Uterine infarctions in cynomolgus monkeys (Macaca fascicularis)

Uterine infarctions have not been reported in domestic animals, and there are few reports in the human medical literature. In a retrospective study, uterine infarctions were identified in 9 of 323 (2.8%) female cynomolgus monkeys (Macaca fascicularis) necropsied over a 13-year period. The infarctions were grossly visible, after fixation, on the serosal surface of the uterus in 2 monkeys; the remainder were first recognized in histologic sections. Histologically, the lesions consisted of well-demarcated regions of endometrial and myometrial necrosis and of hemorrhage. All affected monkeys had histologic evidence of a previous pregnancy, which included enlarged myometrial vessels with an expanded perivascular matrix. In all monkeys with uterine infarctions, there was clinical evidence of severe systemic illness, which included trauma, diarrhea, hypovolemia, or septicemia. The major pathologic findings in affected monkeys included cutaneous or skeletal muscle necrosis (n = 5), enterocolitis (n = 4), pulmonary edema or diffuse alveolar damage (n = 3), and intestinal amyloidosis (n = 1). Histopathologic evidence of intravascular fibrin thrombi in multiple organs of 5 monkeys was consistent with a diagnosis of disseminated intravascular coagulopathy (DIC). Based on these findings, it appears that uterine infarction is an uncommon finding in cynomolgus monkeys and may occur secondary to a severe systemic illness, predisposing to DIC.     

Hepatic alveolar echinococcosis in cynomolgus monkeys (Macaca fascicularis)

Alveolar echinococcosis was diagnosed in 12 cynomolgus monkeys (Macaca fascicularis) at postmortem examination within a period of 6 years. Besides consistent involvement of the liver, parasitic lesions were also present in mesenteric lymph nodes, pancreas, lung, and kidney. In the liver, various patterns of host's responses to parasitic tissue could be distinguished. Infiltration of macrophages, often multinucleated, around usually intact metacestodes was the main feature of one pattern. A second pattern was characterized by the presence of abundant, normally degenerate granulocytes in addition to macrophages surrounding collapsed laminated structures. Finally and as a third pattern, some cysts were surrounded by marked collagen deposition, which was usually not a significant feature of the other foci. Parasitic cysts with protoscolices were observed in foci with the first and third pattern but not in the second one. The simultaneous occurrence of all three patterns was observed in most animals. Type AA amyloid was identified either in the space of Dissé, macrophages or blood vessel walls in nine animals using immunohistochemistry. Identity of parasitic structures such as metacestodes of Echinococcus multilocularis was confirmed immunohistochemically. All animals that could be tested serologically (7/12) had detectable antibodies against the E. multilocularis-specific Em2 antigen. Liver lesions of six animals were additionally analyzed by polymerase chain reaction, yielding the amplification of a specific E. multilocularis DNA fragment in each case.     

Cryptosporidium muris-like infection in stomach of cynomolgus monkeys (Macaca fascicularis)

Abstract. Protozoa were present in routine sections of the gastric fundus of 15 cynomolgus monkeys (Macaca fascicularis) that were being studied in three toxicity studies with novel immunosuppressive agents. Upon detailed light microscopic and ultrastructural evaluation, all stages of parasite development (trophozoites, schizonts, gamonts, and oocysts) were seen and they structurally resembled Cryptosporidium muris, which normally is found in stomachs of rodents. Cryptosporidia were primarily present in the upper one third of fundic glands that were often concurrently colonized by a Helicobacter heilmannii-like organism; however, no clear correlation was found between bacterial burden and the number of protozoa. The primarily mononuclear cellular infiltrate appeared to coincide with the presence of protozoa only in a few animals. Changes in mucous epithelial cells mainly occurred in animals that were part of a 39-week study. Mucous epithelial cells in affected glands contained an increased amount of mucus composed of predominantly acid mucosubstances compared to the normally present neutral mucosubstances. C. muris-like protozoa are newly recognized etiologies for opportunistic infections in the stomach of immunocompromized nonhuman primates. This is the first report of C. muris-like parasite in stomachs of monkeys.     

