing, facial swelling, stridor, nasal discharge (may be bloody or purulent), sneezing, coughing, neurological signs, anorexia, depression, pain, weight loss, anosmia; continued expansion may cause occlusion d. Physical examination findings/diagnostics: obstructed airway may be evident on exam or imaging; cells of origin may be identified by biopsy or analysis of exudate; complete blood count (CBC) could rule out infectious process 103

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pocket handbook of nonhuman primate clinical medicine e. Differential diagnoses: infection, inflammation, tumor, foreign body, neurological disease, abscess, dental disease f. Treatment: steroids, anti-inflammatory drugs, antimicrobials, excision, supportive care g. Prevention: none h. Species differences: chimpanzees

2. Rhinitis/pharyngitis/sinusitis/tonsillitis (White 2011; Spelman 1999, 1–4; Doyle et al. 1989, 304; Sumby, Tart, and Musser 2007, 255–268; Virtaneva et al. 2005, 9014–9019; Cambre et al. 1995, 144–151; Cambre 1986, 182; Bennett et al. 1998, 512; Anonymous 2011b) a. Definition: inflammation or infection of these areas resulting in congestion, swelling, drainage, changes in breathing patterns, and discomfort b. Causes/pathophysiology: infectious, allergic, nonallergic (vasomotor), autoimmune, immunocompromise, injury to or compromise of mucosal surfaces, prolonged or inappropriate antibiotic use c. Clinical signs: abnormal breathing, stridor, facial swelling, nasal discharge (mucoid, purulent, bloody), anorexia, ocular discharge, listlessness, pain d. Physical examination findings/diagnostics: fever, hyperemia of affected areas, CBC to assess infection/inflammation and culture and sensitivity (C&S) to identify etiologic agent and determine course of treatment e. Differential diagnoses: tumor, polyp, foreign body, dental disease f. Treatment: antimicrobial therapy should be based on C&S results; steroids, anti-inflammatories, decongestants, antihistamines, supportive care, environmental controls (for allergens) g. Prevention: none h. Species differences: macaque, chimpanzee, orangutan 3. Air sacculitis (Bennett et al. 1998, 512; Spelman 1999, 1–4; Herrin, Spelman, and Wack 2002, 369–371; Bond and Montali 2001, 362; Strobert and Swenson 1979, 387–388; Gross 1978, 737–741; Giles, Hildebrandt, and Tate 1974, 610–616)

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a. Definition: infection of the laryngeal diverticula used for resonating of vocalizations in some primate species b. Causes/pathophysiology: Untreated cases may result in sepsis or bronchopneumonia. As disease progresses, fluid may become consolidated, making analysis and diagnosis difficult. c. Clinical signs: nasal discharge, halitosis, cervical swelling, cough, changes in breathing patterns (shallow and rapid), anorexia, lethargy d. Physical examination/diagnosis: Presence of fluid on palpation or ballottement of axillary regions may be evident on species with extensive air sacs; radiology may indicate fluid lines or consolidation; endoscopy with subsequent fluid analysis, ultrasound may reveal presence of fluid. e. Differential diagnoses: inflammation or infection elsewhere in the respiratory tract f. Treatment: should be aimed at clearing infection and preventing pneumonia, antibiotics based on C&S results, aspiration, irrigation and drainage, instillation of antibiotics, surgical ablations or permanent fenestrations also attempted g. Prevention: none h. Species differences: chimpanzee, pygmy chimpanzee, gorilla, orangutan, baboon, macaques, owl monkey 4. Tumors (White 2011; Bennett et al. 1998, 512; Lewis and Colgin 2005, 47–74; Anonymous 2011b) a. Definition: Rarely persistent growths in the upper respiratory tract, primarily nasal cavity, nasopharyngeal, and ethmoid regions, that do not respond to therapy may be identified as neoplastic; usually epithelial. b. Causes/pathophysiology: genetic, viral (Epstein-Barr virus) c. Clinical signs: facial swelling, nasal discharge, ocular discharge, visual impairment, pain, dyspnea, stridor, depression, anorexia, neurological signs d. Physical examination/diagnosis: depression; weight loss; imaging may identify location and extent of mass; biopsy or excision could identify cells of origin and malignancy e. Differential diagnoses: foreign body, infection, neurological disease, polyp, abscess, dental disease

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pocket handbook of nonhuman primate clinical medicine f. Treatment: steroids, anti-inflammatories, excision, supportive care g. Prevention: none h. Species differences: macaque, marmoset, baboon

lower airway conditions 1. Pneumonia (Bennett et al. 1998, 512; Szentiks et al. 2009, 236–240; Zou et al. 2010, 417–423; Psirides and Hicks 2008, 55–58; Rivas et al. 2007, 102; Wolf et al. 2006, 64–68; Baxter et al. 2005, 56–57; Umemura et al. 1985, 39–41; Fisher 1959, 154; White 2011; Thrall 2002; Anonymous 2011b) a. Definition: Inflammation of the lung usually identified as bronchopneumonia, lobar pneumonia, or interstitial pneumonia depending on location of origin in the lungs and how it spreads. Also of importance are the agents involved and their route and distribution. b. Causes/pathophysiology: Inciting agents can be infectious, toxic, irritant, immunologic, or the result of physical injury (aspiration) to lung tissue. In bronchopneumonia, aerosolized agents gain access via the bronchoalveolar junction and begin as bronchial inflammation. There is usually a secondary bacterial infection that seeds in cranioventral fields. Lobar pneumonia is similar to bronchopneumonia, but lung lobes have become consolidated, and the pathogenic agent infiltrates into the lung parenchyma. Interstitial pneumonia has a patchy or diffuse pattern easily discernible on thoracic radiographs and involves inflammation of the alveolar septa. It generally results from hematologic spread, inhalation of a toxicant or chemical exposure, or as a sequela of viral or systemic disease. c. Clinical signs: coughing, chest pain, dyspnea, fever, anorexia, depression, weight loss d. Physical examination/diagnosis: auscultation, thoracic radiographs to identify affected fields and extent and type of pneumonia; could see plural effusion (transudate or pyothorax) and interstitial (nodules, masses), alveolar (fluid; air bronchiograms), or bronchial pattern (aspiration pneumonia; chronic inflammation) or combinations;

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bronchoalveolar lavage (BAL) with fluid analysis and possible irritation; C&S of exudate e. Differential diagnoses: tuberculosis (TB) abscesses, infectious processes, metastatic disease, fungal disease f. Treatment: based on etiologic agent; antimicrobials, bronchodilators, anti-inflammatories, immunomodulatory agents, and supportive care g. Prevention: vaccination h. Species differences: chimpanzee, gorilla, squirrel monkey

macaque,

baboon,

2. Neoplasia (Bennett et al. 1998, 512; White 2011; Thrall 2002; Anonymous 2011b) a. Definition: Primary lung tumors are rare; those reported are of epithelial origin and malignant. Unlike in domestic animals, metastasis to the lung is rare in primates. b. Causes/pathophysiology: Tumors have been induced experimentally in a variety of primate species. Both spontaneous neoplastic tumors originating in the lung as well as metastatic tumors are rare. A variety of primary lung tumors and one metastatic tumor have been described. Most are carcinomas. c. Clinical signs: respiratory distress, unthriftiness, rough hair coat, cachexia, weight loss, anorexic, depression d. Physical examination/diagnosis: abnormal auscultation, interstitial pattern noted on thoracic radiographs (nodules, diffuse), abnormal blood results depending on type and severity of disease e. Differential diagnoses: infectious process (bacterial, viral, fungal) f. Treatment: palliative; surgical excision an option g. Prevention: none h. Species differences: macaque, Sykes monkey 3. Pulmonary edema (Bennett et al. 1998, 512; Fisher 1959, 154; Kenny et al. 2003, 394–399; Holcroft et al. 1977, 209– 220; White 2011; Thrall 2002; Anonymous 2011b; Nelson and Couto 1998) a. Definition: A condition arising from disturbances in pulmonary circulation. Can be acute, as in airway obstruction or stroke or brain trauma (neurogenic), or chronic, as

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b.

c.

d.

e.

f.

g. h.

in sequelae to congestive heart failure (CHF; cardiogenic). It can also result from iatrogenic hypervolemia (aggressive fluid therapy). Fluid fills lung parenchyma, and with advanced disease, it can invade the alveolar space. Pleural effusion results when pleural space is filled. Causes/pathophysiology: Generally caused from increases in hydrostatic pressure of the microvascular or permeability in air-blood barrier or both. Some inciting agents include shock, toxins, endotoxins, and caustic gasses. The end result is hypoxia and respiratory distress due to interstitial fluid accumulation in lung parenchyma. As condition progresses, fluid fills alveolar spaces as well. Clinical signs: respiratory distress, anxiety, dyspnea, tachypnea, cyanosis, hemoptysis or other nasal discharge, bloody foamy sputum, exercise intolerance, rough hair coat, unthriftiness, depression, anorexia, neurologic signs if neurogenic Physical examination/diagnosis: abnormal thoracic auscultation (crackles and third heart sounds); poor mucous membrane color; tachycardia; blanched skin; peripheral edema; radiographic lesions consistent with pulmonary edema (interstitial pattern—silhouetting of the heart, hazy parenchyma, obscure vessels lose their definition; pleural effusion if cardiogenic; alveolar pattern with air bronchiograms if noncardiogenic); abnormal electrolyte balance; others depending on inciting cause. Differential diagnoses: pneumonia, infection, other cardiovascular disease (pulmonary edema is hallmark sign of left-sided CHF) Treatment: cardiogenic responds quickly to diuretics; noncardiogenic generally does not; supportive care; others based on history and cause Prevention: cardiac evaluation, careful fluid administration Species difference: orangutan, baboon, gorilla

cardiovascular 1. Cardiomyopathy (Bennett et al. 1998, 512; Rajendra et al. 2010, 143–150; Rush et al. 2010, 395–403; Zabka, Irwin, and Albassam 2009, 814–818; Miller, Amsel, and Slusser 1995,

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583–589; Quesenberry, Liu, and Major 1987, 464; McNamara et al. 1987, 493; Corley, Shiel, and Mauck 1980; Anonymous 2011b; Nelson and Couto 1998; White 2011) a. Definition: Conditions described as either dilated or hypertrophic. In hypertrophic cardiomyopathy (HCM), there is impaired chamber filling capability due to increased wall thickness; in dilated, there is impaired systolic function due to weakened thin chamber walls. Dilated cardiomyopathy (DCM) results in concomitant HCM in other regions due to compensation. b. Causes/pathophysiology: Dilated rarely observed in nonhuman primates (NHPs); vitamin E deficiency, poorly balanced diet, parasitic infections c. Clinical signs: vague, often asymptomatic until sudden cardiac arrest d. Physical examination/diagnosis: echocardiographic changes in wall thickness and contractility, arrhythmias (PVC [premature ventricular fibrillation], A-fib [atrial fibrillation], tachypnea); evidence of left atrial and left ventricle enlargement on electrocardiogram (EKG) e. Differential diagnoses: myocardial infarction, sudden cardiac death f. Treatment: pacemaker implantation, supportive care g. Prevention: none h. Species differences: owl monkey, tamarin, baboon, gorilla, macaque, chimpanzee, wooly monkey, squirrel monkey, capuchin 2. Congestive heart failure (CHF) (Bennett et al. 1998, 512; Tolwani et al. 2000, 42–45; Miller et al. 1999, 262–267; Levin and Carey 1986, 1226–1227; Hansen, Alford, and Keeling 1984, 529–531; Thrall 2002; White 2011; Anonymous 2011a, 2011b) a. Definition: congestion, usually in the lungs, and decreased cardiac output resulting from underlying cardiovascular disease (hypertension, valvular disease, ischemia, cardiomyopathy) b. Causes/pathophysiology: Left-sided heart failure results in pulmonary edema from congestion of the pulmonary veins; right-sided heart failure generally causes fluid accumulation (venous congestion and edema) caudal to the diaphragm (ascites and hepatosplenomegaly) or can cause pleural effusion.

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pocket handbook of nonhuman primate clinical medicine c. Clinical signs: based on history and cause: dyspnea, tachypnea, anxiety, restlessness, cyanosis, poor mucous membrane color, abdominal distention, edema, unthriftiness, exercise intolerance, anorexia, depression d. Physical examination/diagnosis: abnormal thoracic auscultation (rales, crackles, muffled heart sounds); radiographic: enlarged heart and evidence of fluid in lungs (silhouetting, fluid lines, alveolar pattern or air bronchograms); arrhythmias, abnormal EKG e. Differential diagnoses: other pulmonary (inflammation, infection) or cardiac (ischemia, myocarditis, cardiomyopathy, valvular disease) conditions; hypertension f. Treatment: palliative; treat underlying cause; cardiac medications: diuretics, angiotensin-converting enzyme (ACE) inhibitors, A-II receptor blockers, β-blockers, digoxin, positive inotropes g. Prevention: thorough cardiovascular evaluation h. Species differences: chimpanzee, gorilla, baboon, macaque, squirrel monkey, owl monkey

3. Myocarditis (Bennett et al. 1998, 512; White 2011; Anonymous 2011a, 2011b) a. Definition: inflammation of myocardial tissues leading to impaired conduction and contractility; does not involve blockage of the coronary vessels b. Causes/pathophysiology: Usually results from exposure to infectious agent (bacterial; viral from encephalomyocarditis virus (EMCV); parasitic from T. cruzi; fungal), both spontaneous and experimental. Primate facilities also report a regional myocarditis resulting from recurrent catecholamine release causing short periods of intense vasoconstriction with concurrent increased contractility. Inflammation and necrosis eventually result from constant bouts of ischemia and reperfusion. May lead to systemic disease, multiorgan failure, CHF, and sudden cardiac arrest. c. Clinical signs: labored breathing, angina, signs of CHF, exercise intolerance, others based on etiologic agent d. Physical examination/diagnostics: arrhythmia, unthriftiness, seropositive for etiologic agent, T-wave abnormalities, cardiac biopsy; radiographs and ultrasound may be of benefit

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e. Differential diagnoses: CHF, valvular disease, cardiomyopathy f. Treatment: treat underlying disease (antimicrobials); palliative; treat arrhythmias (diuretic, ACE inhibitors, β-blockers) g. Prevention: thorough cardiovascular evaluation h. Species differences: capuchin, macaque, marmoset, baboon, chimpanzee, African green, squirrel monkey 4. Valvular diseases (Bennett et al. 1998, 512; Nelson and Couto 1998; White 2011; Anonymous 2011b) a. Definition: pathology associated with the heart valves (left: aortic and mitral; right: pulmonic and tricuspid); may be acquired or congenital. Any of these valves may be stenotic, resulting in pathology related to obstructed blood flow. Valvular insufficiency leads to leaky valves and subsequent regurgitation. Inflammation results in endocarditis; infectious processes result in infectious endocarditis, and if the valves are thickened, it is vegetative. If they degenerate spontaneously, it is termed endocardiosis. b. Causes/pathophysiology: As the disease state progresses, the valves become less and less able to open and close correctly, leading to a variety of complications, including regurgitation, thrombus formation, CHF, and pathology to the surrounding chambers and great vessels. c. Clinical signs: cyanosis, syncope, unthriftiness, exercise intolerance d. Physical examination/diagnosis: murmurs (mitral insufficiency: systolic with point of maximal impact (PMI) over mitral valve); radiographs and EKG may indicate enlarged heart (all chambers could be affected) or great vessels; echocardiogram will indicate turbulent blood flow e. Differential diagnoses: heart failure f. Treatment: depending on cause g. Prevention: may be none; depending on cause h. Species differences: macaque 5. Conductive diseases or cardiac dysrhythmias (EKG abnormalities) (Bennett et al. 1998, 512; Anonymous 2011b; Nelson and Couto 1998)

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pocket handbook of nonhuman primate clinical medicine a. Definition: A large and varied group of abnormalities describing the heart’s rate, rhythm, and conduction. Some abnormalities may be ascertained via auscultation, but most are picked up on EKG tracings. Many are insignificant and are simply noted and not treated; others may be life threatening. Information regarding the condition of the myocardium, ischemia, toxicities, electrolyte balance, and chamber size may also be gathered. The EKG is a valuable tool when used as part of the cardiac evaluation. b. Causes/pathophysiology: One very common arrhythmia is atrial fibrillation. It is easily diagnosed via auscultation and EKG. Drugs like digoxin are used to attempt to decrease rate, and blood thinners are used to attempt to prevent thrombosis. Some are drug induced (i.e., ketamine), so it is important to note this when using the drug. Some can mimic disease (left and right bundle branch block do not appear to cause disease but mimic ventricular hypertrophy on EKG). Other EKG findings such as S-T elevation can help diagnose myocardial infarction. c. Clinical signs: depending on underlying cause d. Physical examination/diagnosis: depending on underlying cause e. Differential diagnoses: other cardiac disorders f. Treatment: none, depends on underlying cause g. Prevention: depends on underlying cause h. Species differences: none

references Anonymous. The Mayo Clinic. 2011a. Available from http://mayoclinic.org. Anonymous. Wikipedia. 2011b. Baxter, J. R. W., D. M. Bouley, C. L. Buckmaster, B. Lifland, D. Lyons, and G. Otto. 2005. Acute pneumonia in a young male squirrel monkey (Saimiri sciureus sciureus). Contemporary Topics in Laboratory Animal Science 44 (4): 56–7. Bennett, B. T., C. R. Abee, R. Henrickson (editors). 1998. Nonhuman primates in biomedical research: diseases. San Diego, CA: Academic Press.

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Bond, M. R., and R. Montali. 2001. Air sacculitis in orangutans (preliminary results). Paper presented at the APES: Challenges for 21st Century. Conference Proceedings, 362. Brookfield, IL, November. Cambre, R. C. 1986. Ethmoiditis/sinusitis with intracranial extension in a baby orangutan. Proceedings of the Annual Meeting of the American Association of Zoo Vets 1986, p. 182. Cambre, R. C., J. E. Edwards, H. L. Wilson, J. K. Todd, J. D. Strain, R. W. Hendee, J. M. Jaskunas, R. F. Knox, and J. H. T. Chang. 1995. Maxillary and ethmoid sinusitis with orbital and intracranial extension in an infant orangutan (Pongo pygmaeus). Journal of Zoo and Wildlife Medicine 26 (1): 144–51. Corley, K. C., F. O. Shiel, and H. P. Mauck. 1980. Stress-induced cardiomyopathy in squirrel monkey. In The use of nonhuman primates in cardiovascular diseases, ed. S. S. Kalter. Austin: University of Texas Press. pp. 105–109. Doyle, W. J., D. P. Skoner, E. P. Tanner, and P. Fireman. 1989. A monkey model of allergic rhinitis. Journal of Allergy and Clinical Immunology 83 (1): 304. Dumonceaux, G. A., N. Lamberski, D. Cutter, S. M. Nagy Jr., K. Burek, and L. G. Phillips. 1997. Treatment of bilateral nasal polyposis and chronic refractory inhalant allergic rhinitis in a chimpanzee (Pan troglodytes). Journal of Zoo and Wildlife Medicine 28 (2): 215–9. Dumonceaux, G. A., L. G. Phillips, N. Lamberski, D. Clutter, and S. M. Nagy Jr. 1995. Treatment of bilateral nasal polyposis and chronic refractory inhalant allergic rhinitis in a chimpanzee (Pan troglodytes). Proceedings of the Annual Meeting of the American Association of Zoo Vets/American Association of Wildlife Vets Joint Conference Proceedings 1995. pp. 269–270. Fisher, L. 1959. Bilateral pneumonia and pulmonary edema in a gorilla. Veterinary Medicine, Small Animal Clinician 54: 154. Giles, R. C. Jr., P. K. Hildebrandt, and C. Tate. 1974. Klebsiella air sacculitis in the owl monkey (Aotus trivirgatus). Laboratory Animal Science 24: 610–6. Gross, G. S. 1978. Medical and surgical approach to laryngeal air sacculitis in baboon caused by Pasteurella mutocida. Laboratory Animal Science 28: 737–41.

