Zoonotic schistosomiasis in non-human primates: past, present and future activities at the human-wildlife interface in Africa

Schistosomiasis is one of the world's most widely distributed and prevalent parasitic diseases. Less widely recognized is that some species of Schistosoma, including several that commonly affect humans, also cause disease in other mammalian species; in particular, infections in non-human primates are known. With interest increasing in emerging zoonotic diseases, the status of schistosomiasis as a zoonotic infection is in need of re-appraisal, especially in light of advances in application of molecular screening and epidemiological tools where newly reported infections raise general animal welfare and conservation concerns. Focusing on Africa, this review provides a summary of the occurrence of schistosomiasis in non-human primates and discusses new ways in which surveillance for schistosomiasis should be integrated into more effective conservation management and disease control strategies. Emphasis is on the more common forms of human schistosomiasis, their clinical manifestations and epidemiological significance in terms of infection reservoir potential.     

恒河猴在生殖生物学中的应用进展

目的非人灵长类动物在生殖生物学研究领域是一种非常重要的实验动物。人类利用非人灵长类动物与人的生物学等方面相似的特征,开展了生殖生物学、生理学、药理学、毒理学以及生育调节等方面的研究工作,为生殖生物学基础研究以及人类健康和疾病问题的基础研究和临床前研究提供了理想的动物模型。随着生命科学的发展,对非人灵长类实验动物质量提出了更高的要求,人们认识到实验时,应用健康的优质非人灵长类动物的重要性。本文简要概括了非人灵长类动物恒河猴的生物学特性,阐述了非人灵长类动物恒河猴在生殖生物学中的应用研究。     

非人灵长类局部脑缺血动物模型研究现状

非人灵长类动物在种系发生上较啮齿类更接近于人类,用来制备局部脑缺血模型可以更好的拟合临床症状和机理。通过对国内外非人灵长类动物局部脑缺血模型的制备方法和应用现状进行收集、分类和述评,展望非人灵长类动物模型的应用前景,尤其是利用低等灵长类动物树鼩研究缺血性中风的优势。     

The use of non-human primates in biological and medical research: evidence submitted by FRAME to the Academy of Medical Sciences/Medical Research Council/Royal Society/Wellcome Trust Working Group

The Academy of Medical Sciences, the Medical Research Council, the Royal Society and the Wellcome Trust are undertaking a study into the use of non-human primates in biological and medical research. An independent working group of scientific experts, led by Sir David Weatherall, aims to produce a report summarising the findings of this study, early in 2006. The trends in primate research, and the nature and effects of recent and proposed changes in the global use of non-human primates in research, will be investigated. The associated ethical, welfare and regulatory issues, and the role and impact of the Three Rs principles of refinement, reduction and replacement will also be reviewed. As part of this study, a call for evidence was made. The evidence submitted by FRAME emphasised that the use of non-human primates for fundamental research or for regulatory testing still fails to take into account the fact that, although non-human primates are anatomically and physiologically similar to humans, they are not necessarily relevant models for studies on human disease or human physiology. FRAME continues to believe that we have a duty to ensure that these animals are not used without overwhelming evidence that they are the only suitable and relevant models for use in work of undeniable significance.     

Animal models for filovirus infections

The family Filoviridae, which includes the genera Marburgvirus and Ebolavirus, contains some of the most pathogenic viruses in humans and non-human primates(NHPs), causing severe hemorrhagic fevers with high fatality rates. Small animal models against filoviruses using mice, guinea pigs, hamsters, and ferrets have been developed with the goal of screening candidate vaccines and antivirals, before testing in the gold standard NHP models. In this review, we summarize the different animal models used to understand filovirus pathogenesis, and discuss the advantages and disadvantages of each model with respect to filovirus disease research.     

非人灵长类声音通讯的研究进展

声音通讯是非人灵长类研究一个重要的研究领域,有助于了解非人灵长类的社会行为、个体关系、行为进化和社会演化等,甚至对探究人类语言起源和进化等方面也具有十分重要的意义。本文通过对非人灵长类声音通讯的研究内容、影响因素和研究方法等进行了梳理,探讨非人灵长类声音通讯研究的前景和展望,旨在进一步推动国内非人灵长类声音通讯研究的深入,同时为相关研究提供借鉴和参考。     

The contribution of animal models to the understanding of the host range and virulence of influenza A viruses

Since ferrets were first used in 1933 during the initial isolation of influenza A viruses, animal models have been critical for influenza research. The following review discusses the contribution of mice, ferrets, and non-human primates to the study of influenza virus host range and pathogenicity.     

The baboon as a non-human primate model of human schistosome infection

Over the past three decades, intensive studies of murine schistosomiasis have provided important clues to the understanding of the human disease, but growing evidence suggests that these results derived from highly inbred strains of mice might not have direct applicability to the human infection. Recent data based on the baboon indicate that infection in this non-human primate might mirror the human situation. In this review, Mramba Nyindo and Idle Farah demonstrate that baboons provide an excellent non-human primate model that produces pathology and disease closely resembling that observed in humans, and address how studies in baboons can provide insights into mechanisms regulating schistosomiasis mansoni pathology and immunity. They also address, in a general way, issues related to the use of non-human primates in biomedical research.     

