Spontaneous pulmonary adenocarcinoma in a common marmoset (Callithrix jacchus).

A seven-year-old female common marmoset (Callithrix jacchus) presented with weight loss. Imaging revealed a left thoracic mass, confirmed at necropsy. Histology and immunohistochemistry suggested a well-differentiated pulmonary adenocarcinoma. No evidence of local lymphovascular invasion or distant metastasis was observed. This is the first report of pulmonary adenocarcinoma in marmosets.

Functional inactivation of pulmonary MAIT cells following 5-OP-RU treatment of non-human primates.

Targeting MAIT cells holds promise for the treatment of different diseases and infections. We previously showed that treatment of Mycobacterium tuberculosis infected mice with 5-OP-RU, a major antigen for MAIT cells, expands MAIT cells and enhances bacterial control. Here we treated M. tuberculosis infected rhesus macaques with 5-OP-RU intratracheally but found no clinical or microbiological benefit. In fact, after 5-OP-RU treatment MAIT cells did not expand, but rather upregulated PD-1 and lost the ability to produce multiple cytokines, a phenotype resembling T cell exhaustion. Furthermore, we show that vaccination of uninfected macaques with 5-OP-RU+CpG instillation into the lungs also drives MAIT cell dysfunction, and PD-1 blockade during vaccination partly prevents the loss of MAIT cell function without facilitating their expansion. Thus, in rhesus macaques MAIT cells are prone to the loss of effector functions rather than expansion after TCR stimulation in vivo, representing a significant barrier to therapeutically targeting these cells.

Concurrent yellow fever and pulmonary aspergillosis due to Aspergillus fumigatus in a free-ranging howler monkey (Alouatta sp).

Herein, we describe a unique case of concomitant angioinvasive pulmonary aspergillosis due to Aspergillus fumigatus and yellow fever in a free-ranging howler monkey (Alouatta sp). Lung samples were negative for influenza viruses A and B.

Urothelial carcinoma in the urinary bladder of a Japanese macaque (Macaca fuscata).

Tumors of urinary origin are infrequently reported in non-human primates. Urothelial carcinoma involving the urinary bladder was diagnosed in an adult female Japanese macaque that extended transmurally to the uterus and cervix. To our knowledge, this is the first report of a primary cystic urothelial carcinoma in a Japanese macaque.

Diagnosis and treatment of endometriosis in a hooded capuchin (Sapajus apella).

Spontaneous endometriosis is common in women, great apes and Old World monkeys, but rare in New World monkeys. We report on the clinical diagnosis and successful combination of surgical and medical treatment in a case of spontaneous endometriosis in a diabetic hooded capuchin. Addressing this painful condition had a positive welfare impact.

Stress as cause of signs and symptoms of pseudo-Cushing's syndrome in buffy-tufted marmosets (Callithrix aurita).

Hyperadrenocorticism is a medical condition caused by the increase in cortisol production by the cortex of the adrenal gland. Although infrequently described in most animal species, its naturally occurring form, called Cushing's syndrome, is the most prevalent endocrinopathy in dogs. Cushing's syndrome is also present in humans and might be confused with the pseudo-Cushing's syndrome (PCS), rarely described in animals. PCS shares many of the clinical and biochemical features of Cushing's syndrome. However, the hypercortisolemia seen is usually idiopathic and, in some circumstances, associated with psychological disruptions. This report describes PCS-like disorder in two marmosets Callithrix aurita that were exposed to environmental changes, suggesting stress as the main cause of the process and reviewing the mechanisms involved in the pathogeny of the two syndromes.

Two cases of cryptococcus gattii infection in the rhesus macaque (Macaca Mulatta).

Cryptococcus gattii was diagnosed in two female indoor-housed rhesus macaques. Gross and histopathologic findings included an isolated pulmonary cryptococcoma in a non-SIV-infected macaque and disseminated disease centered on the lungs of an SIV-infected macaque. Fungal yeast were positive with special stains, and the diagnoses were confirmed with a lateral flow assay and PCR.

Myeloproliferative Disorder with Intraoral Lesions in an Olive Baboon (Papio anubis).

Spontaneous myeloid leukemia is rarely reported in non-human primates. We report a case of myeloproliferative disorder suggestive of acute myeloid leukemia with intraoral lesions in an olive baboon (Papio anubis). Clinical pathology, radiology, gross examination (pre-mortem and post-mortem), histopathology, and immunohistochemistry findings are provided.