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Hansen, J. F., P. L. Alford, and M. E. Keeling. 1984. Diffuse myocardial fibrosis and congestive heart failure in an adult male chimpanzee. Veterinary Pathology 21 (5): 529–31. Herrin, K. A., L. H. Spelman, and R. Wack. 2002. Surgical air sac resection as a treatment for chronic air sacculitis in great apes. Proceedings of the Annual Meeting of the American Association of Zoo Vets 2002. pp. 369–371. Holcroft, J. W., F. W. Blaisdell, D. D. Trunkey, and R. C. Lim. 1977. Intravascular coagulation and pulmonary edema in the septic baboon. Journal of Surgical Research 22: 209–20. Kenny, D. E., F. Knightly, B. Haas, L. Hergott, I. Kutinsky, and J. L. Eller. 2003. Negative-pressure pulmonary edema complicated by acute respiratory distress syndrome in an orangutan (Pongo pygmaeus abelii). Journal of Zoo and Wildlife Medicine 34 (4): 394–9. Levin, J. L., and K. D. Carey. 1986. Congestive heart failure and pneumonia in a baboon. Journal of the American Veterinary Medical Association 189 (9): 1226–7. Lewis, A. D., and L. M. A. Colgin. 2005. Pathology of noninfectious diseases of the laboratory primate. In The laboratory primate, ed. S. Wolfe-Coote, 47–74. San Diego, CA: Elsevier Academic Press. McNamara, T., E. P. Dolensek, S. K. Liu, and E. Dierenfeld. 1987. Cardiomyopathy associated with vitamin E deficiency in two mountain lowland gorillas. Proceedings, First International Conference on Zoological and Avian Medicine, East Northport, NY, AAV/AAZV. Miller, C. L., A. M. Schwartz, J. S. Barnhart Jr., and M. D. Bell. 1999. Chronic hypertension with subsequent congestive heart failure in a western lowland gorilla (Gorilla gorilla gorilla). Journal of Zoo and Wildlife Medicine 30 (2): 262–7. Miller, M., S. Amsel, and P. Slusser. 1995. Treatment of systemic hypertension and hypertrophic cardiomyopathy in a woolly monkey (Lagothrix lagotricha). Journal of Zoo and Wildlife Medicine 26 (4): 583–589. Nelson, R. W., and C. G. Couto. 1998. Small animal internal medicine. 2nd ed. St. Louis, MO: Mosby. Psirides, A. J., and P. R. Hicks. 2008. Intensive care in an unusual setting: Management of pneumonia in a chimpanzee. Critical Care and Resuscitation 10 (1): 55–8.

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Quesenberry, K. E., S. K. Liu, and A. Major. 1987. Hypertrophic cardiomyopathy with left ventricular moderator bands in a squirrel monkey (Saimiri sciureus). Paper presented at Proceedings, First International Conference on Zoological and Avian Medicine, East Northport, NY, AAV/AAZV. Rajendra, R. S., A. G. Brady, V. L. Parks, C. V. Massey, S. V. Gibson, and C. R. Abee. 2010. The normal and abnormal owl monkey (Aotus sp.) heart: Looking at cardiomyopathy changes with echocardiography and electrocardiography. Journal of Medical Primatology 39 (3): 143–50. Rastogi, R., B. T. Murthy, and Vinudha. 2009. Non-pharmacological management of nasal polyp: A case report. Indian Journal of Physiology and Pharmacology 53 (4): 380–2. Rivas, K., A. Garcia, P. R. Morales, C. A. Matchett, A. Saucedo, and J. L. Wagner. 2007. Methicillin-resistant Staphylococcus aureus (MRSA) pneumonia in rhesus macaque. Journal of the American Association for Laboratory Animal Science 46 (4): 102. Rush, E. M., A. L. Ogburn, J. Hall, D. Rush, Y. Lau, A. R. Dillon, L. Garmon, D. M. Tillson, and G. N. Kay. 2010. Surgical implantation of a cardiac resynchronization therapy device in a western lowland gorilla (Gorilla gorilla gorilla) with fibrosing cardiomyopathy. Journal of Zoo and Wildlife Medicine 41 (3): 395–403. Spelman, L. 1999. Orangutan air sacculitis/rhinitis/bronchitis: Summary of suggested diagnostic and therapeutic methods. Long Call 4 (2): 1–4. Strobert, E. A., and R. B. Swenson. 1979. Treatment regimen for air sacculitis in the chimpanzee (Pan troglodytes). Laboratory Animal Science 29: 387–8. Sumby, P., A. H. Tart, and J. M. Musser. 2007. A non-human primate model of acute group A streptococcus pharyngitis. Methods in Molecular and Cellular Biology 431: 255–68. Szentiks, C. A., S. Koendgen, S. Silinski, S. Speck, and F. H. Leendertz. 2009. Lethal pneumonia in a captive juvenile chimpanzee (Pan troglodytes) due to human-transmitted human respiratory syncytial virus (HRSV) and infection with streptococcus pneumoniae. Journal of Medical Primatology 38 (4): 236–40. Thrall, D. E. 2002. Textbook of veterinary diagnostic radiology. 4th ed. Philadelphia: Saunders.

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Tolwani, R. J., K. S. Waggie, S. L. Green, A. J. Tolwani, D. M. Lyons, and A. F. Schatzberg. 2000. Dilative cardiomyopathy leading to congestive heart failure in a male squirrel monkey (Saimiri sciureus). Journal of Medical Primatology 29 (1): 42–5. Umemura, T., H. Inagaki, M. Goryo, and C. Itakura. 1985. Aspiration pneumonia with adenovirus infection in a Japanese macaque (Macaca fuscata fuscata). Laboratory Animals 19 (1): 39–41. Van Zele, T., P. Gevaert, G. Holtappels, A. Beule, P. J. Wormald, S. Mayr, G. Hens, et al. 2010. Oral steroids and doxycycline: Two different approaches to treat nasal polyps. The Journal of Allergy and Clinical Immunology 125 (5): 1069–76. Virtaneva, K., S. F. Porcella, M. R. Graham, R. M. Ireland, C. A. Johnson, S. M. Ricklefs, I. Babar, et al. 2005. Longitudinal analysis of the group A streptococcus transcriptome in experimental pharyngitis in cynomolgus macaques. Proceedings of the National Academy of Sciences of the USA. Vol. 102 (25):9014–9. White, M. E. 2011. Cornell University College of Vet Medicine consultant: A diagnostic support system for veterinary medicine. Available from http://www.vet.cornell.edu/consultant/consult. asp (accessed January 4, 2011). Wilczynski, K., T. Janeczek, E. Prudlak, Z. Soltysiak, and A. Gucwinski. 2005. [Nasal polyps in chimpanzee.]. Polski Merkuriusz Lekarski 19 (111): 430–1. Wolf, R. E., K. M. Rogers, E. L. Blewett, D. P. Dittmer, F. D. Fakhari, C. A. Hill, S. D. Kosanke, G. L. White, and R. Eberle. 2006. A naturally occurring fatal case of herpesvirus papio 2 pneumonia in an infant baboon (Papio hamadryas anubis). Journal of the American Association for Laboratory Animal Science 45 (1): 64–8. Zabka, T. S., M. Irwin, and M. A. Albassam. 2009. Spontaneous cardiomyopathy in cynomolgus monkeys (Macaca fascicularis). Toxicologic Pathology 37 (6): 814–8. Zou, S., Q. Luo, Z. Chen, A. Cheng, M. Wang, D. Zhu, R. Jia, et al. 2010. Isolation, identification of streptococcus pneumoniae from infected rhesus monkeys and control efficacy. Journal of Medical Primatology 39 (6): 417–23.

7 bacterial, mycotic, viral, and parasitic infections Alfonso S. Gozalo and Karen R. Strait

bacterial diseases Bacterial Gastroenteritis (Shigellosis, Salmonellosis, Campylobacteriosis, Colibacilosis, and Yersiniosis) This section concerns gastroenteritis, including shigellosis, salmonellosis, campylobacteriosis, colibacillosis, and yersiniosis. Table 7.1 provides a formulary of anti-infectives and parasiticides for nonhuman primates (NHPs). 1. Definition: Shigella spp., Salmonella spp., Campylobacter jejuni, C. coli, enteropathogenic Escherichia coli, Yersinia pseudotuberculosis, and Y. enterocolitica are all Gram-negative bacteria transmitted by the fecal-oral route. Rodents are the most common source of Salmonella, rodents and birds for Yersinia. Zoonotic. 2. Causes and pathophysiology: These bacteria can cause intestinal epithelial microvillae architecture distortion and loss, leading to malabsorption and diarrhea with intestinal edema, hemorrhage, and ulceration or necrosis (Figures 7.1, 7.2, and 7.3). In some cases this is associated with cell invasion (E. coli, Shigella, Yersinia, and Campylobacter) and toxin production 117

Enrofloxacin (PO, IM; SID-BID) Erythromycin (PO, IM; BID) Furazolidone (PO; BID-QID) Gentamicin (IM; SID-TID) Kanamycin (IM; BID) Metronidazole (PO, SC; SID-TID) Neomycin (PO: SID-BID) Orbifloxacin (PO; SID) Oxytetracycline (PO, IM: SID-QOD) Penicillin G benzathine (SC, IM: EOD)

Antibacterials Amikacin (IM; SID-TID) Amoxicillin (PO, IM, IV; SID-TID) Amoxicillin/clavulonic acid (PO; BID-TID) Ampicillin (PO, IM, IV; BID-TID) Cefataxime (IM; TID) Cefazolin (IM; BID-TID) Cefpodoxine (PO; SID) Cephalexin (PO; BID-QID) Cephapirin Na (IM, IV; QID) Chloramphenicol (PO; BID-QID) Ciprofloxacin (PO; BID) Doxycycline (PO; SID-BID)

Chimpanzee

2.5–10 mg/kg 25–50 mg/kg 100 mg 3–5 mg/kg n/a 25 mg/kg n/a n/a 250–300 mg 900–1200K U

30–60K U/kg

20 mg/kg n/a 25 mg/kg n/a 250 mg n/a 50 mg/kg 16–20 mg/kg 2–5 mg/kg

25 mg/kg 50 mg/kg 20 mg/kg n/a 25–50 mg/kg n/a 25 mg/kg 10 mg/kg 4 mg/kg then 2.5

2.5–10 mg/kg 30–80 mg/kg 10 mg/kg 3–5 mg/kg n/a 25–50 mg/kg 50 mg/kg n/a 10–50 mg/kg

2.3 mg/kg 250–500 mg day 13.75 mg/kg

5 mg/kg 20–40 mg/kg 6.7–13.3 mg/kg

Macaque

Drug (Route; Frequency)

30K U/kg

25 mg/kg n/a 25 mg/kg 25 mg/kg 25 mg/kg n/a 25 mg/kg 5 mg/kg 4 mg/kg then 2.5 5 mg/kg 25–50 mg/kg n/a 3–7 mg/kg n/a 50 mg/kg n/a 5 mg/kg 25 mg/kg

10 mg/kg 20 mg/kg 20 mg/kg

Baboon

PARASITICIDES FORMULARy

AND

TABLE 7.1: NONHUMAN PRIMATE A NTI-INFECTIVES

15K U

n/a n/a n/a 1–2 mg/kg n/a 25 mg/kg n/a n/a n/a

n/a n/a n/a n/a n/a 20 mg/kg 50 mg/kg n/a n/a

n/a n/a n/a

Cebid

n/a

2.5–5 mg/kg 40–75 mg/kg 1.5 mg/kg 2 mg/kg 7.5 mg/kg n/a 10 mg/kg n/a 10 mg/kg

5 mg 75–100 mg/kg 25 mg/kg n/a n/a n/a 25–50 mg/kg n/a 8 mg/kg

2.5 mg/kg 10 mg/kg n/a

Callitrichid

n/a

5 mg/kg n/a n/a n/a n/a n/a 25 mg/kg n/a n/a

6.6 mg/kg n/a 8–16 mg/kg n/a 22 mg/kg n/a n/a n/a n/a

2.2 mg/kg 10–15 mg/kg 14 mg/kg

Prosimian

118 pocket handbook of nonhuman primate clinical medicine

Antiparasitics Albendazole (PO; SID) Chloroquine phosph. (PO; day 1 ½ dose BID; days 2–3 SID) Diethylcarbamazine (PO; SID × 10 d) Diiodohydroxyquin (SID) Fenbendazole (PO, SID) Iodoquinol (PO; SID-TID × 2–3 wk) Ivermectin (PO; SC)

0.2 mg/kg

0.2 mg/kg

0.2 mg/kg

n/a n/a n/a n/a

n/a

n/a

n/a n/a

n/a n/a

n/a n/a

n/a 25 mg/kga

n/a

30K U n/a 25 mg/kg 20 mg/kg

n/a

20 mg/kg BID x3wk 30–40 mg/kg 50 mg/kg 50 mg/kg 12 mg/kg 630 mg

n/a 500 mg

10–25 mg/kg 10 mg/kg

5–10 mg/kg 100K U

n/a 500 mg

2–20 mg/kg 20 mg/kg

Ketoconazole (PO; BID-TID) Nystatin (PO; TID)

n/a

n/a

n/a 500 mg divided SID-QID 200–400 mg 500–1000K U

600–1000K U n/a 15–20 mg/kg 960 mg

20–40K U 2.5–5 mg/kg 25–50 mg/kg TID 4–25 mg/kg

n/a 20 mg/kg

n/a

6.7–13KU/kg

Antimycotics Amphotericin B (IV; SID) Griseofulvin (PO; SID)

Penicillin G potassium (SC, IM, IV) Penicillin G procaine (SC; SID) Streptomycin (IM; BID) Tetracycline (PO; BID-TID) Trimethoprim-sulfamethoxazole (PO, SC: BID-TID) Trimethoprim-sulfadiazine (IM; QOD) Tylosin (IM; SID) Vancomycin (PO, IM, IV; BID-QID) 12 mg/kg

n/a n/a 55 mg/kg n/a

n/a

0.2 mg/kg

n/a n/a n/a

n/a n/a

n/a

n/a n/a 100 mg/kg 6–30 mg/kg

n/a

20–30 mg/kg n/a

0.2 mg/kg

n/a 50 mg/kg n/a

0.2 mg/kg

n/a n/a n/a

n/a

10 mg/kg n/a

10 mg/kg n/a

0.25–1.0 mg/kg n/a 20 mg/kg 300 mg/kg

n/a 25 mg/kg 10 mg/kg then n/a 5 mg/kg 6–50 mg/kg n/a

n/a n/a

n/a n/a

10 mg/kg QID n/a n/a n/a

n/a

15K U n/a 15 mg/kg 24 mg/kg

20KU/kg

bacterial, mycotic, viral, and parasitic infections 119

n/a n/a n/a 15–40 mg/kg n/a 11 mg/kg 50–100 mg/kg n/a

0.5 mg/kg n/a

12.5–15 mg/kg 5 mg/kg 0.3 mg/kg 11 mg/kg 50–100 mg/kg 150 mg/kg(1st); 77 mg/kg 37.5 mg

Yomesin (PO; SID × 5 d)

n/a

10 mg/kg 100 mg/kg 1250 mg 30–50 mg/kg

7.5–10 mg/kg 22–100 mg/kg 25 mg/kg 13 mg/kg

Chimpanzee

Levamisole (PO; SC; SID) Mebendazole (PO, SC; × 3 d) Mefloquine (PO; once) Metronidazole (PO; BID-TID) (× 5–10 d) Milbemycin (topical; once) Niclosamide (PO; once; repeat in 2–3 wk) Paromomycine (PO; TID) Praziquantel (PO; IM; once) Primaquine (PO; SID × 14 d) Pyrantel pamoate (PO, once) Thiabendazole (PO; SID) Tinidazole (PO; SID × 5 d)

b

Macaque

AND

Drug (Route; Frequency)

TABLE 7.1 (CONTINUED): NONHUMAN PRIMATE A NTI-INFECTIVES

n/a

n/a n/a n/a 11 mg/kg 25 mg/kg n/a

n/a n/a

n/a 100 mg/kg n/a 50 mg/kg

Baboon

n/a

25–30 mg/kg 15–20 mg/kg 0.3 mg/kg 11 mg/kg 50 mg/kg n/a

n/a 150 mg/kg

10 mg/kg 15 mg/kg 20–25 mg/kg 35–50 mg/kg

Cebid

PARASITICIDES FORMULARy

n/a

50 mg/kg n/a n/a n/a n/a 50 mg/kg

n/a n/a

n/a n/a n/a 35–50 mg/kg

Callitrichid

n/a

15 mg/kg n/a n/a 5–10 mg/kg 50 mg/kg n/a

n/a n/a

2.5 mg/kg 10–20 mg/kg n/a 25 mg/kg

Prosimian

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b

a

IV diluted to 100 ml, 50 ml given as a bolus and 50 ml given over 30 min for MRSA (methicillin-resistant Staphylococcus aureus). Extreme caution must be exerted when using levamisole since this drug has a narrow margin of safety.

n/a, dose not available.

Sources: Abee C. 1985. Medical care and management of the squirrel monkey. In Handbook of squirrel monkey research, Eds. Rosenblum LA, Coe CC. Plenum Press, New York, pp. 447–487. Association of Primate Veterinarians. Nonhuman primate drug formulary. http://www.primatevets.org/. Bauer C, and De La Garza M. Personal communication. February 7, 2012. Bernacky BJ, Gibson SV, Keeling ME, Abee CR. 2002. Nonhuman primates. In Laboratory animal medicine, 2nd ed. Eds. Fox JG, Anderson LC, Loew FM, Quimby FW. Academic Press, San Diego, CA, pp. 675–791. Blackwood RS, Tarara RP, Christe KL, Spinner A, Lerche NW. 2008. Effect of the macrolide drug tylosin on chronic diarrhea in rhesus macaques (Macaca mulatta). Comp Med 58 (1):81–87. Brady A. 2000. Research techniques for the squirrel monkey (Saimiri sp.) ILAR J 41:10–18. Chang J, Wagner JL, Kornegay RW. 1980. Fatal Yersinia pseudotuberculosis infection in captive bushbabies. JAVMA 177 (9): 820–821. Flügger M, Pfeiffer J. 1992. Eine kommentierte Bibliographie zu den Krankheiten der Lemuren. In Lemuren im Zoo. Eds. Ceska V, Hoffmann H-U, Winkelsträter K-H. Verlag Paul Parey, Berlin, pp. 273–290. Gass H. 1987. Affen. In Krankheiten der Wildtiere. Eds. Gabrisch K, Zwart P. Schlütersche, Hannover, Germany, pp. 1–43. Gozalo A, Montoya E. 1991. Klebsiella pneumoniae infection in a New World nonhuman primate center. Lab Primate Newsl 30 (2):13–15. Joslin JO. 2003. Other primates excluding great apes. In Zoo and wild animal medicine, 5th ed. Eds. Fowler ME, Miller RE. Saunders,: St. Louis, MO, pp. 346–380. Junge RE. 2003. Prosimians. In Zoo and wild animal medicine, 5th ed. Eds. Fowler ME, Miller RE. Saunders, St. Louis, MO, pp. 334–345. Loomis MR. 2003. Great apes. In Zoo and wild animal medicine, 5th ed. Eds. Fowler ME, Miller RE. Saunders, St. Louis, MO, pp. 381–396. Rensing S, Oeke A-K. 2005. Husbandry and management of New World species: marmosets and tamarins. In The laboratory primate. Ed. Wolfe-Coote S. Elsevier Academic Press, San Diego, CA, pp. 145–162. Tantalean M, Gozalo A. 1994. Parasites of the Aotus monkey. In Aotus: the owl monkey. Eds. Baer JF, Weller RE, Kakoma I. Academic Press, San Diego, CA, pp. 353–374.