Epizootic of tularemia in an outdoor housed group of cynomolgus monkeys (Macaca fascicularis)

Tularemia is a highly contagious infectious zoonosis, transmissible by inoculation, ingestion, or inhalation of the infectious agent Francisella tularensis. The disease is perpetuated by infected rodents, blood-sucking arthropods, and by contaminated water. Therefore, nonhuman primates housed outdoors may be at risk for exposure. An epizootic of F. tularensis occurred in an indoor/outdoor-housed group of cynomolgus monkeys (Macaca fascicularis) at the German Primate Center. Tularemia was diagnosed in 18 out of 35 animals within a period of 2 years. Six animals died with unspecific clinical symptoms; 12 animals developed seroconversion and were still alive. Pathologic findings were similar in all monkeys that died and resembled the clinical picture of the human disease, including an ulceroglandular syndrome with local lymphadenopathy, gingivostomatitis, and systemic spread, with manifestations such as subacute necrotizing hepatitis, granulomatous splenitis, and pneumonia. Tularemia was diagnosed by culture, real-time polymerase chain reaction, and ELISA techniques. This is the largest outbreak in nonhuman primates and the first report of tularemia in cynomolgus monkeys. An overview of the recent literature about tularemia in nonhuman primates is given.     

Spontaneously occurring hepatocellular neoplasia in adolescent cynomolgus monkeys (Macaca fascicularis)

Spontaneous hepatic neoplasms were identified in two adolescent (<5 years of age) male cynomolgus monkeys (Macaca fascicularis). Monkey No. 1 had a solitary hepatocellular carcinoma (HCC). Monkey No. 2 had multiple discrete tumors consisting of several poorly circumscribed HCCs and a mixed hepatocholangiocellular carcinoma (MHC). Metastases were not evident in either monkey. Histochemical and immunohistochemical stains were used to assess phenotypic alterations in the tumors. Many or most neoplastic hepatocytes (NHs) of both monkeys stained positive for low-molecular-weight cytokeratin (LMWCK), cytokeratin (CK) 8, and CK 18. In monkey No. 1, small aggregates of NHs were positive for carcinoembryonic antigen (CEA), glutathione S-transferase-pi (GST), and alpha-fetoprotein (AFP), but NHs were uniformly negative for CK 7. NHs in monkey No. 2 were negative for CEA and AFP but were multifocally positive for GST and CK 7. Broad-spectrum cytokeratin (BSCK), high-molecular-weight cytokeratin (HMWCK), and CK 19 did not react with NHs of either animal. Neoplastic cells forming ductlike structures in the MHC of monkey No. 2 stained with LMWCK, CK 7, CK8, CK 18, BSCK, and GST but not with HMWCK or CK 19. Tumors in both monkeys had enhanced pericellular fibronectin staining. Nonneoplastic parenchyma of both monkeys contained multiple discrete foci of cellular alteration and scattered aggregates of hepatocytes with strong cytoplasmic staining for fibronectin. Staining patterns of these tumors demonstrate immunophenotypic heterogeneity of the neoplastic cells within individual tumors and variability among tumors. This information may serve as a useful reference for others encountering similar lesions in primates.     

Microfilarial granulomas in the spleens of wild-caught cynomolgus monkeys (Macaca fascicularis)

Splenic nodules from 38 cynomolgus monkeys (Macaca fascicularis) which were captured in Malaysia and Indonesia were studied histologically. The lesions were characterized by well-circumscribed focal fibrosis, accumulation of eosinophils and histiocytes, hemorrhage or hemosiderosis, and loss of normal splenic architecture. Small arteries in the lesion frequently had intimal thickening and narrowing of the lumen in addition to the presence of microfilariae. Microfilariae were also seen in the extravascular area of the lesion, and were occasionally engulfed by multinucleated giant cells. The splenic lesion was thought to have been initiated by incomplete infarction caused by intimal thickening and microfilarial occupation of the small arteries.     

