Laboratory Non-human Primates Research Articles

Case report on successful treatment for brain abscess in a Japanese monkey (Macaca fuscata)

BackgroundA brain abscess in human beings is a focal infection of the central nervous system frequently characterized by areas of localized cerebritis and central necrosis surrounded by a well vascularized capsule. A brain abscess, although sporadically reported, is relatively rare disease in domestic animals (horses, cattle, goats and alpacas), companion animals (dogs and cats) and laboratory nonhuman primates. Brain abscesses are life threatening disease that needs early and aggressive veterinary therapy.Case presentationThe purpose of this study on a brain abscess in a Japanese monkey was to report the investigational and therapeutic processes including clinical observations, hematological and serum biochemical profiles, and magnetic resonance imaging (MRI) features, probiotic and antibiotic therapy. In clinical observation, the monkey presented with slowly progressive gentle and depressed behavioral change. Hematological findings showed that slightly declined platelet counts gradually increased in the course of the treatment. Serum biochemical profiles revealed initial markedly elevated. A series of chemotherapy provide prominent relief from the influence of the brain abscess. MRI images illustrated that a brain abscess was located in the right frontal lobe and the mass was delineated by a thick rim, indicating the capsule formation stage. The lesion chronologically decreased in size over the course of treatment. Until 11 weeks after treatment of the brain abscess, the size of brain abscess continued to reduce, leaving an organized lesion trace. To the best of my knowledge, this is the first report on successful treatment for a brain abscess in a Japanese monkey (Macaca fuscata).ConclusionsMedical management of simian brain abscesses is possible based on the controlled and resolving nature of the lesions as determined by MRI and completion of a of chemical antibiotic treatment presented in this study.

Special Issue on the Pathobiology of Laboratory Nonhuman Primates: A Review of Species, Substrain, Geographical Origin, Age, and Modality-Related Factors.

Nonhuman primates (NHPs) are utilized in nonclinical safety testing due to their phylogenetic proximity to humans and similarity in physiology and anatomy. However, ethical considerations and the increased demand for NHPs, coupled with the current shortage in their supply, have increased the calls to minimize their use. In addition, the increased demand and supply shortage of NHPs have increased the use of animals sourced from different geographical origins, and animals of different ages, which can complicate the interpretation of study results. Coupled with the relative uniqueness of findings induced by novel therapeutic modalities, there is an increasing need for a deeper understanding of the systemic pathobiology of NHPs. Here we provide a brief preview of the two main themes discussed in this special issue, which include the influence of geographical origin, age, and sex on background pathology, clinical pathology reference values, other relevant toxicology endpoints, and organ system pathology.

Using non-invasive neuroimaging to enhance the care, well-being and experimental outcomes of laboratory non-human primates (monkeys)

Over the past 10-20 years, neuroscience witnessed an explosion in the use of non-invasive imaging methods, particularly magnetic resonance imaging (MRI), to study brain structure and function. Simultaneously, with access to MRI in many research institutions, MRI has become an indispensable tool for researchers and veterinarians to guide improvements in surgical procedures and implants and thus, experimental as well as clinical outcomes, given that access to MRI also allows for improved diagnosis and monitoring for brain disease. As part of the PRIMEatE Data Exchange, we gathered expert scientists, veterinarians, and clinicians who treat humans, to provide an overview of the use of non-invasive imaging tools, primarily MRI, to enhance experimental and welfare outcomes for laboratory non-human primates engaged in neuroscientific experiments. We aimed to provide guidance for other researchers, scientists and veterinarians in the use of this powerful imaging technology as well as to foster a larger conversation and community of scientists and veterinarians with a shared goal of improving the well-being and experimental outcomes for laboratory animals.

Survey of 2014 behavioral management programs for laboratory primates in the United States.

