Primates as experimental animals

The term "primates" comprises a varied group of animals, consisting of more than 250 different species. The close evolutionary relationship to man resulted in the use of nonhuman primates as subjects of study for scientists from different research fields. In biomedical research the use of primates is restricted to questions which cannot be answered by animals with less developed physiological senses. Primates play an important role in infectious disease research, as many pathogens relevant to humans can be transferred to selected primate species. In the last few decades this applied especially for HIV-infections of man, viral hepatitides, herpesvirus infections and for quite a long time for agents of transmissible spongiform encephalopathies, too. In neurobiology, primates play an outstanding role due to the morphological-structural and functional resemblance of their CNS to that of man. Due to new developments in biomedicine, in particular in the field of gene therapeutics, it has to be expected that primates will have to be used also in future as animal models for the welfare of human health.     

中型非人灵长类动物压缩保定治疗笼的设计制作与应用

物理保定是野生动物饲养管理的重要工作内容之一,在疾病诊治过程中起了重要作用。为了解决中型非人灵长类动物在临床检查和治疗等操作时的物理保定问题,本研究根据中型非人灵长类动物的生物学特点和兽医临床需要,研制了一种压缩保定治疗笼。该笼具为长方体结构,通过滑轮、推拉杆等装置控制后侧面移动,以改变笼体空间大小,实现压缩功能;并配有操作窗口、可拆卸喂食(水)盘、折叠式输液架等结构。临床应用结果表明,该笼具对长臂猿、金丝猴、猕猴等多种中型非人灵长类动物都能实现压缩保定,对提高临床检查效率和治疗效果起到了积极作用。     

Fatal overdose after ingestion of a transdermal fentanyl patch in two non‐human primates

Case history and presentationTwo non-human primates (Macaca fascicularis), weight 3.5 kg, enrolled in an experimental protocol received a 25 μg hour^?1 transdermal fentanyl patch for postoperative analgesia. The following day both animals were clinically normal, but after a new induction of anaesthesia with ketamine, they developed severe and prolonged respiratory distress, profound coma and myosis.Management and follow-upAttempted reversal with naloxone was ineffective. After several hours of ventilation, both primates eventually died, 7 and 15 hours after ketamine injection, respectively. In both cases, the patch was discovered in the animal's cheek pouch. Subsequent fentanyl serum concentration measurements (8.29 and 14.80 μg L^?1) confirmed fentanyl overdose.ConclusionsThis report of two fatal intoxications in non-human primates secondary to ingestion of a transdermal fentanyl patch demonstrates that this method of analgesia is inappropriate for non-human primates, because of their tendency to chew almost anything they can reach.     

Ethical and legal aspects of animal experiments on non-human primates

Animal experiments on non-human primates give cause for ethical concerns for three reasons (1) the inclusion of "ethical animal protection" in the German Constitution (Article 20a of the "Grundgesetz" GG, 2002) has led to real consequences for the application process with respect to the use of primates for fundamental research; (2) the legal requirements in Europe to ensure animal welfare are currently being tightened and (3) the global problem of the protection of species, especially with respect to the capturing and subsequent sale of primates is still unsolved. As a result of the way humans interpret the term justice (the principle of equality) it was to be expected that great apes, being the animals that most closely resemble humans, would play a key role in the establishment of animal protection laws. In 1997,Great Britain and Ireland made it illegal to conduct experiments on great apes. In 1999, New Zealand went even further and created a kind of basic rights for great apes. In 2003,The Netherlands forbade animal experiments using great apes as did Sweden, which also included gibbons in this ban (which is in line with current taxonomy, which considers gibbons to belong to the family Hominidae). In 2006 Austria forbade experiments carried out on chimpanzees, bonobos, gorillas, orang-utans, and gibbons. Only recently, a state commission on ethics in Switzerland demanded that the Swiss government do the same. And the summer of 2006 saw a debate in Spain on the inclusion of the protection of great apes in the primary goals of the state. Due to the principle of equality, a further extension (both geographically and systemically) of the exclusion of great apes from animal experiments is to be expected. Since Article 20a GG on "ethical animal protection" came into effect on August 1,2002, the regulatory authorities in Germany have the right to independently check and control animal experiments as to their ethical tenability (Administrative Court Giessen, confirmed by the Administrative Court of the State of Hessia) i.e. an authorization for experiments in the area of fundamental research may only be given by the authorities if the "ethical tenability" (according to Section 7 paragraph 3 of the German Law on Animal Welfare) is given. The "ethical tenability" of fundamental research experiments follows other rules than those that pertain to applied research. Fundamental research is granted a low to mid-level tolerance of pain and suffering as being ethically tenable; not tenable are stronger or very high doses of pain and suffering. Actually in summer 2006, a proposal for fundamental research using mon-     

