An exploratory deep learning approach to investigate tuberculosis pathogenesis in nonhuman primate model: Combining automated radiological analysis with clinical and biomarkers data.

BACKGROUND: Tuberculosis (TB) kills approximately 1.6 million people yearly despite the fact anti-TB drugs are generally curative. Therefore, TB-case detection and monitoring of therapy, need a comprehensive approach. Automated radiological analysis, combined with clinical, microbiological, and immunological data, by machine learning (ML), can help achieve it. METHODS: Six rhesus macaques were experimentally inoculated with pathogenic Mycobacterium tuberculosis in the lung. Data, including Computed Tomography (CT), were collected at 0, 2, 4, 8, 12, 16, and 20 weeks. RESULTS: Our ML-based CT analysis (TB-Net) efficiently and accurately analyzed disease progression, performing better than standard deep learning model (LLM OpenAI's CLIP Vi4). TB-Net based results were more consistent than, and confirmed independently by, blinded manual disease scoring by two radiologists and exhibited strong correlations with blood biomarkers, TB-lesion volumes, and disease-signs during disease pathogenesis. CONCLUSION: The proposed approach is valuable in early disease detection, monitoring efficacy of therapy, and clinical decision making.

Contribution of ultrasound examination in diagnosing platynosomiasis and correlation with macro and microscopic findings in callitrichids kept under human care.

BACKGROUND: Platynosomiasis in non-human primates kept under human care causes chronic disease of the bile ducts and liver, which initially presents with nonspecific signs and can culminate in the death of the animal. Diagnosing this disease is a challenge, and an ultrasound examination can be an excellent tool when it is suspected. METHODS: This study describes the ultrasound findings from 57 marmosets with suspected infection by Platynosomum sp., the correlated hepatobiliary changes, and the anatomopathological findings that confirmed the occurrence of platynosomiasis. RESULTS: In six marmosets (one C. aurita, two C. jacchus, and three Callithrix sp.), Platynosomum infection was confirmed macroscopically (presence of adult trematodes in the gallbladder) and microscopically (adults, larvae, and eggs in histological examinations and eggs in bile and feces). These findings were compatible with the hepatobiliary changes and with images suggestive of parasitic structures in ante-mortem assessments. CONCLUSION: Ultrasound examination demonstrated its usefulness within the clinical routine for investigating this parasitosis.

A cervical mass in a laboratory rhesus macaque (Macaca mulatta): Suspicion of air sacculitis.

A 13-year-old rhesus macaque presented a cervical swelling associated with sudden deterioration of its condition. This mass was surgically removed, and its histopathological examination revealed a stratified squamous epithelium. This appearance has been reported in some case of air sacculitis in others non-human primate species.

Novel gastrointestinal disease in common marmosets characterised by duodenal dilation: a clinical and pathological study.

Common marmosets (Callithrix jacchus) are frequently used for biomedical research but gastrointestinal diseases have been major health problems to maintain captive marmosets. We have diagnosed a novel gastrointestinal disease in marmosets, as which we propose to call 'marmoset duodenal dilation syndrome'; this disease is characterised by proximal duodenal obstruction and dilation. This study aimed to reveal the clinical and pathological findings of this syndrome and establish appropriate diagnostic imaging methods. Animals with the syndrome comprised 21.9% of the necropsy cases at the Central Institute for Experimental Animals in Kawasaki, Japan. The syndrome is characterised by clinical signs included vomiting, bloating, and weight loss. Grossly, all diseased animals exhibited significant dilation of the descending part of the duodenum, which contained a mixture of gas and fluid. The duodenal dilations were definitively diagnosed by contrast radiography. Moreover, a combination of plain radiography and ultrasonography was found to be a viable screening method for diagnosing duodenal dilation. The animals with duodenal dilation characteristically showed adhesions between the descending duodenum and ascending colon with chronic peritonitis. The cause of marmoset duodenal dilation syndrome remains unknown, but was likely multifactorial, including peritoneal adhesion, chronic ulcer, and feeding conditions in this study.

Retinal Features in Cynomolgus Macaques (Macaca fascicularis) Assessed by Using Scanning Laser Ophthalmoscopy and Spectral Domain Optical Coherence Tomography.