Prevention of immune responses to human erythropoietin in cynomolgus monkeys (Macaca fascicularis)

Genes and proteins of human origin are often administered to monkeys for research purposes, however, it can be difficult to obtain sufficient levels of the products in vivo due to immunological clearance. In this study, we showed that human erythropoietin (hEPO) induces generation of anti-hEPO antibody in cynomolgus macaques (n=2), although 92% of amino acid residues are common between the human and macaque EPO. The administered hEPO was thus eliminated from the animals. On the other hand, when an immunosuppressant, cyclosporin A (CyA), was administered (6 mg/kg) intramuscularly every other day in combination with hEPO (n=2), no anti-hEPO antibody was generated and high serum levels of hEPO were obtained during administration of hEPO, resulting in an increase in serum hemoglobin levels. No adverse effects associated with CyA were observed. Thus, CyA treatment is useful for prevention of immune responses associated with the administration of human proteins in monkeys.     

Measles in the cynomolgus monkey (Macaca fascicularis)

The measles virus is known to infect several species of monkeys. A group of 87 cynomolgus monkeys (Macaca fascicularis) was screened to observe whether there was an association between measles and the cold symptoms seen in most of the animals. Another 23 monkeys were vaccinated with attenuated measles vaccine and their antibody titres monitored to ascertain whether the vaccine would protect them against measles.     

Semiautomated analysis of alkaline phosphatase isoenzymes in serum of normal cynomolgus monkeys (Macaca fascicularis)

Alkaline phosphatase (ALP) isoenzyme analysis, using a combination of wheat germ lectin (WGL) precipitation, levamisole inhibition and an automated p-nitrophenylphosphate assay was validated for use with serum from monkeys (Macaca fascicularis) and used to determine the activities of liver ALP (LALP), bone ALP (BALP) and intestinal ALP (IALP). Based on serial dilution studies and within-run and between-run coefficients of variation, each assay had excellent linearity and acceptable precision. In addition, liver and intestinal mucosa extracts for tissue specific alkaline phosphatases were used to confirm assay validations. Gender-specific differences for total ALP, LALP, and BALP activities were present in sera from normal monkeys between 2 and 4 years of age. Males had 1.3-fold higher total ALP and LALP activities, and 1.5-fold higher BALP activity compared with females. The majority of ALP activity in normal monkey serum was LALP isoenzyme activity, which ranged from 56.7% to 94.7% of total activity. Serum BALP activity ranged from 5.3% to 42.8%. There was negligible IALP activity in all serum samples.     

Collagenofibrotic glomerulonephropathy in a cynomolgus macaque (Macaca fascicularis)

Collagenofibrotic glomerulonephropathy (CFGN) is characterized by the deposition of type III collagen within the mesangial matrix and the absence of mesangial cell proliferation. A case of CFGN in a 2.7-year-old female cynomolgus macaque was investigated in the present study. Clinically, the animal was shown to have severe systemic edema along with hypoproteinemia. At necropsy, the kidneys were swollen and pale. The glomerular lesions were characterized by massive diffuse and global accumulation of fibrous materials in the mesangial areas. Neither mesangial cell proliferation nor changes in other organs were found. The fibrous materials were confirmed by the results of immunohistochemical and electron microscopic findings to consist mainly of randomly arranged, curve-shaped, twisted, and entwined type III collagen. This is the first case report of CFGN in nonhuman primates to date.     