Leptospiral antibodies in captive lion tamarins (Leontopithecus sp) in Brazil

Serum samples from 73 lion tamarins of three species living at the Centro de Primatologia do Rio de Janeiro were tested for antibodies against serovars of Leptospira interrogans by microscopic agglutination test. Antibodies were detected in serum samples of 15% of tested samples. Seroreactivity prevalence was lower than that described in other non-human primates and could be explained by the arboreal behaviour of these animals. Icterohaemorrhagiae was the most common serogroup.     

Species-specific primate husbandry

With about 300 species primates represent one of the largest animal groups within mammals. They are kept in zoological gardens, as laboratory animals or in private ownership. Against this background it is difficult to define all species-specific aspects of a primate husbandry. The paper describes the basic requirements for primates like nutrition, possibilities for social interactions and species specific behaviour, stimuli for activities, health care and environmental conditions. Although no definitive regulations exist by law, the Appendix A (Species-specific Provisions for Non-human Primates) of the European Convention for the Protection of Vertebrate Animals used for Experimental and other Scientific Purposes (ETS 123) will be of great importance in the future.     

Yersiniosis in zoo marmosets (Callitrix jacchuss) caused by Yersinia enterocolitica 4/O:3

The aim of this research was to describe two fatal cases of Yersinia enterocolitica bioserotype 4/O:3 infection in non-human primates and to characterise the isolates by PCR and PFGE. In July 2004, two marmosets (Callitrix jacchuss) born in captivity in Zagreb Zoo, died following a few days of intermittent diarrhoea in intervals of 2 weeks. The pathomorphological diagnosis of the female (born in 1997) and the male (born in 1995) marmoset, was disseminated miliary necrosis of the liver. Y. enterocolitica 4/O:3 was isolated from both livers showing that monkeys are susceptible to this bioserotype. The ail gene, which is an essential chromosomal virulence factor in pathogenic Y. enterocolitica isolates, was present in the marmoset isolates. Two different PFGE patterns were obtained from the isolates of the male liver with NotI enzyme. One genotype of the male marmoset isolate was indistinguishable from the genotype of the female marmoset isolate when NotI, ApaI and XhoI enzymes were used indicating a common infection source for the marmosets. The genotypes of the marmoset isolates differed only slightly from one human (of seven Croatian isolates) and from one pig isolate (representing a common genotype found among human and porcine isolates in Germany) suggesting that raw pork fed to the marmoset could have been the infection source.     

Management of hepatitis B virus infections in two gibbons and a western lowland gorilla in a zoological collection

Since 1996, three primates newly arrived at London Zoo have been found to be infected with hepatitis B virus. The species involved were white-cheeked gibbons (Hylobates leucogenys leucogenys and Hylobates leucogenys siki) and a western lowland gorilla (Gorilla gorilla gorilla). The protocols for the practical management of these cases, including the immunisation of susceptible non-human primates and the staff with recombinant hepatitis B vaccine are described, and the origin and evolution of hepatitis B infection in primates are discussed.     