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Figure 7.1 Shigellosis. Hemorrhagic enteritis caused by Shigella infection. Shigella lesions are usually limited to the cecum and colon with focal or diffuse edema, hemorrhage, and ulceration with pseudomembrane formation in severe cases.

Figure 7.2 Shigellosis. Gingivitis in a rhesus monkey caused by Shigella infection. In rhesus monkeys, gingivitis, abortion, and air sac infections can occur. (E. coli, Shigella, and Campylobacter). Shigellosis may show pseudomembrane. Salmonella and Yersinia may become septicemic, resulting in necropyogranulomatous lesions in liver and other organs.

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Figure 7.3 Campylobacteriosis. Myriad Campylobacter organisms in an intestinal crypt. The small intestine and colon are congested, edematous, and rough. The colonic mucosa is sometimes hyperplastic. (Micrograph courtesy of Dr. Cynthia Courtney.) 3. Clinical signs: Severe watery to bloody mucoid diarrhea, depression, weakness, emaciation, dehydration, vomiting. Asymptomatic carriers are common, and clinical signs may develop under stressful conditions. 4. Physical examination/diagnostics: Leukocytosis (neutrophilia), hyponatremia, hypochloremia, prerenal azotemia, and hyperfibrinogenemia; culture, isolation, and serotyping. 5. Differential diagnoses: Helicobacteriosis in macaques: gastritis, gastric ulcers, vomiting. Parasitic gastroenteritis. Measles in New World monkeys (gastroenteritis). 6. Treatment: Intestinal protectants, parenteral fluid therapy, parenteral antibiotics selected on the basis of in vitro sensitivity testing (broad-spectrum antibiotics such as ampicillin, gentamicin, trimethoprim/sulfadiazine, chloramphenicol, neomycin, and enrofloxacin reported as effective). Campylobacter: ciprofloxacin and erythromycin. Yersinia: trimethoprim/sulfadiazine and gentamicin. 7. Species differences: Yersinia: enlarged cervical lymph nodes characteristic in Saimiri monkeys. In rhesus, Shigella can cause gingivitis, abortion, and air sac infections.

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Tuberculosis and Mycobacteriosis 1. Definition: Mycobacterium tuberculosis and M. bovis are slender, straight or slightly curved acid-fast rods. Tuberculosis is very rare in wild populations. Macaques and baboons are particularly susceptible but the organism can also affect other primates and prosimians. Zoonotic. 2. Causes and pathophysiology: Transmission is by aerosol but also through direct contact, ingestion, and fomites. Mycobacteria survive macrophage phagocytosis, migrating through lymphatics to different organs, causing yellowwhite granulomas microscopically characterized by caseous centers with giant cells, lymphocytes, and epithelioid cells (Figure 7.4). Acid-fast bacilli are difficult to find in lesions. 3. Clinical signs: Vary from none to serous nasal and ocular discharge, wasting, coughing, dyspnea, or sudden death. 4. Physical examination/diagnostics: Difficult antemortem; requires repeated tuberculin tests (old mammalian tuberculin) and confirmation by radiographs, polymerase chain reaction (PCR) (best) or culture. Commercial diagnostic kits are available. Reasons for a false-negative tuberculin test: early or advanced disease, measles infection, and isoniazid therapy. False positives due to exposure to Freund’s complete adjuvant (FCA), trauma during eyelid injection, and nonspecific reactivity to the vehicle.

Figure 7.4 Tuberculosis. Extensive pulmonary inflammatory infiltrate and granulomas caused by tuberculosis infection. Granulomas are characterized by caseous centers with giant cells, lymphocytes, and epithelioid cells.

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5. Differential diagnoses: Nocardiosis, lung mites, yersiniosis, chromobacteriosis, melioidosis, systemic mycoses, and some tumors can all resemble tuberculosis (TB) lesions grossly. 6. Treatment and monitoring: Isoniazid and streptomycin. However, due to public health concerns, euthanasia is recommended. TB testing is an essential component of a preventive medicine program in NHPs. 7. Species differences: New World monkeys are more resistant to infection than Old World monkeys.

Streptococcal Pneumonia 1. Definition: Streptococcus (Diplococcus) pneumoniae is a Grampositive cocci and a common inhabitant of the upper respiratory tract. 2. Causes and pathophysiology: From the pharynx, S. pneumoniae can invade the sinuses, middle ear, and meninges or the lower respiratory tract. The capsule confers partial protection from phagocytosis. Bacteremia can occur in immunesuppressed individuals. In macaques, disease can rapidly progress to fibrinopurulent bronchopneumonia, peritonitis, arthritis, panophthalmitis, meningitis, and death (Figure 7.5). 3. Clinical signs: Depend on organ affected and may range from fever to septicemia. Sneezing, coughing, mucopurulent nasal discharge, lethargy, anorexia, and dyspnea. Occasionally central nervous system signs.

Figure 7.5 Streptococcosis. Purulent bronchopneumonia caused by Streptococcus pneumoniae.

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Figure 7.6 Klebsiellosis. Purulent bronchopneumonia caused by infection with Klebsiella pneumoniae.

Figure 7.7 Klebsiella pneumoniae hypermucoid colony isolated as a pure culture from an owl monkey with peritonitis. Hypermucoid colonies are associated with severe pathology. 4. Physical examination and diagnostics: nasal swab, culture and isolation of Gram-positive globoid to ovoid cocci appearing in chains. 5. Differential diagnoses: Klebsiella pneumoniae: purulent bronchopneumonia and purulent meningitis reported in rhesus monkeys, vervets, and chimpanzees; pneumonia, air sacculitis, meningitis, peritonitis, enteritis, cystitis, and septicemia in New World monkeys (Figures 7.6, 7.7, and 7.8). Pasteurella multocida: abscesses, pneumonia, septicemia, otitis media, meningitis, and myocarditis. Moraxella (Branhamella) catarrhalis: “bloody nose syndrome” in cynomolgus. Staphylococcus aureus: occasionally

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Figure 7.8 Meningoencephalitis. Streptococcus pneumoniae, Klebsiella pneumoniae, and Pasteurella multocida are all capable of infecting brain. Nocardia asteroides can cause brain abscesses in macaques. Occasionally, Pseudomonas aeruginosa has been reported as causing meningitis. causes suppurative bronchopneumonia, liver, renal abscesses, skin lesions, and may be isolated from joint specimens, indwelling catheters and blood. Haemophilus influenzae and Bordetella bronchiseptica: Both may cause serous to purulent sinusitis, rhinitis, tracheobronchitis, or bronchopneumonia. 6. Treatment and monitoring: antibiotics selected on the basis of in vitro sensitivity testing. Penicillin, erythromycin, enrofloxacin, chloramphenicol, and cephalexin are reported as effective and recommended pending sensitivity test results. Supportive treatment: nutritional supplements, fluids, bronchial dilators, and decongestants. 7. Species differences: In chimpanzees, upper respiratory signs followed by neurological signs (pneumococcal meningitis), otitis interna, sinusitis, and tonsillitis. In Callitrichidae and Cebidae, alpha-hemolytic and nonhemolytic streptococci are occasionally isolated from a variety of infectious conditions, like abscesses, wounds, nasal discharge, blood, pericardial fluid, trachea, oropharynx, cellulitis, and hepatic cysts.

bacterial diseases bibliography Bailey C, Mansfield K. 2010. Emerging and reemerging infectious diseases of nonhuman primates in the laboratory setting. Vet Path 47(3):462–81.

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Banish LD, Sims R, Sack D, Montali RJ, Phillips L Jr, Bush M. 1993. Prevalence of shigellosis and other enteric pathogens in a zoologic collection of primates. JAVMA 203(1):126–32. Baze WB, Bernacky BJ. 2002. Campylobacter-induced fetal death in a rhesus monkey. Vet Path 39(5):605–7. Bresnahan JF, Whitworth UG, Hayes Y, Summers E, Pollock J. 1984. Yersinia enterocolitica infection in breeding colonies of ruffed lemurs. JAVMA 185(11):1354–6. Bronson RT, May BD, Ruebner BH. 1972. An outbreak of infection by Yersinia pseudotuberculosis in nonhuman primates. Am J Pathol 69(2):289–308. Carvalho VM, Gyles CL, Ziebell K, et al. 2003. Characterization of monkey enteropathogenic Escherichia coli (EPEC) and human typical and atypical EPEC serotype isolates from neotropical nonhuman primates. J Clin Microbiol 41(3):1225–34. Chang J, Wagner JL, Kornegay RW. 1980. Fatal Yersinia pseudotuberculosis infection in captive bushbabies. JAVMA 177(9):820–1. Dance DA, King C, Aucken H, Knott CD, West PG, Pitt TL. 1992. An outbreak of melioidosis in imported primates in Britain. Vet Rec 130(24):525–9. Fourie PB, Odendaal MW. 1983. Mycobacterium tuberculosis in a closed colony of baboons (Papio ursinus). Lab Anim 17(2):125–8. Fox JG, Rohovsky MW. 1975. Meningitis caused by Klebsiella spp. in two rhesus monkeys. JAVMA 167:634–636. Gibson SV. 1998. Bacterial and mycotic diseases. In Nonhuman primates in biomedical research: diseases, eds. BT Bennett, CR Abee, R Henrickson, 59–110. San Diego, CA: Academic Press. Good RC, May BD. 1971. Respiratory pathogens in monkeys. Infect Immun 3(1):87–93. Gozalo A, Montoya E. 1991. Klebsiella pneumoniae infection in a New World nonhuman primate center. Lab Primate Newsl 30:13–20. Graczyk TK, Cranfield MR, Kempske SE, Eckhaus MA. 1995. Fulminant Streptococcus pneumoniae meningitis in a lion-tailed macaque (Macaca silenus) without detected signs. J Wildlife Dis 31(1):75–8. Liebenberg SP, Giddens WE Jr. 1985. Disseminated nocardiosis in three macaque monkeys. Lab Anim Sci 35(2):162–6.

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McClure HM, Chang J. 1976. Chromobacterium violaceum infection in a nonhuman primate (Macaca assamensis). Lab Anim Sci 26(5):807–10. Padovan D, Cantrell C. 1983. Causes of death of infant rhesus and squirrel monkeys. JAVMA 183(11):1182–4. Panarella ML, Bimes RS. 2010. A naturally occurring outbreak of tuberculosis in a group of imported cynomolgus monkeys (Macaca fascicularis). JAALAS 49(2):221–5. Pucak GJ, Orcutt RP, Judge RJ, Rendon F. 1977. Elimination of the Shigella carrier state in rhesus monkeys (Macaca mulatta) by trimethoprim-sulfamethoxazole. J Med Primatol 6(2):127–32. Sakakibara I, Sugimoto Y, Minato H, Takasaka M, Honjo S. 1984. Spontaneous nocardiosis with brain abscess caused by Nocardia asteroides in a cynomolgus monkey. J Med Primatol 13(2):89–95. Scheifele DW, Daum RS, Syriopoulou VP, Averill DR, Smith AL. 1980. Haemophilus influenzae bacteremia and meningitis in infant primates. J Lab Clin Med 95(3):450–62. Sestak K, Merritt CK, Borda J, et al. 2003. Infectious agent and immune response characteristics of chronic enterocolitis in captive rhesus macaques. Infect Immun 71(7):4079–86. Solleveld HA, van Zwieten MJ, Heidt PJ, van Eerd PM. 1984. Clinicopathologic study of six cases of meningitis and meningoencephalitis in chimpanzees (Pan troglodytes). Lab Anim Sci 34(1):86–90. Twenhafel NA, Whitehouse CA, Stevens EL, et al. 2008. Multisystemic abscesses in African green monkeys (Chlorocebus aethiops) with invasive Klebsiella pneumoniae: identification of the hypermucoviscosity phenotype. Vet Pathol 45:226–31. VandeWoude SJ, Luzarraga MB. 1991. The role of Branhamella catarrhalis in the “bloody-nose syndrome” of cynomolgus macaques. Lab Anim Sci 41(5):401–6. Ward GS, Elwell MR, Tingpalapong M, Pomsdhit J. 1985. Use of streptomycin and isoniazid during a tuberculosis epizootic in a rhesus and cynomolgus breeding colony. Lab Anim Sci 35(4):395–9. Wilson P, Weavers E, West B, Taylor M, Kavanagh J, Jones P. 1984. Mycobacterium bovis infection in primates in Dublin Zoo: epidemiological aspects and implications for management. Lab Anim 18(4):383–7.

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mycotic diseases Dermatophytosis 1. Definition: Fungal infection of keratinized skin layers. 2. Causes and pathophysiology: Several species of Trichophyton and Microsporum can invade the keratinized layer of the skin and hair and cause hyperkeratotic dermal lesions in NHPs and prosimians (Figure 7.9). Zoonotic. 3. Clinical signs: Alopecia, scaly erythematous patches, dermatitis. Head mostly affected followed by flank or, occasionally, entire body. 4. Physical examination/diagnostics: Characteristic gross skin lesions and examination of skin scrapings in wet mounts of 10% KOH and isolation in Sabouraud agar or dermatophyte test medium. 5. Differential diagnoses: Bacterial skin infections, mange, seborrheic and atopic dermatitis. 6. Treatment and monitoring: Griseofulvin orally and topical tolnaftate.

Figure 7.9 Dermatomycosis. Thickening of the epidermis with acanthosis and hyperkeratosis caused by the fungal invasion. Fungal agent is not visible with H&E (hematoxylin and eosin); special stains are required to see the fungus clearly.

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Systemic Mycosis 1. Definition: Systemic fungal infection with any of the following organisms: Coccidioides immitis, Histoplasma capsulatum var. capsulatum; H. capsulatum var. duboisii (African histoplasmosis); Cryptococcus neoformans; Blastomyces dermatiditis; Paracoccidioides brasiliensis; and Mucormycosis (Zygomycosis). Zoonotic. 2. Causes and pathophysiology: Infection occurs by inhalation of spores present in the environment and possibly other routes (oral, wounds). The infection is usually subclinical, but respiratory or disseminated disease may occur with characteristic necropurulent granulomatous inflammation with multinucleated giant cells or, in the case of Cryptococcus neoformans, gelatinous nodules or cystic areas, especially on the meninges (Figures 7.10 and 7.11). 3. Clinical signs: May not be specific; anorexia, conjunctivitis, and weight loss. 4. African histoplasmosis: Infection is usually confined to the skin. Cryptococcosis can cause central nervous system signs and ocular abnormalities. Blastomycosis: Papules or draining abscesses are found on the skin. 5. Physical examination/diagnostics: Radiographs (lung nodules, cavitations, adhesions, enlarged mediastinal lymph nodes,

Figure 7.10 Cryptococcosis. Cryptococcus neoformans organisms in brain. Sparse mononuclear inflammatory cells are observed surrounding abundant yeasts. The organism is surrounded by a thick mucin-positive capsule stained with Mucicarmine.

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Figure 7.11 Coccidiodomycosis. Coccidioides immitis in lung. Note necropurulent granulomatous inflammation. The spherules are large and double contoured. bone lysis). Serologic testing. Biopsy/necropsy with culture and isolation. Coccidioides spherules are found in the lesions, measure 10–60 μm, are double contoured, and may contain smaller endospores visible with periodic acid Schiff (PAS) stain. Histoplasma capsulatum var. capsulatum measures 2–4 μm and is thin walled compared to H. duboisii, which measures 7–15 μm and is thick walled; both visible with hematoxylin and eosin (H&E) stain. Cryptococcus neoformans organisms are 2–10 μm, single buds, surrounded by a thick mucin-positive capsule visible with Mucicarmine stain or India ink. Blastomyces dermatiditis yeasts found in the exudates are 8–25 μm, have single broad-based buds, and are visible with PAS and Gomori’s methenamine silver (GMS) stains. Paracoccidioides brasiliensis lesions contain multiple budding spherical yeast cells 8–20 μm visible with GMS and Gridley fungal stain (GFS). Mucormycosis (Zygomycosis) lesions contain thin-walled, irregularly branched, bulbous, rare septae, large fungal hyphae (7–15 μm in diameter) that are visible with H&E stain. Immunohistochemistry may be required to confirm diagnosis. 6. Differential diagnoses: Tuberculosis, atypical mycobacteria, chromobacteriosis, systemic neoplasias. 7. Treatment and monitoring: Difficult because usually monkeys show no clinical signs until the infection is severe. Ketoconazole, amphotericin B, itraconazole, saramycetin, and 5-fluorocytosine (Acontil/Roche) have been used with variable results.

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Candidiasis (Moniliasis) 1. Definition: Candida albicans is a normal inhabitant of the oral, gastrointestinal (GI) and genital tracts, and skin. Disease has been reported in NHPs and prosimians. 2. Causes and pathophysiology: Disease may occur in immunodeficient or debilitated animals on long-term antibiotic therapy, causing dysbiosis and consequently proliferation and tissue invasion with Candida organisms characterized by white pseudomembranes on oral, esophageal, and intestinal mucous membranes (Figures 7.12 and 7.13). The underlying tissues may be ulcerated. Occasional skin lesions. 3. Clinical signs: Dysphagia associated with white pseudomembranes on oral mucous membranes occurs; sometimes diarrhea. 4. Physical examination/diagnostics: Microscopic examination of wet mount scrapings from lesions in 10% NaOH, 20% KOH, or lactophenol cotton blue. Gram-positive oval budding yeast cells. Organisms can be seen on H&E but are best studied with PAS or GMS stains. Septate pseudohyphae and oval budding blastospores (3–5 μm) are seen in the superficial epithelium but rarely invade past the basement membrane. 5. Differential diagnoses: Oral lesions caused by herpes simplex, herpes B, herpes T, and measles. Dysphagia may be observed in tetanus and rabies. 6. Treatment and monitoring: Topical/Oral nystatin or ketoconazole.

Figure 7.12 Candidiasis. Esophagitis in a rhesus monkey caused by Candida albicans infection. Pseudomembrane is a characteristic lesion. (Micrograph courtesy of Dr. Cynthia Courtney.)

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Figure 7.13 Candidiasis. Esophagitis in a rhesus monkey. Gomori’s methenamine silver stain allows better visualization of the septate pseudohyphae, which are seen in the superficial epithelium. (Micrograph courtesy of Dr. Cynthia Courtney.)

mycotic diseases bibliography Bernstein JA, Didier PJ. 2009. Nonhuman primate dermatology: a literature review. Vet Dermatol 20(3):145–56. Gibson SV. 1998. Bacterial and mycotic diseases. In Nonhuman primates in biomedical research: diseases, eds. BT Bennett, CR Abee, R Henrickson, 59–110. San Diego, CA: Academic Press. Migaki G, Schmidt RE, Toft JD 2nd, Kaufmann AF. 1982. Mycotic infections of the alimentary tract of nonhuman primates: a review. Vet Pathol Suppl 7:93–103. Wilkinson LM, Wallace JM, Cline JM. 1999. Disseminated blastomycosis in a rhesus monkey (Macaca mulatta). Vet Pathol 36(5):460–2.

viral diseases Alphaherpesviruses 1. Definition: Cercopithecine herpesvirus 1, recently renamed Macacine herpesvirus 1, (herpes B, Herpes simiae, B virus) is an enveloped DNA alphaherpesvirus; macaques are natural reservoirs. Zoonotic. Other alphaherpesviruses are found in other NHP species.