The behavioral management of laboratory nonhuman primates in the United States has not been thoroughly characterized since 2003. This article presents the results of a survey behavioral management programs at 27 facilities and covering a total of 59,636 primates, 27,916 housed in indoor cages and 31,720 in group enclosures. The survey included questions regarding program structure, implementation, and methodology associated with social housing, positive reinforcement training, positive human interaction, exercise enclosures, and several categories of inanimate enrichment. The vast majority of laboratory primates are housed socially (83%). Since 2003, the proportion of indoor-housed primates reported to be housed singly has fallen considerably, from 59% to 35% in the facilities surveyed. The use of social housing remains significantly constrained by: 1) research protocol requirements, highlighting the value of closely involved IACUCs for harmonizing research and behavioral management; and 2) the unavailability of compatible social partners, underscoring the necessity of objective analysis of the methods used to foster and maintain compatibility. Positive reinforcement training appears to have expanded and is now used at all facilities responding to the survey. The use of enrichment devices has also increased in the participating facilities. For most behavioral management techniques, concerns over the possibility of negative consequences to animals are expressed most frequently for social housing and destructible enrichment, while skepticism regarding efficacy is limited almost exclusively to sensory enrichment. Behavioral management program staffing has expanded over time in the facilities surveyed, due not only to increased numbers of dedicated behavioral management technicians but also to greater involvement of animal care technicians, suggesting an increase in the integration of behavioral care into animal husbandry. Broad awareness of common practice may assist facilities with program evaluation and assessment of progress in the field can generate recommendations for continuing the advancement of primate behavioral management programs. Am. J. Primatol. 78:780-796, 2016. © 2016 Wiley Periodicals, Inc.

The well-being of laboratory non-human primates.

The well-being of non-human primates in captivity is of joint concern to scientists, veterinarians, colony managers, caretakers, and researchers working with non-human primates in biomedical research. With increased regulatory, accreditation, and research focus on optimizing the use of social housing for laboratory primates, as well as the advent of techniques to assess indices of chronic stress and related measures of well-being, there is no better time to present the most current advances in the field of non-human primate behavioral management. The collective body of research presented here was inspired in part by a 2014 symposium entitled, "Chronic Hormones and Demographic Variables: Center-Wide Studies on Non-Human Primate Well-Being" held at the American Society of Primatologists' 37th Annual Meeting in Decatur, GA. By aiming to target readership with scientific and/or management oversight of captive primate behavioral management programs, this special issue provides badly-needed guidance for implementing social housing programs in a research environment and leverages collaboration across multiple facilities to address key components of behavioral management, explore refinements in how well-being can be measured, and identify the interrelationships between varying indices. Am. J. Primatol. 79:e22520, 2017. © 2016 Wiley Periodicals, Inc.

The Physiological Effect of Human Grooming on the Heart Rate and the Heart Rate Variability of Laboratory Non-Human Primates: A Pilot Study in Male Rhesus Monkeys.

Grooming is a widespread, essential, and complex behavior with social and affiliative valence in the non-human primate world. Its impact at the autonomous nervous system level has been studied during allogrooming among monkeys living in a semi-naturalistic environment. For the first time, we investigated the effect of human grooming to monkey in a typical experimental situation inside laboratory. We analyzed the autonomic response of male monkeys groomed by a familiar human (experimenter), in terms of the heart rate (HR) and heart rate variability (HRV) at different body parts. We considered the HRV in both the time (SDNN, RMSSD, and RMSSD/SDNN) and the frequency domain (HF, LF, and LF/HF). For this purpose, we recorded the electrocardiogram of two male rhesus monkeys seated in a primate chair while the experimenter groomed their mouth, chest, or arm. We demonstrated that (1) the grooming carried out by a familiar human determined a decrement of the HR and an increment of the HRV; (2) there was a difference in relation to the groomed body part. In particular, during grooming the mouth the HRV was higher than during grooming the arm and the chest. Taken together, the results represent the first evidence that grooming carried out by a familiar human on experimental monkeys has the comparable positive physiological effect of allogrooming between conspecifics. Moreover, since the results underlined the positive modulation of both HR and HRV, the present study could be a starting point to improve the well-being of non-human primates in experimental condition by means of grooming by a familiar person.