Zoonoses transmitted by mouse and rat maintained as laboratory or pet animals

Large numbers of mice (Mus spp.) and rats (Rattus spp.) are maintained for scientific reasons and as pet animals in Germany. While laboratory animals are monitored for pathogenic agents, the hygienic status of pet animals is usually completely unknown. Despite great efforts, zoonotic infections were reported even in laboratory settings, e.g. with Hantavirus (Seoul virus), Streptobacillus moniliformis, and Trichphyton mentagrophytes. However, in current reports, zoonotic infections were transmitted by mice and rats maintained as pet animals. This includes infections by Lymphocytic choriomeningitis virus, Leptospira interrogans, Streptobacillus moniliformis, Salmonella enterica, Trichophyton mentagrophytes, and Ornithonyssus bacoti. Furthermore, entero-hepatic Helicobacter spp. of rats and mice are currently discussed to be involved in the etiology of hepatobiliary diseases. Pasteurella spp. of mice and rats do not present a risk for human disease comparable to those species that are transmitted by dogs or cats and might induce serious disease after bites. Altogether, this article lists potential zoonotic agents that were detected in mice and rats and are present in Germany, as well as agents that were reportedly transmitted by mice and rats maintained as laboratory or pet rodents.     

Pathogenesis of quinolone-induced arthropathy: a review of hypotheses

The arthropathogenic effects of quinolones have been described in juvenile animals of multiple species such as dogs, rats, non-human primates, rabbits and guinea pigs. Several studies have been performed to clarify the exact mechanism leading to cartilage damage. In these studies, the investigators focused on the inhibitory effects of quinolones on DNA, collagen and proteoglycan synthesis and on the formation of oxygen-derived reactive molecules. Recently, it was suggested that quinolone-induced arthropathy is possibly associated with the magnesium-chelating properties of quinolones. However, the exact mechanism of quinolone-induced arthropathy is still unkown. This article reviews and summarizes several possible mechanisms for quinolone-induced arthropathy.     

Large granular lymphocytosis in a cynomolgus macaque (Macaca fascicularis) with a subclinical Trypanosoma cruzi infection

A 5.25-year-old cynomolgus macaque (Macaca fascicularis) was found to have a marked leukocytosis due to a lymphocytosis on routine quarantine laboratory data prior to inclusion in a preclinical research study. The majority of lymphocytes were characterized as intermediate to large with round to convoluted nuclei, coarse to clumped chromatin, rare prominent nucleoli, and moderate amounts of lightly basophilic cytoplasm that frequently contained small magenta granules and/or clear vacuoles. The animal had tested negative for several viruses and other etiologic agents found in nonhuman primates 1 week prior to shipment to the research facility. However, further evaluation of the blood smear revealed rare hemoflagellates, and later testing using real-time PCR and ELISA was confirmatory for Trypanosoma cruzi (T cruzi). Trypanosoma cruzi is a zoonotic pathogen responsible for Chagas disease in people and can have negative consequences on study results when positive animals are inadvertently used for preclinical research. This case report describes a marked large granular lymphocytosis in an otherwise healthy macaque as the only indication of infection with T cruzi in an animal believed to be negative for the infection. Additionally, it highlights the diagnostic limitations of screening tests to rule out diseases in animals intended to be used in preclinical studies.     

Molecular identification and characterization of Mycobacterium avium subspecies paratuberculosis in free living non-human primate (Rhesus macaques) from North India

In recent years, Mycobacterium avium subspecies paratuberculosis (MAP) has emerged as major animal pathogen with significant zoonotic concerns, worldwide. MAP infection is endemic in domestic and wild ruminant population in India. However, information on MAP infection in free ranging animal species and non human primates is limited. Present study aimed to estimate the status of MAP infection in free living Rhesus macaques suffering with multiple clinical conditions (coughing and loose stool). A total of 25 stool samples were collected from six colonies of Rhesus macaques from Mathura region (North India) and screened for the presence of MAP, using microscopic examination and IS900 PCR, directly from stool samples. PCR positive DNA samples were further genotyped using IS1311 PCR-restriction enzyme analysis. Of the 25 stool samples, 10 (40.0%) and 2 (8.0%) were positive for MAP using microscopic examination and direct IS900 PCR, respectively. IS900 PCR positive DNA samples were genotyped as ‘Indian Bison type’, which is a major MAP genotype infecting domestic and wild ruminant species and human beings in India. Prevalence of MAP in Rhesus macaques (Indian monkeys) was moderately high and confirmed interspecies sharing of MAP between domestic livestock and non-human primates. Presence of MAP in non-human primates, support the etiological role of MAP in inflammatory bowel disease patients. Indian monkeys may serve as model for understanding the role of non-human primates in sustenance, transmission and pathogenesis of MAP infection.     