Clinical and pathological aspects of first report of Tunga penetrans infestation on southern brown howler monkey (Alouatta guariba clamitans) in Rio Grande do Sul, Brazil.

BACKGROUND: Tungiasis is a neglected neotropical disease caused by penetration of Tunga spp. into the skin of the host. METHODS: Two primates were rescued from nearby different indigenous villages, and the clinical, pathological, and parasitological features of tungiasis were described. Flea identification occurred through their morphometry and was confirmed with the use of a dichotomous key. RESULTS: Monkey 1 was parasitized by 23 sand fleas and, after treatment, was assigned to the animal rehabilitation center. Monkey 2 was in poor body condition and died shortly after clinical examination. At necropsy, this primate was parasitized by 26 specimens of sand fleas. CONCLUSIONS: Both animals altered their tree behavior by staying on the ground for long periods. This parasitic relationship implies the possibility of enlargement of the sand flea dispersion. Thus, this is the first record of Tunga penetrans occurrence in wild Alouatta guariba clamitans.

DIFFUSE IDIOPATHIC SKELETAL HYPEROSTOSIS WITH SECONDARY DYSPHAGIA IN A BLACK-HANDED SPIDER MONKEY (ATELES GEOFFROYI).

A 32-yr-old male black-handed spider monkey (Ateles geoffroyi) with marked kyphosis and reduced spinal range of motion developed intermittent regurgitation, which was managed with an acid reducer. Diffuse idiopathic skeletal hyperostosis (DISH) was suspected in this animal due to radiographically evident ossification of the anterior longitudinal ligament. At repeat radiographic evaluation 1.5 yr later, due to weight loss and increased frequency of regurgitation, the cervical spine was deviated ventrally and appeared to be impinging on the thoracic inlet. The spider monkey was humanely euthanized due to poor prognosis, and the presumptive diagnosis of DISH was confirmed via postmortem computed tomography and necropsy. DISH has not been reported in black-handed spider monkeys, and secondary dysphagia, an uncommon but recognized consequence in humans, has not been reported in a nonhuman primate. Earlier recognition of this possibly underreported disease process may increase treatment options and effectiveness of intervention.

Leukemic histiocytic sarcoma in a captive common squirrel monkey (Saimiri sciureus) with Saimiriine Gammaherpesvirus 2 (Rhadinovirus), Saimiri sciureus lymphocryptovirus 2 (Lymphocryptovirus) and Squirrel monkey retrovirus (ß-Retrovirus) coinfection.

Hematopoietic neoplasia other than lymphoma and leukemia is uncommon among non-human primates. Herein, we provide the first evidence of occurrence of leukemic histiocytic sarcoma in a captive common squirrel monkey with Saimiriine Gammaherpesvirus 2 (Rhadinovirus), Saimiri sciureus lymphocryptovirus 2 (Lymphocryptovirus), and Squirrel monkey retrovirus (ß-Retrovirus) coinfection.

Clinical and Pathologic Features of Spontaneous Klebsiella pneumoniae Infection in 9 Rhesus Macaques (Macaca mulatta).

Klebsiella pneumoniae is a gram-negative bacterium found in the environment and as a commensal in humans and animals. In humans, K. pneumoniae is one of the most serious nosocomial infections encountered currently and is characterized by liver abscesses, pneumonia, and bacteremia resulting in meningoencephalitis and endophthalmitis. K. pneumoniae in veterinary medicine is rarely reported in NHP, and recent literature describing this disease is sparse. In our colony of predominantly outdoor-housed rhesus macaques (Macaca mulatta), K. pneumoniae is cultured infrequently from healthy animals during routine screening and is even rarer in sick animals. This report summarizes the clinical and postmortem findings associated with this pathogen in 9 rhesus macaques and compares these results with the disease outcomes reported for humans. In these cases, K. pneumoniae infection was confirmed through culture or PCR testing or both. In our experience, when this bacterium does cause clinical signs, the disease is rapidly progressive and severe. At necropsy of NHP, the findings are strikingly similar to opportunistic Klebsiella-associated syndromes described in humans and include liver abscesses, meningoencephalitis, and endophthalmitis. In addition, many of the affected macaques had similar risk factors to humans that succumb to disease, thus perhaps indicating that rhesus macaques could be a viable model for investigating these syndromes.