Thoracic mass in a cynomolgus macaque (Macaca fascicularis)

A male cynomolgus macaque at the age of 3 years and 11 months suffered sudden cardiac arrest during a surgical operation. This animal had been clinically asymptomatic for 6 months from the acclimatization period to death. At necropsy, a white mass approximately 5 cm in diameter was found at the base of the heart. Histopathologically, the mass consisted of a granuloma with a number of multinucleated giant cells and multiple necrotic foci. Fungal hyphae characterized by parallel cell walls, distinct septa, and branching were observed in the lesion. The granuloma extended into the thoracic lymph nodes and the subepicardium of the left atrium, compressed the bronchioli, and was separated from the pulmonary parenchyma by a thick fibrous layer. The hyphal morphology and results of polymerase chain reaction assays demonstrated that the pathogen was Aspergillus sp.     

Polyarteritis nodosa in a cynomolgus macaque (Macaca fascicularis)

Polyarteritis nodosa (PAN) is an idiopathic necrotizing vasculitis affecting small- to medium-sized arteries. The disease is well recognized in humans, and PAN-like syndromes have been described in a number of other species. This report describes a case of PAN in a 6-year-old male cynomolgus macaque. The animal had necrotizing arteritis affecting vessels in the kidney, small intestine, colon, heart, spleen, mesentery, urinary bladder, and pancreas. The lesions were segmental in distribution and of varying severity and stage of development. A transmural mixed inflammatory cell infiltrate was present, often accompanied by fibrinoid necrosis of the tunica media and loss of the internal elastic lamina. Immunohistochemical staining showed that many of the infiltrating cells were T lymphocytes and histiocytes, suggesting a cell-mediated component to the pathogenesis.     

Experimental Toxocara canis infection in cynomolgus macaques (Macaca fascicularis)

Visceral larva migrans was produced in 16 cynomolgus macaques (Macaca fascicularis) experimentally inoculated with 45,000 embryonated eggs of Toxocara canis as a single bolus or in 3 divided doses. The hematologic and serologic changes were similar to those observed in children with visceral Toxocara infection. Neurologic signs developed in 3 animals and were characterized by ataxia and nystagmus. Growth rates were diminished in inoculated animals when compared with the rates in noninoculated controls. Diagnostic antibody titers as measured by enzyme-linked immunosorbent assay were noted in all inoculated macaques by the 4th week, and these titers persisted during the 7-month period of observation. Antibody to Toxocara was not detected in the aqueous or vitreous humors. Lesions comprised severe granulomatous hepatitis and encephalomyelitis. Intraocular lesions associated with larval migration were not observed.     

Minimum infusion rate of alfaxalone for total intravenous anaesthesia after sedation with acepromazine or medetomidine in cats undergoing ovariohysterectomy

ObjectiveTo determine the induction doses, then minimum infusion rates of alfaxalone for total intravenous anaesthesia (TIVA), and subsequent, cardiopulmonary effects, recovery characteristics and alfaxalone plasma concentrations in cats undergoing ovariohysterectomy after premedication with butorphanol-acepromazine or butorphanol-medetomidine.Study designProspective randomized blinded clinical study.AnimalsTwenty-eight healthy cats.MethodsCats undergoing ovariohysterectomy were assigned into two groups: together with butorphanol [0.2 mg kg^?1 intramuscularly (IM)], group AA (n = 14) received acepromazine (0.1 mg kg^?1 IM) and group MA (n = 14) medetomidine (20 μg kg^?1 IM). Anaesthesia was induced with alfaxalone to effect [0.2 mg kg^?1 intravenously (IV) every 20 seconds], initially maintained with 8 mg kg^?1 hour^?1 alfaxalone IV and infusion adjusted (±0.5 mg kg^?1 hour^?1) every five minutes according to alterations in heart rate (HR), respiratory rate (f_R), Doppler blood pressure (DBP) and presence of palpebral reflex. Additional alfaxalone boli were administered IV if cats moved/swallowed (0.5 mg kg^?1) or if f_R >40 breaths minute^?1 (0.25 mg kg^?1). Venous blood samples were obtained to determine plasma alfaxalone concentrations. Meloxicam (0.2 mg kg^?1 IV) was administered postoperatively. Data were analysed using linear mixed models, Chi-squared, Fishers exact and t-tests.ResultsAlfaxalone anaesthesia induction dose (mean ± SD), was lower in group MA (1.87 ± 0.5; group AA: 2.57 ± 0.41 mg kg^?1). No cats became apnoeic. Intraoperative bolus requirements and TIVA rates (group AA: 11.62 ± 1.37, group MA: 10.76 ± 0.96 mg kg^?1 hour^?1) did not differ significantly between groups. Plasma concentrations ranged between 0.69 and 10.76 μg mL^?1. In group MA, f_R, end-tidal carbon dioxide, temperature and DBP were significantly higher and HR lower.Conclusion and clinical relevanceAlfaxalone TIVA in cats after medetomidine or acepromazine sedation provided suitable anaesthesia with no need for ventilatory support. After these premedications, the authors recommend initial alfaxalone TIVA rates of 10 mg kg^?1 hour^?1.     