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2. Causes and pathophysiology: Infection occurs through wounds or exposed mucosa, where the virus replicates infecting sensory neurons and migrating intraaxonally to the neuron cell body, remaining as a lifelong latent infection in neuron sensory ganglia. Reactivation of the virus with migration to mucosal epithelium through neuronal axons occurs periodically, usually associated with stressful events. Once in the mucosal epithelium, the virus replicates, and shedding occurs through oral or genital secretions. No, or very mild, mucosal lesions may occur during viral replication, but viral transmission can still happen. Occasionally, the virus may cause a generalized fatal infection in the natural host. In humans, the infection causes fatal encephalitis. 3. Clinical signs: Latent infection, self-limiting oral/genital vesicles/ulcers, rarely disseminated disease (hepatitis/interstitial pneumonia) (Figure 7.14). 4. Physical examination/diagnostics: Oral/genital vesicles/ ulcers may indicate infection. Confirm by serology, viral isolation, immunohistochemistry/electron microscopy. 5. Differential diagnoses: Oral candidiasis, shigellosis (gingivitis in macaques), vitamin C deficiency (gingival hemorrhages in macaques), traumatic oral lesions, and cytomegalovirus (Figure 7.15). 6. Treatment and monitoring: Acyclovir and supportive treatment.

Figure 7.14 Alphaherpesvirus (herpes T) infection in an owl monkey. Liver necrosis with multiple vacuolated hepatocytes with deep eosinophilic intranuclear inclusion bodies.

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Figure 7.15 Cytomegalovirus pneumonia. Rhesus lung with interstitial pneumonia due to cytomegalovirus infection. Note large eosinophilic intranuclear inclusion bodies. Usually asymptomatic. Clinical signs often associated with immunosuppression or intrauterine infection.

7. Species differences: Baboons and African green monkeys are reservoirs of Cercopithecine herpesvirus 2 (Herpesvirus papio 2, SA 8), which causes a subclinical infection with occasional severe genital or oral lesions. Stump-tailed macaques appear to be reservoirs of Cercopithecine herpesvirus 9 (simian varicella virus); this virus is fatal in African green monkeys, Patas, and macaques, causing disseminated vesicular exanthema and death in 48 hr. Squirrel monkeys are natural hosts for Saimirine herpesvirus 1 (Herpes tamarinus, herpes T, Herpes platyrrhine, Cebid herpesvirus 1), a usually subclinical infection with occasional oral vesicles or ulcers in its natural host but in owl monkeys, marmosets, and tamarins causing a fatal generalized disease characterized by a vesicular rash, oral vesicles, and ulcers. Human herpesvirus 1, 2 (Herpes hominus, Herpes simplex) can be transmitted from human to monkey and monkey to monkey; lesions may be local or generalized; oral vesicles and ulcers, conjunctivitis, encephalitis, and death may occur as owl monkeys, marmosets, and tamarins are susceptible to generalized disease. Human herpesvirus 3 (may be simian in origin) causes a mild self-limiting vesicular dermatitis in apes.

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Gammaherpesviruses 1. Definition: Lymphocryptoviruses (Epstein-Barr like) and rhadinoviruses (similar to human herpesvirus 8) are enveloped DNA gammaherpesviruses endemic in macaque populations and do not cause disease unless the animal is immunocompromised. Saimirine herpesvirus 2 (Herpesvirus saimiri 2, Cebid herpesvirus 2) and Ateline herpesvirus 2 (Herpesvirus ateles) are both oncogenic New World primate gammaherpesviruses. The squirrel monkey is the natural host for Saimirine herpesvirus 2, and the spider monkey (Ateles geofroyii) is the natural host for Ateline herpesvirus 2. No disease is apparent in the natural hosts. 2. Causes and pathophysiology: Gammaherpesviruses contain genes that encode viral proteins involved in cellular signaling, transformation, apoptosis modulation, and immune evasion. Most infections are asymptomatic unless the animal is immunocompromised or cross-species infection occurs. Lymphocryptovirus causes lymphadenopathy and lymphocytosis in macaques and B-cell lymphomas in immunosuppressed animals coinfected with simian immunodeficiency virus (SIV). Rhesus rhadinovirus causes marked B-cell lymphocytosis and associated hypergammaglobulinemia, lymphadenopathy, and splenomegaly when coinfected with SIV. Subcutaneous and retroperitoneal fibromatosis is also found in coinfection with SIV. Saimirine herpesvirus 2 is transmitted orally and causes lymphomas in marmosets, owl monkeys, howler monkeys, and spider monkeys. Ateline herpesvirus 2 induces lymphomas in marmosets, tamarins, and owl monkeys. 3. Clinical signs: Lymphadenopathy, hepatomegaly, splenomegaly, and leukemia. 4. Physical examination/diagnostics: Abdominal radiography, ultrasound, positron emission tomographic (PET) scan, blood smears (leukemia), biopsy. Serology, viral isolation, PCR, immunohistochemistry, and electron microscopy. 5. Differential diagnoses: Other neoplasia, hepatosplenomegaly due to other causes (TB, systemic mycosis, viral hepatitis, cytomegalovirus, malaria, leishmaniasis, amyloidosis, chronic hepatitis with portal hypertension). 6. Treatment and monitoring: Supportive.

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Monkeypox 1. Definition: Caused by an orthopoxvirus (enveloped DNA virus) immunologically related to smallpox and vaccinia. Zoonotic. 2. Causes and pathophysiology: Transmission is aerogenous but can also occur through contact and insect bites. Viremia occurs 3–4 days after infection, with virus migrating to different organs, including skin, where it replicates, causing hyperplasia and necrosis of the epidermis with swelling of keratinocytes and large eosinophilic intracytoplasmic inclusions (Guarnieri bodies) and occasional intranuclear inclusion bodies (Figure 7.16). 3. Clinical signs: Two- to three-day fever followed by skin exanthema, small papules/pustules or crusty lesions affecting buttocks, hands, feet, and oral cavity. Small cutaneous papules become pustules, covered by a crust surrounded by peripheral hyperemia; a few days later, the crusts are shed, leaving a small scar. Occasionally, facial edema, dyspnea, oral ulcers, and lymphadenopathy are seen. Usually nonfatal in apes, macaques, and African green monkeys. Spontaneous poxviral infections have been reported in Saimiri sciureus, Callithrix jacchus, and Saguinus oedipus. 4. Physical examination/diagnostics: Characteristic skin lesions suggest monkeypox. Skin lesion biopsy, serology, viral isolation, immunohistochemistry, electron microscopy.

Figure 7.16 Monkey pox infection. Skin with swelling of keratinocytes and large eosinophilic intracytoplasmic inclusions are observed (Guarnieri bodies).

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Figure 7.17 Yaba virus infection. Skin with large pleomorphic histiocytes with large intracytoplasmic eosinophilic inclusion bodies. 5. Differential diagnoses: Yaba virus: Macaques and baboons are natural hosts. Transmission unknown, suspect arthropod vector. Subcutaneous masses on feet, hands, and face (Figure 7.17). May ulcerate, regress in 6 weeks. Oral masses in baboons. Zoonotic. Tanapox virus: Affects macaques, causing small red papules on face, thorax, and perineum. Progress to raised foci. Papules become umbilicated with red margins and may ulcerate. Lesions resolve in 3–8 weeks. Zoonotic. Simian varicella virus: Disseminated vesicular exanthema, death may occur within 48 hr. 6. Treatment and monitoring: Supportive care and wide-spectrum antibiotics to prevent secondary bacterial infections.

Simian Hemorrhagic Fever Virus 1. Definition: Simian hemorrhagic fever virus (SHFV) is an enveloped RNA arterivirus with Patas, African green monkey, and baboon as reservoirs. Highly contagious in Asian macaques. 2. Causes and pathophysiology: Virus is transmitted via aerosol, direct contact, and through fomites invading macrophages, which support viral growth. Vascular endothelial damage and fragility results in capillary-venous hemorrhages in GI tract (hemorrhagic necrosis of the proximal duodenum is characteristic), liver, kidney, lung, and subcutis. Splenomegaly, disseminated intravascular coagulation, lymphoid tissue necrosis, and cortical thymic necrosis.

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3. Clinical signs: Anorexia, bleeding diathesis with fever, mild facial edema, melena, epistaxis, and death. 4. Physical examination/diagnostics: Elevated aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase. Fever, dehydration, proteinuria, cyanosis, hematuria, prolonged partial thromboplastin times, and thrombocytopenia. Serology, viral isolation, immunohistochemistry and electron microscopy. 5. Differential diagnoses: Ebola-Reston virus (filovirus): Macaque suspect reservoir causing multifocal hepatocellular necrosis, multifocal necrosis within zona glomerulosa of the adrenal gland, and mild interstitial pneumonia; these lesions distinguish Ebola-Reston from SHFV. Large eosinophilic or amphophilic intracytoplasmic inclusion bodies may be found in the liver and adrenal gland. No disease reported in humans. Marburg virus (filovirus): African green monkeys are reservoirs; no disease in monkeys but causes hemorrhagic fever in humans. 6. Treatment and monitoring: Supportive.

Measles (Rubeola) 1. Definition: Measles is an enveloped single-stranded RNA virus of the Paramyxovirus family, genus Morbillivirus. Humans are reservoirs. Measles can affect apes, macaques, baboons, African green monkeys, marmosets, owl monkeys, and squirrel monkeys. 2. Causes and pathophysiology: Aerosol transmission. Viral entry occurs through tonsils or respiratory system, replicating in regional lymph nodes, followed by viremia and spread to lymphoreticular organs and epithelial surfaces. Causes temporary immunosuppression and focal necrosis on oral mucous membranes, maculopapular to vesicular rash, interstitial pneumonia, and gastroenterocolitis. Occasionally encephalitis. Syncytial cells and intranuclear and intracytoplasmic inclusion bodies are observed microscopically (Figure 7.18). 3. Clinical signs: The disease may be subclinical or may consist of fever, maculopapular rash, conjunctivitis, facial erythema, respiratory difficulty, and diarrhea.

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Figure 7.18 Measles. Interstitial pneumonia with syncytial cells and eosinophilic intranuclear inclusion bodies. Sometimes intracytoplasmic inclusions can be seen. 4. Physical examination/diagnostics: Mild fever, cutaneous rash, dyspnea, marked leukopenia. Serology, viral isolation, immunohistochemistry, electron microscopy. 5. Differential diagnoses: Monkeypox, Tanapox virus, Yaba virus, and simian varicella virus can cause skin lesions. Shigella, Salmonella, Campylobacter, and Yersinia can resemble measles in marmosets and owl monkeys (gastroenterocolitis). 6. Treatment and monitoring: Canine distemper/measles virus vaccines induce an antibody response in rhesus. Modified– live virus vaccines can cause immunosuppression and interfere with TB testing. Treatment is usually supportive. 7. Species differences: In marmosets and owl monkeys, measles is an often-fatal gastroenterocolitis rather than a predominantly respiratory/mucocutaneous infection.

Retroviruses 1. Definition: Retroviruses are single-stranded enveloped RNA viruses; some of them associated with lymphoproliferative disease and immune deficiency in Old World monkeys and apes. 2. Causes and pathophysiology: Simian retroviruses establish lifelong persistent infections due to proviral integration into the host cell genome. Each retrovirus has different cell tropism. Simian T-cell lymphotropic virus (STLV-1): Usually a subclinical lymphoproliferative disease; occasional T-cell

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pocket handbook of nonhuman primate clinical medicine lymphomas with a high rate of infection in feral and captive Asian and African monkeys and apes. Simian type D retroviruses (SRV/D-1 and SRV/D-2): Primary cause of viral-induced immunodeficiency in captive macaque species, being endemic in several Asian macaque species, with a high prevalence in captive colonies. Transmission is horizontal and vertical. Infection can be subclinical, or some animals develop severe immunodeficiency, persistent lymphadenopathy, or retroperitoneal/subcutaneous fibromatosis. SIV: a lentivirus closely related to human HIV-1 and HIV-2. African monkeys are frequently seropositive. Species of origin identified by subscript (i.e., SIVmac, SIVcpz). Horizontal, sexual, and dam-infant transmission proposed. SIV in macaques is in most cases subclinical but may produce devastating AIDS-like disease, including lymphoid hyperplasia/depletion, nonsuppurative histiocytic meningoencephalitis, giant cell enteropathy, lung arteriopathy, thrombosis and infarcts, giant cell interstitial pneumonia, viral exanthema-perivascular lymphocytic dermatitis, and occasionally lymphomas (Figures 7.19 and 7.20). All three viruses modulate host immune response.

Figure 7.19 SIV infection. Rhesus monkey infected with SIV showing skin rash.

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Figure 7.20 SIV infection. Rhesus monkey infected with SIV showing characteristic giant cell interstitial pneumonia. (Micrograph courtesy of Dr. Cynthia Courtney.) 3. Clinical signs: STLV-1: Anorexia, depression, lymph node enlargement, hepatosplenomegaly. SRV/D-1 and SRV/D-2: Generalized lymphadenopathy or splenomegaly, weight loss, fever, persistent diarrhea, opportunistic infections, noma (cancrum oris), retroperitoneal fibromatosis, hematological abnormalities (anemia, neutropenia, lymphopenia, thrombocytopenia, pancytopenia), bone marrow hyperplasia, characteristic lymph node lesions. Retroperitoneal fibromatosis is most often associated with SRV/D-2 and subcutaneous fibromatosis with SRV/D-1 (nodules in subcutis and oral cavity). SIV: Most common opportunistic infections are Mycobacterium avium complex, cytomegalovirus, adenovirus, papovavirus, pneumocystis, cryptosporidium, cryptococcus, toxoplasma, and candidiasis. 4. Physical examination/diagnostics: Pancytopenia with abnormal hematopoiesis. Weight loss, fever, persistent diarrhea, opportunistic infections, noma (cancrum oris), retroperitoneal fibromatosis. STLV-1: Occasionally,

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pocket handbook of nonhuman primate clinical medicine multilobulated neoplastic lymphocytes are found in peripheral blood. SRV/D-1- and SRV/D-2-infected animals do not always show antibodies. PCR or virus isolation is best. Serology, immunohistochemistry, enzyme immune assay, PCR immunoblotting.

5. Differential diagnoses: Opportunistic infections might mask retroviral infection. 6. Treatment and monitoring: Supportive. Long-term treatment with Tenofovir (30 mg/kg s.c.; SID) has been reported as effective. 7. Species differences: STLV-1 in baboons resembles adult T-cell leukemia/lymphoma in humans.

Rabies 1. Definition: Rhabdovirus (enveloped RNA virus). Carnivores and bats are reservoirs. Fatal zoonotic disease. Reported in tamarins, squirrel monkeys, macaques, and chimpanzees. Unusual but must consider in outdoor housed or wild-caught monkeys. 2. Causes and pathophysiology: Transmitted through saliva, bite from a rabid animal, and aerosol. Initial viral replication occurs within myocytes at the site of entry (bite), and the virus is then transported through peripheral nerves to the central nervous system (CNS), where it infects neurons and replicates, later spreading to peripheral organs near the time of onset of clinical signs. No gross lesions. Microscopically, microglial foci, perivascular lymphocytic cuffing, and neuronal degeneration. Negri bodies are not always found. 3. Clinical signs: Salivation, aggressiveness, automutilation, paralysis of pharyngeal and pelvic muscles, or sudden death. 4. Physical examination/diagnostics: Postmortem virus antigen can be demonstrated by fluorescent antibodies by reference laboratory. 5. Differential diagnoses: other diseases that can course with behavioral/psychomotor changes (i.e., SIV encephalitis, measles encephalitis, SV40, bacterial meningoencephalitis, balamuthia amebic encephalitis, neural larva migrans, toxoplasmosis, brain tumors, tetanus). 6. Treatment and monitoring: Euthanasia. Attenuated vaccine is contraindicated as vaccine-induced disease occurred in New World species.

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Encephalomyocarditis Virus (EMCV) 1. Definition: Nonenveloped RNA virus, genus Cardiovirus, family Picornaviridae. Rodents are reservoir hosts. Causes sudden death in monkeys and apes. 2. Causes and pathophysiology: Oral transmission, possibly other routes. The virus invades and replicates in myocardial cells, causing, along with the host immune response to the infection, cardiac myofiber degeneration and necrosis with inflammatory infiltrates and myocardial edema. Clinically, signs of acute heart failure are noted in live animals. Lesions postmortem include pulmonary hemorrhage and edema, pericardial effusion, and pale areas in the myocardium. Animals that survive the acute infection usually have extensive myocardial scarring. Necrosis of the exocrine pancreas and placental infection and subsequent abortion are also observed. 3. Clinical signs: Acute dyspnea, marked depression, and death. 4. Physical examination/diagnostics: Serology, viral isolation, inmunohistochemistry, and electron microscopy. 5. Differential diagnoses: Coxsackie virus infection, toxoplasmosis, Chagas disease. Callitrichid hepatitis virus (callitrichids infected with lymphocytic choriomeningitis virus) show dyspnea, anorexia, lethargy, jaundice, and death. Subcutaneous and intramuscular hemorrhages, hepatosplenomegaly, and hepatocellular necrosis. 6. Treatment and monitoring: Supportive.

viral diseases bibliography Abildgaard C, Harrison J, Espana C, Spangler W, Gribble D. 1975. Simian hemorrhagic fever: Studies of coagulation and pathology. Am J Trop Med Hyg 24(3):537–44. Ablashi DV, Pearson G, Rabin H, et al. 1978. Experimental infection of Callithrix jacchus marmosets with Herpesvirus ateles, Herpesvirus saimiri, and Epstein Barr virus. Biomedicine 29(1):7–10. Albrecht P, Lorenz D, Klutch MJ, Vickers JH, Ennis FA. 1980. Fatal measles infection in marmosets pathogenesis and prophylaxis. Infect Immun 27(3):969–78.