Cynomolgus macaques are an important and commonly used species in preclinical toxicology studies, but structural reports of in vivo retinal findings are rare in this species. The purpose of this study was to diminish this gap and document optical coherence tomography and scanning laser ophthalmoscopy imaging data in the healthy posterior pole of cynomolgus monkeys' eyes at predose examinations. The current study is a retrospective assessment of baseline spectral domain OCT data obtained from the 768 eyes of 384 cynomolgus monkeys (192 males and 192 females) of Mauritian origin. The data set was obtained from studies conducted over a 4-y period in the context of ocular safety evaluations of various compounds under preclinical development. The most prevalent findings were the presence of Bergmeister papilla and intravitreal hyperreflective spots. Less common findings included disorganization of retinal zones, abnormalities of the retinal vasculature, partial posterior vitreous detachment, and abnormally shaped foveal pits. Thoughtful consideration of these physiologic findings will aid in distinguishing normal features from toxic outcomes in future preclinical ophthalmic studies.

Relationships between Cytokine Levels and Disease Parameters during the Development of a Collagen-induced Arthritis Model in Cynomolgus Macaques (Macaca fascicularis).

In rheumatoid arthritis research, NHP models of collagen-induced arthritis are important because these species share many immunologic and pathologic features with humans. In addition, serum levels of various cytokines in patients with rheumatoid arthritis have been studied as immune markers for disease prediction, early diagnosis, and effective therapeutic management. The purpose of this study was to identify changes in cytokine levels that occur during the development of collagen-induced arthritis in female cynomolgus macaques (n = 8) and to assess the relationships between these changes and various disease parameters. Blood samples were collected weekly before (week 0) and after (weeks 1 through 7) immunization with type II collagen; clinicopathologic and cytokine data from those samples and other clinical parameters were used in correlation analysis. Serum levels of IFN γ, chemokine (C-C motif) ligand 2 (CCL2), and IL6 showed significant changes after generation of collagen-induced arthritis. IFNγ levels showed a strong negative correlation with body weight (an indicator of general body condition), and CCL2 and IL6 showed moderate negative correlation with body weight. Serum IL6 levels showed moderate positive correlation with the soft tissue swelling score and strong positive correlation with serum C-reactive protein levels in our NHP model of collagen-induced arthritis. In addition, serum levels of matrix metalloproteinase 3 increased significantly after inoculation with type II collagen and showed a moderate positive correlation with serum levels of C-reactive protein, IL6, and IL15. These results suggest close correlations between various cytokines and disease parameters in NHP models of rheumatoid arthritis. These cytokines therefore potentially could be used as markers for monitoring the efficacy of novel treatments in NHP models of rheumatoid arthritis.

Hepatic Hemangiosarcoma in a Cynomolgus Macaque (Macaca fascicularis).

An experimentally naïve, 9-y-old, intact male cynomolgus macaque was reported for bleeding from an unidentified site. Sedated physical examination indicated mild gingival separation from the lingual aspect of the upper right canine tooth as the source of the hemorrhage. Physical exam revealed a firm mass adhered to the left zygomatic arch, 2 subcutaneous nodules on the chest, and a large mass in the cranial abdomen. Radiographs revealed a large soft-tissue mass in the cranial abdomen and multifocal nodules in the caudal lung fields. On ultrasonography, the liver was grossly enlarged and contained a cavi- tated mass. Hematology and serum chemistry results demonstrated severe regenerative anemia with normal clotting times and adequate platelet count. For humane reasons, euthanasia was elected. On gross examination, the liver was markedly enlarged by an expansile mass primarily affecting the median lobe, with multiple, smaller nodules throughout the remaining lobes. Multifocal round, firm nodules were observed on the surface of all lung lobes and throughout the omentum. Histologic examination of the hepatic, cutaneous, osseous, and pulmonary lesions demonstrated well-defined, endothelium-lined vascular channels arranged in cords with abundant hemorrhage; endothelial-cell immunomarkers confirmed these results. On the basis of these findings, hepatic hemangiosarcoma, with metastases to the lungs, omentum, subcutis, and bone, was diagnosed. This case study is the first report of spontaneous hepatic hemangiosarcoma in a cynomolgus macaque and the first case with metastasis to bone in a NHP.

Single-photon Emission Computed Tomography-Computed Tomography Using 99mTc-labeled Leukocytes for Evaluating Infection Associated with a Cranial Implant in a Rhesus Macaque (Macaca mulatta).