Blood microsampling from the ear capillary in non-human primates.

Blood sampling from awake non-human primates (NHPs) is classically performed under constraint in the cephalic or saphenous vein. It is a challenging, potentially harmful and stressful procedure which may lead to biased results and raises ethical concerns. Laboratory NHPs undergo a head-restrained procedure allowing for a safer procedure of collecting blood from their ears. Using regular capillary blood collection devices 500 µL of blood can be easily withdrawn per puncture point, which is sufficient for performing most of the usual modern biological assays. This procedure has been validated by measuring total proteins, cortisol and vasopressin concentrations from concomitant blood samples taken from the saphenous vein and the ear capillary vessels of macaques (n = 16). We observed strong correlations between the blood concentrations of total proteins, cortisol and vasopressin (r = 0.72, r = 0.63, r = 0.83, respectively; all P values <0.01) taken from the saphenous vein and from the ear capillary. There were no significant differences between blood concentrations taken from the saphenous vein and the ear capillary. Our alternative to the classical blood collection procedure is harmless and can be routinely performed, which can therefore improve scientific results while increasing animal welfare in accordance with the 3R (replacement, reduction and refinement) principles.

Occurrence of human-pathogenic Enterocytozoon bieneusi, Giardia duodenalis and Cryptosporidium genotypes in laboratory macaques in Guangxi, China

Captive nonhuman primates have been identified as common hosts of Enterocytozoon bieneusi, Giardia duodenalis, Cryptosporidium hominis, and Cyclospora spp., thus are potential reservoirs of some enteric parasites in humans. However, few studies have examined the source and human-infective potential of enteric parasites in laboratory nonhuman primates. In the present work, 205 fecal specimens were collected from three groups of captive Macaca fascicularis kept in different densities in a laboratory animal facility in Guangxi, China, and examined by PCR for E. bieneusi, G. duodenalis, Cryptosporidium spp., and Cyclospora spp. The infection rates of E. bieneusi and G. duodenalis were 11.3% and 1.2% in Group 1 (young animals kept individually; n=168), 72.2% and 11.1% in Group 2 (young animals kept in groups; n=18), and 31.6% and 5.3% in Group 3 (adults kept in groups; n=19), respectively. Sequence analysis of PCR products showed the presence of five E. bieneusi genotypes, with genotype D (in 16/36 genotyped specimens) and a new genotype (in 15/36 genotyped specimens) as the dominant genotypes. All five E. bieneusi genotypes belonged to the zoonotic group (Group 1). The G. duodenalis genotypes (assemblages AII and B) in five specimens and C. hominis subtype (IdA14) in one specimen were also known human-pathogens, although the Cyclospora seen in one animal appeared to be unique to macaque monkeys. The higher infection rate in younger animals reared in groups and common occurrence of zoonotic genotypes indicated that human-pathogenic E. bieneusi could be transmitted efficiently in captive nonhuman primates, and group-housing was a risk factor for transmission of zoonotic pathogens in young nonhuman primates in research facilities.

飼育下にある霊長類の管理と実験使用に関する基本原則

飼育下にある霊長類の管理と実験使用に関する基本原則

Physiological and behavioural stress responses in cynomolgus macaques (Macaca fascicularis) to noise associated with construction work

The aim of the present study was to evaluate the behavioural and physiological responses to environmental disturbances (live and recorded dynamite explosions) in laboratory non-human primates in preparation for a future tunnel construction underneath our animal facility. In a pilot study (A) on 20 female Macaca fascicularis, a day of test blasts resulted in an increase in faecal cortisol and immunoreactive cortisol metabolites (CICM), and the animals reacted behaviourally with vertical flight and vocalizations. In a follow-up study (B), we assessed the impact of 10 days of exposure to recorded detonations on the behaviour and CICM in 16 M. fascicularis. In the latter study we introduced a predictive signal, serving as a conditional stimulus, to half of the animals. We found no significant effects of the noise in the Signal group; while the Control groups' CICM values were affected. The behaviour was largely unaffected in the two groups. It was decided not to introduce a research moratorium on biomedical research planned to be conducted during the future tunnel construction, and that a conditional stimulus ('warning signal') will be used.

