Reference Intervals and Percentiles for Hematologic and Serum Biochemical Values in Captive Bred Rhesus (Macaca mulatta) and Cynomolgus Macaques (Macaca fascicularis)

Several physiological characteristics and housing conditions are known to affect hematologic and serum biochemical values in macaques. However, the studies that have been conducted either report values calculated based on a small number of animals, were designed specifically to document the effect of a particular condition on the normal range of hematologic and serum biochemical values, or used parametric assumptions to calculate hematologic and serum biochemical reference intervals. We conducted a retrospective longitudinal cohort study to estimate reference intervals for hematologic and serum biochemical values in clinically healthy macaques based on observed percentiles without parametric assumptions. Data were obtained as part of the Biomedical Primate Research Centre (Rijswijk, The Netherlands) health monitoring program between 2018 and 2021. In total, 4009 blood samples from 1475 macaques were analyzed with a maximum of one repeat per year per animal. Data were established by species, gender, age, weight-for-height indices, pregnancy, sedation protocol, and housing conditions. Most of the parameters profoundly affected just some hematologic and serum biochemical values. A significant glucose difference was observed between the ketamine and ketamine-medetomidine sedation protocols. The results emphasize the importance of establishing uniform experimental groups with validated animal husbandry and housing conditions to improve the reproducibility of the experiments

Retrospective Evaluation of a Minor Dietary Change in Non-Diabetic Group-Housed Long-Tailed Macaques (Macaca fascicularis)

Macaques in captivity are prone to becoming overweight and obese, which may cause several health problems. A diet that mimics the natural diet of macaques may prevent these problems and improve animal welfare. Adjusting captive diets towards a more natural composition may include increasing fiber content and lowering the glycemic index, i.e., reducing the impact on blood glucose levels. Such a dietary change was implemented in our long-tailed macaque (Macaca fascicularis) breeding colony. The basic diet of monkey chow pellets remained the same, while the supplementary provisioning of bread was replaced by grains and vegetables. This study is a retrospective evaluation, based on electronic health records, that investigated whether this minor dietary change had a beneficial effect on relative adiposity and overweight-related health parameters in 44 non-diabetic, group-housed, female long-tailed macaques. Relative adiposity was measured with a weight-for-height index and blood samples were collected during yearly health checks. Glycemic response and lipid metabolism were evaluated using several biochemical parameters. Relative adiposity and overweight status did not differ after dietary change. Yet, relatively heavy individuals generally lost body weight, while relatively lean individuals gained body weight, leading to a more balanced body weight dynamic. Dietary change did not affect HbA1c and triglyceride levels, while fructosamine and cholesterol levels were significantly reduced. Thus, the minor dietary change had no significant effect on overweight status, but some biochemical parameters related to the risk of diabetes and cardiovascular disease were positively affected. This study emphasizes the importance of evaluating husbandry changes and that critically reviewing husbandry practices can provide valuable insights to improve animal health and welfare

Retrospective Evaluation of a Minor Dietary Change in Non-Diabetic Group-Housed Long-Tailed Macaques (Macaca fascicularis)

Macaques in captivity are prone to becoming overweight and obese, which may cause several health problems. A diet that mimics the natural diet of macaques may prevent these problems and improve animal welfare. Adjusting captive diets towards a more natural composition may include increasing fiber content and lowering the glycemic index, i.e., reducing the impact on blood glucose levels. Such a dietary change was implemented in our long-tailed macaque (Macaca fascicularis) breeding colony. The basic diet of monkey chow pellets remained the same, while the supplementary provisioning of bread was replaced by grains and vegetables. This study is a retrospective evaluation, based on electronic health records, that investigated whether this minor dietary change had a beneficial effect on relative adiposity and overweight-related health parameters in 44 non-diabetic, group-housed, female long-tailed macaques. Relative adiposity was measured with a weight-for-height index and blood samples were collected during yearly health checks. Glycemic response and lipid metabolism were evaluated using several biochemical parameters. Relative adiposity and overweight status did not differ after dietary change. Yet, relatively heavy individuals generally lost body weight, while relatively lean individuals gained body weight, leading to a more balanced body weight dynamic. Dietary change did not affect HbA1c and triglyceride levels, while fructosamine and cholesterol levels were significantly reduced. Thus, the minor dietary change had no significant effect on overweight status, but some biochemical parameters related to the risk of diabetes and cardiovascular disease were positively affected. This study emphasizes the importance of evaluating husbandry changes and that critically reviewing husbandry practices can provide valuable insights to improve animal health and welfare

Overweight Management through Mild Caloric Restriction in Multigenerational Long-Tailed Macaque Breeding Groups

