Naturally occurring infections in non-human primates (NHP) and immunotoxicity implications: Discussion sessions

Olivier, Kenneth J.; Price, Karen; Hutto, David; Lerche, Nicholas W.; Mansfield, Keith G.; Simmons, Joe H.; Taylor, Katrina; Myers, L. Peyton; Ouyang, Yanli; Evans, Evan

doi:10.3109/1547691x.2010.480948

Cited by 6 publications

(6 citation statements)

References 22 publications

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Section: Resultsmentioning

confidence: 99%

“…Mauritius NHP are reported to be free of several simian viruses (Simian Immunodeficiency Virus (SIV), measles, Simian Retroviruses (SRV-1 and -2), Simian T-lymphotrophic Viruses (STLV-I and -III), and B-virus) that can be found in NHPs from other origins. 8 In one study, there were no relevant differences reported on clinical observations and pathogen screening (viral, fecal parasitology and fecal culture) between NHPs of Mauritius (N = 10/sex) and Asian origin (N = 20/sex), 9 although there were fewer spontaneous physiologic and anatomic abnormalities in the Mauritius origin animals compared to Asian origin. This is consistent with findings from another study where there was an increase in lymphoplasmacytic cell infiltrate in the GI tract from Asian origin NHPs.…”

Section: Demographicsmentioning

confidence: 96%

“…NHP exclusion via pre-screening is a critical step in eliminating confounding variables that can impact study data interpretation. 8 Sixty-two percent (62%; 20 of 32) of responses excluded NHPs from supplier shipments for one or more criteria as shown in Figure 2C, while 34% (11 of 32) indicated they did not know/ deferred to CRO practices. Amongst the 20 responses that used pre-defined criteria for exclusion, a majority (>60%) used viral and enteric pathogen screening, followed by body condition score and history of gastroenteritis/diarrhea.…”

Section: Nhp Pre-study Exclusion Criteriamentioning

confidence: 99%

“…These screening practices are required for maintaining and expanding specific pathogen free (SPF) NHP supply as it relates to the risk of disease and complications on studies and have a substantial impact on data interpretations from toxicology studies. 8 There was wide variation in the frequency of viral screening with more frequent screening being associated with fewer health issues. Thirty-six percent (11 of 31) of responses indicated that they screened only once pre-study or preshipment with 10% (3 of 31) screening more frequently and one response screening every 90 days before shipping.…”

Section: Nhp Serology Testing Practicesmentioning

confidence: 99%

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Non-Human Primate Husbandry and Impact on Non-Human Primates Health: Outcomes From an IQ DruSafe/3RS Industrial Benchmark Survey

et al. 2022

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The presence of health issues (diarrhea, poor body condition) in non-human primates can impact animal welfare, confound toxicity study data, and lead to animal exclusion from studies. A working group cosponsored by DruSafe and 3Rs Translational and Predictive Sciences Leadership Groups of the IQ Consortium conducted a survey to benchmark quarantine, pre-study screening, husbandry, and veterinary care practices and their impact on NHP health. Nineteen companies participated in the survey providing separate responses for studies conducted in-house and at Contract Research Organizations from 3 regions (North America (NA), Europe and Asia) for an aggregate of 33 responses. A majority of responding companies conducted studies at North America CROs (39%) or in-house (36%) using primarily Chinese (33%) or Cambodian (27%) and to a lesser extent Vietnam (18%) or Mauritian (15%) origin NHPs. Forty-Five percent of responses had pre-study health issues (fecal abnormalities, etc.) on ≥ 1 studies with the highest incidence observed in Vietnam origin NHPs (80%). The survey suggested variable pre-screening and quarantine practices across facilities. Husbandry practices including behavioral assessments, environmental enrichment and consistent diets were associated with a lower incidence of health issues. The survey also benchmarked approaches used to diagnose and manage abnormal feces in NHPs and has provided strategies to minimize impact on NHP health. The survey highlighted opportunities for harmonizing screening criteria across industry and for improving tracking and sharing of health screening results, leading to further refinement of NHP veterinary care practices, higher quality studies, and reduced NHP use.

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Section: Resultsmentioning

confidence: 99%

Section: Demographicsmentioning

confidence: 96%

Section: Nhp Pre-study Exclusion Criteriamentioning

confidence: 99%

Section: Nhp Serology Testing Practicesmentioning

confidence: 99%

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Non-Human Primate Husbandry and Impact on Non-Human Primates Health: Outcomes From an IQ DruSafe/3RS Industrial Benchmark Survey

et al. 2022

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“…As noted above, NHP may still carry a number of viral, bacterial, or parasitic organisms that under conditions of immunosuppression can become fulminate, leading to moribundity and mortality (Olivier et al 2010). Captive macaques have a high incidence of chronic enterocolitis because of the presence of opportunistic and/or obligate parasites.…”

Section: Rodentsmentioning

confidence: 99%

Small Molecule Immunomodulatory Drugs

Haley

2011

Toxicol Pathol

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As the molecular pathobiology of immunologically based diseases, such as rheumatoid arthritis, has become clearer, pharmaceutical researchers have responded with highly efficacious and selective biological compounds. In contrast to older, nonspecific small-molecule therapeutics, the exquisite species sensitivity of monoclonal antibodies has introduced new challenges to preclinical safety studies. Repeated exposure of animals to biopharmaceutical compounds tends to be restricted in the species in which these compounds have pharmacological action, and it tends to stimulate antidrug immune responses with acceleration of clearance, thereby limiting the duration of repeat-dose studies and potentially resulting in hypersensitivity reactions. Thus, the safety testing of biopharmaceutical compounds has necessitated the use of relatively short-term studies in rodents, whereas nonhuman primates have become the primary tool for large-animal, repeat-dose studies. However, as the number of highly targeted and efficacious small-molecule immunomodulators rapidly increases, these molecules will be developed in a manner similar to that of other small molecules with regard to safety assessment. Because such approaches inherently push drug levels to achieve maximally tolerated doses, the pharmacologic specificity of these new small-molecule drugs may be lost as they affect additional receptors and pathways. Therefore, toxicologic pathologists must refamiliarize themselves with the consequences of profound immunosuppression in species other than nonhuman primates. The interrelationships of cytokine signaling and receptor biology are complex, highly integrated, and at times paradoxical, and the loss of specificity at high doses may result in unforeseen consequences caused by the impact on complex down-stream pathways that culminate in exaggerated and adverse responses. The species specificity of such responses may not be inherently familiar or anticipated.

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Pathology Evaluation for Detection of Immunomodulation

Parker

Snyder

2017

Immunopathology in Toxicology and Drug Development

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Naturally occurring infections in non-human primates (NHP) and immunotoxicity implications: Discussion sessions

Cited by 6 publications

References 22 publications

Non-Human Primate Husbandry and Impact on Non-Human Primates Health: Outcomes From an IQ DruSafe/3RS Industrial Benchmark Survey

Non-Human Primate Husbandry and Impact on Non-Human Primates Health: Outcomes From an IQ DruSafe/3RS Industrial Benchmark Survey

Small Molecule Immunomodulatory Drugs

Pathology Evaluation for Detection of Immunomodulation

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