An adult male rhesus macaque (Macaca mulatta) that was enrolled in a study evaluating cognition and memory presented with suppurative exudate along the margins of a long-standing cranial implant that included a stainless-steel head post, plastic left-sided recording cylinder, and acrylic over a previously placed right-sided recording cylinder. Both cylinders were located at the level of the prefrontal cortex. After treatment comprising systemic antibiotics and daily cleaning with povidone-iodine for several months, the macaque underwent single-photon emission computed tomography-computed tomography (SPECT-CT) in which his neutrophils were labeled with 99mTc-hexamethylpropylene amine oxime ( 99m Tc-HMPAO) to evalu- ate for active infection below the implant. Soft tissue inflammation and osteomyelitis were found at the site of the previous right-sided recording cylinder. Cephalosporin and tetracycline antibiotics were administered for 12 wk. Follow-up SPECT-CT imaging was then performed to evaluate response to medical treatment. Results indicated no change in the degrees of soft tissue inflammation and osteomyelitis associated with the right-sided recording cylinder site. SPECT-CT imaging was used to guide the surgical removal of the implant and debridement of the infected tissue. On removal of the entire cranial implant, the osteomyelitis and soft tissue inflammation observed on the pre- and posttreatment SPECT-CT scans were confirmed. In addition, a large cavitary defect through the calvarium with suppurative exudate was discovered below the base of the head post. Infection in this defect was not apparent on SPECT; however, the bony defect was confirmed on reevaluation of the CT images. We concluded that the infection in this defect was silent on SPECT due to the limited vascularization of the sur-rounding bone and the chronicity of the infection. This case study is the first to describe the use of SPECT-CT for evaluating soft tissue inflammation and osteomyelitis beneath a cranial implant in a NHP.

Hypertrophic osteoarthropathy in an adult macaque.

OBJECTIVE: To evaluate through differential diagnosis whether hypertrophic osteoarthropathy was present on an adult macaque skeleton. MATERIALS: Skeletal remains of a well-preserved adult macaque (Macaca) of unknown species curated by the archaeology department at University College London. METHODS: Macroscopic and radiographic evaluation of pathological lesions. RESULTS: Widespread bilateral and symmetrical periosteal new bone growth primarily affecting the limbs was observed. CONCLUSION: A careful differential diagnosis of the lesions and comparison with previously published cases of hypertrophic osteoarthropathy among humans and non-humans suggests this animal displays a case of Hypertrophic osteoarthropathy. SIGNIFICANCE: Only been three reported cases of HOA in non-human primates have been reported, and all were apes. This study serves as the first reported case of HOA among non-hominoid simians, providing a detailed description of the skeletal lesions to aid future with paleopathological analyses. LIMITATIONS: Small sample sizes for comparison and lack of context for this specimen limits discussion of the scope of this disease among non-human primates. SUGGESTIONS FOR FURTHER RESEARCH: Re-evaluate skeletal collections which have not been subject to recent osteological and pathological analysis.

Complete rectal prolapse in wild anubis baboons (Papio anubis).

This report describes two cases of rectal prolapse in wild anubis baboons (Papio anubis), with one spontaneous resolution. Both occurred after individuals consumed low-water, high-fibre dried maize during provisioning prior to capture, while one also experienced distress during capture.

Longitudinal MRI Evaluation of Ischemic Stroke in the Basal Ganglia of a Rhesus Macaque (Macaca mulatta) with Seizures.

An adult rhesus macaque developed seizures after the induction of ischemic stroke. Initially, on the day of surgery, a focal ischemic lesion was present exclusively in the right caudate nucleus. By 48 h after stroke induction, the lesion had extended into the putamen, when a seizure was observed. Our report highlights the temporal changes in infarction of unilateral basal ganglia after acute stroke and the accompanying clinical symptoms. This unusual case may provide additional information regarding the involvement of the basal ganglia in seizures, given that prior case reports and studies usually have not described the temporal and spatial evolution of the lesion before clinical symptoms emerge.

Thoracic radiography of healthy captive male and female Squirrel monkey (Saimiri spp.).

