Nonhuman Primate Diseases of Relevance in Drug Development and their Impact on the Interpretation of Study Findings

Saravanan, Chandrassegar; Sasseville, Vito G.; Mansfield, Keith G.

doi:10.1016/b978-0-12-417144-2.00010-x

Cited by 9 publications

(9 citation statements)

References 147 publications

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“…Both interstitial and subpleural mineralization was found in 70 marmosets (10.97 %) and was largely regarded to be of metastatic origin as there was co-existing mineralization of other tissues with accentuation on basal lamina structures. Taking into consideration that the diet for young marmosets in the German Primate Center is supplemented with vitamin D to prevent rachitic lesions, soft tissue mineralization in the common marmosets was likely due to hypervitaminosis D, which is a well-known nutritional disease entity in New World monkeys (Hunt, 1969;Kaspareit et al, 2006;McInnes, 2012;Saravanan et al, 2015). Circumscribed areas of interstitial and subpleural fibrosis occurred in 23 juvenile and adult marmosets (3.61 %) and presumably represent residua from earlier tissue damage.…”

Section: Discussionmentioning

confidence: 99%

Spontaneous lung pathology in a captive common marmoset colony (Callithrix jacchus)

et al. 2017

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Abstract. Data on spontaneous pathology are substantially scarce for common marmosets, compared to other laboratory animals, but is essential for the interpretation of histological findings in the context of toxicological and experimental studies. Especially if common marmosets are used as experimental animals in respiratory research, detailed knowledge on the spectrum, occurrence, and incidence of spontaneous histopathological pulmonary lesions in this non-human primate species is required. In this study, lung tissue of 638 common marmosets from the marmoset colony of the German Primate Center was examined histologically. The analysis revealed a high incidence of predominantly mild and multifocal interstitial pneumonia (32.99 %) of unknown etiology in most cases. Only few marmosets exhibited lobar pneumonia (1.41 %) and bronchopneumonia (0.94), which were mainly caused by bacterial pathogens such as Bordetella bronchiseptica and Klebsiella pneumoniae. Lung immaturity and atelectasis were common histological findings in newborn marmosets. Typical background lesions included anthracosis (8.15 %), hemosiderosis (1.72 %), extramedullary hematopoiesis (11.6 %), mineralization (10.97 %), and inflammatory cell foci (10.34 %). In addition, three cases of pulmonary arteriopathy (0.47 %) and 1 case of foreign-body granuloma (0.16 %) were detected in the marmoset study cohort. The high prevalence of circulatory disturbances (congestion, edema, hemorrhage) and changes in air content (secondary atelectasis, alveolar emphysema) could partly be explained by euthanasia-related artifacts or agonal changes. The present study provides a comprehensive overview of the range and incidence of spontaneous pulmonary histopathology in common marmosets, serving as valuable reference data for the interpretation of lung lesions in toxicological and experimental marmoset studies.

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Section: Discussionmentioning

confidence: 99%

Spontaneous lung pathology in a captive common marmoset colony (Callithrix jacchus)

et al. 2017

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“…Humans are the only natural hosts that sustain measles virus transmission 27 . Most NHP species are susceptible to measles infections from their infected human handlers 28 . Measles belongs to the family Paramyxoviridae.…”

Section: Viral Infectionmentioning

confidence: 99%

“…Overview. CMV infects captive rhesus and cynomolgus macaques without clinical signs and seroprevalence of CMV is high (more than 90% in all populations tested and almost 100% in adults 16 , 28 , 35 , 47 , 48 ). Latent CMV activation is one of the most commonly observed opportunistic infections in immunocompromised macaques, which can be attributed to the high prevalence of CMV (similar to that in humans) 49 .…”

Section: Viral Infectionmentioning

confidence: 99%

Pathologic characteristics of infectious diseases in macaque monkeys used in biomedical and toxicologic studies

Ohta

2023

J Toxicol Pathol

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Nonhuman primates (NHPs), which have many advantages in scientific research and are often the only relevant animals to use in assessing the safety profiles and biological or pharmacological effects of drug candidates, including biologics. In scientific or developmental experiments, the immune systems of animals can be spontaneously compromised possibly due to background infection, experimental procedure-associated stress, poor physical condition, or intended or unintended mechanisms of action of test articles. Under these circumstances, background, incidental, or opportunistic infections can seriously can significantly complicate the interpretation of research results and findings and consequently affect experimental conclusions. Pathologists and toxicologists must understand the clinical manifestations and pathologic features of infectious diseases and the effects of these diseases on animal physiology and experimental results in addition to the spectrum of infectious diseases in healthy NHP colonies. This review provides an overview of the clinical and pathologic characteristics of common viral, bacterial, fungal, and parasitic infectious diseases in NHPs, especially macaque monkeys, as well as methods for definitive diagnosis of these diseases. Opportunistic infections that can occur in the laboratory setting have also been addressed in this review with examples of cases of infection disease manifestation that was observed or influenced during safety assessment studies or under experimental conditions.

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“…Lastly, but by no means least, environmental factors including early or later exposure to pathogenic or nonpathogenic infectious agents, microbiome, dietary, and other local ecosystem variability (such as ambient temperatures, water source, indoor/outdoor access), and effects of social hierarchies in group-housed animals can all contribute to the ultimate response of an animal to any given stimulus or a xenobiotic. Animals from the same original breeding colony but housed in varying holding colonies, or sourced from different vendors and mixed in one holding facility can have variable background incidences of, and exposures to, bacterial, viral, parasitic, and fungal agents, resulting in different susceptibility to pathogens and/or innate immune responses once placed together on study (Mansfield, Sasseville, and Westmoreland 2014;Sasseville and Mansfield 2010;Sasseville and Diters 2008;Sasseville et al 2012;Saravanan, Sasseville, and Mansfield 2015).…”

Section: Cynomolgus Macaquesmentioning

confidence: 99%

Impact of the Genetics and Source of Preclinical Safety Animal Models on Study Design, Results, and Interpretation

Colman

2016

Toxicol Pathol

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It has been long established that not only the species but also the strain and supplier of rodents used in preclinical safety studies can have a significant impact on the outcome of studies due to variability in their genetic background and thus spontaneous pathologic findings. In addition, local husbandry, housing, and other environmental conditions may have effects on the development and expression of comorbidities, particularly in longer-term or chronic studies. More recently, similar effects related to the source, including genetic and environmental variability, have been recognized in cynomolgus macaques ( Macaca fascicularis). The increased use of cynomolgus macaques from various sources of captive-bred animals (including nonnative, U.S./European Union-based breeding facilities or colonies) can affect study design and study results and outcome. It is important to acknowledge and understand the impact of this variability on the results and interpretation of research studies. This review includes recent examples where variability of preclinical animal models (rats and monkeys) affected the postmortem observations highlighting its relevance to study design or interpretation in safety studies.

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Nonhuman Primate Diseases of Relevance in Drug Development and their Impact on the Interpretation of Study Findings

Cited by 9 publications

References 147 publications

Spontaneous lung pathology in a captive common marmoset colony (Callithrix jacchus)

Spontaneous lung pathology in a captive common marmoset colony (Callithrix jacchus)

Pathologic characteristics of infectious diseases in macaque monkeys used in biomedical and toxicologic studies

Impact of the Genetics and Source of Preclinical Safety Animal Models on Study Design, Results, and Interpretation

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