鼠疫动物模型:经典与问题

一直以来,鼠疫菌的研究多围绕致病机制、疫苗效果评价及鼠疫治疗方案选择展开,而合理有效的鼠疫动物模型正是这些实验研究的基础与前提。研究者构建了包括小鼠、豚鼠及非人灵长类模型在内的多种动物模型,而这些模型也为人类认识、防御及治疗鼠疫菌提供了帮助,特别是一些经典动物模型沿用至今。但随着研究的深入,有些动物模型由于存在某种问题而逐渐被淘汰。本文就鼠疫菌动物模型构建以来,不同模型的优势与不足及其应用展开综述,以期为研究者提供参考。     

MPTP neurotoxicity: an overview and characterization of phases of toxicity

MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) produces unalloyed parkinsonism in humans when injected systemically, and has been effective in producing an animal model of Parkinson's disease in non-human primates. A distinction between toxic and pharmacologic effects of the compound is drawn, and basic criteria for animal models of human disease are reviewed, particularly as they relate to MPTP. A comparison between a unique population of humans affected by this substance and non-human primates is presented. The syndrome of MPTP intoxication can be divided into three and possibly four phases, and the potential underlying mechanisms for the clinical and behavior observations of each phase are discussed.     

An effort to use human-based exome capture methods to analyze chimpanzee and macaque exomes

Non-human primates have emerged as an important resource for the study of human disease and evolution. The characterization of genomic variation between and within non-human primate species could advance the development of genetically defined non-human primate disease models. However, non-human primate specific reagents that would expedite such research, such as exon-capture tools, are lacking. We evaluated the efficiency of using a human exome capture design for the selective enrichment of exonic regions of non-human primates. We compared the exon sequence recovery in nine chimpanzees, two crab-eating macaques and eight Japanese macaques. Over 91% of the target regions were captured in the non-human primate samples, although the specificity of the capture decreased as evolutionary divergence from humans increased. Both intra-specific and inter-specific DNA variants were identified; Sanger-based resequencing validated 85.4% of 41 randomly selected SNPs. Among the short indels identified, a majority (54.6%-77.3%) of the variants resulted in a change of 3 base pairs, consistent with expectations for a selection against frame shift mutations. Taken together, these findings indicate that use of a human design exon-capture array can provide efficient enrichment of non-human primate gene regions. Accordingly, use of the human exon-capture methods provides an attractive, cost-effective approach for the comparative analysis of non-human primate genomes, including gene-based DNA variant discovery.     

SARS病毒感染动物模型

SARS-CoV感染动物模型的建立可加深对SARS病原学的了解和发病机制的研究,加速实验室诊断技术的建立、抗病毒药物的筛选和疫苗的开发,同时也有助于给该病一个更精确的定义。可以说SARS动物模型的建立,不但是SARS研究的瓶颈问题,其应用更是贯穿SARS研究的整个过程。到目前为止,已经报道有4种非人灵长类动物(恒河猴、食蟹猴、绒猴、非洲绿猴)和6种啮齿类动物(大鼠、小鼠、豚鼠、田鼠、仓鼠、转基因鼠),以及雪貂、家猫等可以作为SARS动物模型用于实验研究,并已经开始利用动物模型进行疫苗和药物的安全性和有效性评价。本文就已报道的各类SARS动物模型进行综述,并根据动物模型和SARS患者的比对,提出动物模型建立的技术要点。     

Seropositivity to HCV in Macaca fascicularis

Several non-human primate species are used as laboratory animals for research purposes. Non human primates represent a potential hazard for laboratory animal handlers as they exceed all other species in importance as potentiators of disease in laboratory personnel (Quist K.D., 1972). Hepatitis viruses cause some of the prevalent diseases in man which constitute an important public health problem. The first outbreak of the infection was related to non human primates and occurred in 1958-1960 in USA, with more then 200 human cases. Chimpanzee is the main species that has been implicated but others have also been involved. We report a case of seropositivity to HCV antigens in Macaca fascicularis using a third generation RIBA assay. The nature of reactivity of the positive samples could not be resolved as no animal in the breeder colony had been exposed to an HCV source. Furthermore, Macaca spp. did not appear to be a susceptible species in previous studies.     

Detection of early secretory antigenic target-6 antibody for diagnosis of tuberculosis in non-human primates

Tuberculosis is one of the most economically devastating, zoonotic infections of captive non-human primates. The limitations of the tuberculin skin test, which is currently used to diagnose tuberculosis in living non-human primates, make it necessary to find new, simple, and economical diagnostic methods. We describe use of an enzyme-linked immunoassay to detect IgG antibodies against early secretory antigenic target (ESAT)-6, a small protein secreted by virulent tubercle bacilli, in paired (pre- and post-outbreak) sera from 57 non-human primates involved in an outbreak of Mycobacterium bovis infection in a research colony. Of 25 animals with tuberculosis lesions at necropsy, 22 (88%) had high serum levels of the ESAT-6 antibody. The ESAT-6 antibody was found in 16% (5/32) of post-outbreak sera from animals in which tuberculosis could not be confirmed at necropsy. The strong association between the ESAT-6 antibody and tuberculosis in non-human primates documented in this study, together with the robustness of the serologic assay, make the ESAT-6 ELISA a valuable tool for diagnosis of tuberculosis in captive non-human primates.     