Spontaneous KRT5 Gene Mutation in Rhesus Macaques (Macaca mulatta): A Novel Nonhuman Primate Model of Epidermolysis Bullosa Simplex.

Epidermolysis bullosa simplex (EBS) is an inherited skin disorder characterized by increased skin and mucous membrane fragility. Most cases are caused by mutations in keratin 5 (KRT5) and keratin 14 (KRT14). Mutations of these genes result in cytoskeletal disruption of the basal keratinocytes. Gross and histopathologic findings of 2 clinically affected homozygous rhesus macaques with an insertion variant mutation in KRT5 are described and compared with 6 deceased phenotypically normal animals that were heterozygous for the KRT5 insertion variant. Animals that were homozygous for the KRT5 insertion variant were stillborn and had widespread loss of the epidermis. Microscopic examination confirmed severe ulceration and basal cell vacuolation with basilar vesicle formation in the remaining intact epidermis. Immunohistochemistry for cytokeratin 5 demonstrated lack of epidermal immunoreactivity in homozygotes. DNA sequencing identified a 34-base pair insertion variant in exon 5 of the KRT5 gene. To our knowledge, this is the first report of epidermolysis bullosa in rhesus macaques.

Atypical presentation and pathogenesis of a macaque lymphocryptoviral-associated B-cell lymphoma in a cynomolgus monkey.

We report the unique pathogenesis and presentation of a rapidly progressive B-cell lymphoma in a 3-year-old female cynomolgus monkey on day 50 of a 13-week toxicity study. Clinical pathology evaluation revealed a marked leukocytosis with bicytopenia. A serum protein electrophoresis was consistent with monoclonal gammopathy. The architecture of the lymph node, spleen, and thymus were variably effaced by neoplastic cells, which also infiltrated other tissues. Immunohistochemistry of the affected tissues confirmed a predominant population of CD20+, CD79a+, CD3-, CD68-, and CD34-neoplastic cells. The full data best support a diagnosis of Stage V lymphoma. Nextgen sequencing and negative prestudy serology results suggested a recent infection by macaque lymphocryptovirus (mLCV) with a unique transcriptional profile comparable with a rarely observed direct LCV infection model. This infection model might be associated with a temporary lack of an LCV antigen-specific cytotoxic T-cell adaptive immune response. Consistent with the established mechanisms of LCV-related lymphoproliferation, MYC and BCL2L11 gene expression were increased and decreased, respectively. While there was no overt immunosuppression, immunophenotyping revealed the index animal had a relatively low NK cell count, which further decreased by >50% on day 24 of the study. In addition to the temporary lack of adaptive immunity, the low NK cell counts were suggestive of an impaired innate immunity to control the virally-transformed cells and the subsequent unchecked lymphoproliferation. To our knowledge, this is the first report of a Stage V lymphoma with a unique pathogenesis in an otherwise immunocompetent cynomolgus monkey.

Neutralization of pertussis toxin by a single antibody prevents clinical pertussis in neonatal baboons.

Pertussis continues to cause considerable infant mortality world-wide, which could be addressed in part by passive immunization strategies. Antibody hu1B7 is a candidate therapeutic that potently neutralizes pertussis toxin in vitro, prevents leukocytosis in mice and treats established disease in weanling baboons as part of an antibody cocktail. Here, we evaluated the potential for hu1B7 and an extended half-life hu1B7 variant to prevent death, leukocytosis and other clinical symptoms in a newborn baboon model that mimics many aspects of human disease. We administered a single antibody dose to newborn baboons five weeks prior to experimental infection. While all animals were heavily colonized with Bordetella pertussis, prophylaxed animals showed significantly greater survival (P < 0.005), delayed and suppressed leukocytosis (P < 0.01) and enhanced clinical outcomes, including coughing (P < 0.01), as compared to controls. Together, this work demonstrates that a single neutralizing anti-PTx antibody is sufficient to prevent clinical pertussis symptoms.

Angiostrongylus cantonensis central nervous system infection in captive callitrichids in Texas.