TT virus infection in gibbons.

TT virus (TTV) is not only an infectious agent of worldwide distribution but has also been demonstrated in various non-human primates in addition to humans. In the present study, we subjected the sera of 67 gibbons to PCR and nucleotide sequencing, with subsequent phylogenetic analysis to determine the nature of the relationship between TTV found in humans and non-human primates. We discovered the virus in 9/67 (13.4%) of the gibbon sera and subjected 6 of those to direct sequencing. The phylogenetic tree constructed encompassed all TTV species known to date, revealing a close proximity between the gibbon virus and those detected in Thai individuals, whereas the chimpanzee strains were phylogenetically more remote.     

Animal models for human metapneumovirus (HMPV) infections

Since its detection in 2001 the human Metapneumovirus (HMPV), a member of the Paramyxoviridae family, was observed to be a serious pathogen in human respiratory infections during childhood. Meanwhile, several animal models have been established to study the virus-host interactions and pathogenic effects. Mainly, small laboratory animals like mice and cotton rats have been used, although the usage of these two species for HMPV research is controversially discussed and contradictious results were obtained by different groups. Further trials with ferrets, hamsters and non human primates were performed revealing different success in their individual usage. In this review we present the different animal models, summarize their advantages and disadvantages, and discuss the controversial results from different studies.     

Stereology of the liver in three species of Leontopithecus (Lesson, 1840) Callitrichidae--primates

Studies on liver morphology and stereology are relevant to the comparative anatomical and pathological research. They also facilitate the use of non-human primates in basic research, which has substantially supported studies in human medicine. Quantitative studies of liver structures have also been more extensive in Old World primates and other vertebrates. Twenty-three livers of adult lion tamarins were studied (six Leontopithecus rosalia, seven Leontopithecus chrysomelas, and 10 Leontopithecus chrysopygus), dissected, and fixed in 10% neutral buffered formalin solution. For stereological quantification, the liver was regarded as consisting of parenchyma (hepatocytes) and stroma (non-hepatocytes). The volume density (V(v)) was determined by point counting, and the disector method was used to obtain the numerical density of hepatocytes (N(v)). Hepatic stereological differences among the three species of lion tamarins were not statistically significant. Therefore, the pooled V(v[hepatocyte]) and V(v[stroma]) could be determined as 96.2 and 7.4%, respectively, and N(v[hepatocyte]) as 500.33 x 10(6) cm(-3). Significantly different, the values found for V(v[hepatocyte]) and N(v[hepatocyte]) in lion tamarins were, respectively, 0.09 and 2.8 times greater than those in baboons, and 0.17 and 3.8 times greater than those in man. However, the V(v[stroma]) was 1.04 times smaller than that in baboons and 1.79 times smaller than that in man.     

Implications of simian retroviruses for captive primate population management and the occupational safety of primate handlers.

Nonhuman primates can be naturally infected with a plethora of viruses with zoonotic potential, including retroviruses. These simian viruses present risks to both captive nonhuman primate populations and persons exposed to nonhuman primates. Simian retroviruses, including simian immunodeficiency virus, simian type D retrovirus, simian T-lymphotropic virus, and gibbon ape leukemia virus, have been shown to cause clinical disease in nonhuman primates. In contrast, simian foamy virus, a retrovirus that is highly prevalent in most nonhuman primates, has not been associated with clinical disease in naturally infected primates. Although it has been shown that human retrovirus infections with human T-lymphotropic virus and human immunodeficiency virus originated through multiple independent introductions of simian retroviruses into human populations that then spread globally, little is known about the frequency of such zoonotic events. In this article, exogenous simian retroviruses are reviewed as a concern for zoo and wildlife veterinarians, primate handlers, other persons in direct contact with nonhuman primates, and other nonhuman primates in a collection. The health implications for individual animals as well as managed populations in zoos and research institutions are discussed, the cross-species transmission and zoonotic disease potential of simian retroviruses are described, and suggestions for working safely with nonhuman primates are provided.     