The purpose of this prospective study was to describe the normal anatomy and provide reference ranges for measurements of thoracic radiography on Squirrel monkeys (n = 13). Thoracic radiography is a common non-invasive diagnostic tool for both cardiac and non-cardiac thoracic structures. Furthermore cardiac disease is a common condition in captive primates. In this study, left-right lateral, right-left lateral and dorsoventral projections of 13 healthy Squirrel monkeys were reviewed during their annual health examinations. The mean Vertebral Heart Score on the left-right and right-left lateral projections were 8,98 ± 0,25 and 8,85 ± 0,35 respectively. The cardio-thoracic ratio on the dorsoventral projection was 0,68 ± 0,03. The trachea to inlet ratio was 0,33 ± 0,04. Other measurements are provided for the skeletal, cardiac and respiratory systems. Knowledge of the normal radiographic thoracic anatomy is fundamental in clinical as well as research settings for accurate diagnosis of diseases.

Acute Abdominal Distension Due to Disseminated Peritoneal Neoplasia in a Rhesus Macaque (Macaca mulatta).

This report describes the clinical, radiographic, and pathologic findings in a female rhesus macaque that presented with acute abdominal distension and tympany. The macaque was euthanized after evidence of severe colonic distension on radiography and observation of widespread peritoneal adhesions on exploratory laparotomy. Gross and histopathologic evaluation revealed extensive entrapment of gastrointestinal and reproductive tracts by serosal fibrovascular proliferative tissue containing foci of endometriosis. The diagnosis of endometrial stromal sarcoma was supported by expression of CD10, Wilm tumor 1, estrogen receptor, and progesterone receptor and failure to express immunohistochemical markers characteristic of a range of differential diagnoses. In humans, this relatively uncommon neoplasm can arise from sites of endometriosis and often presents clinically as intestinal obstruction, similar to the presentation in this macaque.

Lung Lobe Torsion in an Adult Male Common Marmoset (Callithrix jacchus).

A 6-y-old, intact, pair-housed male common marmoset (Callithrix jacchus) presented with acute onset dyspnea and tachypnea immediately after sedation with alfaxalone; a history of gradual weight loss initiated the examination under sedation. Thoracic radiographs revealed significant right-lung consolidation, with a vesicular gas pattern in the right caudodorsal lung field, pleural effusion, and dorsal displacement of the heart. The marmoset was euthanized due to his unstable condition and poor prognosis. At necropsy, the cranial and middle lobes of the right lung were homogenously dark red-brown, enlarged, edematous, and twisted around the longitudinal axis at the hilus. The left lung lobes were pale pink and slightly edematous. In light of the clinical and gross necropsy findings, acute torsion of the right cranial and middle lung lobes was diagnosed. Predisposing conditions for lung lobe torsion include trauma, neoplasia, pulmonary disease, previous thoracic surgery, and diaphragmatic hernia, but none of these applied to this case. Initial therapy for lung lobe torsion is to stabilize the patient and treat for underlying conditions, with prompt surgical resection as the treatment of choice. To our knowledge, this report is the first description of lung lobe torsion in an experimentally unmanipulated New World NHP.

Hepatocellular carcinoma in two captive golden-headed lion tamarins (Leontopithecus chrysomelas).

Two cases of hepatocellular carcinoma (HCC) in 2 female captive golden-headed lion tamarins (Leontopithecus chrysomelas) are described. HCC was diagnosed in both, with pulmonary metastasis in one of them. Neoplastic cells were positive for hepatocyte-specific antigen (HSA) by immunohistochemistry, confirming the diagnosis.

Uterus-like Masses in a Rhesus Macaque (Macaca mulatta).

Endometriosis is a relatively common condition in women and some populations of adult female rhesus macaques. However, endometriosis with extensive smooth muscle proliferation, as occurs in endomyometrioma and uterus-like mass (ULM), is rare in women. This report describes a case of endometriosis with extensive smooth muscle metaplasia resembling multiple ULM in a 20-y-old female rhesus macaque. During a protocol-related procedure, a large, smooth, globoid, freely moveable mass was palpated in the midabdomen. Ultrasonography revealed a cystic structure from which dark brown fluid was aspirated. During exploratory laparotomy, an 8-cm spherical mass in the greater omentum and 3 additional masses (diameter, 2 to 5 cm) attached to the omentum were excised. Microscopic examination of the masses revealed numerous foci of ectopic endometrial glands and stroma frequently surrounded by bundles of smooth muscle and fibrous connective tissue. The gross and histologic lesions in this macaque bore many similarities to ULM in women. To our knowledge, this case represents the first report of endometriosis resembling a uteruslike mass in a NHP.

