The COVID-19 pandemic brings new challenges to the management of non-human primate (NHP) colonies for breeding, research, conservation, or other settings. The increasing human prevalence of the novel coronavirus, SARS-CoV-2, and evolving understanding of its transmission, particularly from asymptomatic carriers, 1-3 requires that the risk of human-to-NHP, NHP-to-NHP, and potentially NHP-to-human transmission be mitigated (Figure 1). Non-human primates (including macaca, cercopithecus, and papio species) can be infected with SARS-CoV-2. 4-6 Conversely, experimental trials to infect marmosets (Callithrix spp.) have not shown any signs of active infection. 7 The potential for SARS-CoV-2 to cause clinical disease in NHPs has been variable under experimental conditions. 8,9 Studies to determine whether certain populations (age, co-morbidities) are at greater risk of infection and/or clinical disease are in progress. 10,11 Although early data indicate that macaques that are experimentally infected are immune to reinfection, 12 the durability
OBJECTIVE To develop a testing algorithm that incorporates multiple assays to evaluate host cellular and humoral immunity and antigen detection concerning Mycobacterium tuberculosis complex (MTBC) infection in captive nonhuman primates. ANIMALS Cohorts of captive-bred and wild-caught macaques from 5 different geographic regions. PROCEDURES Macaques were tested for MTBC infection by use of a γ interferon tuberculosis (GIFT) assay, an interferon-γ release assay, and other assays. In the first 2 cohorts (n = 15 and 181), initial validation of the GIFT assay was performed by use of experimentally infected and unexposed control macaques. In the next 3 cohorts (n = 59, 42, and 11), results were obtained for opportunistically collected samples from macaques exposed during spontaneous outbreaks. RESULTS Sensitivity and specificity of the GIFT assay in the control cohorts were 100% and 97%, respectively, and were variable but enhanced by incorporating results from multiple assays in spontaneous outbreaks. CLINICAL RELEVANCE The detection and management of MTBC infection in captive nonhuman primate populations is an ongoing challenge, especially with animal imports and transfers. Despite standardized practices of initial quarantine with regular intradermal tuberculin skin testing, spontaneous outbreaks continue to be reported. Since infection encompasses a range of disease manifestations over time, a testing algorithm that incorporates multiple assays, such as the GIFT assay, to evaluate host cellular and humoral immunity in addition to agent detection is needed. Testing a combination of samples from controlled studies and spontaneous outbreaks of MTBC infection in nonhuman primates would advance the development and validation of a functional algorithm that incorporates promising tools such as the GIFT assay.
To better understand Simian betaretrovirus (SRV) seropositivity in virus negative macaques, we transfused blood from SRV infected or suspect donors into immunosuppressed naive recipients. Our results do not support typical SRV1-5 infection as the cause, but provide evidence for several possibilities including serological artifact, new/different SRV, or an endogenous virus.
[3H]Cimetidine, a radiolabeled histamine H2 receptor antagonist, binds with high affinity to an unknown hemoprotein in the brain which is not the histamine H2 receptor. Improgan, a close chemical congener of cimetidine, is a highly effective pain-relieving drug following CNS administration, yet its mechanism of action remains unknown. To test the hypothesis that the [3H]cimetidine-binding site is the improgan antinociceptive target, improgan, cimetidine, and 8 other chemical congeners were studied as potential inhibitors of [3H]cimetidine binding in membrane fractions from the rat brain. All compounds produced a concentration-dependent inhibition of [3H]cimetidine binding over a 500-fold range of potencies (Ki values were 14.5 to >8,000 nM). However, antinociceptive potencies in rats did not significantly correlate with [3H]cimetidine-binding affinities (r = 0.018, p = 0.97, n = 10). These results suggest that the [3H]cimetidine-binding site is not the analgesic target for improgan-like drugs.
Introduction In early 2020, the California National Primate Research Center implemented surveillance to address the threat of SARS‐CoV‐2 infection in its nonhuman primate colony. Materials/Methods To detect antiviral antibodies, multi‐antigen assays were developed and validated on enzyme immunoassay and multiplex microbead immunofluorescent assay (MMIA) platforms. To detect viral RNA, RT‐PCR was also performed. Results/Conclusion Using a 4plex, antibody was identified in 16/16 experimentally infected animals; and specificity for spike, nucleocapsid, receptor binding domain, and whole virus antigens was 95.2%, 93.8%, 94.3%, and 97.1%, respectively on surveillance samples. Six laboratories compared this MMIA favorably with nine additional laboratory‐developed or commercially available assays. Using a screen and confirm algorithm, 141 of the last 2441 surveillance samples were screen‐reactive requiring confirmatory testing. Although 35 samples were reactive to either nucleocapsid or spike; none were reactive to both. Over 20 000 animals have been tested and no spontaneous infections have so far been confirmed across the NIH sponsored National Primate Research Centers.
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