Caloric restriction (CR) is an effective method to reduce overweight in captive non-human primates (NHPs). CR has been applied to individually- and pair-housed NHPs, but whether applying CR can be effective and safe in group-housed NHPs has not yet been assessed. This study investigates the effect of mild (20%) CR on adult overweight and biochemical parameters, immature growth, veterinary consultations, and reproductive success in multigenerational long-tailed macaque (Macaca fascicularis) breeding groups. Data were derived from anthropometric measurements and blood samples during yearly health checks, complemented with retrospective data on veterinary consultations and reproductive success. Adult body measures decreased after CR, with heavier individuals and females losing more weight compared to leaner individuals and males. CR lowered cholesterol levels in adults but had no overall effect on other biochemical parameters. Yet, biochemical parameters of individuals with high baseline values were reduced more compared to individuals with low baseline values. Immature growth, veterinary consultations and reproductive success were not influenced by CR. Thus, CR targeted the right individuals, i.e., overweight adults, and had no adverse effects on the variables examined in this study. This implies that mild CR can be a valuable overweight management strategy in group-housed NHPs

Bronchoalveolar lavage affects thorax computed tomography of healthy and SARS-CoV-2 infected rhesus macaques (Macaca mulatta)

Medical imaging as method to assess the longitudinal process of a SARS-CoV-2 infection in non-human primates is commonly used in research settings. Bronchoalveolar lavage (BAL) is also regularly used to determine the local virus production and immune effects of SARS-CoV-2 in the lower respiratory tract. However, the potential interference of those two diagnostic modalities with each other is unknown in non-human primates. The current study investigated the effect and duration of BAL on computed tomography (CT) in both healthy and experimentally SARS-CoV-2-infected female rhesus macaques (Macaca mulatta). In addition, the effect of subsequent BALs was reviewed. Thorax CTs and BALs were obtained from four healthy animals and 11 experimentally SARS-CoV-2-infected animals. From all animals, CTs were obtained just before BAL, and 24 hours post-BAL. Additionally, from the healthy animals, CTs immediately after and four hours post-BAL were obtained. Thorax CTs were evaluated for alterations in lung density, measured in Hounsfield units, and a visual semi-quantitative scoring system. An increase in the lung density was observed on the immediately post-BAL CT but resolved within 24 hours in the healthy animals. In the infected animals, a significant difference in both the lung density and CT score was still found 24 hours after BAL. Furthermore, the differences between timepoints in CT score were increased for the second BAL. These results indicate that the effect of BAL on infected lungs is not completed within the first 24 hours. Therefore, it is of importance to acknowledge the interference between BAL and CT in rhesus macaques

Assessment of Indoor Air Quality for Group-Housed Macaques (Macaca spp.)

Indoor Air Quality (IAQ) is strongly associated with animal health and wellbeing. To identify possible problems of the indoor environment of macaques (Macaca spp.), we assessed the IAQ. The temperature (°C), relative humidity (%) and concentrations of inhalable dust (mg/m3), endotoxins (EU/m3), ammonia (ppm) and fungal aerosols were measured at stationary fixed locations in indoor enclosures of group-housed rhesus (Macaca mulatta) and cynomolgus macaques (Macaca fascicularis). In addition, the personal exposure of caretakers to inhalable dust and endotoxins was measured and evaluated. Furthermore, the air circulation was assessed with non-toxic smoke, and the number of times the macaques sneezed was recorded. The indoor temperature and relative humidity for both species were within comfortable ranges. The geometric mean (GM) ammonia, dust and endotoxin concentrations were 1.84 and 0.58 ppm, 0.07 and 0.07 mg/m3, and 24.8 and 6.44 EU/m3 in the rhesus and cynomolgus macaque units, respectively. The GM dust concentrations were significantly higher during the daytime than during the nighttime. Airborne fungi ranged between 425 and 1877 CFU/m3. Personal measurements on the caretakers showed GM dust and endotoxin concentrations of 4.2 mg/m3 and 439.0 EU/m3, respectively. The number of sneezes and the IAQ parameters were not correlated. The smoke test revealed a suboptimal air flow pattern. Although the dust, endotoxins and ammonia were revealed to be within accepted human threshold limit values (TLV), caretakers were exposed to dust and endotoxin levels exceeding existing occupational reference values

Hepatitis E virus: an underestimated opportunistic pathogen in recipients of allogeneic hematopoietic stem cell transplantation

Hepatitis E virus (HEV) is increasingly acknowledged as a cause of hepatitis in healthy individuals as well as immunocompromised patients. Little is known of HEV infection in recipients of allogeneic hematopoietic stem cell transplantation (alloHSCT). Therefore, we set out to study the incidence and sequelae of HEV as a cause of hepatitis in a recent cohort of 328 alloHSCT recipients. HEV RNA was tested in episodes of liver enzyme abnormalities. In addition, HEV RNA and HEV serology were assessed pre- and post-alloHSCT. We found 8 cases (2.4%) of HEV infection, of which 5 had developed chronic HEV infection. Seroprevalence pre-alloHSCT was 13%. Four patients died with HEV viremia, with signs of ongoing hepatitis, having a median time of infection of 4.1 months. The 4 surviving patients cleared HEV after a median period of 6.3 months. One patient was diagnosed with HEV reactivation after a preceding infection prior to alloHSCT. Although the incidence of developing acute HEV post-alloHSCT is relatively low, the probability of developing chronic hepatitis in severely immunocompromised patients is high. Therefore, alloHSCT recipients should be screened pretransplantation by HEV serology and RNA. Furthermore, a differential diagnosis including hepatitis E is mandatory in all alloHSCT patients with severe liver enzyme abnormalities