Hepatocellular carcinoma with intracranial metastasis in a Japanese macaque (Macaca fuscata).

BACKGROUND: A 23-year-old male Japanese macaque (Macaca fuscata) showed left ptosis, which progressed to exophthalmos. METHODS: The macaque underwent a clinical examination, CT and MRI, and was euthanized. Necropsy and histopathological examination were performed after euthanasia. RESULTS: The CT revealed and MRI confirmed an intracranial mass at the skull base with orbital extension. At necropsy, there were a large hepatic mass and an intracranial mass compressing the left temporal lobe of the brain. Histopathological and immunohistological examinations revealed that the masses were hepatocellular carcinoma (HCC) and a metastatic lesion. In both the primary and metastatic lesions, neoplastic hepatocytes were arranged mainly in a trabecular pattern. Immunohistochemically, the tumor cells were positive for cytokeratin (AE1/AE3 and CAM5.2) and hepatocyte paraffin 1 and negative for cytokeratin 7 and 20 and vimentin. CONCLUSION: To our knowledge, this is the first case report of HCC with intracranial metastasis in a macaque.

Fatal pulmonary acariasis in an aged indoor rhesus macaque (Macaca mulatta).

Pulmonary acariasis is a sporadic, incidental finding in colony-raised rhesus macaques (Macaca mulatta). Prophylactic treatment in indoor-raised and indoor-housed macaques is not routine due to low prevalence, lack of clinical significance, and potential risk of toxicosis. This case is an unusually severe infestation of Pneumonyssus simicola in an indoor-housed rhesus macaque, which ultimately resulted in this animal's death.

Spontaneous telangiectatic osteosarcoma in a rhesus macaque (Macaca mulatta).

Osteosarcoma (OS) is the most common type of bone cancer, especially in young. Telangiectatic osteosarcoma (TO) is a rare variant of OS, and hence, its occurrence, presentation, and prognosis are poorly understood. A 4-year-old female rhesus monkey presenting lameness and swelling was examined for a mass on the right humerus. Radiography revealed fracture and disorganized structure of bone tissue. Histopathological examination revealed malignant neoplasm composed of anaplastic osteoblasts, which invaded the bone marrow and surrounded blood-filled cysts in the epiphysis and diaphysis forming septa. Cytogenetic analysis showed aneuploid cells, supernumerary AgNORs, and a marker fragment. The neoplasm was diagnosed as TO. To our knowledge, the occurrence of TO and its cytogenetic analysis were reported for the first time in non-human primates.

Use of ultrasound imaging for the diagnosis of abnormal uterine bleeding in the bonnet macaque ( Macaca radiata).

Ultrasound is a powerful, low-cost, non-invasive medical tool used by laboratory animal veterinarians for diagnostic imaging. Sonohysterography and transvaginal ultrasound are frequently used to assess uterine anomalies in women presenting with abnormal uterine bleeding (AUB). In the present study, we have evaluated the abdominal ultrasound of bonnet monkeys ( n = 8) showing spontaneous ovulatory ( n = 5) and anovulatory ( n = 3) AUB. The ovulatory ( n = 5) macaques showed cyclic AUB for 7-8 days. The anovulatory ( n = 3) macaques had irregular AUB with menstrual cycles of 40-45 days. The B-mode abdominal, colour Doppler and 3D ultrasound scans were performed during the proliferative phase of the menstrual cycle. Ultrasound examination revealed endometrial polyps in five macaques and endometrial hyperplasia in three animals. The width and length of endometrial polyps was around 0.5-1 cm (average 0.51 ± 0.23 cm × 0.96 ± 0.16 cm) with significant increase in endometrial thickness ( P < 0.0002). 3D ultrasound also showed a homogeneous mass in the uterine cavity and colour Doppler ultrasound showed increased vascularity in the endometrial polyps. Endometrial hyperplasia characteristically appeared as a thickened echogenic endometrium ( P < 0.0002). This study demonstrates the use of non-invasive ultrasound techniques in the diagnosis of AUB in macaques.