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Allen AM, Palmer AE, Tauraso NM, Shelokov A. 1968. Simian hemorrhagic fever. II. Studies in pathology. Am J Trop Med Hyg 17(3):413–21. Batista-Morais N, Neilson-Rolim B, Matos-Chaves HH, de Brito-Neto J, Maria-da-Silva L. 2000. Rabies in tamarins (Callithrix jacchus) in the state of Ceará, Brazil, a distinct viral variant? Mem Inst Oswaldo Cruz 95(5):609–10. Blanchard JL, Soike K, Baskin GB. 1987. Encephalomyocarditis virus infection in African green and squirrel monkeys: Comparison of pathologic effects. Lab Anim Sci 37(5):635–9. Brack M. 1987. Agents Transmissible from Simians to Man. Berlin: Springer-Verlag. Carville A, Mansfield KG. 2008. Comparative pathobiology of macaque lymphocryptoviruses. Comp Med 58(1):57–67. Chapman JL, Nichols DK, Martinez MJ, Raymond JW. 2010. Animal models of orthopoxvirus infection. Vet Path 47(5):852–70. Cho CT, Wenner HA. 1973. Monkeypox virus. Bacteriol Rev 37(1):1–18. Dalgard DW, Hardy RJ, Pearson SL, et al. 1992. Combined simian hemorrhagic fever and Ebola virus infection in cynomolgus monkeys. Lab Anim Sci 42(2):152–7. Elmore D, Eberle R. 2008. Monkey B virus (Cercopithecine herpesvirus 1). Comp Med 58(1):11–21. Estep RD, Messaoudi I, Wong SW. 2010. Simian herpesviruses and their risk to humans. Vaccine 28 Suppl 2:B78–84. Gravell M, London WT, Leon M, Palmer AE, Hamilton RS. 1986. Elimination of persistent simian hemorrhagic fever (SHF) virus infection in patas monkeys. Proc Soc Exp Biol Med 181(2):219–25. Gravell M, Palmer AE, Rodriguez M, London WT, Hamilton RS. 1980. Method to detect asymptomatic carriers of simian hemorrhagic fever virus. Lab Anim Sci 30(6):988–91. Gough AW, Barsoum NJ, Gracon SI, Mitchell L, Sturgess JM. 1982. Poxvirus infection in a colony of common marmosets (Callithrix jacchus). Lab Anim Sci 32(1):87–90. Hall WC, Kovatch RM, Herman PH, Fox JG. 1971. Pathology of measles in rhesus monkeys. Vet Pathol 8(4):307–19. Hubbard GB, Soike KF, Butler TM, et al. 1992. An encephalomyocarditis virus epizootic in a baboon colony. Lab Anim Sci 42(3):233–9.

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Hukkanen RR, Gillen M, Grant R, Liggitt HD, Kiem HP, Kelley ST. 2009. Simian varicella virus in pigtailed macaques (Macaca nemestrina): clinical, pathologic, and virologic features. Comp Med 59(5):482–7. Kalter SS, Heberling RL. 1990. Primate viral diseases in perspective. J Med Primatol 19(6):519–35. Lerche NW. 2010. Simian retroviruses: infection and disease— implications for immunotoxicology research in primates. J Immunotoxicol 7(2):93–101. London WT. 1977. Epizootiology, transmission and approach to prevention of fatal simian haemorrhagic fever in rhesus monkeys. Nature 268(5618):344–5. MacArthur JA, Mann PG, Oreffo V, Scott GB. 1979. Measles in monkeys: An epidemiological study. J Hyg (Lond) 83(2):207–12. Mansfield K, King N. 1998. Viral diseases. In Nonhuman primates in biomedical research: diseases, 1–57, eds. BT Bennett, CR Abee, R Henrickson. San Diego, CA: Academic Press. Mätz-Rensing K, Ellerbrok H, Ehlers B, et al. 2006. Fatal poxvirus outbreak in a colony of New World monkeys. Vet Pathol 43(2):212–8. McClure HM, Keeling ME. 1971. Viral diseases noted in the Yerkes Primate Center colony. Lab Anim Sci 21(6):1002–10. Palmer AE, Allen AM, Tauraso NM, Shelokov A. 1968. Simian hemorrhagic fever. I. Clinical and epizootiologic aspects of an outbreak among quarantined monkeys. Am J Trop Med Hyg 17(3):404–12. Renquist D. 1990. Outbreak of simian hemorrhagic fever. J Med Primatol 19(1):77–9. Richardson JH, Humphrey GL. 1971. Rabies in imported nonhuman primates. Lab Anim Sci 21(6):1083. Steele MD, Giddens WE Jr, Valerio M, Sumi SM, Stetzer ER. 1982. Spontaneous paramyxoviral encephalitis in nonhuman primates (Macaca mulatta and M. nemestrina). Vet Pathol 19(2):132–9. Tauraso NM. 1973. Review of recent epizootics in nonhuman primate colonies and their relation to man. Lab Anim Sci 23(2):201–10. Westmoreland SV, Mansfield KG. 2008. Comparative pathobiology of Kaposi sarcoma-associated herpesvirus and related primate rhadinoviruses. Comp Med 58(1):31–42. Whitney RA Jr. 1979. Primate medicine and husbandry. Vet Clin North Am Small Anim Pract 9(3):429–45.

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parasitic diseases Numerous species of parasites have been reported in nonhuman primates. This section describes the most common or medically important parasites found in macaques. Other medically important nonhuman primate parasites are briefly described in Table 7.2 on page 159.

Protozoa Giardia intestinalis 1. Affected NHPs: New World monkeys, Old World monkeys, apes. 2. Pathophysiology: Transmission occurs through the fecal-oral route. Trophozoites are bilaterally symmetrical, pear-shaped, with two nuclei. Cysts are ovoid. Common inhabitant of the small intestine with unpredictable pathogenicity. 3. Clinical signs: Diarrhea, vomiting. May be asymptomatic. Zoonotic. 4. Diagnosis: Microscopic identification of the organism on a fecal wet mount (trophozoites and cysts) or fecal float (cysts). Fecal sample should be fresh. Diagnosis may require multiple samples collected over several days. Stool antigen detection assays are commercially available. Because of unpredictable pathogenicity, identification of the organism in the feces does not necessarily indicate causation of diarrhea. 5. Treatment and monitoring Medications: Metronidazole 13 mg/kg PO every 8 hr for 5–10 days Albendazole 25 mg/kg PO twice daily for 3–5 days Furazolidone 1.5 mg/kg PO for 7 days (marmosets) Tinidazole 150 mg/kg PO, followed by 77 mg/kg in 4 days Strict sanitation, including vermin control is critical. 6. References: Kramer et al. 2009; Toft and Eberhard 1998; Sasseville and Mansfield 2010.

Cryptosporidium spp. 1. Affected NHPs: Prosimians, New World monkeys, Old World monkeys, apes.

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Figure 7.21 Cryptosporidiosis. Numerous organisms can be seen in small intestinal lumen and crypts. (Micrograph courtesy of Dr. Cynthia Courtney.) 2. Pathophysiology: Oocysts are shed in the feces and are immediately infective. Transmission is fecal-oral. The organism develops in the intestinal epithelium and may invade the biliary tree, causing cholangiohepatitis (Figure 7.21). Zoonotic. 3. Clinical signs: Generally only seen in young or immunosupressed animals. Intractable diarrhea, dehydration, depression, weight loss. 4. Diagnosis: Identification of oocysts on stained fecal smear or concentrate, stool antigen assay, demonstration of organisms on histopathology. Alkaline phosphatase (ALP) may be elevated on serum chemistry in animals with biliary invasion. 5. Treatment and monitoring: Infections are often self-limiting. Treatment consists of supportive care, including fluids, antidiarrheals, and antibiotics for secondary infections. Environmental sanitation is difficult due to oocyte resistance to common disinfectants. 6. References: Toft and Eberhard 1998; Wachtman and Mansfield 2008; Sasseville and Mansfield 2010.

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Figure 7.22 Amebiasis. Marked liver necrosis associated with Entamoeba histolytica trophozoites.

Entamoeba histolytica 1. Affected NHPs: New World monkeys, Old World monkeys, apes. 2. Pathophysiology: Transmission occurs through the fecaloral route. Cysts form in the large intestine and divide into four trophozoites. E. histolytica lives nonpathogenically in the intestinal lumen and becomes pathogenic when it invades the gastrointestinal (GI) mucosa. May invade the liver and cause necrosis (Figure  7.22). Several factors affect pathogenicity, including host species, age, GI bacterial flora, and host nutritional status. E. histolytica must be differentiated from the smaller, nonpathogenic Entamoeba dispar. Zoonotic. 3. Clinical signs: Asymptomatic to severe signs, including anorexia, vomiting, weight loss, and diarrhea, which may be bloody or mucoid. Characteristic flask-shaped ulcers may be seen in the colon at necropsy. Clinical signs may be more severe in young, immunocompromised, or New World monkeys. 4. Diagnosis: Microscopic identification of the organism on a fecal wet mount or identification of the characteristic intestinal lesions. Fecal sample should be fresh to see movement of trophozoites. Smears may be stained with trichrome or Giemsa stains. Trophozoites measure 20–30 μm in diameter and contain ingested red blood cells (in contrast to nonpathogenic E. dispar, which does not ingest red blood cells). Fecal antigen detection tests are available. May be a nonpathogenic commensal organism in some animals, so identification does not necessarily indicate causation of diarrhea.

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5. Treatment and monitoring Medications: Metronidazole 13 mg/kg PO every 8 hr for 5–10 days Paramomycin 12.5–15 mg/kg PO every 6 hr for 5–10 days Tetracycline 25–50 mg/kg PO daily for 5–10 days Reexamine stools on three consecutive days following treatment and at 1, 3, and 6 months. Strict sanitation, including vermin control, is critical. 6. References: Toft and Eberhard 1998; Sasseville and Mansfield 2010.

Balantidium coli 1. Affected NHPs: New World monkeys, Old World monkeys, apes. 2. Pathophysiology: Transmission occurs through the fecal-oral route. Inhabits the cecum in NHPs and is usually nonpathogenic but may become a secondary invader in animals with underlying disease. Clinical disease is usually associated with great apes. Trophozoites are large and ovoid with outer cilia (Figure 7.23). Cysts are spherical to ovoid. Zoonotic. 3. Clinical signs: Asymptomatic (usually) to severe signs, including watery diarrhea, ulcerative colitis, rectal prolapse, weight loss, anorexia, and lethargy.

Figure 7.23 Balantidiasis. Large intestine. Balantidium coli trophozoites are observed associated with sloughing of the intestinal epithelium. Severe infections produce ulcerative colitis.

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4. Diagnosis: Microscopic identification of the organism on a fecal wet mount. Feces should be fresh, and several samples may be required for diagnosis. May be a nonpathogenic commensal organism in some animals, so identification does not necessarily indicate causation of diarrhea. 5. Treatment and monitoring Medications: Metronidazole 13 mg/kg PO every 8 hr for 10 days Tetracycline 13 mg/kg PO every 8 hr for 14–21 days Strict sanitation, including vermin control, is critical. 6. References: Toft and Eberhard 1998; Sasseville and Mansfield 2010.

Toxoplasma gondii 1. Affected NHPs: Prosimians, New World monkeys, Old World monkeys, apes. 2. Pathophysiology: Cats serve as definitive hosts and excrete oocysts into the environment. NHPs may act as intermediate hosts by ingesting oocysts or other intermediate hosts (birds, rodents). In NHPs, the organism replicates extraintestinally and may affect several organs. New World monkeys are very susceptible to disease. Zoonotic. 3. Clinical signs: Signs may include lethargy, listlessness, depression, anorexia, diarrhea, vomiting, dypnea, cough, oculonasal discharge, or neurologic manifestations. Animals may die without any overt clinical signs. 4. Diagnosis: Serology, PCR, usually demonstration of the organisms or immunohistochemistry on tissue sections postmortem. 5. Treatment and monitoring: Emphasis should be on prevention, including sanitation, elimination of cat excreta from the environment, thoroughly cooking meat, and vermin control. There is a single report of successful treatment in a capuchin with clindamycin and trimethoprim-sulfa. A human pediatric dose of pyrimethamine combined with sulfadiazine has been suggested. 6. References: Toft et al. 1998; Gyimesi, Lappin, and Dubey 2006; Fiorello et al. 2006; Wachtman and Mansfield 2008; Johnson-Delaney 2009.

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Nematodes Strongyloides spp. 1. Affected NHPs: New World monkeys (Strongyloides cebus), Old World monkeys (Strongyloides fulleborni ), apes (Strongyloides fulleborni, Strongyloides stercoralis). 2. Pathophysiology: Fecal-oral transmission. Complex life cycle consisting of both free-living and parasitic generations. Adult females and larvae are found in the intestine, while the migrating larvae are found in the lungs and other parenchymous organs (Figure  7.24). Larvae become infective within 48 hr and need moisture to survive. Autoinfection may occur with S. stercoralis, resulting in hyperinfections. Zoonotic.

Figure 7.24 Strongyloidiasis. Squirrel monkey small intestine. Cross sections of larvae are observed along with a mild infiltrate composed mainly of plasma cells and few eosinophils. (Micrograph courtesy of Dr. Cynthia Courtney.)

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3. Clinical signs: Diarrhea, which may be bloody or mucoid, is most common. Other clinical signs include dermatitis, urticaria, anorexia, depression, vomiting, emaciation, cough, and dyspnea. 4. Diagnosis: Identification of the larvae or larvated ova on fecal float. 5. Treatment and monitoring Medications: Ivermectin 200 μg/kg IM, SQ, or PO once, repeated in 3 weeks Levamisole 10 mg/kg PO or SQ daily for 2–3 days Mebendazole 22 mg/kg PO daily for 3 days Pyrantel pamoate 11 mg/kg PO once Thiabendazole 50–100 mg/kg PO for 1, 2, or 5 days Moxidectin 0.5 mg/kg topically once Strict sanitation, including prompt removal of stool Repeat treatment (except Moxidectin) in 2–3 weeks. 6. References: Toft and Eberhard 1998; Dufour et al. 2006; Sasseville and Mansfield 2010.

Trichuris trichiura (Whipworms) 1. Affected NHPs: New World monkeys, Old World monkeys, apes. 2. Pathophysiology: Fecal-oral transmission with direct life cycle. Inhabit the cecum and large intestine. Zoonotic. 3. Clinical signs: Generally asymptomatic. With heavy worm burdens, may have anorexia, diarrhea. 4. Diagnosis: Identification of eggs on fecal float. Eggs have characteristic bipolar plugs (Figure 7.25). 5. Treatment and monitoring Medications: Albendazole 10 mg/kg PO daily for 3 days Levamisole 10 mg/kg SQ or PO once, repeated in 2 weeks Mebendazole 20 mg/kg PO twice daily for 5 days Ivermectin 0.2 mg/kg PO, repeat in 2–3 weeks Strict sanitation 6. References: Toft and Eberhard 1998; Johnson-Delaney 2009; Sasseville and Mansfield 2010.

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Figure 7.25 Trichuris trichiura egg in a rhesus monkey stool sample. Eggs have characteristic bipolar plugs. (Image courtesy of Claudia Cuellar.)

Figure 7.26 Oesophagostomiasis. Nodule on serosal surface of large intestine containing inflammatory infiltrate and cross sections of the nematode.

Oesophagostomum spp. (Nodular Worms) 1. Affected NHPs: Old World monkeys, apes. 2. Pathophysiology: Fecal-oral transmission. Direct life cycle with larvae becoming infective after 1 week. The parasite is generally found in the large intestine and cecum and forms smooth, elevated, white or black nodules on the serosal surface (Figure 7.26). Viable worms may be seen in young nodules. Zoonotic. 3. Clinical signs: Usually asymptomatic. With heavy parasite burdens, may see unthriftiness, weight loss, and diarrhea.

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4. Diagnosis: Identification of eggs on fecal float. Eggs are indistinguishable from other hookworm species, so diagnostic confirmation will require identification of the larvae after stool culture. 5. Treatment and monitoring Medications: Levamisole 10 mg/kg SQ or PO as a single dose Thiabendazole 100 mg/kg PO as a single dose, 50 mg/kg PO daily for 2 days or 25 mg/kg PO twice daily for 2 days Mebendazole 13 mg/kg PO every 8 hr for 3–5 days Repeat all treatments in 2 weeks. Strict sanitation. 6. References: Toft and Eberhard 1998; Sasseville and Mansfield 2010.

Cestodes Echinococcus spp. 1. Affected NHPs: Prosimians, New World monkeys, Old World monkeys, apes. 2. Pathophysiology: NHPs are aberrant intermediate hosts. Infection occurs via ingestion of eggs from the definitive host. Organisms travel via the bloodstream to many organs, with subsequent development of a unilocular cyst, typical of Echinococcus granulosus, or an alveolar cyst, typical of Echinococcus multilocularis (Figures 7.27 and 7.28). 3. Clinical signs: Often subclinical but may present as a neoplasm after the cyst reaches a considerable size, often in the liver and lungs. Clinical signs will vary with the size of the cyst and location. Cyst rupture may result in anaphylactic shock and death. 4. Diagnosis: Imaging to identify characteristic cysts (ultrasound, radiographs), immunoblot, enzyme-linked immunosorbent assay (ELISA), PCR, or identification at necropsy. 5. Treatment: No effective treatment. Possible drainage of cyst or surgical removal. 6. References: Toft and Eberhard 1998; Rehmann et al. 2003, 2005; Bacciarini et al. 2004; Tappe et al. 2007; Plesker et al. 2001; Goldberg et al. 1991; Johnson-Delaney 2009.

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Figure 7.27 Echinococcosis. Rhesus monkey liver with Echinococcus cyst. An inflammatory infiltrate is noted surrounding the cyst and an area of mineralization. (Micrograph courtesy of Dr. Cynthia Courtney.)

Figure 7.28 Echinococcosis. Rhesus monkey liver Echinococcus cyst showing inflammatory infiltrate surrounding the cyst wall and within the cyst Echinococcus protoscoleces. (Micrograph courtesy of Dr. Cynthia Courtney.)

Arthropods Pneumonyssus spp. 1. Affected NHPs: Old World monkeys, apes. 2. Pathophysiology: Pneumonyssus simicola is found in nearly 100% of imported rhesus macaques. Mites form pale yellow to gray cystic nodules throughout the lung (Figures 7.29 and 7.30).

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Figure 7.29 Pulmonary acariasis in a macaque. Cross section of a pulmonary mite surrounded by a dense inflammatory infiltrate and pigment.

Figure 7.30 Pulmonary acariasis and streptococcal pneumonia in a macaque. Cross section of what appears a dead mite surrounded by cell debris and polymorphonuclear infiltrate.

3. Clinical signs: Usually asymptomatic, but may uncommonly see sneezing or coughing. 4. Diagnosis: Difficult and usually made at necropsy. Mite larvae may be found in tracheobronchial washes, but a negative sample is not conclusive that there is no infection. 5. Treatment and monitoring: Ivermectin 200 μg/kg IM, PO, or SQ once. 6. References: Toft and Eberhard 1998.

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Other Nonhuman Primate Parasites

TABLE 7.2: OTHER IMPORTANT PARASITES

IN

NONHUMAN PRIMATES

Parasite

NHP Affected

Organ/Tissues Affected

Hemoflagellates Trypanosoma cruzi

NWM, OWM, Apes

blood, muscle, heart, other blood

Trypanosoma spp. Enteric Flagellates Chilomastix spp. Enteromonas hominis Giardia spp. (discussed in text) Hexamita spp. Pentatrichomonas hominis Retortamonas intestinalis Trichomonas spp. Dientamoeba fragilis Enteric Amoebae Endolimax nana Entamoeba spp. E. gingivalis E. histolytica (discussed in text) Balamuthia mandrillaris and other free-living amoeba Coccidians Entopolypoides macaci Babesi spp. Hepatocystis spp. Plasmodium spp. Eimeria spp. Isospora spp. Cyclospora spp. Cryptosporidium spp. (discussed in text) Sarcocystis spp. Toxoplasma gondii (discussed in text)

Prosimians, NWM, OWM, Apes

Prosimians, NWM, OWM, Apes OWM, Apes

cecum

OWM, Apes NWM, OWM, Apes OWM, Apes Prosimians, OWM, Apes OWM

cecum, colon cecum, colon cecum intestine, mouth cecum, colon

NWM, OWM, Apes NWM, OWM, Apes OWM, Apes

cecum, colon cecum, colon mouth

OWM, Apes

brain, lung, kidney, liver

OWM Prosimians, OWM Prosimians, OWM, Apes Prosimians, NWM, OWM, Apes Prosimians Prosimians, NWM, OWM, Apes OWM, Apes

red red red red

Prosimians, NWM, OWM

intestine

blood blood blood blood

cell cell cell cell

intestine intestine intestine

muscles, heart

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TABLE 7.2 (CONTINUED): OTHER IMPORTANT PARASITES Parasite

IN

NONHUMAN PRIMATES

NHP Affected

Organ/Tissues Affected

NWM

bile ducts

OWM Prosimians, NWM, OWM, Apes

cecum, colon mesenteric/abdominal/ portal veins

OWM, Apes

small intestine

Prosimians, NWM, OWM, Apes

small intestine

OWM

nasal cavity, pharynx

Prosimians, NWM, OWM, Apes NWM NWM NWM

large intestine

Ciliates Balantidium coli (discussed in text) Trematodes Athesmia foxi (= A. heterolecithoides) Gastrodiscoides hominis Schistosoma spp. Cestodes Bertiella studeri Echinococcus spp. (discussed in text) Hymenolepis spp. Leeches Dinobdella ferox Nematodes Strongyloides spp. (discussed in text) Enterobius spp. Trypanoxyuris spp. Filaroides spp. Filariopsis spp. Oesophagostomum spp. (discussed in text) Ternidens deminutus Gongylonema spp.

