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BACKGROUND: A survey was developed to characterize disease incidence, common pathology lesions, environmental characteristics, and nutrition programs within captive research marmoset colonies. METHODS: 17 research facilities completed the electronic survey. RESULTS: Nutritional management programs varied amongst research institutions housing marmosets; eight primary base diets were reported. The most common clinical syndromes reported were gastrointestinal (GI) disease (i.e. inflammatory bowel disease (IBD) like disease, chronic lymphocytic enteritis (CLE), chronic malabsorption, chronic diarrhea), metabolic bone disease or fracture, infectious diarrhea, and oral disease (tooth root abscesses, gingivitis, tooth root resorption). The five most common pathology morphologic diagnoses were colitis, nephropathy/ nephritis, enteritis, chronic lymphoplasmacytic enteritis, and cholecystitis. Obesity was more common (average 20% of a reporting institution’s population) than thin body condition (average 5%). CONCLUSIONS: Through review of current practices, we aim to inspire development of evidence based practices to standardize husbandry and nutrition practices for marmoset research colonies.

Non-human primate models will expedite therapeutics and vaccines for coronavirus disease 2019 (COVID-19) to clinical trials. Here, we compare acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in young and old rhesus macaques, baboons and old marmosets. Macaques had clinical signs of viral infection, mild to moderate pneumonitis and extra-pulmonary pathologies, and both age groups recovered in two weeks. Baboons had prolonged viral RNA shedding and substantially more lung inflammation compared with macaques. Inflammation in bronchoalveolar lavage was increased in old versus young baboons. Using techniques including computed tomography imaging, immunophenotyping, and alveolar/peripheral cytokine response and immunohistochemical analyses, we delineated cellular immune responses to SARS-CoV-2 infection in macaque and baboon lungs, including innate and adaptive immune cells and a prominent type-I interferon response. Macaques developed T-cell memory phenotypes/responses and bystander cytokine production. Old macaques had lower titres of SARS-CoV-2-specific IgG antibody levels compared with young macaques. Acute respiratory distress in macaques and baboons recapitulates the progression of COVID-19 in humans, making them suitable as models to test vaccines and therapies.

SummaryThere are no known cures or vaccines for COVID-19, the defining pandemic of this era. Animal models are essential to fast track new interventions and nonhuman primate (NHP) models of other infectious diseases have proven extremely valuable. Here we compare SARS-CoV-2 infection in three species of experimentally infected NHPs (rhesus macaques, baboons, and marmosets). During the first 3 days, macaques developed clinical signatures of viral infection and systemic inflammation, coupled with early evidence of viral replication and mild-to-moderate interstitial and alveolar pneumonitis, as well as extra-pulmonary pathologies. Cone-beam CT scans showed evidence of moderate pneumonia, which progressed over 3 days. Longitudinal studies showed that while both young and old macaques developed early signs of COVID-19, both groups recovered within a two-week period. Recovery was characterized by low-levels of viral persistence in the lung, suggesting mechanisms by which individuals with compromised immune systems may be susceptible to prolonged and progressive COVID-19. The lung compartment contained a complex early inflammatory milieu with an influx of innate and adaptive immune cells, particularly interstitial macrophages, neutrophils and plasmacytoid dendritic cells, and a prominent Type I-interferon response. While macaques developed moderate disease, baboons exhibited prolonged shedding of virus and extensive pathology following infection; and marmosets demonstrated a milder form of infection. These results showcase in critical detail, the robust early cellular immune responses to SARS-CoV-2 infection, which are not sterilizing and likely impact development of antibody responses. Thus, various NHP genera recapitulate heterogeneous progression of COVID-19. Rhesus macaques and baboons develop different, quantifiable disease attributes making them immediately available essential models to test new vaccines and therapies.