Incidences and Range of Spontaneous Findings in Control Cynomolgus Monkeys (Macaca fascicularis) Used in Toxicity Studies

The authors performed a retrospective study to determine the incidences and range of spontaneous pathology findings in control cynomolgus monkeys. Data were collected from 570 monkeys (285 animals per sex), aged twelve to thirty-six months, from sixty regulatory studies evaluated at our laboratory between 2003 and 2009. The most common finding overall was lymphoplasmacytic infiltrates observed in the following incidence: liver (60.7%), kidneys (28.8%), heart (25.8%), salivary glands (21.2%), and stomach (12.1%). Inflammation also commonly occurred in the heart, kidneys, lungs, and stomach. The most common degenerative changes were localized fatty change in the liver, myocardial degeneration, and mineralization and pigment deposits in various tissues. Parathyroid, thyroid, and pituitary cysts; ectopic thymus in the parathyroid or thyroid gland; accessory spleen within the pancreas; and adrenohepatic fusion were among the most common congenital findings. Some incidental findings bearing similarities to drug-induced lesions were also encountered in various organs. It is hoped that the results presented here and elsewhere could form the groundwork for the creation of a reliable database of incidental pathology findings in laboratory nonhuman primates.

REVIEW PAPER: Emerging and Reemerging Infectious Diseases of Nonhuman Primates in the Laboratory Setting

Despite numerous advances in the diagnosis and control of infectious diseases of nonhuman primates in the laboratory setting, a number of infectious agents continue to plague colonies. Some, such as measles virus and Mycobacterium tuberculosis, cause sporadic outbreaks despite well-established biosecurity protocols, whereas others, such as retroperitoneal fibromatosis-associated herpesvirus, have only recently been discovered, often as a result of immunosuppressive experimental manipulation. Owing to the unique social housing requirements of nonhuman primates, importation of foreign-bred animals, and lack of antemortem diagnostic assays for many new diseases, elimination of these agents is often difficult or impractical. Recognition of these diseases is therefore essential because of their confounding effects on experimental data, impact on colony health, and potential for zoonotic transmission. This review summarizes the relevant pathology and pathogenesis of emerging and reemerging infectious diseases of laboratory nonhuman primates.

Accidental induced seizures in three cynomologus macaques following administration of ceftriaxone dissolved in 1% lidocaine diluent

Following initial signs of dural infection, or as prophylactic postoperative therapy, three cynomologus macaques were given an intramuscular or a subcutaneous injection of ceftriaxone dissolved in a 1% lidocaine diluent (CL). Two to 15 min later, all three monkeys experienced a long-lasting generalized apnoeic clonic convulsive seizure. The injected doses of lidocaine (0.7-2 mg/kg) were as low as 7-20-fold less than the experimental intravenous dosage (14.2 +/- 3.2 mg/kg) previously reported to induce seizure in healthy rhesus monkeys. Under different clinical conditions, the same three animals were either once (1 animal) or repeatedly given CL without any resultant neurological alterations. The monkeys had a cranial device implanted and two of them were craniotomized. This first report of accidental lidocaine-induced seizure in laboratory non-human primates following CL injection strongly suggests increased susceptibility when lidocaine administration is associated with central nervous system alteration. A novel hypothesis, the possible role of cytokine in lowering the lidocaine seizure threshold, is suggested.