OWM, Apes NWM, OWM

Molineus torulosus Nochtia nochti Streptopharagus spp. Dipetalonema spp.

NWM OWM OWM, Apes Prosimians, NWM

Mansonella spp.

Prosimians, NWM, OWM, Apes OWM NWM, OWM, Apes

Anatrichosoma cutaneum Capillaria hepatica (=Calodium hepaticum) Trichuris spp. (discussed in text) Baylisascaris spp.

NWM, OWM

large intestine lungs lungs

cecum, colon oral cavity, esophagus, stomach small intestine stomach stomach, rectum peritoneal cavity, subcutis peritoneal cavity, subcutis nasal mucosa, skin liver

larvae in brain and viscera

bacterial, mycotic, viral, and parasitic infections TABLE 7.2 (CONTINUED): OTHER IMPORTANT PARASITES

IN

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NONHUMAN PRIMATES

Parasite

NHP Affected

Organ/Tissues Affected

Acantocephalans Prosthenorchis spp.

Prosimians, NWM

ileum, cecum, colon

OWM, Apes NWM, Apes

hair hair

Prosimians, NWM, OWM Prosimians, NWM, OWM, Apes

thoracic/abdominal cavities thoracic/abdominal cavities

Arthropods Pedicinus spp. Pediculus spp. Pneumonyssus simicola (discussed in text) Pentastomids Porocephalus spp. Armillifer spp.

NWM = New World monkeys; OWM = Old World monkeys For a comprehensive list of parasites reported in nonhuman primates, refer to Toft, J. D. and M. L. Eberhard. 1998. Parasitic diseases. In B. T. Bennett, C. R. Abee, and R. Henrickson (eds.), Nonhuman Primates in Biomedical Research: Diseases. San Diego: Academic Press.

parasites references Bacciarini, L. N., B. Gottstein, O. Pagan, P. Rehmann, and A. Grone. 2004. Hepatic alveolar echinococcosis in cynomolgus monkeys (Macaca fascicularis). Vet Pathol 41 (3):229–34. Dufour, J. P., F. B. Cogswell, K. M. Phillippi-Falkenstein, and R. P. Bohm. 2006. Comparison of efficacy of moxidectin and ivermectin in the treatment of Strongyloides fulleborni infection in rhesus macaques. J Med Primatol 35 (3):172–6. Fiorello, C. V., D. J. Heard, H. L. Heller, and K. Russell. 2006. Medical management of toxoplasma meningitis in a white-throated capuchin (Cebus capucinus). J Zoo Wildl Med 37 (3):409–12. Goldberg, G. P., J. D. Fortman, F. Z. Beluhan, and B. T. Bennett. 1991. Pulmonary Echinococcus granulosus in a baboon (Papio anubis). Lab Anim Sci 41 (2):177–80. Gyimesi, Z. S., M. R. Lappin, and J. P. Dubey. 2006. Application of assays for the diagnosis of toxoplasmosis in a colony of woolly monkeys (Lagothrix lagotricha). J Zoo Wildl Med 37 (3):276–80. Johnson-Delaney, C. A. 2009. Parasites of captive nonhuman primates. Vet Clin North Am Exot Anim Pract 12 (3):563–81.

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Kramer, J. A., A. M. Hachey, L. M. Wachtman, and K. G. Mansfield. 2009. Treatment of giardiasis in common marmosets (Callithrix jacchus) with tinidazole. Comp Med 59 (2):174–9. Plesker, R., C. Bauer, K. Tackmann, and A. Dinkel. 2001. Hydatid echinococcosis (Echinococcus granulosus) in a laboratory colony of pig-tailed macaques (Macaca nemestrina). J Vet Med B Infect Dis Vet Public Health 48 (5):367–72. Rehmann, P., A. Grone, B. Gottstein, J. Vollm, H. Sager, M. Janovsky, and L. N. Bacciarini. 2005. Detection of Echinococcus multilocularis infection in a colony of cynomolgus monkeys (Macaca fascicularis) using serology and ultrasonography. J Vet Diagn Invest 17 (2):183–6. Rehmann, P., A. Grone, A. Lawrenz, O. Pagan, B. Gottstein, and L. N. Bacciarini. 2003. Echinococcus multilocularis in two lowland gorillas (Gorilla g. gorilla). J Comp Pathol 129 (1):85–8. Sasseville, V. G., and K. G. Mansfield. 2010. Overview of known nonhuman primate pathogens with potential to affect colonies used for toxicity testing. J Immunotoxicol 7 (2):79–92. Tappe, D., K. Brehm, M. Frosch, A. Blankenburg, A. Schrod, F. J. Kaup, and K. Matz-Rensing. 2007. Echinococcus multilocularis infection of several Old World monkey species in a breeding enclosure. Am J Trop Med Hyg 77 (3):504–6. Toft, J. D., and M. L. Eberhard, 1998. Parasitic diseases. In Nonhuman Primates in Biomedical Research: Diseases, eds. B.T. Bennett, C.R. Abee, and R. Henrickson, San Diego, CA: Academic Press. Wachtman, L. M., and K. G. Mansfield. 2008. Opportunistic infections in immunologically compromised nonhuman primates. ILAR J 49 (2):191–208.

acknowledgments Dr. Alfonso Gozalo’s contribution to this review was done as part of the author’s official duties as an employee at the National Institutes of Health, National Institute of Allergy and Infectious Diseases.

8 gestational concerns* when to intervene and what to do Angela Courtney

1. Pregnancy a. Vaginal bleeding: Mild vaginal bleeding can be normal days 1–50 of gestation. Most commonly seen days 18–45, termed a “placental sign.”1 This is not seen in baboons and apes. Vaginal bleeding after day 50 should be cause for concern. Rule outs include placental-based conditions; trauma to the vaginal vault; abortion; other organ sources of bleeding such as enteritis, colitis, and urinary tract infection can be considered as sources of blood in the region. b. Abortion: Conduct a full physical exam, blood work, ultrasound; consider serum banking for further diagnostics, and blood cultures may be indicated. Potential causes include trauma, uterine neoplasia, uterine anatomical defects that can interrupt conceptus development, cervical abnormalities, metabolic conditions, infectious and bacterial agents such as Listeria, Yersinia, Salmonella, Shigella, Pneumococcus, Toxoplasma, measles, rubella, adenovirus, lymphocytic choriomeningitis virus.1 Ectopic pregnancies can present as abortion but often will present as a medical emergency, although rare; ultrasound should *

Excerpted from resident’s journal, this chapter is composed of class notes and clinical experience at UC Davis California National Primate Research Center Residency.

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pocket handbook of nonhuman primate clinical medicine be strongly considered to evaluate the reproductive tract and abdomen.1 c. Placental-based conditions i. Placenta previa (marginal, partial, and complete): A portion of the placenta covers a portion of the cervical os.1 As the cervix dilates, the placenta can tear, resulting in serious hemorrhage. Generally diagnosed via ultrasound. The placenta can potentially migrate away from the cervix as gestation continues, but the condition should be closely monitored if diagnosed early and before hemorrhage and complications are seen.1 A cesarean section should be considered at term. Clinical signs of concern include weakness, shock from blood loss. Generally, the condition does not appear to present with a level of pain as seen in placenta abruption.1 ii. Placenta abruption: This is considered a medical emergency. The placenta prematurely separates from the uterine wall, and massive hemorrhage results.1 The hemorrhage can be into the uterine cavity itself and not visualized as external hemorrhage. When this occurs, the true magnitude of the hemorrhage may not be readily apparent to the clinician. Clinical signs include hypovolemic shock, extreme pain; potentially, the patient can bleed to death.1 The fetus is generally deceased, and immediate cesarean section is required in conjunction with intensive supportive care as indicated.1

2. Delivery concerns Gestation normal ranges should be known for your colony of animals. Although there are normal ranges published for the species, each colony may have an average gestational date that differs from another colony of animals while remaining within the published ranges. When a female extends beyond this normal colony range, an ultrasound is in order to determine if there is reason for concern. a. What to evaluate during a gestational ultrasound: i. Fetus: Position; heart rate (less than 120 or greater than 190 beats per minute [BPM] is cause for concern); development ii. Placenta: Position, attachment, overall condition

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iii. Amniotic fluid: Adequate, volume, clarity (particulates such as meconium are cause for concern) iv. Cervix: Dilation, length b. Dystocia: Abnormal labor due to malposition or malpresentation of the fetus in relation to the maternal pelvic canal.1 Clinical signs include weakness, contracted firm uterus on abdominal palpation. Pain may be present. The fetus may be palpated visualized and position determined; gentle manual transabdominal manipulation of the fetus may assist in expulsion. Gentle manual removal of the fetus vaginally may be attempted, but if truly lodged and attempts are unfruitful, then cesarean section should be performed. Potential complications include endometritis and metritis, which are very high postdystocia; antibiotics should be instituted postdystocia. Evaluate the urinary tract postdystocia for signs of rupture, blockage, and trauma. c. Uterine inertia/cervical concerns: May contribute to dystocia. Contractions that do not progress. Considerations include exhaustion of the dam, closed or partially closed cervix. Misoprostol 100 μg/tablet; place one tablet near the cervix to induce cervical softening, and dilation can be used. Treat dam based on presentation and clinical pathology and blood sample results; fluid treatment may be required; consider oxytocin (see next item) once cervix is open. d. Stillbirths and retained deceased fetus: Consider systemic abnormalities that may be causative in the dam, such as toxicities, endocrinopathies, and nutritional deficiencies; see also abortion rule outs.1 Complete physical examination should be performed. Fetuses can be retained deceased in utero without clinical signs of concern to alert to the condition. If the cervix is closed, a fetectomy should be performed. If the cervix is open and the uterus is not degenerated, oxytocin (0.1 ml IM of 20 units per ml concentration = 2.0 units per dose; maximum 3 doses 1 hr apart; can be administered via intravenous and subcutaneous routes as well; can be used to assist in milk let down) may assist in delivery of the deceased fetus. 3. Postpartum conditions a. Uterine/cervical prolapse: Prolapse can occur during gestation; determine if a fetus is present, viable, and

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pocket handbook of nonhuman primate clinical medicine gestational age; cesarean section may be required if near term. Historically, it has been noted that vaginal deliveries are possible with a prolapse present.1 If the tissue is viable, cleanse and protect the tissues against drying; manually reduce the prolapse if possible and place a purse string. If a purse string has been placed, caution, extreme care, and critical monitoring must be instituted if a viable fetus is present with a purse string in place. If not reducible or the tissue is badly damaged, consider reduction via laparotomy and assess for hysterectomy. b. Retained placenta: Placentas are generally found by personnel or ingested by the animal, but retention is common. Clinical signs: postpartum lethargy, poor maternal care of infant, possible shock and secondary sepsis. Ultrasound confirmation of the condition, oxytocin administration, gentle manual removal of the placenta transvaginally ensure the entire placenta is removed. Generally, concurrent manual massage of the uterus via the abdomen assists in removal. Antibiotic coverage is a must due to the ease of infection that occurs; enrofloxacin is a good choice for coverage. Pain control should be considered. Treat secondary complications based on presentation. c. Anemia: Secondary to blood loss during parturition. If not severe enough to require blood transfusion, iron supplementation should be considered. Use caution in using iron supplementation in the face of infection, which can increase the level of infection present. Resolve infection and then institute iron treatments (iron dextran 10.0 mg/ kg IM every 7 days; can be administered once weekly for 30 days). d. Mastitis: Clinical signs are pain; resistance to nursing of the infant; hard, swollen breast tissue. Disinfect nipple; culture milk obtained. Institute antibiotics. Warm compresses assist in stripping the gland daily. The infant can be left with the dam but monitor the infant’s weight. Supplementation, fostering, or nursery rearing may be necessary if unable to feed properly. Pain control can be considered. e. Endometriosis: Clinical signs are anorexia, lethargy, heavy menses, hematochezia. Palpation of pelvic masses may be possible; ultrasound and percutaneous aspiration generally reveal a “chocolate-colored” fluid sample. Treat

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anemia. (See anemia and infection precautions above.) Treatment options include ovariectomy, gonadotropins; pregnancy can cause temporary relief of the condition; use surgical excision and debridement especially if obstructing colon or urinary tract.1 Pain control should be instituted; supportive care, fluids, oral gastric tube feeding (20–30 ml/kg of liquid high-calorie/protein supplement such as Boost®), blood transfusion if required. f. Neoplasia: Uterine leiomyomas (fibroids) are seen with some frequency in large colonies. They can be an incidental finding and can be quite large and extensive. Clinical signs vary from no change in physical presentation to presenting with similar signs to endometriosis dependent on size of the mass. Ultrasound confirmation, pain control, and hysterectomy should be considered.

reference 1. Medical Primatology 2006. UC Davis. VME 413. Spring quarter.

9 dentistry in NHPs Margaret S. McTighe

Overall, dental procedures in nonhuman primates (NHPs) are the same as those in other species; however, when possible, it is especially important to salvage the canine teeth as loss can lead to changes in social status. Horizontal fractures of the canines can be treated with root canal procedures, provided you have dental radiography available to ensure adequate fill of the pulp cavity (Frost, 1985). Note also that removal of teeth (for reasons other than medical) is not permitted, and blunting of canines is no longer encouraged (USDA Animal Care Resource Guide, 2007; AVMA Policy, 2007). Clues to dental problems may include weight loss, salivation, or change in food preferences, such as avoidance of citrus fruits and hard biscuits. Dental injuries can occur in males that fight, display aggressively, or chew excessively on caging. Dental injuries have been observed in chimpanzees following syncopal episodes or epileptic seizures (Reifenberg et al., 2010). Safety first: Oral cavities of many nonhuman primate species contain viruses and bacteria that may be hazardous to your health. Establish appropriate personal protective equipment (PPE) and safety policies in conjunction with recommendations from your occupational health program. As a minimum, consider the following: gloves, respiratory protection, eye protection, and dedicated clothing. Face shields may also be warranted. Dental procedures should always be conducted in intubated, anesthetized animals. 169

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Most NHPs have deciduous and permanent teeth, with eruption dates specific for the species; however, there can be sexual dimorphism in eruption times due to differences in rates of maturity. Dentition and wear can be used to estimate age. Primate Products has an excellent Normal Values Chart that includes dentition. This can be requested at http://www.primateproducts.com (Turner). In most NHPs, the permanent dentition formula is 2(I)-1(C)-3(PM)-2(M)/2(I)1(C)-3(PM)-2(M), where I is incisor; C is canine, PM is premolar, and M is molar. In prosimians, the mandibular incisors or canines may be elongated to form a “tooth comb,” which is used for grooming and scraping bark off trees (Godfrey, 2005). 1. Examination of the face and oral cavity: a. Observe the NHP before sedation, looking for facial swelling, particularly in the zygomatic areas. This is the most common site to notice a developing periapical abscess. b. Once sedated, examine the face for symmetry. Asymmetry and firm areas along the maxilla or mandible may be due to a tooth root abscess (see Figure 9.1). c. Examine the oral cavity, looking for draining tracts above/ below the gum lines (Figure 9.2). Also, look for ulcerative areas on the gums (see renal and infectious disease chapters). Many infectious diseases that cause vasculitis will result in painful gingivitis. d. If the animal is young, check for retained deciduous teeth, especially canines.

Figure 9.1 Examining the face for symmetry.

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Figure 9.2 Examining the oral cavity for draining tracts.

Figure 9.3 The “second tongue” is used for grooming.

e. Tongue: Lacerations on the tongue can result in poor appetite and can occur with trauma or with other injuries. Up to a third of the tongue can be removed if necessary without impacting diet or overall well-being (my personal experience). Pseudofilm can be found on the tongue in animals with candidiasis. Candidiasis can occur in immunosuppressed animals or secondary to antibiotic use. Some prosimians will have a “second tongue,” which is used for grooming and lies beneath the real tongue. This can be mistaken for a plastic foreign body by those who have not seen it before (Figure 9.3).

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pocket handbook of nonhuman primate clinical medicine f. Check the cheek pouches and empty them if any material is present. Macaques will hide small objects here that can later become (ingested) foreign bodies. g. Extend the mandible and check the temporomandibular joints for normal range of motion and check occlusion. h. Primary oral tumors are uncommon in NHPs, with oral tumors occurring very rarely. The most commonly reported oral tumor in macaques is squamous cell carcinoma of the tongue (Shaley et al., 1980). Marmosets are also reported with oral and nasopharyngeal squamous cell carcinoma (Betton, 1984). Radiography and biopsy are indicated if neoplasia is suspected.

2. Dental equipment and tool recommendations (Wiggs, 2006) a. Ultrasonic scaler with polisher and drill b. Hand tools: periosteal elevators in a variety of sizes, explorer with markings to measure pocket depth, hand scaler, curette, calculus forceps c. Dental radiography unit and film developing box (highly recommended) 3. Cleaning the teeth (Peak, 2006) a. Probe the gingiva around each tooth in three or four places on both the buccal and lingual sides of the teeth. Note any gingivitis or dental pockets. b. Use the explorer to check the pulp cavity on any fractured teeth. If the pulp is not sealed, extraction or restoration will be needed. c. Remove tartar with calculus forceps. The application of Softscale® 15 min prior to scaling the teeth will greatly assist stubborn calculus removal. d. Scale (ultrasonic scaler) and polish the enamel of the teeth with a pumice paste. Remove any loose or damaged teeth that cannot be restored. e. Calculus in pockets smaller than 5 mm can be removed with a hand curette. f. Apply doxycycline gel into pockets to promote healing of the pocket. It will stay in the pocket for up to 6 weeks. g. Apply a fluoride treatment following the manufacturer’s recommendations.