Bronchoalveolar lavage affects thorax computed tomography of healthy and SARS-CoV-2 infected rhesus macaques (Macaca mulatta)

Medical imaging as method to assess the longitudinal process of a SARS-CoV-2 infection in non-human primates is commonly used in research settings. Bronchoalveolar lavage (BAL) is also regularly used to determine the local virus production and immune effects of SARS-CoV-2 in the lower respiratory tract. However, the potential interference of those two diagnostic modalities with each other is unknown in non-human primates. The current study investigated the effect and duration of BAL on computed tomography (CT) in both healthy and experimentally SARS-CoV-2-infected female rhesus macaques (Macaca mulatta). In addition, the effect of subsequent BALs was reviewed. Thorax CTs and BALs were obtained from four healthy animals and 11 experimentally SARS-CoV-2-infected animals. From all animals, CTs were obtained just before BAL, and 24 hours post-BAL. Additionally, from the healthy animals, CTs immediately after and four hours post-BAL were obtained. Thorax CTs were evaluated for alterations in lung density, measured in Hounsfield units, and a visual semi-quantitative scoring system. An increase in the lung density was observed on the immediately post-BAL CT but resolved within 24 hours in the healthy animals. In the infected animals, a significant difference in both the lung density and CT score was still found 24 hours after BAL. Furthermore, the differences between timepoints in CT score were increased for the second BAL. These results indicate that the effect of BAL on infected lungs is not completed within the first 24 hours. Therefore, it is of importance to acknowledge the interference between BAL and CT in rhesus macaques

Bronchoalveolar lavage affects thorax computed tomography of healthy and SARS-CoV-2 infected rhesus macaques (Macaca mulatta)

Medical imaging as method to assess the longitudinal process of a SARS-CoV-2 infection in non-human primates is commonly used in research settings. Bronchoalveolar lavage (BAL) is also regularly used to determine the local virus production and immune effects of SARS-CoV-2 in the lower respiratory tract. However, the potential interference of those two diagnostic modalities with each other is unknown in non-human primates. The current study investigated the effect and duration of BAL on computed tomography (CT) in both healthy and experimentally SARS-CoV-2-infected female rhesus macaques (Macaca mulatta). In addition, the effect of subsequent BALs was reviewed. Thorax CTs and BALs were obtained from four healthy animals and 11 experimentally SARS-CoV-2-infected animals. From all animals, CTs were obtained just before BAL, and 24 hours post-BAL. Additionally, from the healthy animals, CTs immediately after and four hours post-BAL were obtained. Thorax CTs were evaluated for alterations in lung density, measured in Hounsfield units, and a visual semi-quantitative scoring system. An increase in the lung density was observed on the immediately post-BAL CT but resolved within 24 hours in the healthy animals. In the infected animals, a significant difference in both the lung density and CT score was still found 24 hours after BAL. Furthermore, the differences between timepoints in CT score were increased for the second BAL. These results indicate that the effect of BAL on infected lungs is not completed within the first 24 hours. Therefore, it is of importance to acknowledge the interference between BAL and CT in rhesus macaques

Retrospective Evaluation of a Minor Dietary Change in Non-Diabetic Group-Housed Long-Tailed Macaques (Macaca fascicularis)

Macaques in captivity are prone to becoming overweight and obese, which may cause several health problems. A diet that mimics the natural diet of macaques may prevent these problems and improve animal welfare. Adjusting captive diets towards a more natural composition may include increasing fiber content and lowering the glycemic index, i.e., reducing the impact on blood glucose levels. Such a dietary change was implemented in our long-tailed macaque (Macaca fascicularis) breeding colony. The basic diet of monkey chow pellets remained the same, while the supplementary provisioning of bread was replaced by grains and vegetables. This study is a retrospective evaluation, based on electronic health records, that investigated whether this minor dietary change had a beneficial effect on relative adiposity and overweight-related health parameters in 44 non-diabetic, group-housed, female long-tailed macaques. Relative adiposity was measured with a weight-for-height index and blood samples were collected during yearly health checks. Glycemic response and lipid metabolism were evaluated using several biochemical parameters. Relative adiposity and overweight status did not differ after dietary change. Yet, relatively heavy individuals generally lost body weight, while relatively lean individuals gained body weight, leading to a more balanced body weight dynamic. Dietary change did not affect HbA1c and triglyceride levels, while fructosamine and cholesterol levels were significantly reduced. Thus, the minor dietary change had no significant effect on overweight status, but some biochemical parameters related to the risk of diabetes and cardiovascular disease were positively affected. This study emphasizes the importance of evaluating husbandry changes and that critically reviewing husbandry practices can provide valuable insights to improve animal health and welfare