Icterus and amaurosis caused by lead poisoning in a cynomolgus monkey (Macaca fascicularis)

The diagnosis and treatment of a case of lead poisoning in a cynomolgus monkey (Macaca fascicularis) are described. The clinical signs were jaundice and amaurosis. Clinicopathological findings suggested cholestasis. A tentative diagnosis of lead poisoning was made when basophilic stippling of erythrocytes was observed in a peripheral blood smear. The diagnosis was confirmed by finding a lead concentration of 2280 micrograms/litre in a venous blood sample. Cage bars painted with red lead appeared to be the source of the poison. The lead was chelated by the intramuscular administration of 2,3 dimercapto-1-propanol (BAL) and calcium disodium edetate for seven days, followed by oral D-penicillamine for five weeks. The encephalopathy was treated with dexamethasone sodium phosphate. Recovery from the blindness was noted after 10 days and marked improvement of the general well being of the animal was observed after one month.     

Congenital cystic adenomatoid-like malformation in a cynomolgus monkey (Macaca fascicularis)

Congenital cystic adenomatoid malformation (CCAM) is a developmental lung abnormality characterized by abnormal proliferation of mesenchymal elements and failure of bronchiolar structures to mature, ultimately resulting in the compression of normal pulmonary tissue and mediastinal shift with rapid expansion of cysts. Although various clinical and pathologic studies of CCAM in humans exist, CCAM has yet to be reported in animals, even in nonhuman primates. In the present study, histopathologic analyses of a neonatal cynomolgus monkey that died 17 days after birth revealed that normal lung architecture was replaced by disorganized overgrowths of cysts lined with simple cuboidal epithelium. The epithelium projected a few ciliates into the air spaces and produced mucus. To our knowledge, this is the first case study describing CCAM or a CCAM-like lesion in nonhuman primates.     

Detection of Echinococcus multilocularis infection in a colony of cynomolgus monkeys (Macaca fascicularis) using serology and ultrasonography.

Five animals in a colony of cynomolgus monkeys (Macaca fascicularis) died or were euthanatized because of alveolar echinococcosis, during a period of 5 years. The remainder of the colony was screened for possible infection with Echinococcus multilocularis, using serology and ultrasonography. A total of 46 animals out of a group of 55 were examined. The presence of anti-Em2 antibodies analyzed with enzyme-linked immunosorbent assay was demonstrated in 3 monkeys. In 2 of these 3 monkeys, multilocular structures compatible with metacestodal cysts in the liver were identified, using ultrasonography. The presence of alveolar echinococcosis was subsequently confirmed at postmortem examination in 1 animal. The other animals are still alive. Two other monkeys were negative in the serological examination but had cystic structures in the liver, which were identified as bile duct cysts at postmortem examination in 1 animal. The other monkey is still alive. These findings suggest that serology for antibodies against the Em2 antigen may represent a useful method in identifying animals that might be infected with E. multilocularis and are therefore at risk of developing fatal alveolar echinococcosis.