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4. Evaluate areas of concern with radiography (Lobprise, 2006). a. Used human dental radiography equipment is readily available and relatively inexpensive. Hand developer boxes/kits are also inexpensive and easy to use. b. Radiograph teeth with pockets, and root or furcation exposure. Root planning and doxycycline treatment may save these teeth, or extraction may be indicated as further deterioration may place adjacent teeth at risk. 5. Perioperative analgesia: Injectable analgesics: Ketoprofen or carprofen injectable may be given prior to extraction to assist in pain management. 6. Extraction is warranted when the tooth is cracked, exposing pulp; when there is malalignment preventing normal jaw function; when the tooth is worn or fractured below the gum line; roots are exposed; there are supernumerary teeth, retained deciduous teeth, or teeth loose secondary to periodontal disease (Frost, 1985). a. By hand: Loose teeth and small diseased teeth (incisors) are easily removed by hand using periosteal elevators to free the gingival attachment and to provide leverage adjacent to periodontal ligaments to loosen the teeth. Sustained leverage pressure (10–30 sec) is effective at loosening the fibers of the periodontal ligaments. Take your time to avoid breaking the teeth (Carmichael, 2006a). b. With drill: Teeth with more than one root can be split with a high-speed water-cooled drill with a round or taper fissure crosscutting burr to facilitate removal (Carmichael, 2006b). c. Surgical: The buccal surface of the gum of canines can be elevated to facilitate extraction. The buccal cortical bone overlying the tooth root can be removed with a watercooled high-speed drill using a #4 round burr to assist in freeing the root from the alveolar bone (Carmichael, 2006b). d. In uninfected sockets, fill the socket with Consil®, a bioglass product. This product accelerates healing and helps protect the alveolar bone (Figure  9.4). Infected sockets should be flushed with dilute chlorhexidine solution and left open to heal.

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Figure 9.4 Uninfected sockets are filled with a product that promotes healing and helps protect the alveolar bone. 7. Restoration: When possible, try to salvage teeth (especially canines) by restoration. Work with a dentist if possible to learn these techniques. a. Apicoectomy: This is a surgical procedure typically performed on a long canine, with or without a root canal. Typically, the last 3–4 mm of the apex of the root and surrounding damaged tissue are removed, and the abscess is drained. The area is prepared and filled with an amalgam (Frost, 1985). b. Root canal: The damaged pulp is removed from the tooth. The pulp cavity is prepared mechanically and chemically, then cleaned and filled with an amalgam (Frost, 1985). 8. Postdental care a. Softened biscuits or canned diet for 2–3 days. If biscuits need to be softened following a dental procedure (or other surgery), Purina recommends softening them in fruit juice as water will inactivate the vitamin C (Purina, 2009). b. Antibiotics are indicated postdentistry when infection is present (Table 9.1). Antibiotics of choice include clindamycin, amoxicillin, or enrofloxacin. c. Analgesics: Ketoprofen or carprofen injectable may be given at the time of extraction or restoration followed by 3–5 days of continued oral analgesia. Oral analgesics include Tylenol with codeine, carprofen, naproxen, or ibuprofen.

dentistry in NHPs TABLE 9.1: DRUG DOSAGES

FOR

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DENTAL CARE

Antibiotics: Amoxicillin Chimpanzee: 500 mg IV/IM/PO TID Monkey: 6.7–13.3 mg/kg IM/PO TID Clindamycin Chimpanzee: 150–300 mg PO QID; 300–600 mg IM BID/TID Monkey: 12.5 mg/kg IM TID Enrofloxacin Chimpanzee: 5 mg/kg IM, PO SID Monkey: 5 mg/kg PO SID/BID Analgesics: Carprofen Chimpanzee: 2 mg/kg PO BID Monkey: 2 mg/kg PO BID Ketoprofen Chimpanzee: 2 mg/kg IM SID Monkey: 2 mg/kg IM SID Tylenol with codeine Chimpanzee: 24–36 mg (10–15 ml) PO q 6 hr Naproxen Chimpanzee: 5 mg/kg PO SID Ibuprofen Chimpanzee: 200–400 mg PO SID Monkey: 7 mg/kg PO BID Source: Lee DR, Doane CJ. Formulary Association of Primate Veterinarians. http://www.primatevets.org (accessed March 3, 2011).

9. Preventive care a. Dental diets: Commercial laboratory animal diets are available with ingredients that reduce tartar buildup. Purina currently has these diets available with DentaGuard, which reduces dental calculus: i. 5LGI Advanced Protocol® Old World Primate Diet with DentaGuard ii. 5LG2 Advanced Protocol New World Diet with DentaGuard b. Enrichment toys such as Nylabone® (original or flavored) and Kong® promote chewing and healthy gums. c. Some NHPs have been trained with positive reinforcement techniques to allow tooth brushing. This practice should be encouraged.

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pocket handbook of nonhuman primate clinical medicine d. Dental examination/care can be conducted with annual or semiannual exams.

references AVMA Policy on Removal or Reduction of Canine Teeth in Captive Nonhuman Primates or Exotic and Wild (Indigenous) Carnivores. Revised June 2007. AVMA Web site. http://www.avma.org/ (accessed February 25, 2011). Betton GR. 1984. Spontaneous neoplasms of the marmoset (Callithrix jacchus). Oral and nasopharyngeal squamous cell carcinomas. Vet Pathol 21:193–197. Carmichael D. 2006a. How to perform a nonsurgical extraction. In Veterinary Medicine Resource Guide. Duluth, MN: Advanstar Veterinary Healthcare Communication; 36–38. Carmichael D. 2006b. How to perform a surgical extraction. In Veterinary Medicine Resource Guide. Duluth, MN: Advanstar Veterinary Healthcare Communication; 39–42. Frost P. 1985. Canine Dentistry. A Compendium. 2nd ed. Mount Kisco, NY: Day Communications. Godfrey LR. 2005. General anatomy. In Wolfe-Coote S, ed. The Laboratory Primate. San Diego, CA: Elsevier; 29–45. Lobprise HB. 2006. Periodontal disease: more than just a dirty mouth. In Veterinary Medicine Resource Guide. Duluth, MN: Advanstar Veterinary Healthcare Communication; 18–25. Peak RM. 2006. Dental prophylaxis: examination, cleaning and home care. In Veterinary Medicine Resource Guide. Duluth, MN: Advanstar Veterinary Healthcare Communication; 11–17. Purina 5LGI Advanced Protocol® Old World Primate Diet w/DentaGuard [package insert]. December 2009. PMI St. Louis, MO. http://www. labdiet.com/primate_diet.html (accessed February 28, 2011). Reifenberg S, Lammey ML, Sleeper M, et al. 2010. Diagnosis and treatment of epilepsy in an adult captive female chimpanzee (Pan troglodytes). JAALAS 49(1): 49. Shaley M, Fox JG, Wallstrom AC, et al. 1980. Myxoma of bone in a nonhuman primate. Cancer 45(10): 2573–2582. Turner K. Normal Values Poster. Primate Products Web site. http:// www.primateproducts.com (accessed March 2, 2011).

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USDA Animal Care Resource Guide. 2007. Veterinary Care. Policy 3. Declawing and Defanging Practices in Wild or Exotic Carnivores or Nonhuman Primates: 3.3–3.4. Wiggs RB. 2006. Dental equipment: using the right tools to provide the best care for your patients. In Veterinary Medicine Resource Guide. Duluth, MN: Advanstar Veterinary Healthcare Communication; 3–10.

10 dermatologic and ophthalmologic conditions Karen Strait

dermatologic conditions 1. Alopecia (Novak and Meyer 2009; Bernstein and Didier 2009; Steinmetz et al. 2005) a. Definition: Hair loss, the extent of which may vary from thinning to large patches of bald skin to whole body hair loss. b. Causes/Pathophysiology: Etiology is poorly understood. May include seasonal variation, aging, nutritional imbalance (zinc, protein, or folic acid deficiency, zinc excess), endocrine (hypothyroidism, hyperadrenocorticism), pregnancy, immunologic (lupus erythematosus, alopecia areata), genetic (mutations of the hr gene), infectious (bacterial, parasitic, fungal), inflammatory (atopic dermatitis), psychological (excessive hair plucking by self or others, stress). c. Clinical Signs: Hair loss on the whole or part of the body. May be accompanied by pruritus or inflamed, reddened skin. d. Exam/Diagnostics: Observe animal for scratching or hair pulling. Determine pattern and quantity of hair loss and 179

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pocket handbook of nonhuman primate clinical medicine evaluate the skin. Videotaping may help determine if hair loss is due to plucking/over-grooming by self or others. A CBC and serum chemistry are recommended as part of the initial diagnostic work-up. If skin is inflamed, take biopsies to rule out bacterial, parasitic, and fungal infections and to determine hair follicle quality and pathologic changes in the skin that may help indicate the underlying cause. Blood work may be taken to assess hormone levels. For cases with mild hair loss and normal skin appearance, or those which are likely due to aging, seasonal variations, or pregnancy, careful monitoring without further diagnostics may be appropriate. e. Treatment: Treat underlying cause. Environmental enrichment, including social housing, may be useful for self-induced alopecia. Seasonal or pregnancy-associated hair loss should resolve in 4–8 months. f. Species Differences: Macaca arctoides characteristically show androgenetic balding of the head with the onset of sexual maturity. Both males and females are affected.

2. Anatrichosoma Cutaneum (Bernstein and Didier 2009, Toft and Eberhard 1998, Flynn and Baker 2007) a. Definition: Infection with the nematode parasite Anatrichosoma cutaneum, also known as Anatrichosoma cynomolgi. b. Causes/Pathophysiology: Transmission is unknown. Female worms migrate and deposit eggs in the cutaneous and nasal epithelium. Cutaneous infection is rare. Zoonotic. c. Clinical Signs: White, serpentine tracts along the palms of the hands or soles of the feet. May be pruritic. Nasal infections are typically not apparent. d. Exam/Diagnostics: Skin scrapes of the affected area or nasal swabs to identify the characteristic eggs or adult worms. Eggs are elliptical with bipolar plugs. e. Treatment: Treatment is not well described. Treatments effective for Trichuris spp. are likely effective for Anatrichosoma cutaneum. f. Prevention: Routine anthelmintic use. g. Species Differences: Old World monkeys susceptible.

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3. Atopic Dermatitis (Ovadia et al. 2005; Torreilles et al. 2009; Novak and Meyer 2009, Morris and Etheridge 2007; Macy et al 2001) a. Definition: A chronic, pruritic, inflammatory skin condition of unknown origin. b. Causes/Pathophysiology: Etiology is not fully understood. Usually thought to develop subsequent to allergen or irritant exposure, with a likely genetic component. In humans, there appears to be an association with other type I hypersensitivity disorders such as asthma and food allergies. Secondary bacterial infections may occur. c. Clinical Signs: Intense pruritis, alopecia, erythema, maculopapular lesions, scaling, lichenification, excoriation, and crusting. Clinical course is chronic or chronic relapsing. d. Exam/Diagnostics: Diagnosis is difficult and is mainly one of exclusion. Histopathologic examination of skin biopsies from affected and non-affected areas may provide the most information. Take a skin scrape, skin culture, and hair pluck for dermatophyte culture to rule out parasitic, bacterial, and fungal infections, respectively. Serum IgE or intradermal allergen testing may be useful, although normal serum IgE does not rule out atopic dermatitis. e. Treatment: Potentially effective treatments include essential fatty acids, corticosteroids, immunomodulators (cyclosporine, tacrolimus), and topical emollients. Remove inciting substance (i.e., specific food, bedding, latex) if identified (usually not possible). Antihistamines may provide relief for pruritus (diphenhydramine 1 mg/kg PO, SQ every 6–12h; cetirizine 5 mg/kg PO once a day). Antibiotics are indicated for secondary bacterial infections. 4. Benign Epidermal Monkey Pox ( Bielitzki 1998; Mansfield and King 1998; Bernstein and Didier 2009; Brunetti et al. 2003) a. Definition: Infection with the Yaba-like disease virus, also known as Or-Te-Ca. b. Causes/Pathophysiology: Poxvirus (genus Yatapoxvirus) etiology. Transmission is unknown. Zoonotic. c. Clinical Signs: Multifocal red papules that progress to circular, raised, crusted foci on the face, trunk, and extremities, up to 1 cm in diameter. May have an abrupt onset of fever lasting 3–4 days.

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pocket handbook of nonhuman primate clinical medicine d. Exam/Diagnostics: Biopsy. Visualization of epithelial hyperplasia with eosinophilic intracytoplasmic inclusion bodies may aid in diagnosis; however, electron microscopy, immunohistochemistry, viral isolation, or molecular techniques may be necessary. e. Treatment: None. Lesions resolve in 3–8 weeks. f. Prevention: Previous infection is protective. g. Species Differences: Reported in macaques.

5. Calcinosis Circumscripta (Wachtman et al. 2006; Line et al. 1984; Radi and Sato 2010; Cohen and Sharma-Reddy 2008; Marini et al. 1999; Bielitzki 1998) a. Definition: Ectopic mineralization in which insoluble calcium salts are deposited in the skin and subcutaneous tissues. b. Causes/Pathophysiology: Ectopic mineralization may be dystrophic, metastatic, or idiopathic. Dystrophic calcification occurs secondary to tissue damage due to a localized pH increase and precipitation of calcium and phosphorous salts and is likely the most common cause in NHPs. May be associated with trauma, foreign bodies, injection of compounds, degenerative skin disease, or neoplasia. Metastatic calcification is related to abnormal calcium and phosphorous metabolism, as occurs with renal disease or secondary hyperparathyroidism. c. Clinical Signs: Single to multiple firm, dermal, or subcutaneous nodules, often at the site of a previous trauma (such as digit amputation sites). Lesions may ulcerate and extrude a white, gritty material. Generally appears to be non-painful. d. Exam/Diagnostics: Biopsies are diagnostic. Radiographs of the area are taken to identify the extent of mineralization. Animals often have a history of trauma at the site. Check serum chemistry for elevated calcium and phosphorous levels. e. Treatment: Surgical excision. May recur. 6. Candidiasis (Bernstein and Didier 2009; Bielitzki 1998) a. Definition: Fungal skin infection with Candida albicans. b. Causes/Pathophysiology: Candida albicans is a ubiquitous yeast that is a normal inhabitant of the skin and mucous

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membranes. Moist areas (such as in skin folds), overuse of antibiotics, and immunosuppression may lead to overgrowth of the fungus. Infections in severely immunocompromised patients may become systemic. Obese animals are at increased risk due to large skin folds. c. Clinical Signs: Superficial skin infections appear as a pruritic, erythematous, maculopapular rash. White plaques may be observed on the oral or genital mucosa. d. Exam/Diagnostics: The location and appearance of the lesions are often indicative of candidiasis. Potassium hydroxide wet mounts or a periodic acid-Schiff (PAS) stain of skin scrapings may be microscopically examined for yeast and fungal hyphae. Alternatively, candidiasis may be diagnosed via fungal culture or skin biopsy. A thorough exam including blood work is indicated in animals in which underlying immunosuppression is suspected. e. Treatment: Nystatin 100,000 units PO every 6 hours (infants), Fluconazole 5 mg/kg PO daily. f. Prevention: Judicious use of antibiotics, keep skin clean and dry. 7. Cutaneous Acariasis (Bernstein and Didier 2009; Bielitzki 1998; Toft et al. 1998; Starost et al. 2005; Lee at al. 1981; Atkins et al. 2008 ; Nagarajan et al. 2004; Graczyk et al. 2001; Kalema-Zikusoka et al. 2002) a. Definition: Skin infestation by various mite spp. b. Causes/Pathophysiology: Demodex spp., Sarcoptes spp., and Psoregates spp. c. Clinical Signs: Demodex lesions are nonpuritic with alopecia and thickening. Folliculitis and furunculosis have been described in rhesus macaques. Sarcoptes lesions may be severely pruritic with alopecia, erythema, thickening, scaling, and crusting. Bacterial infections may occur secondarily due to intense scratching. Psoregates lesions are variably pruritic circumscribed papules with scaling, crusting and alopecia. d. Exam/Diagnostics: Deep skin scrapes for microscopic identification of mites or skin biopsy. e. Treatment: For Sarcoptes and Psorergates, administer ivermectin 0.2 mg/kg PO, SQ, or IM and repeat in 3 weeks

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pocket handbook of nonhuman primate clinical medicine if necessary. Amitraz 250 p.p.m. dips every two weeks are effective for Demodex. Treat secondary bacterial infections with antibiotics. f. Prevention: Some reports indicate transfer of mites from humans to animals. Proper personal protective equipment is advised.

8. Cutaneous Neoplasia (Beniashvili 1989, Bernstein and Didier 2009) a. Definition: Neoplasia affecting the skin. b. Causes/Pathophysiology: Various benign and malignant cutaneous neoplasms have been reported in nonhuman primates including squamous cell carcinomas, melanomas, fibrosarcomas, basal cell carcinomas, fibromas, lymphomas, and lipomas, among others. Lymphomas may be related to STLV or SIV infection. c. Clinical signs: Variable and will depend on the type of neoplasia. May appear as a nodule or ulcerated mass. d. Exam/Diagnostics: Cytology and/or biopsy. Radiographs may be useful to rule out metastasis. e. Treatment: Typically unrewarding. Depends on tumor type but may require surgical excision or chemotherapy. 9. Dermatophytosis (Bernstein and Didier 2009; Bielitzki 1998; Avni-Magen 2008) a. Definition: A fungal infection of keratinized skin layers caused by a dermatophyte. b. Causes/Pathophysiology: Microsporum canis and Trichopyton mentagrophytes most commonly. Other species of Microsporum and Trichophyton have been reported. Infections in captivity are often associated with human contact or domestic pets. Zoonotic. c. Clinical Signs: Circumscribed, dry, scaly, hyperkeratotic lesions with alopecia. d. Exam/Diagnoses: Microscopic examination of hair follicles, potassium hydroxide wet mounts of skin scrapings, dermatophyte culture, or biopsy. e. Treatment: Topical antifungals may be effective, but are often impractical. Griseofulvin, ketoconazole, lufenuron, and itraconazole are possible treatment choices.

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f. Prevention: Prevent direct contact with infected humans, animals. 10. Frostbite (Laber-Laird et al. 1988; Bielitzki 1998; Line 1998) a. Definition: Tissue damage due to cold exposure. b. Causes/Pathophysiology: Under cold temperature conditions, blood vessels in the skin constrict. With prolonged cold exposure, ischemic tissue damage occurs. c. Clinical Signs: Edema, skin blisters, necrosis, sloughing (Figure 10.1). Lesions may not be apparent for several days after cold exposure. d. Exam/Diagnostics: Typically the digits and tail are affected. A history of cold exposure with associated tissue damage in the extremities is sufficient for diagnosis. Animals should be evaluated for secondary infection. e. Treatment: Move animals to a warm environment. Generally, amputation of the affected area is the treatment of choice. Tissue that can be saved should be protected with soft, non-compressive bandages. Provide analgesics (NSAIDs, opioids) for pain. Antibiotics are indicated for secondary infections.

Figure 10.1 Frostbite on the tail of a macaque. Affected skin appears leathery and is beginning to slough. (Photo courtesy of Dr. Cassandra Bauer)

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pocket handbook of nonhuman primate clinical medicine f. Prevention: Protect non-acclimated animals from prolonged cold exposure.

11. Herpes B (Elmore and Eberle 2008; Cohen et al. 2002; Morton et al. 2008) a. Definition: Infection with Macacine herpesvirus 1 (formerly Cercopithecine herpesvirus 1). Also known as B virus, Herpesvirus simiae. b. Causes/Pathophysiology: Caused by Macacine herpesvirus 1, an alphaherpesvirus similar to herpes simplex viruses in humans. The virus is of minor clinical significance in the natural macaque host, but is of serious concern when transmitted to humans as it may cause fatal encephalitis. Spread via sexual, ocular, or oral contact (such as bites). Prevalence in macaque colonies may approach 100% with prevalence increasing with age. After primary infection, the virus establishes latency in the sensory ganglia near the site of infection. Periodic reactivation and shedding may occur, typically associated with stress or immunosuppression. c. Clinical Signs: Typically, asymptomatic in healthy macaques. Those with clinical signs have characteristic vesicle formation and ulcers at the mucocutaneous junctions and mucous membranes (oral cavity, conjunctiva, prepuce, vulva) at the site of infection. Animals with recurrent infections may shed virus asymptomatically. d. Exam/Diagnostics: Characteristic lesions are highly suggestive. Diagnosis is typically via serology. Direct virus culture requires a biosafety level 4 containment facility. The National B Virus Resource Center at Georgia State University can assist with diagnosis and other information. e. Treatment: Usually unnecessary in macaques. f. Prevention: Specific pathogen-free macaque colonies that are negative for B virus are available; however, procedures should be followed as if all macaques are infected, and appropriate PPE worn when handling macaques. Exposed humans should follow institutional guidelines, including washing the affected area with a detergent soap and water for 15 minutes. g. Species Differences: Natural infection in macaques may be fatal in aberrant NHP hosts.