Gastrointestinal disease is a frequently encountered problem among captive common marmoset (Callithrix jacchus) colonies. Management can be challenging due to the number of etiologies responsible for gastrointestinal disease in this species, limitations on diagnostic capabilities, and lack of effective treatments. Understanding commonly described GI diseases in the captive marmoset can provide insight on the impact these diseases have on research studies and aid in the development of appropriate management strategies. A review of commonly encountered GI disease processes as well as routinely implicated causes of GI disease in the common marmoset are provided. Current strategies in clinical management of GI disease in the common marmoset, including approaches to colony health, diagnostic testing, and commonly employed treatments are discussed.

Vitamin D(3) (cholecalciferol) is endogenously produced in the skin of primates when exposed to the appropriate wavelengths of ultra violet light (UV-B). Common marmosets (Callithrix jacchus) maintained indoors require dietary provision of vitamin D(3) due to lack of sunlight exposure. The minimum dietary vitamin D(3) requirement and the maximum amount of vitamin D(3) that can be metabolized by marmosets is unknown. Observations of metabolic bone disease and gastrointestinal malabsorption have led to wide variation in dietary vitamin D(3) provision amongst research institutions, with resulting variation in circulating 25-hydroxyvitamin D(3) (25(OH)D(3)), the accepted marker for vitamin D sufficiency/deficiency. Multiple studies have reported serum 25(OH)D(3) in captive marmosets, but 25(OH)D(3) is not the final product of vitamin D(3) metabolism. In addition to serum 25(OH)D(3), we measured the most physiologically active metabolite, 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)), and the less well understood metabolite, 24,25-dihydroxyvitamin D(3) (24,25(OH)(2)D(3)) to characterize the marmoset’s ability to metabolize dietary vitamin D(3). We present vitamin D(3) metabolite and related serum chemistry value colony reference ranges in marmosets provided diets with 26,367 (Colony A, N = 113) or 8,888 (Colony B, N = 52) international units (IU) of dietary vitamin D(3) per kilogram of dry matter. Colony A marmosets had higher serum 25(OH)D(3) (426ng/ml (SD 200) versus 215ng/ml (SD 113)) and 24,25(OH)(2)D(3) (53ng/ml (SD 35) versus 7ng/ml (SD 5)). There was no difference in serum 1,25(OH)(2)D(3) between the colonies. Serum 1,25(OH)(2)D(3) increased and 25(OH)D(3) decreased with age, but the effect was weak. Marmosets tightly regulate metabolism of dietary vitamin D(3) into the active metabolite 1,25(OH)(2)D(3;) excess 25(OH)D(3) is metabolized into 24,25(OH)(2)D(3). This ability explains the tolerance of high levels of dietary vitamin D(3) by marmosets, however, our data suggest that these high dietary levels are not required.

Anesthetic and analgesics are essential components of both clinical and research procedures completed in marmosets. A review of current anesthetic and analgesic regimens for marmosets has been complied to provide a concise reference for veterinarians and investigator teams. Published dose regimens for injectable and inhalant anesthetic drugs and analgesic drugs are included. Appropriate physiological monitoring is key to the success of the procedure and perianesthetic options are provided. Although recent publications have refined anesthesia and analgesia practices, our review demonstrates the continued need for evidence-based resources specific to marmosets.

Many studies address the influence of the gut microbiome on the immune system, but few dissect the effect of T cells on gut microbiota and mucosal responses. We have employed larval thymectomy in Xenopus to study the gut microbiota with and without the influence of T lymphocytes. Pyrosequencing of 16S ribosomal RNA genes was used to assess the relative abundance of bacterial groups present in the stomach, small and large intestine. Clostridiaceae was the most abundant family throughout the gut, while Bacteroidaceae, Enterobacteriaceae, and Flavobacteriaceae also were well represented. Unifrac analysis revealed no differences in microbiota distribution between thymectomized and unoperated frogs. This is consistent with immunization data showing that levels of the mucosal immunoglobulin IgX are not altered significantly by thymectomy. This study in Xenopus represents the oldest organisms that exhibit class switch to a mucosal isotype and is relevant to mammalian immunology, as IgA appears to have evolved from IgX based upon phylogeny, genomic synteny, and function.