Angiostrongylus cantonensis is a tropical lungworm of rats known for central nervous system migration in aberrant primate hosts. Here, we describe A. cantonensis infection in three captive callitrichids from a Texas zoo. The affected animals included a Goeldi's monkey (Callimico goeldii), a cotton-top tamarin (Saguinus oedipus), and a pied tamarin (Saguinus bicolor) that ranged from 8 to 18 years old. Clinical signs included lethargy, ataxia, and seizures. Histologically, these animals had an eosinophilic meningoencephalitis to myelitis and some areas had abundant macrophages and parasite migration tracts. All cases had intralesional metastrongyle parasites, and nematodes were extracted from the formalin-fixed brain specimen in one case. This extracted parasite was identified as Angiostrongylus cantonensis based on morphologic features and diagnosis was confirmed with PCR. These cases represent the first report of this parasite in non-human primates in Texas, highlighting the western spread of A. cantonensis in the continental United States.

Gingival histoplasmosis: An atypical presentation of African histoplasmosis in three baboons (Papio spp).

Gingival lesions as the sole manifestation of African histoplasmosis (Histoplasma capsulatum var. duboisii) have never been reported in baboons. Grossly, lesions can be indistinguishable from bacterial ulcerative gingivitis or gingival hyperplasia. Clinical outcomes of primary gingival histoplasmosis in baboons are unknown and may complicate colony management decisions.

Evaluation of the guaiac fecal occult blood test for detection of gastrointestinal bleeding in the rhesus macaque (Macaca mulatta).

BACKGROUND: Gastrointestinal (GI) hemorrhage accompanies several common diseases of rhesus macaques (Macaca mulatta). Guaiac fecal occult blood testing (gFOBT) is a non-invasive means to detect such bleeding in several species; however, there are currently no data indicating reliability of this test to detect GI hemorrhage in macaques. METHODS: We evaluated sensitivity and specificity of gFOBT to detect simulated and biopsy-associated bleeding in the stomach, duodenum, and colon of 15 rhesus macaques. Fecal samples were analyzed via gFOBT for 72 hours. RESULTS: Guaiac fecal occult blood testing was more sensitive to detect lower vs upper GI bleeding; sensitivity was volume-dependent in the upper GI tract. Single-test specificity was 95.2%. Repeated fecal collections increased gFOBT sensitivity without affecting specificity. CONCLUSIONS: Guaiac fecal occult blood testing is a useful screening test for both upper and lower GI bleeding in rhesus macaques. For highest sensitivity, gFOBT should be performed on three fecal samples collected 24 hours apart.

YERSINIA PSEUDOTUBERCULOSIS INFECTIONS IN PRIMATES, ARTIODACTYLS, AND BIRDS WITHIN A ZOOLOGICAL FACILITY IN THE UNITED KINGDOM.

Infection with Yersinia pseudotuberculosis can be difficult to diagnose and treat successfully. Twenty-four cases from the Zoological Society of London (ZSL) London Zoo and ZSL Whipsnade Zoo were identified between 2001 and 2019. Husbandry, medical, and postmortem records for six primates, 10 artiodactyls, and eight birds were reviewed to identify common clinical signs and gross lesions. Most cases occurred during the winter; however, an outbreak in four primates occurred during the summer following a period of stress associated with increased ambient noise and activity. Common clinical signs included lethargy (6/6 primates, 4/10 artiodactyls, 4/8 birds) or death without premonitory signs (3/10 artiodactyls, 4/8 birds). Once clinical signs were observed, disease progressed quickly. Poor condition was common in mammals (6/6 primates, 9/10 artiodactyls), but often went undetected until postmortem examination. Neurological signs occurred in three of six primates. Diarrhea and anorexia were uncommon in all animals. Hepatitis was observed in all groups (4/6 primates, 2/10 artiodactyls, 4/8 birds), mesenteric lymphadenomegaly was common in mammals (4/6 primates, 8/10 artiodactyls), and gastroenteritis was common in artiodactyls (7/10). Erythematous, punctate rashes, which have only been reported with yersiniosis in humans, were present in three of six primates. Bacterial cultures from the liver in primates and birds or enlarged mesenteric lymph nodes in artiodactyls were often diagnostic. All isolates were susceptible to marbofloxacin, oxytetracycline, streptomycin, ceftazidime, amoxicillin clavulanic acid, trimethoprim sulfamethoxazole, azithromycin, and doxycycline, and resistant to clindamycin. Histopathology and Perl's Prussian blue stains were performed on available liver samples (n = 18). Intracellular hemosiderin was present in 17 of 18 cases. Additional research is needed to determine if there is a relationship between hemosiderosis and yersiniosis.