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12. Irritant Contact Dermatitis (Bielitzki 1998) a. Definition: Skin damage and inflammation due to contact with harsh chemicals or other substances. b. Causes/Pathophysiology: Usually results from contact with chemical disinfectants and cleaners that have not been adequately rinsed from the housing area, but may also occur due to repeated contact with urine (urine scald) or feces (“diaper rash” in infants). Unlike allergic dermatitis, irritant contact dermatitis is not immune-mediated and does not require a period of sensitization. c. Clinical signs: May range from mild erythema to ulcerations and sloughing of the skin (Figure  10.2). Typically observed on the hands and feet where chemical contact is most likely to occur. In infants, it is usually observed around the genital area where there has been repeated contact with moisture, urine, and/or feces. d. Exam/Diagnostics: History of recent enclosure cleaning or chemical usage. Infants usually have a history of diarrhea. Examine affected areas for extent of tissue damage and the presence of secondary infection. e. Treatment: Rinse area thoroughly to ensure inciting substance is gone. Topical emollients may help soothe and protect skin. NSAIDs, such as meloxicam 0.1 mg/kg SQ, IM, or PO daily or flunixin meglumine 1 mg/kg every 6h

Figure 10.2 Irritant contact dermatitis on a macaque hand. (Photo courtesy of Dr. Margaret McTighe)

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pocket handbook of nonhuman primate clinical medicine SQ or IM, and topical corticosteroids may help to reduce pain and inflammation. Bandaging as for thermal injuries may be necessary for more severe chemical wounds. Antibiotics are indicated for deeper wounds at risk of secondary infection. Treat infants with “diaper rash” for diarrhea and keep area clean and dry. Ointments marketed for human infants, such as those containing zinc oxide, may be useful in nonhuman primates. f. Prevention: Thoroughly rinse all chemicals from areas with which nonhuman primates may be in contact. Keep infants clean and dry.

13. Papillomavirus (Patterson et al. 2005; Ostrow et al. 1995; Chen et al. 2009; Joh et al. 2009; Wood et al. 2004) a. Definition: Infection with one of the many nonhuman primate papillomaviruses, of which at least 30 have been identified in NHPs. b. Causes/Pathophysiology: Papillomaviruses infect cutaneous and mucosal epithelial cells causing proliferative lesions which may be benign or malignant. Transmitted via direct contact. Papillomavirus-associated genital neoplasia similar to that seen in humans has been reported in macaques. c. Clinical Signs: Proliferative squamous epithelial lesions on the skin or genital or oral mucosa with a caulifloweror wart-like appearance. d. Exam/Diagnostics: Diagnosed via biopsy of the lesion followed by immunohistochemistry or molecular assays. e. Treatment: Often of no clinical significance although some animals may develop neoplasia. May resolve spontaneously. Consideration should be made towards removing breeding animals with genital lesions from the breeding colony. f. Prevention: Prevent direct contact with infected animals. 14. Pyoderma (Bernstein and Didier 2009; Kolappaswamy et al. 2008; Wilk et al. 2008) a. Definition: Bacterial skin infection caused by pus-producing bacteria. b. Causes/Pathophysiology: Caused by a variety of bacteria, most commonly Staphylococcus aureus, Streptococcus

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pyogenes, and Pseudomonas spp. Infections are often associated with trauma/fight wounds, environmental conditions, or compromised immune systems. Infections may be superficial or deep (cellulitis). S. aureus is often a secondary invader through damaged skin or catheters, and infections may become systemic. S. pyogenes is a common cause of infection in moist environments (such as a nursery incubator). Pseudomonas aeruginosa is usually associated with immunocompromised patients. c. Clinical signs: May range from superficial erythema, pustular dermatitis, and crusting, to deeper infections with cellulitis, abscess formation, or draining tracts (Figure 10.3). Lesions are variably pruritic. Severe infections can become systemic and animal may present with depression, lethargy, or poor appetite. d. Exam/Diagnostics: Make a smear from a lesion aspirate or an impression and stain to look for bacteria. Take a swab for culture and sensitivity. Skin scrapings and fungal cultures will rule out parasitic and fungal organisms, respectively. Skin biopsies of the affected area may be helpful in complicated cases. A CBC, serum chemistry, and blood

Figure 10.3 Pyoderma on the finger of a bonnet macaque. (Photo courtesy of Dr. Margaret McTighe)

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pocket handbook of nonhuman primate clinical medicine culture are indicated for severe infections with suspected systemic involvement. e. Treatment: Clip hair and clean skin with antibacterial scrub/shampoo (such as chlorhexadine). If wounds are present, clean and debride as appropriate. Abscesses should be lanced to allow drainage. Treat with antibiotics. Choice of drug may be empiric for superficial infections or based on culture and sensitivity for deep infections. Ceftriaxone 25mg/kg SQ or IM daily or cephalexin 25 mg/kg PO every 12 hours is commonly used in NHPs. Methicillin-resistant Staph spp. have been reported. f. Prevention: Appropriate wound management, provide a clean and dry environment, catheter maintenance.

15. Thermal Injury (Bielitzki 1998; Line 1998) a. Definition: Skin damage due to excessive heat exposure. b. Causes/Pathophysiology: Usually associated with use of heating pads or other supplemental heat sources. Burns may be first-degree (superficial), second-degree (partial thickness), or third-degree (full thickness), each with increasing tissue damage respectively. With severe burns, inflammation disrupts the cell membrane causing the cell to leak fluid and protein with subsequent edema formation. c. Clinical Signs: First degree burns are minor and may involve skin redness only. Skin blisters are seen with second degree burns and the skin is reddened. Third degree burns may be dark or white in color, and the skin feels dry and leathery. d. Exam/Diagnostics: Diagnosis is made via a history of heat exposure with the appearance of burn-like wounds. Often occurs on the bony protuberances due to increased contact with the heat source. e. Treatment: Minor burns may be treated with analgesics, such as an NSAID, and cooling of the affected site only. For more severe burns, clean and debride the area and apply a xeroform bandage or silver sulfadiazine with a sterile gauze bandage. Bandages should be changed frequently. Surgical excision of the damaged tissue with primary closure may be the best option for smaller burns. Antibiotics should be given prophylactically for secondary infections. Analgesics such as opioids or NSAIDs are

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essential. NSAIDs may aid in suppressing the inflammatory response. Administer parenteral lactated ringer’s solution as required to maintain fluid balance. Check serum protein and albumin levels and administer colloids if necessary. Monitor patient’s temperature. Tetanus prophylaxis is recommended. f. Prevention: Keep heating pads below 102ºF (low setting), and periodically change the patient position. Always monitor the animal when using a heating pad as the unit may accidentally overheat. Maintain heat lamps at a distance of 4ft. Forced air units may cause burns when used without a warming blanket. g. Trauma: refer to Chapter 3. 16. Simian Varicella Virus (Gray 2008; Halliday and Fortman 2011; Hukkanen et al. 2009) a. Definition: Infection with the virus Cercopitheceine herpesvirus 9, also known as Medical Lake macaque virus, Liverpool vervet virus, patas herpesvirus, and Delta herpesvirus. b. Causes/Pathophysiology: Caused by Cercopitheceine herpesvirus 9, a naturally occurring alphaherpesvirus of Old World monkeys that is similar to varicella-zoster virus (VZV), the causative agent of chicken pox in humans. Transmission is via inhalation of aerosolized infectious droplets. Highly contagious. Like other neurotropic herpesviruses, simian varicella virus develops latency in neural ganglia and may be reactivated with immunosuppression or stress. c. Clinical Signs: Clinical signs range from asymptomatic or mild to severe. Generalized vesicular and maculopapular skin rash which first appears in the inguinal region, and progresses to involve lesions on the thorax, abdomen, face, and oral cavity, but not the palms, soles, or ischial callosities. Vesicles eventually rupture and scab. Fever, lethargy, and mild hepatitis may be observed with acute infection. In severely affected animals, a severe hemorrhagic rash associated with pneumonia and hepatitis may be seen and is coupled with poor prognosis. d. Exam/Diagnostics: Appearance of vesicular dermatitis is suggestive but must be differentiated from measles and

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pocket handbook of nonhuman primate clinical medicine herpes B. Monitor temperature for pyrexia. Collect a CBC and serum chemistry. Elevated serum alanine aminotransferase may be seen due to hepatitis. Thrombocytopenia has been reported with severe infections in macaques. Diagnosis is made via PCR or viral isolation of blood, skin/ vesicle specimens, or other infected tissues (in animals with active infection), or serology. e. Treatment: Infection is usually self-limiting, and most immunocompetent animals will recover within 3 weeks. Provide supportive care including parenteral fluids if necessary. Antibiotics are indicated for secondary infections of ulcerated areas. Antiviral agents such as acyclovir, which is used to treat VZV in humans, may be useful to treat simian varicella. Animals should be quarantined. f. Prevention: Quarantine or euthanize affected animals to prevent spread. A specific simian varicella virus vaccine is not available although the human varicella vaccine may be protective. g. Species differences: The virus is of particular significance in patas, African green, and macaque monkeys.

17. Yaba Monkey Tumor Virus (Schielke et al. 2002; Bielitzki 1998) a. Definition: Infection with the Yaba monkey tumor poxvirus. b. Causes/Pathophysiology: Poxvirus (genus Yatapoxvirus) etiology. Method of transmission is unknown but may be via an arthropod vector, trauma, or contaminated equipment (such as tattoo needles). The virus infects histiocytes, causing proliferation and formation of a benign histiocytoma. Zoonotic. c. Clinical Signs: Rapidly growing subcutaneous nodules on the head or limbs, up to 4 cm in diameter. d. Exam/Diagnostics: Biopsy. Visualization of eosinophilic intracytoplasmic inclusion bodies may aid in diagnosis; however electron microscopy, immunohistochemistry, viral isolation, or molecular techniques may be necessary. e. Treatment: None. Tumors are self-limiting. Lesions usually slough and heal within 2–3 months. f. Species Differences: Natural infection reported in rhesus macaques and baboons. New world primates are resistant.

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g. Other Infectious (measles, monkeypox, retroviruses, histoplasmosis): refer to Chapter 7.

ophthalmologic conditions 1. Anterior Uveitis (Hoffman et al. 2007; Schmidt 1971; Severin 1995 ) a. Definition: Inflammation of the iris and ciliary body. b. Causes/Pathophysiology: Disruption of the blood–ocular barrier due to inflammation leads to increased vascular permeability which causes leakage of proteins, white blood cells, and the release of inflammatory mediators. Etiology may include trauma, lens-induced, infectious, neoplasia, or idiopathic. c. Clinical Signs: Blepharospasm, miosis, hyperemia, vision difficulties/blindness.

conjunctival

d. Exam/Diagnostics: Perform a complete eye exam on both eyes, and a CBC and serum chemistry to look for the underlying cause. Uveitis in both eyes indicates a systemic cause. Check intraocular pressure for decreased pressure. May see abnormal particles within the anterior chamber such as protein (aqueous flare), red blood cells, white blood cells, fibrin, or keratic precipitates. e. Treatment: Treatment should be aimed at the underlying cause if identified. Controlling inflammation is the mainstay of therapy. Administer topical corticosteroids such as 1% prednisolone acetate every 4–6h. This is generally not practical, so systemic prednisolone 0.5-1 mg/ kg every 12 hours for 5–7 days then tapering is effective. Administer systemic NSAIDs such as flunixan meglumine 1mg/kg every 6–12 hours if steroids are contraindicated. Topical 1% atropine ointment every 6–12 hours will help reduce pain and aqueous flare. As an alternative to topical treatment, corticosteroids and atropine can be given as a subconjunctival injection in animals for which frequent treatment is not possible. Note: Topical corticosteroids are generally contraindicated in cases with a corneal ulcer. Atropine is contraindicated in glaucoma.

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pocket handbook of nonhuman primate clinical medicine g. Prevention: Timely treatment is important to prevent possible sequella including posterior synechia, cataracts, glaucoma, and phthisis bulbi.

2. Cataract (Plesker et al. 2005; Vieira et al. 2009; MontianiFerreira 2010, Ribka and Dubielzig 2008; Beltran et al. 2007; Schmidt 1971; Severin 1995) a. Definition: Lens opacity. b. Causes/Pathophysiology: Cataracts may be hereditary, spontaneous, or secondary to diabetes mellitus, infection, or trauma. Cataracts may occur in different parts of the lens and can be classified by the stage of progression: incipient, immature, mature, and hypermature. Animals may not have visual difficulties until cataracts are mature. c. Clinical signs: Animal may appear to have difficulty seeing. The lens will contain some opacity depending on the stage of the cataract. d. Exam/Diagnostics: Perform a complete ophthalmic exam. Check blood and urine glucose for diabetes. Cataracts that begin to resorb may cause a lens-induced uveitis. e. Treatment: Phacoemulsification. f. Prevention: Hereditary cataracts can be eliminated through careful breeding. 3. Conjunctivitis (Merrill 2008; Macy et al. 2001; Hoffman et al. 2007; Matz-Rensing 2009; Mansfield and King 1998; Schmidt 1971; Severin 1995) a. Definition: Inflammation of the conjunctiva. b. Causes/Pathophysiology: allergic, infectious (i.e. measles, herpesvirus, bacterial, fungal), irritant (soap), trauma, secondary to intraocular disease (i.e. glaucoma, anterior uveitis). c. Clinical Signs: Conjunctival hyperemia, discharge, chemosis, blepharospasm. d. Exam/Diagnostics: Perform a complete eye exam including fluorescein stain to rule out corneal ulcers and intraocular pressure to rule out glaucoma. Collect a conjunctival scraping and culture to check for infectious organisms and cell population (usually not necessary in mild, acute cases). A biopsy may be necessary in chronic cases.

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Examine animal for other signs of underlying disease such as nasal discharge or cough. Collect swab for viral culture and blood for viral isolation and titers if necessary. e. Treatment: Treatment depends on the underlying cause. For uncomplicated conjunctivitis, apply topical Neo/Poly/ Dex ophthalmic ointment or drops up to every 6 hours, or as feasible in anesthetized animals. A subconjunctival injection of antibiotics (such as 10 mg gentamicin) or steroids (such as dexamethasone—short term effect, or DepoMedrol—long term effect) may be indicated in patients where topical treatment is not possible. Administer systemic NSAIDs such as flunixan meglumine 1mg/kg every 6–12 hours. An antihistamine such as cetirizine 5 mg/kg PO once daily may be helpful when underlying allergies are suspected. Note: Topical/subconjunctival corticosteroids are generally contraindicated in cases with a corneal ulcer or infection. f. Prevention: Vaccination (for measles-associated conjunctivitis). 4. Corneal Perforation (Severin 1995; Ribka and Dubielzig 2008) a. Definition: Perforation of the cornea. b. Causes/Pathophysiology: Fighting, injury with a foreign body such as a stick, infection. c. Clinical Signs: Hemorrhage, anterior uveitis. Protruding iridal tissue may be seen or a foreign body may be observed. d. Exam/Diagnostics: Perform a complete eye exam. If not immediately apparent, stain eye with fluorescein stain to determine if cornea is perforated; Seidel test. Assess consensual PLR to determine if animal has severe intraocular damage and check for lens perforation. Check eye for any remaining foreign body. e. Treatment: Treat as an emergency and consult an ophthalmologist. Lens lacerations and gaping corneal lacerations require surgery. Obtain specimen for bacterial culture if possible. Start systemic analgesics and broad-spectrum antibiotics. Enucleation is often necessary.

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5. Corneal Abrasion/Ulcer (Severin 1995) a. Definition: Partial or full thickness loss of corneal epithelium. b. Causes/Pathophysiology: Trauma, chemical (soap), infectious. c. Clinical signs: blepharospasm, periorbital erythema, epiphora, conjunctival hyperemia. The eye appears painful and the animal may be observed rubbing the area. Often presents as a “red eye.” d. Exam/Diagnostics: Stain eye with fluorescein dye and evaluate the cornea for stain uptake using a cobalt blue light. The area of fluorescein stain uptake will indicate the size and location of the ulcer. Evaluate adnexa in the area of the corneal ulcer for any foreign objects. e. Treatment: Anesthetize the cornea by applying proparacaine drops. Debride ulcer with a cotton-tip applicator. Healing may be enhanced by performing a grid keratotomy with a small gauge needle. A temporary tarsorrhaphy may be necessary to protect the cornea during healing in animals that continually rub the eye. Apply ophthalmic antibiotic ointment or drops up to every 6 hours and atropine 1% ointment every 6–12 hours. Often, a single dose at the time of exam is sufficient. A subconjunctival injection of antibiotics and atropine may be indicated in animals where frequent topical treatment is necessary and difficult. Systemic NSAIDs, such as flunixin meglumine 1 mg/kg every 6–12 hours SQ or IM can be useful as an adjunct therapy to control pain and inflammation. Eyes should be rechecked in 3–5 days. Uncomplicated ulcers should heal within a few days. Deep ulcers may require surgery. f. Prevention: Thoroughly rinse all caging/equipment to avoid animal contact with chemicals. 6. Exophthalmos (Haines et al. 1997; Rosenberg and Blouin 1979; Baskerville 1984) a. Definition: Anterior displacement of the globe in the orbit secondary to a mass in the retrobulbar space. b. Causes/Pathophysiology: Orbital cellulitis, abscess, carotid–cavernous sinus fistula, orbital neoplasia (lymphoma most common).

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c. Clinical Signs: exophthalmos, +/- pain. d. Exam/Diagnostics: Cellulitis and abscesses usually have a more acute onset than neoplasia. Check mouth for a possible tooth root abscess. Imaging (radiographs, MRI, orbital ultrasound) can help diagnose and localize disease. Run CBC and serum chemistry, and stain eye with fluorescein to check for corneal ulcers. e. Treatment: Treatment depends on the underlying cause. For abscess/cellulitis, treat with systemic antibiotics. For severe cases that are unresponsive to treatment, the abscess may need to be surgically drained and submitted for culture. Extract tooth in cases of tooth root abscess and consider systemic antibiotics. Treatment of neoplasia will depend on the tumor type. f. Species Differences: Lymphoma may occur in SIV-infected macaques. 7. Glaucoma (Bito 1979; Dawson et al. 1998; Toris et al. 2010) a. Definition: Increased intraocular pressure. b. Causes/Pathophysiology: Caused by impaired outflow of the aqueous humor due to narrowing or blockage of the iridocorneal angle. Glaucoma may be primary (inherited defect) or secondary (uveitis, neoplasia, lens luxation). Animals eventually develop optic neuropathy and blindness. c. Clinical Signs: Blepharospasm, buphthalmos, conjunctival hyperemia, vision difficulties, corneal edema, mydriasis. d. Exam/Diagnostics: Measure intraocular pressure (IOP) in both eyes. Normal IOP in an adult rhesus macaque is similar to humans, with one report giving 14.9 ± 2.1 mmHg and another using a cutoff of