非人灵长类个体的迁移与扩散

迁移现象在群居动物中普遍存在、在非人灵长类中尤为突出。在非人灵长类中,大多数的迁移表现出强烈的雄性偏向性和雌性不进行迁移的形式。在一些少数的物种中,也存在雌雄双方都进行迁移以及雌性偏向性迁移而雄性不迁移的形式。群居种类、一夫一妻制种类、独居种类的迁移模式上各有特色且不尽相同,这是动物社群结构多样性的体现。驱赶和异性的吸引是推动个体迁移的两大动力,驱赶多发生在一雄多雌的社群中,异性吸引多发生在无亲缘关系的个体之间。个体迁移过程,是个体付出与收益的平衡。迁移不仅是非人灵长类动物生活史中的一个重要环节,同时在不同种群间个体基因交流上也有明显的作用。     

Olive baboon (Papio anubis anubis) as a model for intrauterine research

BACKGROUND: The Olive baboon is a popular animal model for reproductive and surgical research. The Institute of Primate Research, Nairobi, Kenya, has been using the animal for reproductive research for many years. In the baboon, compared with other smaller non-human primates, it is possible to insert uterine probes such as, catheters, curettes and other linear instruments (to cannulate cervix for uterine procedures like flushing, endometrium biopsy, embryo transfer, etc.). METHODS: However we noticed in a few animals this was difficult and problematic, particularly in some stages of the menstrual cycle, in retroverted uteri, in extensive adhesions or in some anatomically unique animals and we have developed a technique called 'Chai technique' for this purpose. RESULTS AND CONCLUSIONS: The Chai technique is unique to the baboon and not possible in human. It does not seem to cause injuries as frequently as uterine perforation and, in our experience, has been surprisingly successful.     

Animal models for gastric Helicobacter immunology and vaccine studies

Over the last decade animal models have been used extensively to investigate disease processes and therapy for Helicobacter pylori infections. The H. pylori animal models which have been used in pathogenesis and vaccine studies include the gnotobiotic pig, non-human primates, cats, dogs, and several species of rodents including mice, rats, gerbils and guinea pigs. H. felis infection of mice and H. mustelae infection of ferrets have also been used. Recently, investigators have begun using transgenic mice and gene-targeted 'knock-out' mice to investigate Helicobacter infections. Each of these animal models has distinct advantages and disadvantages which are discussed in this minireview. The choice of an animal model is dictated by factors such as cost and an understanding of how each model will or will not allow fulfillment of experimental objectives.     

促进人工饲养实验猕猴心理康乐

目的促进实验猕猴心理康乐,既能减少动物异常行为的发生、获得可靠的科学数据,同时也是实现这一珍贵非人灵长类实验动物福利的重要内容。实验猕猴社会化集群、环境优化、婴猴饲养方式是影响动物心理康乐几个较大的因素,本文对其研究进展进行了综述,对推进我国灵长类实验动物福利具有积极作用。     

Advantages and limitations of nonhuman primates as animal models in genetic research on complex diseases

Abstract: The genetic similarity between humans and nonhuman primates makes nonhuman primates uniquely suited as models for genetic research on complex physiological and behavioral phenotypes. By comparison with human subjects, nonhuman primates, like other animal models, have several advantages for these types of studies: 1) constant environmental conditions can be maintained over long periods of time, greatly increasing the power to detect genetic effects; 2) different environmental conditions can be imposed sequentially on individuals to characterize genotype-environment interactions; 3) complex pedigrees that are much more powerful for genetic analysis than typically available human pedigrees can be generated; 4) genetic hypotheses can be tested prospectively by selective matings; and 5) essential invasive and terminal experiments can be conducted. Limitations of genetic research with nonhuman primates include cost and availability. However, the ability to manipulate both genetic and environmental factors in captive primate populations indicates the promise of genetic research with these important animal models for illuminating complex disease processes. The utility of nonhuman primates for biomedical research on human health problems is illustrated by examples concerning the use of baboons in studies of osteoporosis, alcohol metabolism, and lipoproteins.     

A review of the use of primates in studying human schistosomiasis

Rodents, useful models for studies of human schistosomiasis not ethically possible in man, are not satisfactory in every respect. Primates, in many ways better models than rodents, though too expensive for general use, remain invaluable for testing the relevance of rodent findings to man. Higher primates such as chimpanzees are ideal models but, as endangered species, should only be used for critical studies for which lower, nonhuman primates are unsuitable.