Occurrence of hemotropic mycoplasmas in non-human primates (Alouatta caraya,Sapajus nigritus and Callithrix jacchus) of southern Brazil

Hemoplasmas, the erythrocyte-associated mycoplasmas, have been detected in several primates, causing mostly subclinical infection. This study aimed to determine the prevalence of hemoplasma infection in captive and free-ranging monkeys from southern Brazil, as well as factors and hematological abnormalities associated with infection. Blood samples from 40 non-human primates (NHP) were tested for hemoplasmas and coinfections. An overall of 10/40 (25.0%) NHP tested positive for hemoplasmas using PCR-based assays, including 9/14 (64.3%) black howler monkeys (Alouatta caraya) and 1/24 (4.2%) black-horned capuchin (Sapajus nigritus). Infection was not statistically associated with anemia, but wild-born monkeys and male black howler monkeys were more likely to be positive when compared with captive-born animals and female black howler monkeys, respectively. The sequences from the black howler monkey hemoplasma were similar (94% identity) to the squirrel monkey hemoplasma (“Candidatus Mycoplasma kahanei”) and were phylogenetically located in a different cluster when compared to the human hemoplasma (“Candidatus Mycoplasma haemohominis”).     

Canine periodontitis: the dog as an important model for periodontal studies

Periodontal disease (PD) refers to a group of inflammatory diseases caused by bacterial plaque in the periodontium and ranges from an early stage (gingivitis) to an advanced stage (periodontitis). It is a multifactorial disease that results from the interaction of the host defence mechanisms with the plaque microorganisms. Early detection, diagnosis and treatment are essential in the control of this disease. PD has an enormous impact on human and veterinary medicine due to its high prevalence. The most common animal PD models use dogs and non-human primates, although other animals (rats, mice, hamsters, rabbits, miniature pigs, ferrets, and sheep) have also been employed. Dog models have contributed significantly to the current understanding of periodontology. The most important clinical aspects of canine PD are considered in this review and the various animal models are examined with an emphasis on the role of the dog as the most useful approach for understanding human PD and in the development of new therapeutic and preventive measures.     

Genetics and disease resistance

Genetic components of disease resistance have been described in most of important diseases in human as well as in laboratory and livestock animals. However the basic mechanisms have been established in a few examples only. The reasons herefore are the mostly polygenic inheritance of disease resistance traits, the missing of suitable animal models and the dominance of environmental effects like infection pressure, immune status, and stressors, limiting the view on responsible gene variants. Ethical and practical aspects may further hinder research on disease resistance in certain species. Livestock animals play a crucial role in disease resistance research, because of distinct genetic diversity within and between breeds, because of an often distinct metabolic congruency with humans, and aiming towards the improvement of hygiene and economy of production and animal welfare. The following sections will review disease resistance in livestock animals and their practical implications, completed by examples of our own research activities.     

Anatomy of the dura mater venous sinus of Alouatta belzebul

The anatomy of the dura mater's venous sinuses is important in the veterinary clinical and surgical area, for cranial procedures and interventions of wild animals, in addition to assisting in the management of neurological diseases, which can prevent serious complications. The macroscopic anatomy of the venous sinuses of the dura mater of Alouatta belzebul was studied. Five adult specimens, males and females, were dissected and fixed in 10% formaldehyde solution. In the dura mater of the Alouatta belzebul, nine venous sinuses were observed, being them dorsal sagittal sinus, ventral sagittal sinus, transverse sinus, straight sinus, sigmoid sinus, temporal sinus, parietal sinus, basilar sinus and cavernous sinus, with morphological similarities in origin, path and destination of blood flow to the internal jugular vein, assisting in the venous drainage function of the brain in this species. These data are similar to those found in other species of non-human and human primates such as Saimiri sciureus, Sapajus libidinosus and Homo sapiens. Of the venous sinuses observed, the cavernous sinus was of considerable clinical and surgical importance in Alouatta belzebul due to its topographic arrangement next to the internal carotid artery and pituitary gland, data that corroborate Sapajus libidinosus, Macaca fascicularis, Macaca mulatta, Papio ursinus, Cercopithecus pygerithrus and Galago senegalensis. In this context, the knowledge of the macroscopic anatomy of the venous sinuses of the dura mater may contribute to the role of veterinarians in less invasive surgical procedures in non-human primates such as Alouatta belzebul and other mammals.