Development, Application, and Quality Control of Serology Assays Used for Diagnostic Monitoring of Laboratory Nonhuman Primates

The careful development, validation, and implementation of serodiagnostic assays can provide reliable results that make them a valuable tool in microbial quality control for nonhuman primates. This article includes identification and description of the components of assay development, including formulas for calculating the number of positive serum samples needed for assay validation and methods for calculating their diagnostic sensitivity and specificity. To ensure that assays are performing within predetermined specifications, there must be a quality control system that includes appropriate system and sample suitability controls as well as mechanisms to track assay performance over time. The section on quality assurance includes definitions of precision and accuracy in assay performance, and how to interpret these two factors using the Levey-Jennings chart, Westgard's rules, and other monitoring methods. Because all serologic assays are prone to false positive and false negative results, it is essential to interpret all diagnostic test results using both the expected prevalence of disease in the population and the population-specific assay performance characteristics that are determined during assay validation. The discussion on interpreting diagnostic test results also includes guidelines for calculating the positive and negative predictive values of an assay and for interpreting results based on the disease prevalence of the test population. A glossary provides definitions of commonly used terms.

Spontaneous Lesions of the Cardiovascular System in Purpose-Bred Laboratory Nonhuman Primates

This retrospective study was performed to determine the range, occurrence and incidence of spontaneously arising histopathological findings of the cardiovascular system in purpose-bred laboratory nonhuman primates. Data were collected from 84 controlled toxicological studies with equal numbers of male and female animals and full tissue lists. Attempts were also made to standardize pathological terms used by various original pathologists. Tissue sections from 2464 animals, which included 2050 cynomolgus monkeys (Macaca fascicularis), 284 common marmosets (Callithrix jacchus) and 130 rhesus monkeys (Macaca mulatta) were examined. The most common cardiac finding was focal myocardial inflammation, subcategorized as either "inflammatory cell infiltration" (339) or "focal myocarditis" (131). Other cardiac findings included mineralization (29), endocarditis (16), pericarditis (10), squamous cysts (6) and ectopic thyroid tissue (5). Perivasculitis/vasculitis in the kidney, lung, meninges, sciatic nerve, and other tissues (206) was the most common vascular lesion. Focal myocarditis was more common in male (60%) than female (40%) animals. Cardiac mineralization and extramedullary hematopoiesis were more common in marmosets than other species while ectopic thyroid tissue was present in marmosets and cynomolgus monkeys. To our knowledge, this is the first study to demonstrate the range and incidence of spontaneous cardiovascular lesions in laboratory nonhuman primates.

Restraint Methods of Laboratory Non-Human Primates: A Critical Review

AbstractPublished information provides scientific evidence that traditional, involuntary restraint techniques of research non-human primates are intrinsically a source of distress resulting from fear. It has been documented that common methods of enforced restraint result in significantly increased adrenal activity as well as significant changes in a variety of other physiological parameters. There is no scientific evidence that the animals adequately habituate to involuntary restraint. Numerous reports have been published demonstrating that non-human primates can readily be trained to cooperate rather than resist during common handling procedures such as capture, venipuncture, injection and veterinary examination. Cooperative animals fail to show behavioural and physiological signs of distress. It was concluded that the advantages of training techniques over traditional restraint techniques will have to be explored more extensively in the future for the sake of research subjects and scientific methodology.

Training a Large Troop of Rhesus Macaques to Co-Operate During Catching: Analysis of the Time Investment

AbstractThis study demonstrates that only a minimal time investment was needed to train a large troop of laboratory non-human primates to co-operate in the catching procedure. A group of 45 rhesus macaques (Macaca mulatta) was trained to enter a chute system voluntarily and be caught one by one. The total duration of the training sessions was under six hours, with less than 15 total work-hours invested by three people. The result was an improved capture procedure which minimized risk to personnel and distress to the animals.

M.R.C. Laboratory Animals Centre Report on Laboratory Non‐Human Primates for Biomedical Research in the United Kingdom. By K. R. Hobbs &amp; J. Bleby.

Journal of Small Animal PracticeVolume 18, Issue 6 p. 435-435 M.R.C. Laboratory Animals Centre Report on Laboratory Non-Human Primates for Biomedical Research in the United Kingdom. By K. R. Hobbs & J. Bleby. First published: June 1977 https://doi.org/10.1111/j.1748-5827.1977.tb05908.xAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume18, Issue6June 1977Pages 435-435 RelatedInformation